Embryopathy. Pathology of intrauterine development. Gametopathy, blastopathy, embryopathy and fetopathy. The importance of critical periods in the pathology of intrauterine development
Embryophetopathies: pathogenesis, clinical picture, diagnosis, prevention
Yu.I. Barashnev
Embryofetopathies: pathogenesis, clinical picture, diagnosis, prevention
Scientific Center for Obstetrics, Gynecology and Perinatology named after IN AND. Kulakova, Moscow
The article presents modern ideas about the pathogenesis, clinical picture, diagnosis and prevention of congenital malformations of the brain. Particular attention is paid to congenital errors in histogenesis (9-40 weeks of gestation). Violation during this period of the processes of proliferation, migration and differentiation of nerve cells, as well as the processes of synaptogenesis and stabilization of connections in the already formed brain leads to a disorder of its functions. In this case, the cardinal symptoms are delayed psychomotor development and seizures. The first clinical signs are found in the neonatal and early postnatal periods of development. With the help of magnetic resonance imaging, a number of internal deformities of the brain and especially the cerebral cortex are revealed.
Key words: newborn children, embryopathies, fetopathies, congenital malformations.
The paper gives the present views of the pathogenesis, clinical picture, diagnosis, and prevention of congenital brain malformations. Special attention is given to innate errors in histogenesis (9-40 weeks of gestation). Impairments in nerve cell proliferation, migration, and differentiation in this period and those in synaptogenesis and stabilization of connections in the already formed brain lead to its dysfunction. Moreover, retarded psychomotor development and cramps are cardinal symptoms. The first clinical signs are detectable in neonatality and early postnatality. Magnetic resonance tomography reveals a number of internal malformations of the brain, and cerebral cortex in particular.
Key words: neonatal infants, embryopathies, fetopathies, congenital malformations.
The main criterion for success in perinatal medicine is considered to be a decrease in the rates of perinatal morbidity and mortality, as well as the morbidity of newborns. The use of high medical technologies has radically changed the situation in all civilized countries. The main difficulties exist only in the provision of medical care to high-risk pregnant women and newborns. At the same time, great importance is attached not only to preserving the life of newborns through the use of new technologies (intensive therapy and resuscitation), but also to the quality of their health. When analyzing the health status of such newborns, the term "increased survival" is used, which implies a pessimistic prognosis of their subsequent development.
It is surprising that the creation and implementation of new prenatal diagnostic technologies did not lead to any significant decrease in
Original Russian Text © Yu.I. Barashnev, 2010
Ros Vestn Perinatol Pediat 2010; 4: 6-12
Correspondence address: Barashnev Yuri Ivanovich - Doctor of Medical Sciences, Prof., Department of Newborns of the Scientific Center for Obstetrics, Gynecology and Perinatology named after V.I. IN AND. Kulakova 117997 Moscow, st. Academician Oparin, 4
the frequency of congenital malformations. It remains within the same limits. Moreover, according to modern data, 20-30% of infant mortality and 30-50% of postnatal mortality are due to precisely recorded malformations. A certain stability of these indicators is also convinced by the data of the children's hospital, which analyzed the activities over the past 40 years. Approximately 18% of hospitalized children had birth defects of Mendelian or chromosomal origin; more than 40% of admissions to surgical departments were associated with congenital anomalies. Modern data are convincing that chromosomal abnormalities occurred in 3.9% of deceased newborns. At the same time, malformations of the heart are recorded in 22.2% of deceased children, malformations of the nervous system - in 12.2%, of the urogenital tract - in 5.9%, of the musculoskeletal system - in 7.3%. All this allows us to assert that the problem of congenital malformations, despite the achievements in this area, in no way loses its relevance and still needs intensive scientific research.
Depending on the timing of formation, several types of congenital malformations are distinguished.
Gametopathies and blastopathies occur in the early stages of gestation (the stage of a fertilized ovum-zygote or 4-15 days after fertilization). The pediatrician usually does not face these outcomes of missed pregnancies. This is the lot of obstetricians. Most pregnancies end in spontaneous abortions or stillbirths.
The doctor can theoretically only deal with embryopathies and fetopathies. These terms are well known. Embryopathies include pathology that arose from the 16th day after fertilization to the end of the 8th week of gestation. Fetopathies are fetal injuries resulting from the harmful effects of various factors from the 9th to the 40th week of intrauterine development. However, it is noteworthy that the diagnosis of embryopathy appears in the case histories of newborns often, and the diagnosis of fetopathies is extremely rare. Even in cases where the term "fetopathy" is used, it is not deciphered, its basis remains unclear. What is the difference between embryopathy and fetopathy?
The term "embryopathy" means congenital errors of morphogenesis. The biological bases of dysmorphogenesis are associated with harmful effects in the early stages of embryogenesis. Epidemiological studies based on the results of monitoring more than 2 million newborns made it possible to assert that gross, multiple birth defects occur at the stage of blastogenesis. This is due to the fact that in the early period of embryogenesis, the organs of the unborn child are laid. This position can be clearly demonstrated by the example of the formation of the central nervous system. The neural plate of the embryo, which appeared in the 3rd week of gestation, is intensively forming and by the beginning of the 2nd month (!) Has the rudiments of all parts of the brain and spinal cord. Thus, primary neurulation occurs at 3-4 weeks of gestation, and the formation of a neural tube and its sewerage - at 4-7 weeks. In parallel (at the 5-6th week of gestation), other equally important transformations occur, and above all the anlage of the forebrain, which includes the final (telencephalon) and intermediate (diencephalon) brain. Defects that arise in the phase of proencephalization are distinguished by gross morphological changes in the most important structures of the forebrain. In this case, hereditary factors play a huge role, as evidenced by the existence of more than 1759 hereditary nosological forms and more than 1000 congenital syndromes, accompanied by gross changes in morphogenesis.
The significance of the stage of blastogenesis and the stage of gastrula is explained by the fact that during this period of embryo development, activation of tissue-specific proteins and cell differentiation begins.
The period of organogenesis is characterized by the greatest
gene activity, and the overwhelming majority of mutant genes show their activity during this period, which contributes to the formation of malformations.
According to the modern classification, congenital and hereditary errors of morphogenesis are attributed to four groups:
Progenetic group (gonadogenesis, gametogenesis, including a large number of abnormalities);
Blastogenesis group (first 4 weeks of development);
Organogenesis group (5-8th week of gestation);
Fetogenesis group (9-40th week of gestation).
Diagnosis of blunders of morphogenesis is usually
does not present any particular difficulties, developmental anomalies are obvious. Difficulties at the attending physician are associated with the allocation of specific nosological forms.
Prenatal diagnostics is a huge achievement of recent decades, which has made it possible to create a reliable system for the prevention of congenital morphological developmental defects. An example of a really operating system can be the many years of experience of the Scientific Center for Obstetrics, Gynecology and Perinatology. This work on the active diagnosis and prevention of congenital malformations is based on close interaction of obstetricians, functionalists, geneticists, neonatologists, surgeons, etc. A decision is collegially made, agreed with the woman, on the preservation or termination of pregnancy, on the possibility of providing surgical care to the newborn. The experience of this interaction is reflected in the monograph “High-risk newborns. New diagnostic and treatment technologies "(2006).
A retrospective analysis of the results of prenatal diagnosis of CNS malformations at the Scientific Center for Obstetrics, Gynecology and Perinatology (L.A. Petrova) showed that over a five-year period (2000-2005) neural tube defects were detected in 164 cases, including 106 (64%) fetuses and 58 (36%) newborns. Among the prenatally diagnosed congenital defects of the neural tube were anencephaly, holoprosencephaly, myelomeningocele, spina bifida, agenesis of the corpus callosum, hydrocephalus, etc. Based on a decision agreed with women, 59 of them (out of 106) had pregnancy terminated. Thus, the birth of 59 children with gross and irreversible brain pathology was prevented.
As an example, we can present the results of prenatal diagnosis in 33 fetuses with gross external-internal hydrocephalus. The timing of prenatal diagnosis ranged from 17 to 38 weeks of gestation: up to 25 weeks of gestation in 21 women, 26-38 weeks of gestation in 8 women (due to late treatment). Pregnancy was terminated in 22 women, childbirth took place in 11
shin at 37-38 weeks of gestation. Of the 11 children born, one child died in childbirth, 4 were discharged home, and 6 of the children were abandoned by their mothers in the maternity hospital.
As the methods of prenatal diagnostics were introduced, it became obvious that they were aimed not only at preventing the birth of children with gross irreversible malformations, but also at providing timely highly qualified assistance to newborns with corrected birth defects.
A completely different group is represented by diseases of the nervous system related to fetopathies.
The term "fetopathy" should be understood as disorders that occur in the period of 8-40 weeks of gestation and are assessed, in contrast to embryopathies, as congenital errors of histogenesis. If in the early stages of embryogenesis (before the 8th week of gestation) the organs of the unborn child are laid, then at 9-40 weeks no less important formation processes take place - the improvement of the internal structures of the brain (the phase of histogenesis). These processes are extremely vulnerable and determine the quality of subsequent postnatal life. These include:
Neuronal proliferation (2-4 months of gestation);
Migration of nerve cells (3-5th month of gestation);
Differentiation of nerve cells;
Apoptosis;
Growth processes of nerve processes;
Synaptogenesis;
Formation of cell aggregates (6th month of gestation);
Stabilization of nerve connections;
Myelination.
Violations of the normal course of the processes of internal improvement in the developing nervous system lead to developmental abnormalities that are detected soon after birth or during the first year of a child's life. The specificity of these congenital histogenesis defects is as follows.
With violations of the processes of neuronal proliferation (2-4 months of gestation), an abnormal formation of the cerebral hemispheres occurs in combination with microgyria and polygyria. The corpus callosum may be absent, porencephalia and changes in the basal ganglia are found.
In case of disturbances in the phase of neuronal migration, the migration of nerve cells to the brain zones "intended" for them by the genetic program changes, which leads to changes in the structures and functions of the central nervous system, neuronal heterotopies ("lost" nerve cells), agiria, pachigiria, polymycrogyria, agenesis of the corpus callosum are found and etc. .
With violations in the phase of differentiation of nerve cells, a number of other gross deviations occur. In the process of differentiation, a large role belongs to intercellular interaction and such processes as induction, recognition and adhesion, which determine not only the determination of the potencies of neuroepithelial cells, but also the directed growth of axons and the formation of specific nerve connections. Differentiation leads to the fact that the emerging types of nerve cells differ from each other in biochemical and physiological characteristics, as well as their localization in the nervous system.
In the phase of organization, when most of the brain structures are normally already formed, no gross brain defects are found. Basically, we are talking about changes in the ultrastructures of brain tissues, in particular, the occurrence of dendritic anomalies. They are the basis for delayed psychophysical development, mental retardation with EEG changes and the manifestation of myoclonic seizures (!). These new data are of extreme importance for elucidating the true genesis of the so common undifferentiated developmental delay and subsequent oligophrenia.
Disruption of myelination processes occurs in many congenital and hereditary diseases. At the same time, movement disorders, seizures and mental retardation, autism, behavioral disorders and schizophrenia come to the fore in the clinical picture.
The first signs of dysfunction in the functioning of various organs and systems can appear in children from the moment of birth in the form of respiratory and cardiovascular disorders, depression and hyperexcitability syndrome, convulsive readiness, attacks of cyanosis and even sudden death. In recent years, researchers have succeeded in elucidating the hereditary component of the detected congenital changes in the histogenesis of the cortex, identifying the genes responsible for disorders of cortical development. Thus, mutations in the FLNA / Filamin1 (Xq28) gene have been identified in bilateral perivetricular heterotopy accompanied by epilepsy; with classic lissencephaly (MSer-Dieker syndrome) - mutations of genes localized in the 17p13.3 region. In other forms of lissencephaly, accompanied by mental deficiency and epilepsy, mutations in the adjacent RABAN1B1 and LIS1 genes have been established. Lisencephaly linked to the X chromosome is caused by mutations in the LISX1 and DCX genes (region Xq22.3-q23); in boys, this form is more severe than in girls.
When studying the pathogenesis of the occurrence of such cardinal symptoms of congenital errors, histo-
genesis, as mental failure and seizures, the results of histological studies are of particular interest. They demonstrate a spectrum of changes in different parts of the brain - in the cellular structure, in the distribution of neurons, in a decrease in the number of inhibitory GABA-ergic neurons in the chain, in damage to the glutamate receptor in dysplastic neurons. From the entire list of possible causes, an imbalance of glutaminergic excitation and GABA-ergic inhibition is distinguished. This assumption is based on the results of experimental studies, which clearly show the presence of an imbalance between the receptors of excitation and inhibition. Animals with undifferentiated GABA receptors develop spontaneous epilepsy, hyperalgesia, and memory impairment, although their brain morphology appears to be normal. The impaired activity of inhibiting GABA-ergic neurons, indeed, can be the cause of epilepsy, since in the presence of heterotopies in children, immaturity of GABA-networks is revealed. This, in turn, can produce an excess of excitation compared to inhibition in the neuronal circuit, inducing pathological activity. The disrupted neural network of the brain spreads epileptogenicity in the central cortex.
It was also possible to establish that patients with focal cortical dysplasia exhibit focal cortical thickening, a simplified structure of the convolutions, which leads to early manifesting drug-resistant epilepsy.
Regional hyperexcitability may also be the result of an increased number of glutaminergic excited neurons, as is the case with cortical dysplasia and tuberous sclerosis. This suggests that there may be fundamental differences in epileptogenesis between various disorders of cortical migration and organization.
Thus, the quality of life of a child, and subsequently of an adult, is largely determined by how harmoniously the CNS histogenesis phase proceeded, since when its normal course is disturbed, various fetopathies or congenital histogenesis errors are formed. In the process of differentiation of cerebral cortex defects, the modernized classification A Barkovich (2001) is used, which is based on data on the stages of brain development, the significance of pathological neurological symptoms, the results of genetic and neurovisual studies (computed and magnetic resonance imaging).
CONCLUSION AND DISCUSSION
In recent decades, there has been an intense
active study and formation of ideas about the molecular bases of the morphogenesis of congenital defects. On this database, the concept of the causes of malformations was developed, the general principles of differentiation and morphogenesis and, in particular, the characteristics of the development of the nervous system were proposed. These studies emphasize that the origins of the formation of the modern concept of the emergence of congenital malformations originate in the last century. One of the great achievements of this period is the use of human biochemical genetics to explain many of the complex details of intermediate metabolism. The knowledge gained about normal biochemical processes and their genetic control made it possible to understand deviations from the norm. In this regard, Archibald Garrod is recognized as the founder of human biochemical genetics. Subsequently, a broader panorama of congenital metabolic errors was presented in the works of G. Harris, C. Scriver, W. Stanbury and others. In turn, D. Smith in 1970 was able to collect a huge collection of congenital syndromes accompanied by morphogenetic disorders. It is used by clinicians as a “bible” for recognizing congenital syndromes.
However, in the 70s of the last century, there was no conceptual explanation for the genetic mechanisms that cause congenital syndromes. With the discovery of enzymes and their role in the occurrence of conditions such as mucopolysaccharidosis, osteogenesis imperfecta, thoughts appeared about the pathogenetic role of enzymes and structural proteins (collagen, fibrillin). The nineties of the last century were marked by reports of gene mutations. It has been shown that transcription factors, receptors of various types, growth factors, cell adhesion molecules, gap junctions and G-proteins cause congenital developmental abnormalities, which are the result of either spontaneous or induced mutations. Subsequent intensive research made it possible to formulate the general principles of the processes of differentiation and morphogenesis.
During the last decade, new knowledge has been added to the basic principles of developmental biology. They cover:
Differentiated gene expression mechanisms;
Combinatorial logic of amplification and activation;
Signal transduction;
Mechanisms of the formation of hereditary syndromes;
Mechanisms of dominant or recessive transmission of traits;
Repertoire of morphogenetic interactions and their molecular implications;
The role of stochastic variability in morphogenesis.
From a clinical standpoint, the topic under discussion is extremely important, since it allows for a new assessment of a seemingly well-known pathology. For many years, the opinion was formed that for the emerging new life, the first 8 weeks after fertilization pose a particular risk. It was believed that after this high-risk period (blastogenesis), the further development of the fetus would proceed relatively safely and without the appearance of gross defects in it. If we agree with the term "embryopetopathy", then it should be recognized that at all stages of intrauterine development of the embryo and fetus there is always a potential risk of perverting the normal course of embryo or fetogenesis.
The state of the problem looks completely different from new positions when it comes to fetopathies, the presence of which no one denies, but practically no one diagnoses. The data given on what important processes of maturation of already formed brain structures occur in the fetal period (9-40 weeks of gestation) convince that harmful effects at these stages of fetogenesis can and do lead to congenital errors in histogenesis or to abnormalities of the internal structures of the brain, and in the future and to violations of its basic functions. The genesis of neuropsychiatric disorders (mental retardation, tendency to convulsive states, behavioral disorders, etc.) often remains unclear for the attending physician. Only subsequent targeted study of congenital errors in brain histogenesis can create the basis for understanding the pathogenetic mechanisms of mental retardation and epilepsy. This, in turn, will serve as a pretext for the development of corrective therapy.
With a high degree of probability, it can be assumed that embryophetopathies most often occur in women belonging to the high-risk group, when, before the onset of pregnancy and throughout pregnancy, powerful harmful effects of both the mother's diseases themselves, which impaired her reproduction, are on the woman's body and the fetus. and a whole range of non-harmless medicines used to maintain pregnancy. The absence of visible deformities during the generally accepted scheme of prenatal diagnostics reassures the pregnant woman and the doctor, but the genesis of the appearance of a number of symptoms in newborns and children of the first year of life remains unclear - general lethargy, poor sucking, recurrent signs of cyanosis, respiratory disorders, or unexplained hyperexcitability. convulsions and even sudden death. Most often, these common symbols
It is customary to explain ptomes by two difficult-to-prove states: immaturity and hypoxia. Even in the section, in the event of the death of children, it is extremely difficult to argue for such a tragic and unexpected outcome. In those situations when it comes to lesions of the central nervous system, the most convincing evidence of congenital errors in histogenesis can be the results of computed and magnetic resonance imaging (MRI) and histological examination of brain tissue (the presence of changes in the cerebral cortex, agiria, schizencephaly, dysplasia, heterotopias - "Lost neurons", etc.).
Underestimation of neurological disorders in the neonatal period and in the early stages of postnatal development leads to the formation of a significant group of undifferentiated neuropsychiatric diseases in young children. These children (often disabled since childhood) "migrate" in search of the true cause of the disease from doctor to doctor, from city to city.
Neurological examination using MRI of this group of children, selected by life itself, convinces that in 2/3 of cases the doctors who sent children for additional examination were right when their disability was associated with the previous hypoxia. Indeed, the tomograms clearly show cerebral disorders characteristic of hypoxic effects. However, 1/3 of children in this group show clear signs of congenital underdevelopment of the brain and its individual structures - timely undiagnosed congenital errors of morpho- and histogenesis (embryophetopathy). According to our data, in 106 out of 300 such children, MRI examination revealed gross hypoplasia of the brain - cerebral hemispheres, stem structures, cerebellar worm and tonsils, subcortical nuclei. Along with this, a number of congenital malformations were diagnosed: Ki-ari anomalies, Dandy-Walker syndrome, schizencephaly, liss encephaly, heterotopias, agenesis of the corpus callosum, delayed myelination, etc.
Our own experience also convinces us that these neurovisual changes can also be found in the neonatal period in term infants with so-called dysadaptation. This pathology, of course, cannot be diagnosed in an ordinary maternity hospital. For this, regional perinatal centers are being created, the main task of which is reduced to timely and highly specialized medical care for pregnant women and newborns at high risk. The task of perinatal centers should include not only diagnostic and therapeutic measures, but also determining the future fate of the child: discharge home under the regular supervision of a district neuropathologist, transfer to a specialized clinic.
stationary, etc.
For the purpose of early detection of congenital errors in histogenesis, the advisability of changing the scheme of neuroimaging studies in both the fetus and the newborn child should be discussed. In our opinion, it is necessary to distinguish four high-risk groups.
The first group should include women who need to apply intensive measures to preserve pregnancy due to the repeated threat of its spontaneous termination. Ultrasound scanning can detect a variety of gross malformations of the fetus. However, additional use of MRI makes it possible to obtain a wider range of changes in the internal structure of the brain.
The second group should include premature newborns, whose premature birth may be a consequence of embryophetopathies, when there is a combination of congenital errors of morpho- and histogenesis. This group presents the greatest differential diagnostic difficulties.
The third group includes full-term newborns with normal Apgar scores. A feature of children in this group is a sudden deterioration in general condition (lethargy, refusal to breast, recurrent attacks of cyanosis, cardiovascular disorders, convulsive readiness or convulsions). These sudden onset disorders may be based on functional impairment due to congenital errors in histogenesis, manifested under new conditions of existence. It is necessary to include MRI in the complex of mandatory studies, and in case of sudden death of children, conduct a thorough
histological examination of the cerebral cortex and other brain structures.
The fourth group includes children of the first year of life with delayed neuropsychiatric development, mental retardation and seizures, which are cardinal symptoms of congenital histogenesis errors.
Taking into account the nature of the occurrence of embryophetopathies, it can be concluded that all newborns born to women of high risk groups need special attention. Newborns with recurrent functional disorders should be under constant medical supervision.
Without diminishing the diagnostic significance of ultrasound diagnostics in the prenatal period and postnatal life, it should be emphasized the predominant role of MRI and computed tomography in identifying congenital histogenesis errors. Regional perinatal centers should ensure the availability of such high technologies as MRI, special incubators, and others for newborns (full-term and premature). MRI and EEG should be included in the mandatory set of diagnostic measures in case of uncontrolled convulsive conditions.
Carefully collected and analyzed data of pedigree and obstetric history can provide real help in identification and urgent examination. In case of suspicion of the congenital nature of the pathology, it is necessary to use karyotiping of the child and his parents. Careful and versatile pathological control is necessary in the event of sudden and unexpected deaths.
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The frequency of congenital and hereditary pathologies in the population is on average 5% of the number of newborns. Monogenic diseases occur in 5-14 children per 1000 newborns, chromosomal diseases - in 4-7, congenital malformations - in 19-20. In the structure of perinatal mortality and morbidity in children, congenital and hereditary pathology takes 2-3 place.
The concept of "prenatal (antenatal) pathology" includes all pathological processes and conditions of the human embryo from the moment of fertilization to the birth of a child. A person's prenatal period is 280 days, or 40 weeks, after which childbirth begins.
The antenatal period begins from the moment the zygote is formed and ends with the onset of labor. From an ontogenetic point of view, it is advisable to divide the antenatal period into embryonic (from the moment of zygote formation to 12 weeks), early fetal (from the beginning of the 12th to the 29th week of intrauterine development) and late fetal (from the 29th week to childbirth).
Under the influence of unfavorable factors on the fetus in the early fetal period, there is a decrease in the mass of organs and tissues of the fetus, as well as hypoplasia of the placenta. For this period, a typical clinical manifestation of intrauterine diseases is a symmetrical form of intrauterine growth retardation (IUGR) and a pronounced failure of the uteroplacental circulation. In the late fetal period - a violation of the processes of morphological and functional maturation of the fetus. Chronic insufficiency of the uteroplacental circulation is accompanied by the development of an asymmetric form of IUGR, chronic intrauterine hypoxia of the fetus, immune and infectious factors cause acute congenital diseases - hemolytic disease of the fetus and newborn, hepatitis, pneumonia, myocarditis, encephalitis, etc.
Typical manifestations of antenatal pathology are congenital malformations - gross anatomical changes in an organ and tissues (or organ system), leading to functional disorders.
Depending on the timing of the onset of intrauterine pathology, its following forms are distinguished: gametopathy and cymatopathy (blastopathy, embryopathy, fetopathy).
Gametopathies
Gametopathy encompasses all types of damage to the male and female gametes (ovum and sperm) that occur during ovo and spermatogenesis prior to fertilization. Gametopathies are mainly due to mutations. Depending on which structures of the hereditary apparatus of the gamete the mutation has occurred, the development of various mutations is possible: gene, chromosomal or genomic.
Gametes are carriers of genes inherited from their parents and from all distant ancestors. Severe damage to gametes can lead to their death, the development of infertility and spontaneous abortions. A gamete with a defect in a gene or genes can become a source of hereditary congenital malformations.
Blastopathies
Blastogenesis pathology is limited to the first 15 days after fertilization. The main end-results of blastopathies include:
- empty germ sacs(they are formed due to aplasia or early death of the embryoblast with its subsequent resorption);
- hypoplasia and aplasia of extraembryonic organs(amnion, amniotic leg, yolk sac);
- twin malformations(symmetrical and asymmetrical, that is, twins that are not fully or partially separated);
- ectopic or ectopic pregnancy(implantation of a fertilized egg in the ovary, fallopian tube, rudimentary horn of the uterus and in the internal os of the uterus) or violation of the depth of implantation (superficial, unusually deep).
The cause of blastopathies is most often chromosomal aberrations in combination with the influence of the environment (for example, endocrine, cardiovascular diseases of the mother, hypoxia, etc.).
The developmental pathology of the entire embryo is a general disorder, in most cases incompatible with life. Most of the embryos damaged as a result of blastopathies are eliminated by spontaneous abortion, and elimination, as a rule, does not occur at the time of damage to the embryo or even its death, but somewhat later, usually after 3-4 weeks.
Embryopathies
All types of embryo pathology (from 16 to 75 days of gestation), induced by exposure to damaging factors, are called embryopathies. Embryopathies are characterized by abnormalities in the formation of organs, which ultimately end in either the death of the embryo or congenital malformations. The term "congenital malformation" should be understood as persistent morphological changes in an organ or the whole organism, occurring in utero, going beyond their possible structure and leading to functional disorders. The severity of congenital malformations is different: from minor deviations in the structure of one organ to severe changes in many organs that are incompatible with life.
Developmental microanomalies (stigma of dysmorphogenesis) are morphological changes that are not accompanied by impaired function. For example, telangiectasias, "freckles", a gray strand above the forehead, low hair growth on the forehead or on the neck, deformity of the auricles, Mongoloid and antimongoloid eye incisions, epicanthus, blue sclera, sinofrisis, smoothed filter, pterygoid folds on the neck, polythelium, arachnodactyly and etc.
Often, there is a combination of organ defects characteristic of the period of blastogenesis, with defects in which developmental disorders are observed at the level of tissue differentiation, usually in terms corresponding to the early fetal period. Thus, blastopathies are often associated with early fetopathies. Congenital malformations are very diverse, their nosological forms number in the thousands.
Congenital malformations include the following developmental disorders:
- aplasia (agenesis)- complete congenital absence of an organ or part of it. In most cases, both terms are used synonymously, however, to emphasize not only the absence of an organ, but also its rudiment, the term agenesis is used. The absence of individual parts of an organ in some cases is indicated by a term derived from the Greek word oligos (small) and the name of the affected organ (for example, "oligodactyly" - the absence of one or more fingers, "oligogyria" - the absence of individual convolutions of the brain;
- congenital hypoplasia- underdevelopment of the organ, manifested by a deficit in the relative mass or size of the organ. A decrease in the body weight of the fetus or newborn is called "congenital malnutrition (hypoplasia)". In relation to older children, the term "nanism" (dwarfism, microsomia) is used to refer to reduced body size;
- congenital hypertrophy (hyperplasia)- an increase in the relative mass (or size) of an organ due to an increase in the number (hyperplasia) or volume (hypertrophy) of cells. Macrosomia (gigantism) - an increase in the length and weight of the whole body. To indicate an increase in organs or their parts, the prefix from the Greek is used. pachis (thick) (for example, "pachigiria" - thickening of the gyrus of the brain, "pachiacria" - thickening of the phalanx of the fingers). Doubling, as well as an increase in the number of one or another organ or part of it (doubling of the uterus, double aortic arch) is indicated by the term with the prefix "poly" (from the Greek poly - a lot) (for example, "polygyria", "polydactyly", "polysplenia" );
- atresia- complete absence of a channel or natural opening;
- stenosis- narrowing of the channel or opening;
The name of the defects that determine the non-division of the limbs or their parts begins with the Greek prefix syn, sym (together), for example, "syndactyly" - non-division of the fingers, "sympodia" - non-division of the lower extremities;
-ectopia- displacement of the organ, that is, its location in an unusual place (for example, the location of the kidney in the small pelvis, the location of the heart outside the chest;
-persistence- preservation of embryonic structures that normally disappear by a certain period of development. One of the forms of persistence is dysraphia (araphia) - non-closure of the embryonic fissure (cleft lip, palate, spine, urethra);
-heterotopy- the presence of cells, tissues or entire areas of an organ in another organ or in those areas of the same organ where they should not be (for example, areas of the pancreas in a Meckel diverticulum, islets of cartilage in the lungs outside the bronchial wall). Such displacements of cells and tissues, as a rule, are detected only under a microscope. They are sometimes called choristias (from the Greek chorista - separating), in contrast to hamartia (from the Greek gamartus - an error), which is understood as an incorrect ratio of tissues, accompanied by tumor-like growth. An example of hamartia can be the proliferation of fibrous tissue in the kidney in the form of an islet devoid of epithelial structures.
Fetopathies
Fetopathy (from Lat. Fetus - fetus) is a consequence of damage to the fetus from the 12th week to the moment of birth. Distinguish between early (up to 28 weeks of gestation) and late (from 28 weeks to delivery) fetopathies. Fetopathies are characterized by the following features:
The rarity of congenital malformations caused by exposure to teratogenic factors during the fetal period;
Any damage during this period entails the development of defects at the tissue level. In this case, either an incorrect ratio of organ tissues can be observed, or a delay in their maturation.
The presence of predominantly generalized forms of infections. Characterized by multiple foci, mainly alterative inflammation in the parenchymal organs, or the presence of generalized granulomatosis (for example, with congenital listeriosis);
Infectious and toxic processes are accompanied by pronounced hemorrhagic diathesis (petechiae on the skin, mucous membranes, hemorrhages in internal organs);
There is a delay in involution and excessive proliferation of cells in the foci of extramedullary hematopoiesis;
Hypertrophy and tissue regeneration mainly due to hyperplasia of mesenchymal elements, which leads to excessive development of connective tissue (for example, with cystic fibrosis - in the pancreas, with fibroelastosis of the heart - the proliferation of elastic and fibrous tissue in the endocardium).
The concept of periodization and patterns of progenesis and kimatogenesis
The concept of "prenatal (antenatal) pathology" includes all pathological processes and conditions of the human embryo, starting with fertilization and ending with the birth of a child. The prenatal period of a person is calculated by the duration of pregnancy - 280 days, or 40 weeks, after which childbirth occurs.
The doctrine of intrauterine pathology (deformities and malformations) arose a long time ago. In the Arab medicine of the XI, XII and XIII centuries, there were already detailed descriptions of various congenital defects. Ambroise Paré (1510-1590) wrote a book about them. However, the scientific study of this issue began at the beginning of the 20th century (Schwalbe). At the same time, most researchers believed that heredity plays the main role in the development of congenital malformations in humans. Of great importance for understanding the influence of environmental factors on the formation of malformations was the discovery of the Australian ophthalmologist Gregg, who in 1951 published data on the significance of the rubella virus (rubeola) in the occurrence of multiple congenital malformations in humans. He showed that with a mother's disease with rubella in the first third of pregnancy, 12% of children develop congenital defects and stillbirth in 7.2%, 3.9 and 4.6%, respectively, in the second third of pregnancy, the fetus does not arise, and stillbirth occurs in 1.7% of cases. From that moment on, the doctrine of the possibility of manifestation of malformations in humans, caused by the influence of exogenous factors, was formed, and the data on the main value of the time of exposure of these factors to the developing embryo were confirmed.
Currently, prenatal human pathology has grown into a problem that is no less important in medicine than the problem of cardiovascular diseases, tumors and mental illnesses.
All development, from the maturation of the reproductive cell (gametes) to the birth of a mature fetus, is divided into two periods - the period of progenesis and the period of cymatogenesis (from the Greek. kyema- embryo) (Fig. 291). Period progenesis corresponds to the maturation of gametes (ovum and sperm) before fertilization. During this period, the occurrence of gamete pathology is possible - gametopathy. Depending on in which structures of the hereditary apparatus of the gamete the mutation has occurred, there are gene, chromosomal and genomic mutations. Hereditary diseases, including malformations
Rice. 291. Kimatogenesis and types of pathology of the embryo. Left - normal progenesis and cymatogenesis, right - pathology of progenesis and cymatogenesis (according to Gertler)
vitia, may be the result of gamete mutations of the child's parents (spontaneous mutations) or his distant ancestors (inherited mutations).
Period cymatogenesis calculated from the moment of fertilization and the formation of the zygote to childbirth and is divided into three periods. The first period - blastogenesis - lasts from the moment of fertilization until the 15th day of pregnancy, when the egg is cleaved, ending with the release of embryo and trophoblast. Second period - embryogenesis - covers the period of time from the 16th to the 75th day of pregnancy, when the main organogenesis is carried out and the amnion and chorion are formed. Third period - fetogenesis - lasts from the 76th to the 280th day, when the differentiation and maturation of fetal tissues, as well as the formation of the placenta, end in the birth of the fetus. The period of fetogenesis is divided into early fetal (from the 76th to the 180th day), by the end of which the immature fetus acquires viability, and the late fetal (from the 181st to the 280th
day), when the maturation of the fetus is completed with the simultaneous aging of the placenta. The pathology of the entire period of kimatogenesis is called kymatopathy. According to the periods of kimatogenesis, the following are distinguished: blastopathy, embryopathy, early and late fetopathy 1.
Etiology. After the discovery of rubeolar embryopathy, ideas about the influence of exogenous factors leading to cymatopathies expanded. This has been confirmed in numerous experimental studies.
According to modern data, 20% of malformations (the main pathology of the period of kimatogenesis) are associated with gene mutations, 10% - with chromosomal aberrations, about 3-4% - with the influence of exogenous factors, more than 60% - with an unexplained etiology. It is believed that multifactorial etiology prevails in the pathology of the embryo, i.e. a combination of hereditary and exogenous factors.
TO exogenous factors that can cause cymatopathy in humans include viruses and some other microorganisms, namely rubella, human immunodeficiency virus (HIV), measles, chickenpox, herpes simplex, hepatitis, as well as mycoplasma, listerrella, treponema, toxoplasma, less often - mycobacterium teberculosis, etc. In addition to infectious agents, kymatopathies can be caused by the influence of radiation energy (γ-rays), ionizing radiation, some drugs - thalidomide, hydantoin, phenytoin, cytostatic drugs, hormones, vitamins (in particular, vitamin D), quinine, etc., alcohol, hypoxia of various origins, endocrine diseases of the mother - diabetes mellitus, thyrotoxic goiter. Alcohol consumption during pregnancy leads to the development of alcoholic embryopetopathy, characterized by general hypoplasia, moderate prematurity, microcephaly, combined with ptosis of the eyelids, epicanthus, microgenia. Congenital heart defects are less common.
Nowadays, in connection with new methods of treatment, they have gained particular importance diabetic and thyrotoxic feto- and embryopathy. Pregnancy was rare in women with diabetes before insulin treatment. At present, the fertility of these women is the same as that of healthy women. However, in children whose mothers are sick with diabetes mellitus, malformations are more common. To the so-called diabetic embryopathy include malformations of the skeleton, cardiovascular, central nervous and genitourinary systems. Diabetic fetopathy manifests itself in the form of prematurity or the birth of a giant cushingoid fetus. With increased and decreased functions of the thyroid gland, there is a tendency to abortion and miscarriage. Among developmental defects in thyrotoxicosis
1 In the narrow sense of the word, only those diseases of the embryo that are caused by exogenous factors are referred to blasto-, embryo- and fettspathies.
anencephaly, heart defects, hypothyroidism with mental retardation - the so-called thyrotoxic embryophetopathy.
Pathogenesis. The mechanism of development of kymatopathy is currently widely studied using many modern methods. The complexity of the study lies in the fact that one has to deal with two biological objects - the mother and the embryo, the connection between which is carried out by a barrier organ - the placenta.
The first pattern characteristic of the pathology of the prenatal period with any pathogenic effect, is a mandatory distortion of the normal course of development of the embryo. Therefore, to understand the pathogenesis of prenatal pathology, it is of great importance to study the reactivity of the embryo in different periods of kimatogenesis, since the main vital function of the embryo is the continuously going process of morphogenesis. The formation processes are primarily affected by the influence of pathogenic factors.
Violation of the course of morphogenesis is called dysontogenesis. However, in different periods of kimatogenesis, disorders of dysontogenesis arise at different levels - from gross violations of the development of the embryo, incompatible with life at its early stages, to changes in the fine ultrastructures of cells and tissues at later stages. As the embryo matures, it gradually develops the ability to respond to various pathogenic influences not only by a violation of morphogenesis, but also by the development of reactive pathological processes - alteration, complete and incomplete tissue regeneration, inflammation, immunomorphological and compensatory-adaptive shifts.
The second regularity, characteristic of the pathology of the late periods of kimatogenesis is a combination of morphogenesis disorders with other pathological processes, for example, heart malformations with hyperplasia of mesenchymal tissues, cerebral malformations with the presence of necrosis, hemorrhages, etc.
The third regularity, determining the pathogenesis of any of the periods of kimatogenesis and of great importance in the development of one or another pathological state of the embryo is the time of exposure to the pathogenic agent.
So, during the period of blastogenesis, the embryo responds to any impact with a violation of the implantation of a fertilized egg or the development of an embryo- and trophoblast. During the period of embryogenesis, when the main morphogenesis of the internal organs and parts of the embryo's body is carried out, almost any damage leads to the development of one or another congenital defect or to the death of the embryo.
During the period of fetogenesis, when tissue differentiation of organs is carried out, almost any damage leads to the development of defects at the tissue level.
According to Russian embryologists, prenatal death of the embryo is more often observed at certain periods of its intrauterine life. For the embryo,
In the case of hogs and humans, such periods of particularly high sensitivity to pathogenic agents are implantation of a fertilized egg into the mucous membrane of the uterus, which corresponds to 14 days of intrauterine development, and placentation is the beginning of the formation of the placenta, which corresponds to the 3-6th week of intrauterine development. These two periods of the greatest sensitivity of the embryo to the effects of damaging agents are called the first and second critical periods.
The factors causing developmental defects are called teratogenic(from the Greek. teratos- ugliness). It turned out that different teratogenic agents can lead to the same malformation depending on the time of exposure to the embryo; for example, the influence of radiation energy and quinine at the 3rd week of intrauterine development leads to disturbances in the formation of the neural tube of the embryo.
At the same time, the same teratogenic agent can cause different malformations by acting at different times of embryogenesis.
It is known that when the embryo is damaged by the rubella virus, rubeolar embryopathy (Gregg's syndrome) occurs, which consists in malformations of the eyes, heart, brain, dental germs and inner ear. At the same time, eye malformations (cataracts, microphthalmia, etc.) appear in cases where the mother suffers rubella in the last decade of the first month or in the first two decades
II month of pregnancy, malformations of the brain (microcephaly) - during the entire II month, the inner ear - in the third decade of the II month and in the first decade
III month of pregnancy.
For each organ, there is a certain period of time during which, when exposed to a teratogenic agent, a malformation of this organ occurs. This period of time was named teratogenic termination period (from lat. teratos- ugliness and terminus- limit, border), i.e. the maximum period during which a teratogenic factor can cause a congenital malformation (Fig. 292). Using the data of embryology, one can judge the timing of the onset of a particular malformation and draw up the so-called teratological descriptions.
Rice. 292. Schematic representation of the teratogenic termination period of individual organs and body parts (according to Gertler)
lendarii for malformations of various organs. As the data of experimental teratology show, the higher the mitotic activity of developing tissues, the more sensitive they are to the effects of a teratogenic agent.
However, it should be borne in mind that a damaging agent may have a greater or lesser affinity for certain tissue rudiments, which sometimes determines some specific features characteristic of a certain pathogenic agent.
So, from 1957 to 1964, the so-called thalidomide catastrophe took place in Germany and other countries of the world. Thalidomide has been used as a sedative (sleeping pill). It turned out that small doses of this agent are dangerous for the human embryo; they have no effect on animals. Many women who took thalidomide in the second month of pregnancy gave birth to children with severe malformations of the limbs - amelia, phocomelia. In 40% of cases, the upper limbs were affected, in 10% - the lower ones, in 20% - the upper and lower limbs, in 20% - the limbs (upper and lower), the organs of hearing and vision (data from 1961 and 1962). According to 1964 data, in 45% of cases thalidomide embryopathies proceeded with malformations of internal organs. From the above observation, it can be seen that thalidomide has a special tropism for the developing anlages of the extremities.
In addition to disturbances in morphogenesis, it was possible to show that the embryo can exhibit resorption of its necrotic tissues, tissue edema, hemorrhage, and at the end of embryogenesis even incomplete regeneration with the formation of scars. It should be borne in mind that the death of tissue primordia is also observed during the normal course of morphogenesis, for example, with the fusion of individual primordia, the formation of cavities in them, rupture of membranes (pharyngeal, cloacal), etc. However, in terms of volume and nature, the process of physiological cell death differs from necrosis in pathological conditions , it is not accompanied by scarring, and most importantly does not lead to a violation of the formation processes. Extensive necrosis of embryonic tissue with scarring appears, probably in embryopathies caused by the action of exogenous agents. With genotypic malformations, there is no significant alteration of organ rudiments, but there is only a delay in the processes of differentiation of the rudiments.
In the overwhelming majority of cases, the morphology of the existing malformation is nonspecific. Therefore, it is impossible to distinguish genotypic defect from phenocopy 1 in appearance. The main manifestation of the pathology of the embryonic period is dysontogenesis in the form of congenital malformations of organs or parts of the body of the embryo.
To fetal period, the main organogenesis ends and further growth and differentiation of fetal tissues.
In the early fetal period, organogenesis of the cerebral hemispheres and the central organ of immunogenesis - the thymus
1 Phenocopy - a developmental defect arising under the influence of exogenous agents, morphologically identical to the genotypic defect.
glands, therefore, in this period, malformations of the brain and a delay in the maturation of thymic tissues may occur.
In addition to dysontogenesis, other pathological processes sometimes occur in the fetus, since its reactive capabilities increase in comparison with the embryo. The fetus has alterative changes, reduced inflammation (see. Inflammation), immunomorphological changes (see. Immunopathological processes), disorders of blood and lymph circulation, hyperplasia and regeneration. Therefore, in the fetal period, there are diseases similar to those of the extrauterine period. For fetal diseases - fetopathies - the following features are characteristic.
1. Any painful form in the fetal period is combined with a violation of ontogenesis, but at the tissue level. In this case, there may be either incorrect proportions of organ tissues, or a delay in their maturation. For example, for megaduodenum, megacolon there is an excessive development of muscle tissue in the intestinal wall in the absence of sufficiently developed neural devices in it; there is a delay in the maturation of the kidneys with an abundance of embryonic type of glomeruli (Fig. 293), etc.
2. With infectious fetopathies, generalized damage to the tissues and organs of the fetus is always noted. Typically, the presence of multiple foci of predominantly alterative inflammation in the parenchymal organs or generalized granulomatosis (for example, with congenital syphilis, listeriosis).
3. As a rule, a pronounced hemorrhagic syndrome develops with petechial rashes on the skin, mucous membranes, and hemorrhages in internal organs.
Rice. 293. Germ-type glomeruli in the kidney cortex in a 7-day-old boy
4. There is a delay in involution and excessive proliferation of cells in the foci of extramedullary hematopoiesis with their appearance outside the optional hematopoietic organs. In a mature healthy fetus, by the time of delivery, the foci of extramedullary hematopoiesis are reduced.
5. The processes of hypertrophy and regeneration proceed with a predominance of hyperplasia of mesenchymal tissues, which leads to excessive development of connective tissue (for example, in the urinary tract with megaureter with a simultaneous loss of muscle fibers; with cystic fibrosis - in the pancreas; with fibroelastosis of the heart - with excessive development of elastic and fibrous tissues in the endocardium, etc.).
The pathogenesis of the listed features of fetal diseases is closely related to the structure and functional immaturity of its tissues and organs that regulate their functions.
Therefore, the listed features of diseases of the fetal period force them to be distinguished in comparison with diseases of the extrauterine period into a special group of fetopathies.
Diseases of progenesis and kimatogenesis
Gametopathies
Gametopathies is a gamete pathology. These include any damage to the egg and sperm during ovo- and spermatogenesis before fertilization. The concept of "gametopathy" covers all types of damage to the male and female gametes: gene mutations and the occurrence of hereditary diseases and hereditary malformations, chromosomal aberrations with the occurrence of more often not inherited chromosomal diseases, genomic mutations - changes in the number of gamete chromosomes, usually leading to spontaneous abortion or chromosomal disease ... In addition, it should be borne in mind that severe damage not only to the nucleus, but also to the cytoplasm of the gametes becomes the source of their death with the development of sterility and infertility or spontaneous abortions and miscarriages. It follows from this that gametopathies are one of the factors of intrauterine mortality, which is not yet amenable to accurate registration.
If the nucleus of the gamete is damaged, changes in the genetic apparatus can occur. Changes in genes, their mutations lead to the consolidation of these changes in subsequent cell generations. It should be borne in mind that gametes are carriers of genes inherited by them from all distant ancestors. Therefore, the concept of gametopathy includes the defeat of not only the gametes of the parents, but also the more distant ancestors of the proband. A gamete with a defect in a gene or genes can become a source of hereditary malformations or diseases that manifest themselves at different stages of intrauterine and extrauterine development.
Gene defects and diseases can be inherited by autosomal recessive, autosomal dominant types or the mutant gene may be linked to the sex X chromosome. With an autosomal recessive type of inheritance in a proband
the defect is eliminated only if the mutant gene was obtained from both the father and the mother. The parents of the proband themselves can be healthy, being only heterozygous carriers of the mutant gene. In the autosomal dominant mode of inheritance, the mutant gene is transmitted from the father or from the mother, who themselves suffer from a similar defect.
Defects whose genes are localized on the X chromosome, in turn, can be inherited in a recessive or dominant manner. Defects linked to the X chromosome, transmitted in a recessive manner, are usually observed in boys, since their only X chromosome is affected. The mutant gene is passed on by a non-sick mother. It is very rare for a girl to be a bearer of a vice. This happens if the father was sick, and the mother was the carrier of the mutant gene.
In addition to local damage to the genetic apparatus of the gamete nucleus due to gene mutations, mutations of chromosomes may appear during gametogenesis in the form of changes in their number and structure. Chromosome mutations are named chromosomal aberrations. Chromosomal aberrations occur most often at the time of the reduction division of gametes. Their consequence is chromosomal diseases, which, however, in most cases are not inherited, since their carriers more often die in childhood or are infertile.
Typical examples of chromosomal disorders are Down's disease(trisomy for the 21st pair of autosomes), Patau syndrome(trisomy for the 13-15th pair of autosomes), Shereshevsky-Turner syndrome(sex chromosome monosomy - 45 HO), etc.
Down's disease observed in newborns in a ratio of 1: 600, 1: 700, occurs most often. Clinically, children have a marked retardation of mental and physical development from birth. Patients have a typical appearance: an oblique section of the eyes, a sinking nasal bridge, a high palate, a low location of small auricles, pronounced muscle hypotonia. Children die more often from intercurrent diseases. Most of them have malformations of the heart and great vessels (tetrad of Fallot, etc.), less often malformations of the digestive and genitourinary systems. These children have underdevelopment of the cerebral hemispheres, especially its frontal lobes with delayed differentiation of neurons, impaired myelination processes, and the architectonics of the blood vessels of the brain.
Patau syndrome in newborns and stillborns, it occurs with a frequency of 1 in 5149 births. Characterized by pronounced general hypoplasia, anomalies of the skull and face: a low sloping forehead, narrow eye slits, sunken nose, wide base of the nose, hypotelorism, "scalp defects", low deformed auricles, typical clefts of the upper lip and palate. Polydactyly and flexor position of the hands, microphthalmia, coloboma and corneal opacity are noted. On the part of the brain, microcephaly, arineencephaly (absence of the olfactory brain), aplasia or hypoplasia of the cerebellar worm, etc. are noted. Congenital defects of the heart, digestive system, urinary system, etc. are also noted. Children are not viable.
Blastopathies
Blastopathy- blastocyst pathology that occurs during the period of nidation and cleavage in the first 15 days from the moment of fertilization to the isolation of embryo and trophoblast.
Etiology and pathogenesis. The cause of blastopathy is most often chromosomal aberrations in combination with environmental influences (endocrine diseases of the mother, hypoxia, etc.). Pathogenesis depends on the type of blastocyst lesion. So, for example, the pathogenesis of twin deformities is associated with the appearance during crushing of two or more independently growing centers. It is believed that if these centers are disconnected from each other, then two independently growing identical twins develop, the normal development of which should not be attributed to blastopathies. If the growth centers are located close and have an intermediate zone common for two twins, then two accrete twin. In both cases, development is possible symmetrical and asymmetric twins.
The morphology of blastopathy is diverse. These include disorders of blastocyst implantation, namely ectopic pregnancy, superficial or very deep implantation of a blastocyst into the endometrium, disorientation of the developing embryoblast in the blastocyst in relation to the endometrium, aplasia or death of the developing embryoblast with the formation of an empty embryo sac, malformations of the entire embryo, some solitary defects, twin deformities and, finally, aplasia or hypoplasia of the forming trophoblast - amnion, amniotic leg, yolk sac. Superficial or overly deep implantation of blastocyst leads to malformations of shape, localization, as well as placental accreta (see below), which are fraught with fetal death during the act of childbirth. Embryoblast orientation disorders with complete topographic inversion, they end in the death of the embryoblast. With incomplete inversion, umbilical cord malformations are observed (see below), which can lead to fetal death during childbirth. Empty embryo sacs are blastocysts that do not contain an embryoblast or contain its remnants. Sometimes they can find amniotic membranes, umbilical cord, yolk sac.
Developmental pathology Total embryo is a general, severe disorder that is incompatible with life.
Single and multiple malformations that occur during the blastula period (in the first 8-12 weeks) are found in 14.3-22.9% of all spontaneously aborted embryos. Moreover, in 46.2% of cases, they are accompanied by anomalies of the placenta. This combination often leads to the death of the embryo.
Twin deformities are found in the form of accrete twins. If the fused twins consist of equal symmetrically developed components, it is called diplopagus (diplopagus from the Greek. diplos- double, agus- connect); if it consists of asymmetrically developed com-
Twin deformities are combined with non-vitality. In rare cases, a significant life span of such twins has been described until adulthood. In mild cases of only soft tissue adhesions, surgical correction is possible.
Embryopathies
Embryopathy- pathology of the embryonic period from the 16th day of pregnancy to the 75th day inclusive, during which the main organogenesis ends and the formation of the amnion and chorion. The main types of embryopathies include congenital malformations.
Congenital malformation is called a persistent morphological change in an organ, part of the body or the whole organism, which goes beyond the variations in the normal structure of a certain biological species, arising in utero as a result of disturbances in morphogenesis. Since organogenesis ends mainly in the embryonic period, most malformations appear precisely at this stage of intrauterine existence. However, in addition to congenital malformations with disorders of the basic morphogenesis of organs or body parts, there are congenital malformations in which developmental disorders are observed at the level of tissue differentiation. They are often systemic, for example, malformations of striated muscles (congenital Oppenheim's myatonia), connective tissue (Marfan's disease), skin (congenital ichthyosis), cartilaginous bones (congenital chondrodysplasia), etc. Malformations can also affect tissues of one organ, for example, hypoplasia smooth muscle tissue with megaureter, nervous intramural apparatus - with megacolon, lung tissue - with cystic lung, etc. According to the timing of occurrence, these defects are early fetopathies. Early fetopathies are often associated with embryopathies; for example, congenital ichthyosis and chondrodysplasia - with malformations of the face, Marfan's disease - with malformations of the face and aorta, etc. The frequency of congenital malformations, according to WHO, is 1.3% of the total number of births.
Any congenital defect can manifest itself in the form of: 1) the absence of any organ or part of the body (agenesis, aplasia); 2) underdevelopment of the organ (hypoplasia); 3) excessive development (hyperplasia) or the presence of an excessive number of organs (doubling, etc.); 4) changes in shape (fusion of organs, atresia, stenosis of holes, canals, dysraphia - non-closure of embryonic fissures, exstrophy - eversion, etc.); 5) changes
in the location of organs (ectopia); 6) persistence of embryonic provisional (preexisting) organs.
Classification. Congenital malformations are divided according to the degree of prevalence in the body, according to localization in a particular organ, according to etiology. By prevalence congenital defects can be: 1) isolated - with damage to one organ; 2) systemic - with damage to several organs of one of the systems; 3) multiple - with damage to organs of different systems. By localization distinguish between malformations of the central nervous, cardiovascular, digestive, genitourinary and other systems. Congenital malformations of the named localization are of the greatest importance in pathology. Most often, malformations of the central nervous and cardiovascular systems occur, since it is these systems that have the greatest teratogenic termination period (see Fig. 292). Isolated malformations are more common than multiple, despite the fact that the teratogenic termination period for many organs coincides in time.
The most perfect is the classification of malformations according to etiology, however, the level of modern knowledge does not yet allow adhering to it. However, certain types of systemic and multiple congenital malformations associated with a specific etiology are known, for example, rubeolar embryopathy, alcoholic, thalidomide embryopathy, etc., as well as hereditary genotypic congenital defects and congenital defects due to chromosomal aberrations; the latter, as a rule, are plural.
The differentiation of genotypic congenital malformations from their phenocopies is possible using the genealogical method of studying the pedigree, the cytogenetic method, which makes it possible to study the karyotype of the tissues of the defect carrier during their cultivation, using the twin method based on the frequency of detecting congenital defects in identical twins and the dermatoglyphics method - studying a complex of skin patterns located on the palms, soles and flexor surface of the fingers, which is used for the urgent diagnosis of chromosomal diseases.
Congenital malformations of the central nervous system
Congenital malformations of the central nervous system in frequency they rank first among other defects, occur in 30% of cases among developmental defects found in children.
Etiology and pathogenesis. Of the exogenous factors, the value of rubella virus, human immunodeficiency, herpes simplex is precisely established, the influence of cytomegalovirus, Coxsackie viruses, drugs (quinine, hydantoin, etc.), alcohol, radiation energy, hypoxia is assumed. Gene mutations are of undoubted importance; in chromosomal diseases, they are found almost as a rule among multiple defects. The development of the defect is associated with the effect of a damaging agent throughout the entire embryonic period, including the early fetal period.
The most severe defects occur when damage occurs at the beginning of the laying of the neural tube (3-4 weeks of intrauterine life).
Pathological anatomy. The main most severe types of congenital malformations of the central nervous system include the following. Anencephaly- agenesis of the brain, in which the anterior, middle, and sometimes posterior parts of it are absent. The medulla oblongata and spinal cord are preserved. In place of the brain, connective tissue is found, rich in vessels, in which individual neurons and neuroglia cells meet. Anencephaly is combined with acrania - the absence of the bones of the cranial vault covering their soft tissues and skin.
Microcephaly- hypoplasia of the brain, a decrease in its mass and volume; combined with a simultaneous decrease in the volume of the cranium and thickening of the bones of the skull; different degrees of severity of this defect are possible. Microgyria- an increase in the number of cerebral convolutions along with a decrease in their size.
Porencephaly- the appearance of cysts of various sizes in the brain, communicating with the lateral ventricles of the brain, lined with ependyma. A false porencephaly should be distinguished from true porencephaly, in which cysts do not communicate with the outflow pathways of the cerebrospinal fluid and are formed at the site of the former softening of the brain tissue.
Congenital hydrocephalus- excessive accumulation of cerebrospinal fluid in the ventricles of the brain (internal hydrocephalus) or in the subarachnoid spaces (external hydrocephalus) (Fig. 294) is accompanied by an increase in the cerebral skull and its sharp discrepancy with the facial one - the face seems small, the forehead - overhanging. There is a discrepancy and
Rice. 294. Hydrocephalus (according to A.V. Zinserling)
thinning of the bones of the skull, bulging fontanelles. Atrophy of the substance of the brain increases, in most cases associated with impaired outflow of cerebrospinal fluid due to stenosis, bifurcation or atresia of the cerebral aqueduct (Sylvian aqueduct), atresia of the median and lateral openings of the IV ventricle and interventricular opening.
Cyclopia- a rare defect characterized by the presence of one or two eyeballs located in one orbit, with a simultaneous malformation of the nose and the olfactory lobe of the brain. Named because of the similarity of the face of the fetus with the face of the mythical monster - the Cyclops.
Head hernia and spinal cord are protrusions of the substance of the brain and its membranes through defects in the bones of the skull, their seams and the spinal canal. Hernias of the brain: if there are only the membranes of the brain and cerebrospinal fluid in the hernial sac, they are called meningocele, membranes and substances of the brain - meningoencephalocele, substances of the brain and cerebral ventricles - encephalocystocele. More common are hernias of the spinal cord, associated with the splitting of the dorsal vertebrae, which are called spina bifida. Hernias of the spinal cord, like the brain, depending on the contents of the hernial sac, can be divided into meningocele, myelocele, meningomyelocele. Very rare rachioschiz- complete defect of the posterior wall of the spinal canal, soft tissues, skin and meninges; while the spinal cord is spread open on the front wall of the canal, there is no protrusion.
Forecast with congenital malformations of the central nervous system, it is unfavorable, most of them are incompatible with life. Surgical correction is effective only in some cases of cerebral and spinal hernias. Children often die from the addition of intercurrent infectious diseases. Cerebral and spinal hernias are complicated by a purulent infection with the development of purulent meningitis and meningoencephalitis.
Congenital heart disease
Congenital heart disease in frequency they rank second after malformations of the central nervous system. According to different authors, they are found in 16-40% of other defects and in 3-8% of cases according to the autopsy data of children who died in the perinatal period.
Etiology and pathogenesis. The causes of these defects are varied and are not associated with the influence of any specific exogenous factors. Gene mutations and chromosomal aberrations are of undoubted importance. Among the multiple defects observed in chromosomal diseases, heart defects are less common than defects of the central nervous system. The development of the defect is associated with the effect of a damaging agent on the embryo from the 3rd to the 11th week of intrauterine development. Various types of defects depend on the distortion of the stages of the morphogenesis of the heart, of which the main ones are defects of the originally paired anlages of the heart, irregular bends of the primary heart tube, developmental delay or improper location of the heart septa dividing it and the arterial trunk into
right and left halves, persistence of atrioventricular connections existing during intrauterine life.
Pathological anatomy. With congenital heart defects, in the process of myocardial hypertrophy in children at the age of the first 3 months of life, not only an increase in the volume of muscle fibers with hyperplasia of their ultrastructures is involved, but also a true hyperplasia of cardiomyocytes. At the same time, hyperplasia of reticulin argyrophilic fibers of the heart stroma develops. Subsequent dystrophic changes in the myocardium and stroma, up to the development of micronecrosis, lead to a gradual proliferation of connective tissue and the emergence of diffuse and focal cardiosclerosis.
Compensatory restructuring of the vascular bed of the hypertrophied heart is accompanied by an increase in intramural vessels, arterio-venous anastomoses, and the smallest veins (the so-called Viessen-Tebezia vessels) of the heart. In connection with sclerotic changes in the myocardium, as well as increased blood flow in its cavities, a thickening of the endocardium appears due to the growth of elastic and collagen fibers in it. Reconstruction of the vascular bed also develops in the lungs. In children with congenital heart defects, general physical development is retarded.
Death occurs in the first days of life from hypoxia in especially severe forms of defects or later from the development of heart failure. With the progress of thoracic surgery, it became possible to treat many congenital defects using surgical correction and prosthetics, which markedly changed the course and outcomes of congenital heart defects in children. Due to the complexity of the processes of embryogenesis of the heart, its congenital defects are diverse. However, most of them are associated with abnormal communications between the pulmonary and large circulatory systems, constrictions in these systems or with the absence of normal communications between them, up to a complete separation of the pulmonary and large circulatory systems incompatible with life. Depending on the degree of hypoxia caused by a decrease in blood flow in the pulmonary circulation and the direction of blood flow through abnormal pathways between the pulmonary and large circulation, heart defects can be divided into two main types - blue and White. With vices blue type there is a decrease in blood flow in the pulmonary circulation, hypoxia and the direction of blood flow along an abnormal path - from right to left. With vices white type hypoxia is absent, the direction of blood flow is from left to right. However, this division is schematic and not always applicable to all types of congenital heart defects.
Congenital defects with violation of the division of the cavities of the heart.Ventricular septal defect occurs often, its occurrence depends on the growth retardation of one of the structures that form the septum, as a result of which an abnormal communication develops between the ventricles. More often there is a defect in the upper connective tissue (membranous) part of the septum (Fig. 295). Blood flow through the defect
Rice. 295. Defect in the interventricular septum of the heart (according to A.V. Tsinserling)
is carried out from left to right, therefore cyanosis and hypoxia are not observed (white type of defect). The degree of the defect can vary, up to the complete absence of the septum. With a significant defect, hypertrophy of the right ventricle of the heart develops, with an insignificant one, no significant changes in hemodynamics occur.
Atrial septal defect in the form of an isolated defect is rare. It occurs either with violations of the development of the primary atrial septum at the 5th week of embryogenesis, or later, with the formation of the secondary septum and foramen ovale. Primary septal defect has the form of an opening located directly above the valves of the ventricles; in case of a defect secondary septum there is a wide open oval hole, devoid of a flap. In either case, the blood flow occurs from left to right, there is no hypoxia and cyanosis (white type of defect). Overflow of blood to the right half of the heart is accompanied by hypertrophy of the right ventricle and expansion of the trunk and branches of the pulmonary artery. The complete absence of interventricular or interatrial septa leads to the development of a three-chambered heart - a severe defect, in which, however, during the compensation period, complete mixing of arterial and venous blood is not observed, since the main flow of one or another blood retains its direction and therefore the degree of hypoxia increases as decompensation progression.
Congenital heart defects with disorders of the division of the arterial trunk. The common arterial trunk in the complete absence of division of the arterial trunk is rare. With this defect, one common arterial
the trunk originates from both ventricles, at the exit there are 4 semilunar valves or less; the defect is often combined with a defect of the interventricular septum. The pulmonary arteries branch off from the common trunk near the valves, to the branches of the large vessels of the head and neck, they may be completely absent, and then the lungs receive blood from the dilated bronchial arteries. With this defect, severe hypoxia and cyanosis (blue type of defect) are observed, children are not viable.
Complete transposition of the pulmonary artery and aorta occurs with the wrong direction of growth of the septum of the arterial trunk, when it does not grow in a spiral, but in the direction opposite to the rest, normally developing parts of the heart. In this defect, the aorta is placed in front and to the right of the right ventricle of the heart, the pulmonary artery lies behind the aorta and departs from the left ventricle. Arterial blood can enter the systemic circulation only with defects in the septa of the heart or with non-closure of the arterial (botallov's) duct and foramen ovale. The defect is accompanied by severe hypoxia and cyanosis (blue type of defect).
The myocardium suffers significantly, since the coronary arteries do not receive arterial blood. Children are not viable.
Stenosis and pulmonary atresia observed when the septum of the arterial trunk is displaced to the right, often combined with a defect of the interventricular septum and other defects. With a significant narrowing of the pulmonary artery, blood enters the lungs through the arterial (botall) duct and expanding bronchial arteries. The defect is accompanied by hypoxia and severe cyanosis (blue type of defect).
Aortic stenosis and atresia are a consequence of the displacement of the septum of the arterial trunk to the left. They are less common than displacement of the septum to the right, often accompanied by hypoplasia of the left ventricle of the heart. In this case, there is a sharp degree of hypertrophy of the right ventricle of the heart, expansion of the right atrium and a sharp general cyanosis. Children are not viable.
Narrowing of the aortic isthmus (coarctation) up to its atresia, it is compensated by the development of collateral circulation through the intercostal arteries, arteries of the chest and sharp hypertrophy of the left ventricle of the heart.
Non-clogging of the arterial (botallov) duct can be considered a defect if it is present with a simultaneous expansion in children over 3 months of age. In this case, the blood flow is carried out from left to right (white type of defect). An isolated defect lends itself well to surgical correction.
Combined congenital heart defects. Among the combined vices, the triad, tetrad and pentad of Fallot are more common. Fallot Triad has 3 signs: a defect of the interventricular septum, stenosis of the pulmonary artery and, as a consequence, hypertrophy of the right ventricle. Fallot's tetrad has 4 signs: defect of the interventricular septum,
constriction of the pulmonary artery, dextraposition of the aorta (displacement of the orifice of the aorta to the right) and hypertrophy of the right ventricle of the heart. Pentad of Fallot, in addition to these four, includes the 5th sign - atrial septal defect. The most common tetrad of Fallot (40-50% of all congenital heart defects). For all defects of the Fallot type, blood flow from right to left, a decrease in blood flow in the pulmonary circulation, hypoxia and cyanosis (blue type of defects) are noted. Rarer combined congenital defects include ventricular septal defect with left atrioventricular stenosis (Lyutambashe disease), ventricular septal defect and aortic dextraposition (Eisenmenger's disease) and a branching of the left coronary artery from the pulmonary trunk (Bland-Garland-White syndrome) pulmonary hypertension (Aerz's disease), depending on the hypertrophy of the muscular layer of the vessels of the lung (small arteries, veins and venules), etc.
Congenital malformations of the digestive system occur in 3-4% of autopsies in the perinatal period and account for 21% of all congenital malformations of this period. They most often represent atresia and stenosis of the digestive tract.
Etiology and pathogenesis. Anal atresia, like other defects of the caudal end of the embryo, is more common in diabetic embryopathy. In general, the origin of these defects is different.
Pathogenesis is associated with a violation of the formation of holes in the digestive tube in the period from the 4th to the 8th week of intrauterine development, since at first this tube ends blindly at both ends. The delay in recanalization is also important, since at the 8th week of intrauterine life, the growing epithelium completely closes the lumen of the intestinal tube, which is subsequently restored during the formation of the mucous membrane.
Atresia and stenoses more often observed in the esophagus, duodenum, proximal skinny and distal segment the ileum, in the area of rectum and anal opening. They are rare in the colon. In addition, in the esophagus, tracheoesophageal fistula(Fig. 296), the formation of which depends on the violation of the division of the primary intestine into the esophagus and trachea. These fistulas lead to the development of severe aspiration pneumonia. Intestinal atresia can be single or multiple, and with the latter, the intestine resembles a "bunch of sausages." In the area of atresia, the intestine looks like a dense connective tissue cord, which, under the influence of peristalsis, can stretch and rupture, which leads to perforated peritonitis in the first days of a newborn's life.
Atresia and stenosis of the rectum and anus can be observed in different ways: 1) anal atresia only- with normal development, the rectum is separated from it by a membrane; 2) rectal atresia only- the anus leads to a short blind canal,
Rice. 296. Tracheoesophageal fistula. The upper segment ends blindly, sharply widened; the lower segment opens into the trachea in the area of its bifurcation (according to A.V. Zinserling)
above it lies the cord of the underdeveloped rectum; 3) anal atresia and rectum- the anus is absent, the blind end of the rectum is located high; 4) fistulous atresia- The rectum opens into the bladder, urethra, vagina, scrotum, perineum and other organs of the genitourinary system.
Doubling of individual sections of the intestine most often concerns only the mucous membrane, the muscular membrane is common. The duplicated area can be in the form of a cyst, diverticulum, or tube. The defect is complicated by bleeding, inflammation, necrosis with perforation.
Hirschsprung's disease(refers to early fetopathies) - segmental agangliosis, megacolon- the absence of neurons in the intermuscular (so-called Auerbach) plexus of the lower segment of the sigmoid and rectum. Due to the preservation of the submucosa (so
called Meissner), the plexus of the aganglionic section of the intestine is spasmodically reduced, above it there is a stretching of the intestine with meconium or feces with the development of subsequent compensatory hypertrophy of the muscular membrane; ulceration is sometimes observed in a stretched segment. Patients suffer from constipation, obstruction develops.
Hypertrophic pyloric stenosis(refers to early fetopathies) - congenital hypertrophy of the muscles of the pyloric stomach with a narrowing of its lumen; the most common congenital malformation of the stomach, the etiology and pathogenesis of which have not been clarified. It occurs in 0.3% of newborns, in boys - 5-7 times more often. The family character of the disease is noted. Instead of a normal pyloric ring, there is a tube with a narrow lumen and thick, dense walls that protrudes into the duodenum. Persistent vomiting is observed, starting from the 3-4th week of life, up to the development of a coma from the loss of chlorides. Surgical treatment leads to a complete cure.
Digestive tract defects associated with the preservation of some embryonic structures. These include a hernia of the navel, cysts and fistulas of the umbilical ring and Meckel's diverticulum.
Hernia of the navel- defect of the anterior abdominal wall in the umbilicus with protrusion of a translucent hernial sac formed by the umbilical cord and amnion, containing loops of the small intestine. The defect occurs due to the fact that the intestinal loops do not pass into the abdominal cavity at the 8-10th week of intrauterine development. Amenable to surgical treatment. It should be distinguished from eventration of the abdominal organs with its hypoplasia, in which the abdominal wall is wide open, the hernial sac is absent, surgical treatment is ineffective. Cysts and fistulas areas of the umbilical ring are formed due to the persistence of the yolk duct, which connects the intestinal tube to the yolk sac in the early stages of intrauterine development. If the duct is completely saved, a umbilical fistula, from which the feces are allocated to the outside. If it is partially preserved, an intestinal cyst forms in the navel - enterocystoma, partial preservation of the duct in the intestinal region leads to the formation Meckel diverticulum- a finger-like protrusion of the wall of the ileum, usually located 25 cm above the ileal cecum (the so-called bauhinia) valve. Between them and the umbilical ring, the remainder of the vitelline duct is sometimes preserved in the form of a connective tissue cord. All these defects can lead to bleeding, inflammation, including peritonitis, obstruction, intussusception; are subject to surgical treatment.
Congenital malformations of the liver and biliary tract.Polycystic liver disease- multiple cysts of different sizes, lined with epithelium and filled with a clear liquid, - is rare, often combined with polycystic kidney and pancreas.
Atresia and extrahepatic bile duct stenosis can occur in one or all three ducts. Agenesis and hypoplasia of intrahepatic bile ducts(refers to early fetopathies) - a decrease in the number or complete absence of bile ducts in the portal tract in the area of the triads. The etiology is associated with the hepatitis virus. Family cases have been reported. It is considered as a consequence of violations of the formation of ducts from the hepatic diverticulum (5-8th week) or delayed recanalization (8th week of intrauterine development). Jaundice is very intense, develops on the 3-5th day of life, the defect leads to biliary cirrhosis of the liver. With agenesis and hypoplasia of the intrahepatic ducts, the development of congenital, biliary cirrhosis is possible. Children live up to 6-7 months. With congenital cirrhosis, they die in the first days of life from liver failure.
Congenital hyperplasia of the intrahepatic bile ducts(refers to early fetopathies) - a bizarre proliferation of bile ducts in the area of the portal tract with excessive development of connective tissue - combined with small cystic kidneys. Jaundice is uncharacteristic, it appears in the case of the addition of secondary purulent cholangitis. This defect occurs in adults as well. When combined with small renal cystic disease, death occurs from renal failure in the first days of life.
Congenital malformations of the kidneys, urinary tract and genitals
Etiology. The development of defects is not associated with the action of certain exogenous agents. Many of them are hereditary or familial. They are found in chromosomal syndromes. These defects are diverse and occur during the 4-8th week of cymatogenesis.
Congenital malformations of the kidneys.Renal agenesis- congenital absence of one or both kidneys (arenia) - is rare, while the newborn has a wrinkled skin, a puffy, senile face, the ears are low, the nose is wide and flat, the frontal tubercles protrude; congenital defects of other organs are observed. Children are not viable.
Renal hypoplasia- congenital decrease in their mass and volume, can be one- and two-sided; with unilateral hypoplasia, vicarious hypertrophy of the second normal kidney is observed.
Kidney dysplasia- hypoplasia with the simultaneous presence of embryonic tissues in the kidneys. Microscopically, nephroblastoma foci, primitive tubules and glomeruli, cysts, islets of cartilage and smooth muscle tissue are found in the kidney tissue. Combined with aplasia, hypoplasia or atresia and ureteral stenosis. With bilateral pronounced hypoplasia and renal dysplasia, children are not viable.
Large cystic kidneys(polycystic kidney disease of the adult type) - bilateral significant enlargement of the kidneys with the formation in their cortical layer of a large number of large cysts with transparent contents, between the cysts - areas of normal renal tissue (Fig. 297). The defect is combined with cysts of the liver and pancreas, and is inherited in a dominant manner. Its pathogenesis is associated with a violation of the connection of the rudiments of metanephrogenic tissue and the urethral tube, retention cysts are formed.
Rice. 297. Polycystic kidney (macrocystosis)
Small cystic kidneys(polycystic "infantile" type) - bilateral significant enlargement of the kidneys with the formation of numerous small cysts in the cortical and medullary layers, closely adjacent to each other. The kidneys look like a large-porous sponge. On microscopic examination, the entire renal tissue looks completely replaced by cysts lined with cubic epithelium. The defect is combined with liver cysts and hyperplasia of the bile ducts. Children are not viable.
Fusion of the kidneys(horseshoe kidney) and dystopia are not clinically apparent.
Congenital malformations of the urinary tract. The main ones are: 1) doubling of the pelvis and ureters; 2) agenesis, atresia, stenosis of the ureters, ectopia of their mouths; 3) megaloureter refers to early fetopathies - a sharp expansion of the ureter (one or two) due to hypoplasia of muscle tissue or nervous apparatus; 4) exstrophy of the bladder as a result of aplasia of its anterior wall, peritoneum and skin in the pubic region; 5) agenesis of the bladder; 6) atresia, stenosis of the urethra (more often in girls) and hypospadias - a defect of the lower wall, epispadias - a defect in the upper wall of the urethra in boys.
All defects of the urinary tract lead to impaired outflow of urine and, without timely surgical treatment, which is currently successfully performed, lead to renal failure. The most severe of them (for example, agenesis, atresia of the urinary tract) lead to death from uremia soon after birth, others may not manifest clinically for a long time, but gradually lead to hydronephrosis, sometimes to the formation of stones, the onset of ascending chronic pyelonephritis, which threatens the development of renal failure , ending with the death of the patient (usually at 20-30 years old) from uremia.
Congenital malformations of the genital organs. They are often associated with diseases of the endocrine glands (adrenal glands, pituitary gland) of the mother and the fetus, with the intake of hormonal drugs during pregnancy; established hereditary transmission in a recessive manner. These include: cryptorchidism- retention of the testicles in the abdominal cavity or in the inguinal canal (in newborns it should not be considered a defect, since they have cryptorchidism in 30% of cases, by the age of 12-16 it is observed only in 2-3% of cases and then it is regarded as a defect); cervical atresia and vagina, doubling of the uterus; hermaphroditism- the presence of signs of both sexes in one person. Distinguish true hermaphroditism - the simultaneous presence of female and male sex glands and false - the external genital organs of the sex opposite to the sex glands. Genital malformations are not life threatening, in some cases surgical treatment is possible.
Congenital malformations of the respiratory system are often combined with other defects and are found in 4.2% of those who died in the perinatal period, in 3% of children who died before 1 year.
Aplasia and bronchial hypoplasia and lungs, one lung or its lobes are more common. Lung hypoplasia is predominantly secondary when chest dysplasia occurs.
Lung cysts(refer to early and late fetopathies) can be multiple (polycystic lung disease), located in one lung, in one lobe, or be single. Cysts have different origins - they are formed during agenesis of one of the bronchial branching orders. In the first case, gas exchange is not carried out, since the blindly ending branches of the bronchi are surrounded by connective tissue. In the second case, large and medium bronchi pass directly into the lung tissue or bronchioles. In the postnatal period, the established act of breathing leads to ectasia of bronchial cysts with the development of the so-called congenital bronchiectasis(fig. 298).
Congenital emphysema(refers to early and late fetopathies) - a sharp swelling more often of the upper lobe of the left lung due to hypoplasia of cartilage, elastic and muscle tissues of the bronchi. It causes the displacement of the mediastinal organs in the opposite direction. The defect is detected only in the postnatal period.
Congenital lung defects if they are compatible with life, lead to complications in the form of a secondary infection with the development of chronic bronchitis and pneumonia, which result in pneumosclerosis, obliteration of the pleural cavities, cor pulmonale, followed by its failure. Death from these complications is more common in adults.
Rice. 298. Congenital bronchiectasis (according to A.V. Tsinserling)
Congenital malformations of the osteoarticular and muscular systems
Congenital malformations of the skeleton and muscular system are found, according to autopsies, in 0.5-0.8 and 13.5% of cases, respectively, among all defects in those who died in the perinatal period. In their etiology, thalidomide is of particular importance among exogenous factors. Distinguish between systemic and isolated skeletal defects.
Systemic defects of the osteoarticular system.Chondrodysplasia(refers to early fetopathies) - a group of congenital defects characterized by significant shortening and thickening of the limbs. Fetal chondrodysplasia, or lethal micromelia (Fig. 299), - shortening and thickening of the limbs, their skin forms large folds, the newborn's head is enlarged, the nose is saddle-shaped, the mouth is open, the tongue is thick, the neck is short, the vertebral bodies are also thickened, the chest is hypoplastic; the defect is combined with hypoplasia of the lungs. Another type of chondrodysplasia is achondroplasia, characterized only by shortening and thickening of the limbs and impaired development of the bones of the facial skeleton. The defect manifests itself later, when the child's growth retardation becomes noticeable; inherited in a dominant manner, spontaneous gene mutations are possible. The essence of the defect is a violation of the development of bones of cartilaginous origin, bones of a connective origin develop normally.
Microscopic examination reveals a change in enchondral bone formation while maintaining the periosteal bone, which leads to a violation of the growth of tubular bones in length. The prognosis for life is favorable, there is no mental retardation.
Osteogenesis imperfecta(early fetopathy) - congenital fragility of bones, inherited in a dominant manner. The defect is characterized by multiple, often congenital fractures with curvature of the limbs and ribs. The cranial vault is built only of connective tissue; otosclerosis, blue sclera, hydrocephalus are observed.
Rice. 299. Chondrodysplasia (according to A.V. Zinserling)
Congenital marble disease(early fetopathy) - severe osteosclerosis with a simultaneous violation of the development of hematopoietic tissue of a hereditary nature. Children die in the first months, less often in the first years of life.
Isolated defects of the osteoarticular system. These include congenital dislocation and hip dysplasia one or two-sided (early fetopathy), congenital amputation and aplasia (amelia) of the extremities, phocomelia- underdevelopment of the proximal extremities, when the feet and hands start directly from the trunk, polydactyly- an increase in the number of fingers, syndactyly- fusion of fingers, etc.
Systemic hypoplasia of muscle tissue. An example of it would be Oppenheim's congenital myatonia (refers to early fetopathies), in which there is hypoplasia of striated muscles. In the first months of life, children die of pneumonia, the development of which is associated with hypoplasia of the respiratory muscles, with the exception of the diaphragm.
Isolated malformations of the muscular system. The most important of them are: congenital true and false diaphragmatic hernia. When false hernial sac is absent, there is a defect in the diaphragm, the volume of which varies, through it the abdominal organs, more often the intestinal loops, can penetrate into the chest cavity. Congenital torticollis characterized by shortening of the sternocleidomastoid muscle due to its focal fibrosis, which causes the child's head to tilt to the affected side.
Congenital malformations of the face. The main birth defects are: heiloschis- cleft upper lip, palatoskhiz- splitting of the hard palate, micrognathia- hypoplasia of the lower jaw, hypertelorism- wide distance between the eyes. These defects are often combined with other multiple malformations.
Fetopathies
Fetopathies- pathology of the fetal period from the 76th to the 280th day of pregnancy, during which the main tissue differentiation of organs and the formation of the placenta ends. A characteristic feature of fetopathy is a combination of two types of lesions - disorders of tissue morphogenesis with reactive changes in the form of circulatory disorders, dystrophy, necrosis, inflammation, immune reactions, compensatory and adaptive processes, regeneration. At early fetopathies are dominated by disorders of tissue morphogenesis, with late- reactive processes. A distinction should be made between infectious and non-infectious fetopathies.
Infectious fetopathies
Etiology and pathogenesis. Infectious fetopathies can be associated with exposure to viruses, many bacteria and other pathogens. In this case, inflammation often occurs in the placenta.
Fetal infection occurs most often hematogenous way. The pathogen through the placenta through the umbilical vein enters the fetus. When the inflammatory process passes from the placenta to the membranes, it is possible infection of the amniotic fluid followed by swallowing or aspiration the fetus of the pathogen. Less commonly, infection is carried out upward path through the vagina into the cervical canal or downward path through the tubes, if the mother has an inflammation in the abdominal cavity. The source of infection is often sluggish chronic or latent infections of the mother, since in such forms of the course of infectious diseases, the content of immunoglobulins and the titer of the corresponding immune antibodies are insufficient both to complete the process in the mother herself and to prevent fetal disease. Such ratios are observed, for example, with toxoplasmosis, serum hepatitis.
Pathological anatomy. With all infectious fetopathies, there is a generalized, and with bacterial and fungal septic type of changes with the formation of multiple foci areactive necrosis in parenchymal organs and the brain (with congenital chickenpox, herpes simplex, cytomegaly, infection with the Coxsackie virus) or productive diffuse inflammatory infiltrates in combination with areactive necrotic foci (congenital serum hepatitis, cytomegaly, rubella, toxoplasmosis) granulomas in many organs (congenital syphilis, listeriosis, tuberculosis, fungal infection). At the same time, against the background of generalized lesions, changes in certain organs may prevail, for example, with toxoplasmosis - in the brain, with serum hepatitis - in the liver, with infection with the Coxsackie virus - in the myocardium and brain, etc. As a rule, a pronounced hemorrhagic syndrome in the form of petechiae on the skin, mucous and serous membranes, hemorrhages in internal organs, the tendency to which increases during the infectious process due to the development of generalized vasculitis. Immune reactions of the fetus are expressed in a delay in the maturation of the thymus gland, in its atrophy with a decrease in its volume and weight, in the presence of foci in full-term fetuses extramedullary hematopoiesis, and in premature babies - in an increase in their volume, which is accompanied by hepato- and splenomegaly. Conjugational jaundice, tissue immaturity of organs in full-term or prematurity and general fetal malnutrition are often observed.
Forecast in most cases, unfavorable, death occurs in the first days or in the first 3 months of life. With recovery, persistent changes in organs remain, leading to disability or death from failure of vital organs in other periods of life.
Non-infectious fetopathies
To basic forms non-infectious fetopathy include hemolytic disease of the newborn, fetal cystic fibrosis, fibroelastosis
endocardium, diabetic fetopathy and many, mainly early, fetopathies. Early fetopathies are manifested in the form of isolated congenital malformations (hypertrophic pyloric stenosis, megacolon, megaloureter, agenesis, hypoplasia and hyperplasia of the bile ducts, pulmonary cystosis, etc.), as well as systemic congenital malformations of osteoarticular and muscle tissues, skin, etc.
Fetal cystic fibrosis- a perinatally emerging form of cystic fibrosis (cystic fibrosis of the pancreas). The disease is accompanied by a change in the nature of mucus and other secrets secreted by the epithelium of the excretory glands, which occurs, according to the autopsy data of children, in 0.1-0.2%. The most common is the pulmonary-intestinal form, which children of the first months of life suffer from, less often there is an isolated pulmonary or intestinal form, which is observed in children at any age. It is very rare to find forms with the development of biliary cirrhosis of the liver (found in older children and adults). Fetal cystic fibrosis develops in utero or in the first days of life.
Etiology and pathogenesis. The disease is inherited in an autosomal recessive manner. The pathogenesis is probably based on fermentopathy, the nature of which has not been disclosed, leading to a violation of the structure of glycoproteins (mucoids). The secret of many glands becomes thick, viscous, which leads to a delay in its evacuation, the development of retention cysts and to a violation of patency through natural channels. First of all, the excretory apparatus of the pancreas, the mucous glands of the respiratory and digestive tracts, the biliary tract, the salivary, sweat and lacrimal glands are affected.
Pathological anatomy. On macroscopic examination pancreas the gland can be unchanged, in rare cases, there is a seal, an emphasized pattern of lobules, the appearance of small cysts. Microscopically, a thickening of the secretion is observed in the cystic ducts and in the acini. The glandular parenchyma is atrophic, the islet apparatus is preserved, diffuse fibrosis and lymphohistiocytic infiltrates are noted in the interstitium (Fig. 300). Changes can range from cystic enlargement of single ducts and acini to cystic transformation of the entire excretory glandular parenchyma. As a result of thickening of mucus in bronchus obstructive atelectasis occurs with inevitable secondary infection and development chronic bronchitis, pneumonia with bronchiectasis and abscess formation. V intestines there is a thickening of feces with the development of coprostasis, perforation and fecal peritonitis. Changes in the properties of feces are facilitated not only by thickening of mucus, but also by insufficiency of the pancreas (lack of lipase, lipocaine and trypsin). V liver there is fatty infiltration. Thickening of bile leads to cholestasis and biliary cirrhosis. Fetal cystic fibrosis manifests itself as meconium intestinal obstruction(meconium ileus). In the pancreas
Rice. 300. Cystic fibrosis of the pancreas with cystic fibrosis
pronounced cystic changes may be absent. The entire small intestine up to the ileal cecum (bauginia) valve is filled with greenish-olive thick, viscous meconium; the colon is collapsed, it looks like a so-called microcolon. After perforation between the loops of the intestine, masses of meconium and fibrinous-purulent overlays on the peritoneum are visible. At intrauterine meconium peritonitis adhesions are formed between the intestinal loops with greenish lumps of meconium embedded in them. Such plaque-like dense overlays are found on the parietal peritoneum, on the capsule of the spleen and liver.
Complications. In addition to complications directly related to the underlying disease (chronic pneumonia, fecal and meconium peritonitis, cirrhosis of the liver), patients experience progressive general depletion, which depends on disorders of lipid, protein, vitamin metabolism (vitamins A, D, E and K, soluble in lipids) as a result of increasing pancreatic insufficiency.
Death comes from pulmonary heart failure, peritonitis, hepatic coma. With meconium ileus, children die in the first days of life.
Endocardial fibroelastosis- a congenital disease in which sclerosis with an abundance of elastic fibers is observed in the endocardium and in the subendocardial layer of the myocardium. Rare.
Etiology and pathogenesis. The family character of the disease is noted, suggesting the influence of the cytomegalovirus, protein starvation of the mother, vitamin deficiencies, fetal hypoxia. The pathogenesis is not clear. It is possible that the leading role belongs to myocardial damage, in response to which the elastic and collagen tissues of the endocardium grow compensatory.
Pathological anatomy. The heart is enlarged 2.5-4 times compared with the norm due to significant hypertrophy, predominantly of the left ventricle, its endocardium is sharply thickened, whitish-yellow. WHO-
it is possible to simultaneously damage the endocardium of the rest of the heart. In half of the cases, there is a thickening and deformation of the mitral and aortic valves, in 1/3 of cases - a combination with congenital defects, more often with narrowing of the aorta.
Significant endocardial sclerosis and cardiosclerosis lead to a decrease in myocardial contractility.
Death comes from acute heart failure (fulminant form) in the first days of life or from growing heart failure with intercurrent diseases (pneumonia) in the first months of life.
Diabetic fetopathy- fetal disease caused by maternal prediabetes and diabetes.
Etiology and pathogenesis. Of major importance are fetal carbohydrate metabolism disorders under the influence of constant changes in the level of glucose in the mother's blood, especially significant in poorly treated pregnancy diabetes. In connection with an attempt to compensate for the level of glucose in the blood, the fetus develops hypertrophy of the insular apparatus, followed by its depletion and dystrophy of β-cells, as well as Itsenko-Cushing's syndrome. After birth, when the influence of maternal diabetes decreases, restoration of the function of the fetal pancreas and normalization of metabolism can occur. If this does not happen, severe suffering develops - diabetes of the newborn. However, newborn diabetes is not always associated with maternal diabetes, as it may depend on damage to the insular apparatus of a fetus of a different origin. In contrast to this diabetic fetopathy is associated only with diabetes and maternal prediabetes.
Pathological anatomy. With this fetopathy, there is a tendency to give birth to large fetuses - with a body weight of 4-6 kg, although this is not necessary. The body of the fetus is covered with abundant cheese-like lubricant, the skin is purplish blue with petechiae, the neck is short, the face is puffy, edematous, the soft tissues of the trunk and extremities are pasty (Fig. 301), there are signs of immaturity - the absence of a core of ossification of the thigh or a decrease in its size, etc. and cardiomegaly. Microscopic examination in the pancreas shows hypertrophy of the islets of the pancreas with an increase in the number of β-cells. Along with this, degranulation, vacuolization and pycnosis of the nuclei of these cells are noted, indicating the depletion of their secretion. The liver has diffuse fatty infiltration, extensive foci of extramedullary hematopoiesis, and sometimes necrosis. In the myocardium, vacuolar dystrophy, micronecrosis are noted, in the kidneys - the deposition of glycogen in the convoluted tubules, in the spleen - extramedullary hematopoiesis. In the vessels of the microvasculature of the kidneys, skin, and retina of the eye, there is a thickening of the walls due to the deposits of SHIK-positive material, proliferation of the endothelium, along with significant tortuosity and ectasia of the vascular bed.
Rice. 301. Diabetic fetopathy
From complications fetuses and newborns with diabetic fetopathy often develop hypoxia during childbirth, education hyaline membranes in the lungs, which depends on the deficiency of the antiatelectatic factor - a surfactant, a substance of a phospholipid nature - as a result of disorders in diabetic fetopathy not only of carbohydrate, but also of lipid metabolism.
Death comes from asphyxia of the fetus or newborn, as well as from hypoglycemia that occurs after birth stress.
Antenatal (prenatal) fetal care is a complex of diagnostic, therapeutic and preventive measures carried out to ensure the normal intrauterine development of the body from conception to birth. Aimed at eliminating factors: negatively affecting the formation and development of the embryo and fetus, prevention of congenital pathology, reduction of perinatal mortality (mortality of the fetus and newborn in the period from the 28th week of pregnancy to 7 days of life) After a woman smokes a cigarette, a spasm of blood vessels occurs the placenta and the fetus are in a state of oxygen starvation for several minutes. All toxic components of tobacco smoke easily penetrate the placenta, and due to the lack of the delivered amount of oxygen, intrauterine development of the fetus is delayed. Moreover, the concentration of all toxic components in the fetus is much higher than in the mother's blood. Complications of pregnancy and childbirth, spontaneous abortions, tubal pregnancies, and premature births occur much more often in women who smoke. Fetal Alcohol Syndrome (FAS) is a fetal disease caused by intrauterine alcohol injury, which is the main cause of congenital intellectual retardation in a child. This syndrome is characterized by specific facial anomalies: a short palpebral fissure, strabismus, flattening of the occiput, smooth nasolabial fold, as well as a lag in physical and intellectual development, damage to the heart and other organs. Children are usually irritable, restless, with a weak grasping reflex, poor coordination, defects in the development of the central nervous system are observed. 3rd month of intrauterine development. The causes of Embryopathy can be genetic disorders; hypoxia, intoxication, infectious diseases and other pathogenic factors that affect the embryo through the maternal body. Embryopathies lead to a violation of the formation of the organs of the embryo and are the cause of malformations, spontaneous abortions. For the prevention of Embryopathy, it is important to protect the health of a woman in the 1st month of pregnancy. Fetopathies are diseases and functional disorders that arise in the fetus under the influence of exogenous influences from the 11th week of pregnancy to birth. Depending on the pathogenesis and etiological factor, infectious and non-infectious fetopathies are distinguished. Infectious fetopathies arise under the influence of any infectious agent (from viruses to protozoa and fungi) and tend to generalize the process, leading to specific changes in the fetus (congenital syphilis, tuberculosis, herpes infections).
Non-infectious fetopathies (hypotrophy and hypoxia) develop as a result of placental insufficiency and metabolic disorders in the fetus in the pathology of pregnancy and extragenital diseases (especially with their exacerbations during pregnancy). Non-infectious fetopathies include fetal hemolytic disease; congenital generalized calcification of the arteries, myocardial fibroblastosis, diabetic, thyrotoxic, alcoholic fetopathy. Fetopathies of any etiology have a number of common clinical and morphological features: changes in body length and weight parameters (increase or, more often, decrease); lag in the morphological and functional maturation of organs (central nervous system, lungs, kidneys, hematopoietic organs, thymus, liver); the predominance of hypertrophy and hyperplasia of the mesenchymal elements in the regeneration processes, which leads to the excessive development of connective tissue; infectious and toxic fetopathies are accompanied by severe hemorrhagic diathesis and hepatosplenomegaly.
Diabetic embryopetopathy is a serious disorder of the health of a newborn child, which manifests itself in the neonatal period, is accompanied by profound metabolic disorders, dysfunction of the endocrine system, involvement of almost all organs and systems of the body in the pathological process.
The very name of this pathology explains the reasons for its occurrence. Diabetic embryophetopathy develops in children whose mothers suffer from diabetes mellitus or have other diseases accompanied by disorders of carbohydrate metabolism and hormonal status.
According to official statistics, the incidence of diabetes among pregnant women in the Russian Federation has increased by 20% over the past 10 years. All women with type 1 and 2 diabetes mellitus, regardless of the time of the onset of the disease and its duration, have a high probability of a complicated course of pregnancy, the threat of its termination, the development of complications in childbirth, and the risks of having a baby with embryophetopathy. This applies to both cases of diabetes mellitus diagnosed before pregnancy and gestational diabetes.
Diabetes mellitus during pregnancy is labile, characterized by significant fluctuations in blood sugar levels during the day (from hypo - to hyperglycemic states), a tendency to decompensation, and rapid progression of vascular complications.
The prognosis for the mother and the fetus depends not so much on the duration of the disease, but on the degree of its compensation before and during pregnancy, the initial complications and their subsequent progression.
The greatest risks of developing gestational diabetes are women over 25 years old, with previous obesity, a large increase in body weight during pregnancy, the presence of relatives with diabetes mellitus. Risks increase if previous pregnancies were accompanied by hyperglycemia, impaired carbohydrate tolerance, the birth of a child weighing more than 4000 g, and a large fetus (fetal macrosomia) and polyhydramnios were diagnosed during this pregnancy.
Gestational diabetes usually develops in the second or third trimester of pregnancy (more than 20 weeks on the rocks). During this period, the placenta is formed and begins to actively function - a new endocrine gland that produces chorionic lactosomatotropin, which is similar in biological properties to the growth hormone, which ensures the growth and development of the fetus. High levels of this hormone in the blood of a pregnant woman helps to reduce the sensitivity of tissues to insulin, the main regulator of glucose metabolism. In addition, lactosomatotropin activates the processes of glucose formation in liver cells - gluconeogenesis. The resulting hyperglycemia leads to a significant increase in the body's need for insulin, its relative deficiency, since the woman's pancreas cannot produce more insulin (taking into account the needs of the child). Violation of insulin metabolism in a pregnant woman leads to a pathological increase in body weight, fluid retention in tissues, the development of edema, polyhydramnios, and increased blood pressure.
For the developing organism of a child, problems begin long before birth, even in the embryonic period of development. Chronic maternal hyperglycemia leads to an increase in the baby's blood glucose. In the early stages of pregnancy (in the first 9-12 weeks), the fetal pancreas is not yet able to produce its own insulin. During this period, the laying and differentiation of the child's organs occurs, therefore, maternal hyperglycemia can contribute to the formation of heart defects, spine, spinal cord and organs of the gastrointestinal tract of the fetus. The most common malformation in children whose mothers have diabetes mellitus is the "caudal dyskinesia syndrome", in which the sacrum, coccyx, sometimes lumbar vertebrae, and thigh bones are absent or underdeveloped. There are increased risks of developing cerebral defects (anencephaly), underdevelopment or absence of the kidneys (hypo - aplasia), doubling of the ureters, heart defects, and reverse arrangement of organs.
From the 12th week of intrauterine development, in conditions of excess glucose intake, active transport of amino acids and ketone bodies through the mother's placenta, the baby's pancreas begins to produce large amounts of insulin.
As a result of hyperinsulinemia, excessive deposition of adipose tissue develops, fetal macrosomia. The inhibition of lecithin synthesis explains the high frequency of the so-called respiratory distress syndrome — respiratory distress in newborns. Lack of formation in the lungs of a surfactant - a substance that allows the lung tissue to expand on the first breath, leads to shortness of breath or respiratory arrest already in the first hours of a newborn's life with embryopetopathy. An increase in the volume and functional activity of β-cells that produce insulin leads to severe and prolonged hypoglycemia in newborns immediately after birth.
A newborn child with diabetic embryophetopathy has a number of characteristic external signs: babies weigh more than 4-6 kg, a reddish-bluish tinge of the skin, a petechial rash in the form of punctate subcutaneous hemorrhages is typical on the skin. These children have abundant dampness of the skin in the form of a whitish-gray mass. The skin and soft tissues are swollen, the "puffy" face draws attention. The abdomen is usually large due to the overdeveloped subcutaneous fat. The limbs appear short. Newborns tend to have long-term jaundice, which is a sign of pathological changes in the liver and requires treatment. Neurological disorders can also manifest themselves in the first hours of life: muscle tone is reduced, children suck sluggishly, decreased activity is replaced by hyperexcitability syndrome (anxiety, sleep disturbance, tremors of the limbs).
There are typical "acute", life-threatening complications of diabetic fetopathy and its long-term consequences. Among acute ones - neonatal hypoxia - a condition characterized by an insufficient oxygen content in the blood and tissues of the fetus and newborn, respiratory failure, as the most common cause of death among children born with diabetic fetopathy, acute hypoglycemia (a critical decrease in blood glucose levels), impaired mineral metabolism in a newborn (lack of calcium and magnesium), which adversely affects the function of the central nervous system.
Among the long-term consequences are the transformation of diabetic fetopathy into neonatal diabetes mellitus of newborns, obesity, mental retardation, mental disorders.
The clinical symptoms of hypoglycemia in newborns are varied: hyperexcitability, revitalization of reflexes, tremors, cyanosis, convulsions, apnea attacks, irritable crying, less often lethargy, nystagmus. The decisive diagnostic sign, in addition to determining blood sugar, is the disappearance of pathological symptoms after the administration of glucose.
It should be emphasized that the diagnosis of diabetic fetopathy should be established even before the birth of the child based on the collection of a life history, a comprehensive examination of a pregnant woman, and ultrasound diagnostics of the fetus. An obstetrician-gynecologist should send a pregnant woman for an ultrasound scan already at the first visit to the antenatal clinic. The following ultrasound examinations should be performed during the 2nd and 3rd trimesters of pregnancy. This will reveal possible pathologies of fetal development. In cases where a pregnant woman is diagnosed with insulin-dependent diabetes mellitus, ultrasound examination is performed at 30–32 weeks of pregnancy, and then weekly, until delivery.
Prevention of diabetic embryophetopathy and disorders of adaptation of newborns in mothers with diabetes mellitus includes a number of measures: achieving full compensation of diabetes mellitus before and during pregnancy; rehabilitation of chronic foci of infection in mothers; therapy aimed at improving the structural and functional state of the placenta and uteroplacental circulation; stimulation of the maturation of the pulmonary surfactant in the fetus; maintaining normal maternal glycemic levels during labor.
It should be especially noted that the optimal method of treating diabetes mellitus during pregnancy is intensive insulin therapy with strict control of carbohydrate metabolism indicators.
The prognosis and dispensary observation of children with diabetic embryopetopathy is determined by the severity and the totality of the disorders that developed in the child immediately after childbirth. In children who do not have congenital defects, by 2-3 months, there is a complete reverse development of the signs of fetopathy. The likelihood of developing diabetes mellitus in the future is not high, however, there is a tendency to obesity. There is a risk of organic damage to the nervous system due to hypoglycemia. Minimal cerebral dysfunction is subsequently diagnosed in every third child, functional changes in the cardiovascular system - in half of the cases. In case of intercurrent diseases, children with previous diabetic fetopathy need to determine blood and urine sugar, and once a year, conduct a standard glucose tolerance test.
Rakitskaya Elena Viktorovna
Doctor of Medical Sciences, Professor of the Department of Pediatrics, Pediatric Infectious Diseases and Neontology of the Far Eastern State Medical University of the Ministry of Health of the Russian Federation, pediatric endocrinologist of the highest category
Alcoholic embryopetopathy of newborns
Alcoholic embryophetopathy develops in 30-50% of children born to mothers suffering from chronic alcoholism.
When alcohol is consumed by the mother in the first weeks of pregnancy, the embryotoxic effect of ethanol and acetaldehyde is revealed (the embryo lacks alcohol dehydrogenase) - inhibition of the synthesis of DNA and proteins (including enzymes), primarily in the brain rudiment.
In addition, with alcoholism, people usually have a number of concomitant diseases, eating disorders, and other bad habits (smoking, etc.).
- high frequency of intrauterine growth retardation (IUGR) of dysplastic (less often hypotrophic) type and childbirth in asphyxia;
- craniofacial dysmorphism in 80-90% of children (microcephaly; microphthalmia with shortening of the length of the palpebral fissure in full-term and premature babies with a gestation period of more than 32 weeks - less than 14 mm, and with long periods of prematurity - less than 13 mm; flat wide root of the hypoplastic nose , low forehead, high palate, flattening of the occiput; less common epicanthus, squint, blepharophimosis, prognathia, a large mouth with a thin upper lip and an elongated filterrum - labial, nasal groove - "fish mouth", oblique upper curl and low location of the auricles, hypoplasia middle face);
- congenital malformations in 30-50% of children (hearts - more often septal defects; genitals - hypospadias, hypoplastic labia in girls, doubling of the vagina, etc., as well as the anus - its closure with a septum, displacement; extremities - abnormal arrangement of fingers, hypoplasia nails, syndactyly, clinodactyly, hip dysplasia, incomplete extension in the elbow joints; chest; hemangiomas; excess hair, especially on the forehead, wrinkles; abnormal lines on the palms and other dermatoglyphic disorders);
- cerebral insufficiency and mental retardation with subsequent oligophrenia, hyperreactivity and aggressiveness, muscle hypotonia.
Most children with alcohol embryopetopathy are girls. Male embryos are likely to die at the earliest stages of development (embryotoxic effect of ethanol).
Sometimes in the first hours of life, hyperexcitability is so pronounced that, along with shortness of breath, tremors, restless screaming, convulsions appear that pass after giving the child 0.5 g of alcohol; the child is diagnosed with alcohol withdrawal syndrome.
physical development (microcephaly becomes more distinct), dementia and other neuropsychiatric diseases, endocrine disorders.
Materials from the book: N.P. Shabalov. Neonatology., Moscow, "MEDpress-inform", 2004
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What is alcoholic embryopetopathy in newborns?
Alcoholic embryophetopathy in newborns - this concept in itself sounds terrible. This disease develops in 40% of babies whose mothers suffer from chronic alcoholism.
Alcohol and baby
For a future baby, even conception is dangerous if the mother is intoxicated. With systematic use, alcohol can cause dystrophic and degenerative changes before fertilization in the germ cells. And alcoholism in the father can cause encephalopathy in the child. If the mother consumes alcohol in the first weeks of pregnancy, the embryotoxic effect of acetaldehyde and ethanol is revealed, and the synthesis of DNA and proteins is inhibited. Folic acid and zinc deficiencies are also harmful to the human fetus. Due to mother's alcoholism, a violation of the placental circulation may occur, as a result of fetal hypoxia.
The general picture of alcoholic embryopetopathy
Because of this problem, children are observed: shortening of the length of the palpebral fissure, flat wide root of the nose, high palate, low forehead, flattening of the occiput, squint, large mouth with a thin upper lip, "fish mouth", low location of the auricles, defects of the heart septum , genitals, abnormal position of the fingers, chest, hip dysplasia, excess hair, abnormal lines on the palms. Delays in mental development are also possible, we are talking about oligophrenia, which will only progress in the future. By the way, most children with alcoholic embryophetopathy are babies. They are characterized by a syndrome of hyperexcitability, often difficulty in swallowing, sucking, motor coordination. In infants in the first hours of life, shortness of breath, tremors, restless screaming, convulsions may appear. All this usually go away after taking 0.5 g of alcohol. So the baby is diagnosed with alcohol withdrawal syndrome.
Health problems
In such children, the lag in physical development, dementia, and endocrine disorders are often recorded. Diseases of the respiratory tract are possible, since such babies have a defect in secretory immunity, problems with the respiratory tract, and disorders of mucociliary transport. Even if at birth the baby does not show signs of alcoholic embryophetopathy, a child from alcoholic families has a low IQ, speech disorders, aggressiveness, neuroses, epilepsy, enuresis, mental retardation, hearing and vision abnormalities. We are talking about the prenatal effects of alcohol, that is, the "behavioral" teratogenic effect.
Diagnosis of hereditary diseases in the neonatal period. Embryophetopathy of newborns. Endocrinopathies of newborns.
Problem number 1.
A child aged 3 days is in a maternity hospital. It is known that mothers are 25 years old, from the 2nd pregnancy, 1st birth, a medical abortion in the anamnesis, 11 years of heroin addiction, the entire pregnancy took 3 grams of heroin per day, registered from 12 weeks. Suffers from chronic gastritis, hepatitis B and C.
Delivery at 35 weeks of gestation. Body weight 2000, body length 45 cm. Apgar score 6/8 points, state at the time of birth of moderate severity.
By the end of the third day, there is a deterioration in the condition. The child reacts to examination with a piercing unemotional cry, chaotic motor activity, hyperesthesia phenomena, tremors of the extremities, obsessive sucking movements not associated with feeding are observed. Tendon reflexes are revitalized. Restless sleep. Sucks not actively, regurgitates, “chokes”. Breathing through the nose is difficult, there is no visible discharge. The skin is pale, with a pronounced marbled pattern. Breathing is puerile. The tones are slightly muted. Heart rate per minute. The abdomen is swollen, palpation is available in all departments. Umbilical remainder under the brace. Free, painless urination.
2. Prescribe treatment.
3. Due to what there is a deterioration in the child's condition.
5. What complications can be observed in children from mothers with such a history.
Problem number 2.
Child K., 3 days old, is in a maternity hospital, was born from a mother of 27 years. The mother suffers from chronic alcoholism. History of 2 medical abortions. Real pregnancy 3, unwanted. She was not registered with the antenatal clinic, was not examined. Childbirth at 37 weeks of gestation, in cephalic presentation: 1st period - 3 hours, 2nd - 20 minutes, anhydrous interval - 8 hours. Amniotic fluid is cloudy with an unpleasant odor. Apgar score 7/8 points. Body weight at birth 2100 g, body length 48 cm, head circumference 28 cm, chest circumference 32 cm. In the maternity unit, the upper respiratory tract was sanitized, inhaled with humidified oxygen through a mask.
By the end of the first day, the child is in the neonatal unit. On examination, a state of moderate severity due to the central nervous system arousal syndrome, the child is restless, does not suck well, spits up. Reacts to inspection with a shrill cry. Increased physical activity. With anxiety, there is a tremor of the limbs. Attention is drawn to a small head, wide-set small eyes, a short nose. Leather
pale, cyanosis of the nasolabial triangle, aggravated by exertion. The internal organs were normal.
1. Make a presumptive diagnosis for this child.
2. Determine the tactics of conducting, examination.
3. What causes the severity of the condition.
4. Describe the clinical picture of this condition.
5. What can we observe in children from mothers with such anamnesis?
Problem number 3.
Child K., from 2 pregnancies, 1 childbirth, mother of 24 years. 1 pregnancy ended in early miscarriage. The mother suffers from chronic gastritis. From the age of 15 he is an active smoker (5 cigarettes a day). Registered in the antenatal clinic from 11 weeks. The first trimester proceeded with the threat of miscarriage, a rise in blood pressure up to 160/100 mm Hg, and mild anemia.
A full-term, living child was born. The amniotic fluid is green, turbid. Apgar score 7/8 points. Body weight 2890, length 50 cm.
Two hours later, in the children's department, the child has: tremor of the limbs, a piercing cry, hyperesthesia, increased muscle tone, "fierce sucking of fists" is observed, constantly yawns. The skin is pale and clear. Sniffles, no visible discharge. Breathing is puerile, no wheezing. Heart sounds are rhythmic. The abdomen is soft and painless. The liver and spleen are not enlarged. Umbilical cord remainder under the brace.
1. Make a presumptive diagnosis for this child.
2. Determine the tactics of conducting.
3. Due to what there is a deterioration in the state of health of this child.
4. Describe the clinical picture of this condition.
5. For what reasons can intrauterine pathology develop?
Problem number 4.
Boy T. was removed at 36 weeks of gestation by a caesarean section performed without labor in connection with a scar on the uterus in a woman suffering from obesity and gestational diabetes mellitus diagnosed at 28 weeks of gestation.
The second pregnancy, proceeded with a moderate increase in blood pressure from the 31st week, there were edema of the legs, traces of protein in the urine, polyhydramnios.
The child's body weight is 3800 g, height 51 cm, head circumference 34 cm, chest circumference 36 cm. The Apgar score is 8/8 points. On examination, a disproportionate physique was noted with a predominant deposition of fat on the upper half of the body, small hands and feet, bright pink skin color, peripheral cyanosis, pastiness, pronounced lanugo.
An hour after birth, the child showed a decrease in muscle tone, physiological reflexes, the appearance of tremors of the extremities, increased excitability, muffled heart sounds, shortness of breath up to 70 per minute. The abdomen is rounded. Liver + 2.5 cm from under the costal margin.
1. Make a presumptive diagnosis for this child.
2. What laboratory examination should be carried out
3. Prescribe treatment.
4. Give a clinical description of the condition.
5. Keeping this child in the clinic.
Problem number 5.
Boy, 14 days from 5th pregnancy, second birth. The first pregnancy ended with the birth of a healthy child, the second and third pregnancies - honey. abortion, the fourth - a miscarriage at 10 weeks. This pregnancy proceeded with early preeclampsia; in the second trimester of pregnancy, the mother was treated in a hospital for the threat of miscarriage. Childbirth with rhodostimulation. The child screamed at once, body weight at birth 4150.0 g, length 52 cm, attached to the chest for 3 days. Sucked satisfactorily, but vomited profusely.
Body weight on the 7th day of life 3850.0. The child was transferred to a hospital on the 12th day of life with symptoms of an increase in exsicosis and toxicosis. Upon admission, the body weight is 3030.0 g. The child's condition is serious, the cry is weak. The subcutaneous fat layer is absent, the skin is dry, wrinkled. Suffering facial expression. Sunken eyes, "blue" under the eyes. The abdomen is moderately distended, with a pronounced venous network. The liver and spleen are enlarged. The genitals are formed correctly, according to the male type, the penis is slightly enlarged in size, the pigmentation of the scrotum is enhanced. Muscular hypotension. Reflexes are depressed. Hand tremor. Stool 8 times a day, liquefied.
Clinical blood test: HBg / l, L - 10.0 x 10 9 / l, n 5%, with 48%, limf. 40%, mon 7%, ESR 4 mm / h,
KOS: pH - 7.30, pCOmm. rt. Art., BE - 7 mmol / l, Biochemical blood test: K - 8.4 mmol / l, Na - 80 mmol / l. The daily urinary excretion of 17-KS is 3.2 mg / day.
1. Make and justify the diagnosis.
2. Describe the pathogenesis of the disease.
3. Describe the typical clinical picture of this disease.
4. Indicate the diagnostic criteria.
5. Provide emergency care.
Problem number 6.
When you visit a 2-week-old baby, the mother complains of constipation, jaundice, lethargy and drowsiness. Physical examination reveals: the child's well-being is somewhat impaired, physical activity is reduced, the child is sluggish, the head is of normal size, the small fontanel is 0.5 * 0.5 cm, the large 2.5 * 3 cm, eutonic, tissue turgor is increased, slight yellowness is noted swelling of the face and trunk, distended abdomen, moderate bradycardia in a sleeping child.
From the anamnesis it is known: the child was born from a mother of 30 years, from 2 pregnancies, 1 childbirth, 1 pregnancy - artificial abortion, registered from 10 weeks. In the 8th week of pregnancy, the mother was ill with the flu. Delivery is urgent at 41 weeks. Score on the Apgar scale 7/8 points, state at birth of moderate severity. The child's body weight at birth is 4000 g, length is 55 cm.
The results of the neonatal test carried out in the maternity hospital: TSH - 30 mIU / L, Tnmol / L.
1. Make a presumptive diagnosis for this child.
2. Describe the pathogenesis of this condition.
3. Give a clinical description of the condition.
4. Indicate the diagnostic criteria.
5. Prescribe treatment. Define a forecast.
Problem number 7.
Girl M. 1 day. From the anamnesis it is known that she was born from 11 pregnancies, the second urgent delivery. The first pregnancy ended in childbirth, the child is healthy. Subsequent pregnancies - 9 induced abortions. This pregnancy came at 39 years old, proceeded with preeclampsia of the 1st trimester and the threat of termination for a week. Delivery is urgent, by caesarean section. Apgar score 7/8 points. Body weight at birth 2670 g., Length 48 cm.
On examination: a state of moderate severity, there is a predominance of the facial skull over the brain, a flat occiput, oblique eye section, epicanthus, hypertelorism, macroglossia, deformed auricles, imbalances of the trunk and limbs, a transverse groove on the palms. Severe hypotension, hyporeflexia, and joint laxity are noted. Heart sounds are muffled. On auscultation in the lungs, puerile breathing. The abdomen is flattened. The liver from under the costal margin is 2.0 cm along the mid-clavicular line. The spleen is not enlarged. There was no stool after birth. Rarely urinates.
1. Make a presumptive diagnosis for this child.
2. Indicate the etiology of the disease.
3. Schedule an examination.
4. Give the clinical characteristics of the disease.
5. Determine the forecast.
Problem number 8.
The girl was admitted to the ICU of the maternity hospital for 1 day. It is known that the child from the mother is 17 years old, the mother suffers from epilepsy, chronic pyelonephritis. Real pregnancy 1, desired, registered from 8 weeks. Pregnancy proceeded with gestosis, in the early stages of exacerbation of the underlying disease, inpatient treatment. Childbirth premature at 36 weeks, a girl was born, weighing 2900 g 49 cm with an Apgar score of 5-7 points. The condition from birth is severe due to respiratory disorders. Clinical examination revealed a characteristic "bird" face with an underdeveloped lower jaw, a cleft of the hard and soft palate.
1. Make a presumptive diagnosis for this child.
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Embryo and fetopathy of newborn children. Diagnostics, treatment and prevention
progenesis cymatogenesis
1) Blastogenesis
2) Embryogenesis
3) Fetogenesis, from the 76th to the 280th day, when the placenta was formed, differentiation and maturation of fetal tissues occur. The period of fetogenesis is divided into early fetal period(from the 76th to the 180th day), by the end of which the immature fetus acquires vitality, and late fetal period(from the 181st to the 280th day), in which the fetus ripens with the simultaneous aging of the placenta. The late fetal period turns into a short-term intranatal period(from the time of the onset of contractions until the time of the ligation of the umbilical cord), which lasts from 2-4 hours.
A. If your blood glucose is below 2.6 mmol / L (45 mg / dL) but above 1.1 mmol / L (25 mg / dL)
1. To put the baby to the breast more often. If the baby cannot breastfeed, it is necessary to give expressed breast milk using an alternative method (cup, spoon, syringe, gastric tube).
2. Determine the blood glucose level after 6 hours:
If your blood glucose is still below 2.6 mmol / L (45 mg / dL) but not below 1.1 mmol / L (25 mg / dL), you should increase the frequency of breastfeeding and / or the volume of expressed breast milk. If the blood glucose level has not reached normal levels, then consider the appointment of an intravenous glucose infusion;
If blood glucose is below 1.1 mmol / L (25 mg / dL), treat as described below.
B. Blood glucose level below 1.1 mmol / L (25 mg / dL)
1. Provide intravenous access if not already done. Intravenous stream, slowly, within 5 minutes, enter a 10% glucose solution at the rate of 2 ml / kg of body weight.
2. If the intravenous catheter cannot be inserted quickly, give a 10% glucose solution at the rate of 2 ml / kg body weight by mouth (through a gastric tube if the baby is unable to suck).
3. Continue intravenous administration of a 10% glucose solution in a volume corresponding to the child's age-specific daily needs (an average of 90 ml / kg / day).
4. Determine the blood glucose level 3 hours after the start of treatment;
If the blood glucose level remains below 1.1 mmol / L (25 mg / dL), repeat the glucose jet as described above and continue the infusion;
If the blood glucose level is higher than 1.1 mmol / L (25 mg / dL), but below 2.6 mmol / L (45 mg / dL) with each determination, continue the continuous infusion and determine the blood glucose level every 6 hours until it reaches 2.6 mmol / l (45 mg / dl) or more in two consecutive analyzes;
5. To put the baby to the breast more often. If the baby cannot breastfeed, give expressed breast milk or formula using an alternative feeding method (cup, spoon, syringe, gastric tube).
6. With the improvement of enteral feeding, reduce the volume of intravenous glucose slowly (within 3 days), while increasing the oral food intake.
Do not abruptly interrupt the glucose infusion.
Forecast for DF. Perinatal mortality of children with DF is about 2-5 times higher than the regional average. In the group of children from mothers with diabetes, complicated by proliferative retinopathy and diabetic cardiopathy, it reaches 6-10%. Although it is believed that in children with DF who survived the neonatal period and who do not have congenital defects, by 2-3 months there is a complete reverse development of all signs of fetopathy, nevertheless, in 1 / 3-1 / 4 children, cerebral dysfunctions are subsequently revealed (in including in 2-3% - infantile cerebral palsy, epilepsy or convulsive syndrome), in about half - functional abnormalities from the cardiovascular system, in 1/3 - disorders of carbohydrate metabolism. The risk of juvenile diabetes in children with DF is 2% (with diabetes in the father - 6%).
Children from mothers with thyroid disease. It is believed that about 0.5-1.0% of pregnant women have thyroid diseases, however, only with some of them (diffuse toxic goiter, autoimmune thyroiditis with a high antibody titer during pregnancy) an increased incidence of embryo and fetopathies, primarily hypoplasia, has been proven or aplasia of the thyroid gland (congenital hypothyroidism is diagnosed in 12-15% of newborns from mothers with diffuse toxic goiter) and transient dysfunctions of the thyroid gland (transient neonatal thyrotoxicosis - in 1.0-1.5%).
Thyrotoxic embryopathy can develop in the case of diffuse toxic goiter in the first trimester of pregnancy, especially with the primary appointment of mercazolil: intrauterine growth retardation of the dysplastic type and often congenital malformations of the heart, kidneys, microcephaly, hydrocephalus and other lesions of the central nervous system (their frequency is 5-7 times higher than in children from healthy mothers). Therefore, diffuse toxic goiter in the first trimester of pregnancy is an indication for its termination. A pregnancy that is relatively safe for the fetus is possible no earlier than 2 years after successful conservative or surgical treatment of the mother and provided that her autoantibodies in the thyroid gland disappear.
Alcoholic embryophetopathy develops in 30-50% of children born to mothers suffering from chronic alcoholism. However, even conception while intoxicated is dangerous for the unborn child. Such children have significantly lower IQ at school age, neuroses, enuresis, anomalies of vision, hearing, and increased aggressiveness are more often observed. Considering that alcohol, with systematic use, can cause degenerative and dystrophic changes in the germ cells before fertilization, the father's alcoholism, although it does not cause alcohol fetopathy, can be the cause of encephalopathy, manifested by the symptoms described above.
When alcohol is consumed by the mother in the first weeks of pregnancy, the embryotoxic effect of ethanol and acetaldehyde is revealed (the embryo lacks alcohol dehydrogenase and the activity of acetaldehydrogenase is sharply reduced) - inhibition of the synthesis of DNA and proteins (including enzymes), primarily in the brain rudiment. Among the pathogenetic factors of the damaging effect of alcohol on the human embryo, there is also a deficiency of folic acid and zinc, prostaglandin E, activation of free radical lipid peroxidation, impaired placental circulation and hence fetal hypoxia. In addition, with alcoholism, people usually have a number of concomitant diseases, eating disorders, and other bad habits (smoking).
Clinical manifestations of alcohol embryophetopathy: 1) intrauterine growth retardation (IUGR) of the dysplastic (less often hypotrophic) type and the birth of a child in asphyxia;
2) craniofacial dysmorphism in 80-90% of children (microcephaly; microphthalmia with shortening of the length of the palpebral fissure in full-term and premature babies with a gestation period of more than 32 weeks - less than 14 mm, and with long periods of premature birth - less than 13 mm; flat wide root of the hypoplastic nose, low forehead, high palate, flattening of the occiput; less common epicanthus, strabismus, blepharophimosis, prognathia, large mouth with a thin upper lip and an elongated filterrum - labial, nasal groove - "fish mouth", oblique upper curl and low location of the auricles, hypoplasia of the middle face);
3) congenital malformations in 30-50% of children (hearts - more often septal defects; genitals - hypospadias, hypoplastic labia in girls, doubling of the vagina; anus - its closure by a septum, displacement; limbs - abnormal arrangement of fingers, nail hypoplasia, syndactyly , clinodactyly, hip dysplasia, incomplete extension in the elbow joints; chest; hemangiomas; excess hair, especially on the forehead; wrinkles; abnormal lines on the palms and other dermatoglyphic disorders);
4) cerebral insufficiency and mental retardation with subsequent oligophrenia, hyperreactivity and aggressiveness, muscle hypotonia.
Most children with alcohol embryopetopathy are girls. Male embryos are likely to die at the earliest stages of development (embryotoxic effect of ethanol).
In the neonatal period, the syndrome of hyperexcitability is typical, there are often difficulties in sucking, swallowing, motor coordination, hypoglycemia. Sometimes in the first hours of life, hyperexcitability is so pronounced that, along with shortness of breath, tremors, restless screaming, convulsions appear that pass after giving the child 0.5 g of alcohol; the child is diagnosed with alcohol withdrawal syndrome.
In the future, children with alcohol fetopathy have a lag in physical development (microcephaly becomes more pronounced), dementia and other neuropsychiatric diseases, endocrine disorders. Frequent diseases of the respiratory tract in such children are caused by a defect in secretory immunity and cilia of the ciliated epithelium of the respiratory tract, disorders of mucociliary transport.
Even in the absence of signs of alcoholic embryophetopathy at birth, children from families of alcoholics often have a low IQ, aggressiveness, speech disorders, neuroses, enuresis, epilepsy, mental retardation, visual and hearing anomalies, i.e. prenatal exposure to alcohol has a "behavioral" teratogenic effect.
Autopsy of the corpses of children born with alcoholic embryophetopathy reveals severe malformations of the brain: underdevelopment of the cerebral cortex, choroid plexuses of the ventricles and cerebellum, gliosis, atypical arrangement of cell layers.
It should be noted that there is no “safe” level of alcohol consumption during pregnancy and the prohibition of its intake by pregnant and lactating women is absolute.
Fetal tobacco syndrome is possible not only in active smokers (using more than 5 cigarettes a day), but also in passive ones.
In women, the frequency of miscarriages, preeclampsia, prematurity, previa and placental abruption, bleeding during childbirth increases; in a child - IUGR of a hypotrophic type due to intrauterine hypoxia, hypovitaminosis (in particular, deficiency of folic acid, folicobalamin), accumulation of toxic substances in the fetal blood (carboxyhemoglobin, nicotine, thiocyanate), cleft lip and palate, birth in asphyxia, perinatal morbidity and mortality, including the development of sudden death syndrome.
Difficulty adapting newborns to extrauterine life - polycythemic syndrome, activation of the sympathetic-adrenal system with hyperexcitability syndrome, slow recovery of transient weight loss and jaundice, more active and prolonged synthesis of fetal hemoglobin and 2,3-diphosphoglycerate - are signs of persisting tissue hypoxia.
In addition, the child, both in the neonatal period and in the future, increases the risk of breathing disorders during sleep (noisy, wheezing, snoring), pulmonary pathology (ARVI, bronchitis), delayed psychomotor and physical development, sudden death syndrome during the first 8 months life.
It is also believed that the consequence of antenatal exposure to tobacco can be a decrease in intellectual abilities, an early tendency to smoke. There are works in which it has been established that the birth of children with congenital malformations affecting the fate of the child is 2 times more frequent, among fathers who are heavy smokers.
Smoking can also reduce the amount of milk in the mother, and nicotine, cigarette smoke products, are found in the mother's milk.
Children of mothers with substance abuse and drug addiction. In modern megacities, 2-3% of children are born to mothers who are drug addicts or drug addicts. As a rule, drug addicts and drug addicts use more than one substance, they abuse a variety of drugs, and, in addition, they smoke, consume alcohol, have concomitant diseases (anemia, cardiopathy, liver, kidney, nervous system, mental disorders), diseases transmitted sexually.
Women drug addicts, as a rule, are dystrophic and often live in poor living and social conditions. Pregnant drug addicts usually go late to medical institutions or do not register at all in the antenatal clinic.
Of course, each of the substances listed above has specific features that determine the characteristics of the pathology of the mother, damage to the embryo and fetus, but there are also general effects that occur with a high frequency:
1) miscarriage of pregnancy, miscarriages and stillbirths;
2) gestosis, eclampsia, abnormal fetal position, pathology of the placenta (presentation, abruption, placental insufficiency, and hence chronic fetal hypoxia);
3) IUGR of the fetus according to the hypoplastic or hypotrophic and even dysplastic type;
4) abnormal labor (premature discharge of water, weakness of labor, chorioamnionitis);
5) antenatal encephalopathy in the fetus (first of all, anomalies in the development of the brain - both visible, obvious congenital malformations, and defects detected only with additional studies), congenital malformations of various organs and systems (heart, genito-urinary system), often combined, or an abundance of stigmas of dysembryogenesis;
6) the birth of children in asphyxiation with aspiration of meconium;
7) intracranial hemorrhages in children;
8) pulmonary pathology in the early neonatal period;
9) perinatal infections in a child, including due to perinatally acquired immunodeficiency;
10) maternal and perinatal mortality, sudden death syndrome in a child both in the neonatal period and later.
Of course, in a particular child, all of the above pathology, as a rule, does not happen. For example, it is believed that the main problem for children from mothers who use cocaine is prematurity.
The most typical problem for a neonatologist when working with children of mothers who are drug addicts and drug addicts is the development of withdrawal symptoms in them - drug deprivation syndrome.
Withdrawal syndrome can develop in newborn mothers who are drug addicts and drug addicts, as well as alcoholics or who have been treated shortly before childbirth with barbiturates, tranquilizers, antidepressants, diphenhydramine and other histamine blockers. The clinical picture of withdrawal syndrome is characterized by profuse sweating, increased neuro-reflex excitability with a "piercing" unemotional cry, chaotic motor activity with "freezing" in pretentious positions, hyperesthesia and hyperacusis light), tremors, revitalization of tendon reflexes, "convulsive readiness" or convulsions; sleep disorders, persistent sucking of fingers, hand, but poor sucking from the chest or bottle, regurgitation, "choking" (children "choke"), vomiting, diarrhea, abdominal distension, nasal congestion, sneezing, tachycardia or bradycardia, tachypnea or shortness of breath, seizures apnea for more than 10 seconds, different types of periodic breathing, muscle hypertension, clonus, nystagmus, rapid cooling or overheating, vegetative-vascular disorders ("marbling" of the skin and its increased vulnerability, Harlequin's symptom), subfebrile and sometimes febrile body temperature, pronounced transient jaundice ...
The diagnosis is based on a careful history of the mother, conversations with her relatives and people around her, an analysis of the clinical picture in the mother and the child, data on drug addiction testing of the mother's and child's urine, and sometimes their blood.
The diagnosis of withdrawal syndrome is made on the basis of the total assessment on the L. Finnegan scale - 9 points or more.
Newborn withdrawal syndrome assessment system (according to L. Finnegan modified by J.Yoon)
Usually withdrawal syndrome occurs clinically immediately after birth, more often in the first 72 hours of a newborn's life, but its delayed appearance is possible, and even in the 2-3rd week of life. The duration of acute manifestations is usually from several days to a week, although longer cases have been described, even up to several weeks.
Treatment is carried out according to the following scheme. It is desirable to place the mother and child in the same ward and their constant contact (like "kangaroo"). It is necessary to feed the child more often - 8-10 times a day, with artificial feeding, hypercaloric mixtures are useful. Shows a protective mode, minimization of injections. Of the drugs with very strong excitement of the child, convulsions, phenobarbital is the first choice: the first day in a "loading" daily dose - 20 mg / kg, divided into 3 doses, and then 4.5 mg / kg once a day.
Shock doses of phenobarbital are not prescribed if the child has respiratory distress syndrome, especially if breathing with constant positive airway pressure (positive expiratory pressure) is used. The drug of the second choice is diazepam (seduxen, sibazone). It must be remembered that the maximum clinical severity of the withdrawal syndrome is 3-5 days of life, and then its intensity decreases. The duration of pharmacotherapy is usually at least 7-10 days. Other therapy is symptomatic; for example, in case of asphyxia, the appointment of nalorphine (0.01 mg / kg) is indicated.
In the follow-up, such children often reveal delays in psychomotor and physical development, hearing deficit, low intelligence quotient, anomalies in sexual development and behavior.
Industrial fetal syndrome is a recently isolated and not yet clearly delineated syndrome characterized by undermaturity or IUGR of all types, difficulty in adapting to extrauterine life, pronounced transient jaundice, a child's tendency to bleeding due to vitamin K deficiency, infections, large losses of initial body weight and its slow recovery, neurological disorders.
Isolation of the syndrome is caused by environmental hazards, environmental pollution by products of incomplete combustion of oil, dioxidine, lead, silicon, herbicides and other industrial emissions. The accumulation of these and other products in the placenta leads to a violation of its barrier and other functions, intrauterine hypoxia and trophic disorders in the fetus, primarily to a violation of the functional state of the liver and brain. It is clear that such children have an increased frequency of birth in asphyxia, neurological disorders both in the neonatal period and in the future.
The teratogenic effect of the following xenobiotics has been established: gasoline vapors, dioxins, isocyanates, carbon monoxide, pesticides (hexachlocyclohexane, diphenylchloroethane, chlorophos), polychlorinated hydrocarbons, mercury, lead, toluene.
It is believed that an increased frequency of this syndrome is observed in women living near gas stations, crossroads of highways, in large ecologically unfavorable cities, working as chauffeurs, at gas stations, chemical industry enterprises, with pesticides in agriculture. Of course, in each specific case, it is necessary to carefully assess the mother's history, age and state of health, working conditions, placenta, and only then make a judgment. Each chemical causes a specific injury. For example, with massive contact of a pregnant woman with methylated mercury, in 60% of cases, the fetus develops microcephaly, and then delayed psychomotor development, blindness, deafness, spasticity, convulsions, eye abnormalities are revealed; with lead - an increased frequency of stillbirths and miscarriages, cerebral malformations.
Radiation embryopathy. It is believed that it occurs when a pregnant woman is irradiated in the early stages, but does not have a specific picture: IUGR of the hypoplastic type with microcephaly and sometimes nephropathy, and later, varying degrees of pronounced defects in psychomotor development. In later life, an increased frequency of leukemia, malignant tumors, infertility. The most sensitive indicator of a possible radiation embryopathy is an increased frequency of a complex of cytogenetic abnormalities in peripheral blood cells. Such anomalies were found in 39% of people 20 years old who were exposed to radiation in the womb at a dose of about 100 rad or more (2% in the control group).
Medicinal embryophetopathies. Currently, there are about 5 million drugs and xentobiotics that humans have contact with, but only 1600 of them have been studied in experiments on pregnant animals. At the same time, the risk of side effects of drugs on the fetus in a person is rather difficult to assess, because it is necessary to take into account the mother's diseases, both recognized and unrecognized, complications of the course of pregnancy, the nutrition of the pregnant woman and her existing hypovitaminosis, the genotype, the age of the mother and father, their occupational hazards, the frequency of spontaneous defects, the ecological situation and, probably, some unknown factors.
There are embryotoxic, teratogenic and specific and nonspecific pharmacological effects of drugs and xentobiotics (foreign chemicals for humans) on the fetus.
Embryotoxic action xenobiotics consists in the negative effect of the substance on the zygote and blastocysts located in the lumen of the fallopian tubes or in the uterine cavity. The consequence of embryotoxicity can be termination of pregnancy, the formation of twins, malformations with a violation of the axis of the embryo.
Teratogenic action - the ability to disrupt the normal development of the embryo and cause the appearance of various congenital defects and anomalies. The most dangerous periods in this plan are the days of intrauterine life.
Specific and non-specific pharmacological effect of drugs on the fetus used for the treatment of an intrauterine patient (for example, with cardiac arrhythmias in the fetus), but it can also lead to complications that develop like in the fetus (drug fetotoxicity), and manifested only in a newborn.
There is a group of drugs, embryotoxic, teratogenic action of which has been established or there are serious reasons to assume their embryotoxicity (class D): androgens, their derivatives (including danazol, retabolil, etc.) and antiandrogens, estrogens, antiestrogens, progestogens, antithyroid and oral antidiabetic drugs , oral contraceptives (taken during pregnancy), anticancer drugs, antimetabolites, antiepileptic drugs (especially diphenin), antimalarial drugs, D-penicylamine, oral anticoagulants - vitamin K antagonists, tetracycline anesthetics (for ward staff), streptocides ... These drugs should not be prescribed to pregnant women if there are no life-threatening conditions in the mother for which they should be used (for example, lymphogranulomatosis or other neoplastic diseases, epilepsy with recurrent seizures).
The second group includes drugs, information on the embryotoxic effect of which is contradictory (class C): corticosteroids, tranquilizers, antidepressants, antipsychotics, thyroid hormones, antiemetic drugs, anti-tuberculosis and anti-inflammatory drugs (salicylates), sulfonamides, barbiturates, antidepressants, diagonistamines. These drugs should not be widely prescribed to pregnant women in maximum doses and, if possible, should be prescribed in short courses; they should be avoided in the first two months of pregnancy. Since the mid-80s in England, acetylsalicylic acid (aspirin), prescribed at a dose of 1-2 mg / kg / day, has become widespread in the treatment of gestosis. At this dose, aspirin, inhibiting the synthesis of thromboxane A 2, does not change the synthesis of prostacyclin and other vasodilating and inhibiting platelet aggregation prostaglandins, which leads to an improvement in the rheological properties of blood, blood flow in the placenta, sharply reduces the severity of uteroplacental insufficiency, fetal hypoxia. Aspirin is given for a long time - several months, while without any complications in the fetus. However, aspirin should be discontinued 2 weeks before delivery. Treatment with acetylsalicylic acid is contraindicated in women with hemorrhagic diathesis, in particular with hereditary thrombocytopathies.
In mothers with hereditary thrombocytopathies (approximately 5% of all women), bleeding of varying severity is possible, which they can transmit to the child, not only with aspirin treatment, but also under the influence of several platelet inhibitors simultaneously prescribed.
Medicinal fetotoxicity can cause various pathological syndromes in newborns.
Hemorrhagic disease of newborns is facilitated by anticonvulsants (suxilep), salicylates, indirect anticoagulants, carbenicillin, antidiabetic derivatives of sulfanylthiourea, hypothiazide, furosemide, prescribed by the mother shortly before childbirth.
Hyperbilirubinemia can cause sulfonamides, chloramphenicol, barbiturates, amidopyrine, phenacetin, antipyrine, PASK, novobiocin, glucocorticoid hormones prescribed in the last stages of pregnancy.
Asphyxia at birth , the delay in the appearance of the first breath is caused by narcotic drugs, general anesthetics.
Swelling of the nasal mucosa and hence obstruction of the nasal passages in newborns can provoke antihypertensive drugs taken by the mother shortly before childbirth (reserpine and others). The same drugs can lead to fetal bradycardia, paralytic intestinal obstruction.
Low birth weight can be caused by a course of chloramphenicol (in addition, "gray syndrome", bloating, collapse and anemia), aminoglycosides (along with this and deafness), beta-blockers.
Respiratory distress syndrome may be facilitated by the use of ethanol to suppress premature labor.
Heart failure of a newborn can be provoked by the appointment of salicylates, indomethacin to the mother during pregnancy, because they, inhibiting the synthesis of prostaglandins, cause spasm of the arterial duct of the fetus.
Fetoplacental insufficiency, or fetal distress, is the most universal symptom complex reflecting the unfavorable condition of the fetus, which can be briefly described as follows:
Symmetrical (hypoplastic) or asymmetric (hypotrophic) forms of intrauterine growth retardation (IUGR).
Fetal cardiac disorders (episodes of pulse acceleration to beats per minute, extrasystoles, episodes of pulse deceleration with a frequency of less than 110 beats per minute).
Changes in the frequency of respiratory movements of the fetus (FDP): increase - more than 60 per 1 minute, decrease - less than 45 in 1 minute, shortening of the duration of DDP less than 30 seconds, no DDP.
Changes in fetal motor activity (one or two episodes of generalized movements, isolated movements of only limbs, erratic fetal motor activity, lack of movement).
Changes in the tone of the fetus (the trunk does not unbend, only the extensor movements of the limbs, the extended position of the fetus, the absence of return during movements to the initial flexion position are recorded).
Placental abnormalities (according to ultrasound) - signs of lagging or advancing the degree of maturity of the placenta (state of the placenta that does not correspond to the gestational age), abnormal location, pathological inclusions in the placenta, placental edema.
Change in the volume of amniotic fluid (polyhydramnios, low water).
The clearest data for the registration of placental insufficiency in the fetus is obtained by assessing the "biophysical profile" of the fetus and Doppler analysis (assessment of blood flow in the arteries of the umbilical cord, aorta and middle cerebral artery). The most frequent manifestations of placental insufficiency in a newborn are: birth in a state of asphyxia or depression of respiration, signs of IUGR, impaired adaptation to the conditions of extrauterine life, and increased infectious morbidity.
Multiple pregnancies: The birth rate of twins is approximately 1:80, with variations from country to country ranging from 1: 500 births in Asia to 1:20 births in Africa. Monozygous couples make up approximately 30% and dizygotic couples make up 70% of all twins. Twins have an increased incidence of IUGR, congenital malformations, especially in monochorionic monozygous ones. Approximately 10% of twins have fetal transfusion with polycythemia in one of them and anemia in the other. If this occurred in the early fetal period, then the consequences can be very serious for both fetuses.
With a frequency of 1: 35,000 births, there is a syndrome of reversed arterial perfusion with acardia or acephaly in one of the twins and the provision of blood flow at the expense of the other. There are also conjoined twins - thoracopagi (common chest), xyphopagi (common anterior abdominal wall - from the xiphoid process to the navel), picopagi (common gluteal region, buttocks), craniopagi (common head).
A twin who is born second has a 2-4 times higher risk of developing asphyxia, SDS syndrome, while infectious complications are more frequent in the first twin.
In the last decades of the XX century, a fundamentally new direction in medicine has emerged - fetal therapy. When diagnosing a fetus with hemolytic disease (erythroblastosis), replacement blood transfusions are performed, anemia - transfusion of erythrocyte mass through the umbilical cord vessels, the introduction of recombinant erythropoietin.
If hypothyroidism is detected in the fetus, thyroxin is injected into the amniotic fluid, adrenogenital syndrome - dexamethasone is prescribed for the pregnant woman, gross cardiac arrhythmias and other cardiac disorders - β-blockers, calcium channel inhibitors, cardiac glycosides, etc.
If a congenital malformation is found in a fetus, the obstetrician, pediatric surgeon and pediatrician discuss the tactics of labor management, management and treatment of the child immediately after birth. According to the literature, consultation with a surgeon is necessary in about 5% of pregnant women. Currently, many successful intrauterine surgical interventions in the fetus have been described - the imposition of a nephrostomy or the creation of a vesico-amniotic shunt in obstructive nephropathy and hydronephrosis of the fetus, thoracocentesis in hydrothorax, removal of embryonic tumors, etc.
With ante- and perinatal pathology, prevention is complex and begins even before pregnancy; it must be of a state nature and be primary and secondary:
Every girl and young woman should be treated like a mother-to-be during the prophylactic examination. In the complex of health-improving measures, it is important to focus on the state of the genitourinary sphere and the early appointment of corrective or therapeutic measures, in connection with which early diagnosis and referral to a pediatric gynecologist with disharmonious sexual development are important.
It is necessary to sanitize chronic foci of infection, protect against drugs that promote sensitization (immunoglobulins, blood infusions, plasma), timely prescribe rubella vaccinations (if the girl did not have it), and foster a sense of the need for motherhood. Activities aimed at the rational physical and sexual education of girls, the creation of specialized offices for antenatal clinics for adolescent girls and children's gynecological departments, extensive medical and genetic counseling are important links in the prevention of antenatal pathology.
For a sick teenage girl, a pediatrician, a therapist, a gynecologist and, if necessary, narrow specialists should develop a specific individual set of health-improving measures.
Embryo and fetopathy of newborn children. Diagnostics, treatment and prevention
Intrauterine development, from the maturation of the reproductive cell (gametes) to the birth of a mature fetus, is divided into progenesis and cymatogenesis. Time progenesis maturation of gametes (egg and sperm) before fertilization, time cymatogenesis calculated from the moment of fertilization until birth.
The intrauterine (gestational) stage of childhood development (kimatogenesis) lasts 280 days (40 weeks) from the moment of fertilization to the birth of the child. Since it is impossible to accurately determine the time of fertilization, in practice, gestational age is considered starting from the first day of the last menstrual cycle in the mother. The intrauterine stage is divided into three periods:
1) Blastogenesis, from the moment of fertilization until the 15th day of pregnancy, when the egg is cleaved, ending with the formation of embryo and trophoblast;
2) Embryogenesis, from the 16th to the 75th day of pregnancy, when the main organogenesis takes place, and the amnion and chorion are formed;
3) Fetogenesis, from the 76th to the 280th day, when the
Mechanical retention of earth masses: Mechanical retention of earth masses on a slope is provided by buttress structures of various designs.
Organization of surface water runoff: The largest amount of moisture on the globe evaporates from the surface of the seas and oceans (88 ‰).
Papillary patterns of the fingers are a marker of athletic ability: dermatoglyphic signs are formed at 3-5 months of pregnancy, do not change throughout life.
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