Birth Defects and Prenatal Diagnosis
Ass. Prof. Dr. Malak A. Al-yawerBirth Defects
Birth defect, congenital malformation, and congenital anomaly are synonymous terms used to describe structural, behavioral, functional, and metabolic disorders present at birth.
Teratology Dysmorphology
are Terms used to describe the study of these disorders Dysmorphologists are usually within a department of clinical genetics.
Major structural anomalies
Occur for a total of 4 to 6. 2 to 3 of live born infants, and 2 to 3 are recognized in children by age 5 years,
Birth defects
are the leading cause of infant mortality, (approximately 21 of infant deaths) .
Causes Of Birth defects
Causes Of Birth defects
occur in approximately 15 of newborns. minor anomalies serve as clues for diagnosing more serious underlying defects.
Microtia (small ears), pigmented spots, and short palpebral fissures, are not themselves detrimental to health but, in some cases, are associated with major defects
Types of Abnormalities
Malformations Anomelies Deformation Disruption Dysplasia
Malformations
are gross structural abnormalities occur during formation of structures e.g. during organogenesis. They may result in complete or partial absence of a structure
Anomalies
Include not only gross structural defects but also microscopic malformations , inborn error of metabolism , and mental retardation
Deformations
Disruption
Morphological alterations of already formed structures
Disruptions are due to destructive processes .e.g. vascular accidents leading to bowel atresia and amniotic bands
Dysplasia
Abnormal organization of tissues at the cellular level . e.g. Marfan syndrome
Syndrome
Is a group of anomalies occurring together and have a specific common cause This term indicates that a diagnosis has been made and that the risk of recurrence is known.
Association
Is the non random appearance of two or more anomalies occur together more frequently but whose cause has not been determined VACTERL Vertebral, Anal, Cardiac , trachea , Esophageal, Renal and limb abnormalities
The times in gestation versus the risks of birth defects
Graph showing the times in gestation versus the risks of birth defects being induced
Teratology
is the branch of science that studies the causes, mechanisms, and patterns of abnormal development.
A teratogen
Is a factor that has an adverse effect on an embryo or fetus from fertilization to birth The term teratogen is usually limited to environmental agents e.g. drugs and viruses
principles of teratology
1. The conceptus and maternal genome
Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this genetic composition interacts with the environment.
The maternal genome is also important with respect to drug metabolism, resistance to infection, and other biochemical and molecular processes that affect the conceptus.
2.The developmental stage at the time of exposure
Susceptibility to teratoge
3. Mechanisms And pathogenesis
Teratogens act in specific ways (mechanisms) on developing cells and tissues to initiate abnormal embryogenesis )pathogenesis).
Mechanisms may involve inhibition of a specific biochemical or molecular process pathogenesis may involve cell death, decreased cell proliferation, or other cellular phenomena.
4. Manifestations of abnormal development depend on dose and duration of exposure to a teratogen.
5. Manifestations of abnormal development are death, malformation, growth retardation, and functional disorders.
Environmental factors
1. drugs , hormons and vitamins
The role of pharmaceutical drugs in the production of abnormalities in humans is difficult to assess for two reasons
1. studies are retrospective, relying on the mothers memory for a history of exposure and 2. pregnant women take a large number of pharmaceutical drugs.
Few of the many drugs used during pregnancy have been positively identified as being teratogenic
the anticonvulsants
Antipsychotic agents
Are major and minor tranquilizers are suspected producers of congenital malformations. The antipsychotics phenothiazine and lithium carbonate have been implicated as teratogens.
Antianxiety agents
The anticoagulant agents
Antihypertensive agents
that inhibit angiotensin-converting enzyme (ACE inhibitors) produce growth retardation, renal dysfunction, fetal death, and oligohydramnios.
Antibiotics
Thyroid Drugs
Aspirin (salicylates)
Epidemiologic studies indicate that aspirin is not a teratogenic agent but large doses should be avoided, especially during the first trimester.
Isotretinoin ( An analogue of vitamin A )
Is used for treatment of skin conditions such as cystic acne it is highly teratogenic and can produce virtually any type of malformation. Even topical retinoids, such as etretinate, may have the potential to cause abnormalities.
a number of other compounds that may damage the embryo or fetus
sulfonamides (kernicterus), the antidepressant imipramine (limb deformities), amphetamines (oral clefts and cardiovascular abnormalities), and quinine (deafness).
Social drugs
Social drugs
Social drugs
In the case of LSD, limb abnormalities and malformations of the central nervous system have been reported. Cocaine has been reported to cause a number of birth defects, possibly due to its action as a vasoconstrictor that causes hypoxia.
There is a well-documented association between maternal alcohol ingestion and congenital abnormalities.
Cigarette smoking
contribute to intrauterine growth retardation and premature delivery. There is also evidence that it causes behavioral disturbances.
Hormones
Hormones
Androgens ( testestorone ) causes masculinization of the external gentelia of female infants
Synthetic estrogens (diethylstilbesterol )
Environmental estrogens
Decrease sperm count and increase incidence of testicular cancer and abnormalities of the human reproductive tract together with CNS abnormalities ( masculinization of female brains and feminization of male brains
ORAL CONTRACEPTIVES
containing estrogens and progestogens, appear to have a low teratogenic potential. use of oral contraceptives should be discontinued if pregnancy is suspected.
Cortisone
In mice and rabbit , causes a high percentages of cleft palate In human, not documented
2. Maternal disorders
1. age of pregnant 2. Maternal diabetes 3. phenylketoneuria 4. nutritional deficiencies
Age of pregnant
Congenital abnormalities of the CNS and abdominal walls are more frequent in infants of mothers under 20 or more than 40 years
Maternal diabetes
Phenylketonuria
Mothers with Phenylketonuria ( increase serum concentration of phenyl analine due to deficient phenyl analine hydroxylase ) are at risk of having infants with mental retardation , microcephaly and cardiac defects )
Women with Phenylketonuria should maintain in diet with low phenyl analine prior to conception to reduce the risk of these abnormalities
Nutritional deficiencies
Vitamin deficiency have been proven to be teratogenic in laboratory animals , the evidence in human is sparse with the exception of iodine deficiency ( endemic cretinism )
Poor maternal nutrition prior to and during pregnancy contributes to low birth weight and birth defects
Infectious Agents 3.
Infectious Agents
4. Radiation
Ionization radiation is potent teratogen . It kills rapidly proliferating cells Radiation is also mutagenic ( genetic alteration of germ cells and subsequent malformation ) Radiation from nuclear expulsions is also teratogenic
5. Obesity
Prepregnancy obesity, defined as having a body mass index (BMI) 30 kg/m2. Causation has not been determined but may relate to maternal metabolic disturbances affecting glucose, insulin, or other factors.
Prepregnancy obesity is associated with a two- to threefold increased risk for having a child with a neural tube defect. increases the risk for having a baby with a heart defect, omphalocele, and multiple anomalies.
6. Hypoxia
Lead has been associated with increased abortions, growth retardation, and neurological disorders.
Prevention of birth defects
Prevention of birth defects
Prenatal diagnosis
1. ultrasonography
Important parameters revealed by ultrasound include
characteristics of fetal age and growth presence or absence of congenital anomalies status of the uterine environment, including the amount of amniotic fluid placental position and umbilical blood flow and whether multiple gestations are present.
Fetal age and growth are assessed by
Congenital malformations that can be determined by ultrasound include
the neural tube defects anencephaly and spina bifida abdominal wall defects, such as omphalocele and gastroschisis and heart and facial defects, including cleft lip and palate
Prenatal diagnosis
2. Maternal Serum Screening
2. Maternal Serum Screening
noninvasive technique for an initial assessment of fetal well-being. 1.serum a-fetoprotein (AFP) concentrations 2. human chorionic gonadotropin (hCG) and 3. unconjugated estriol
serum a-fetoprotein (AFP) concentrations
serum a-fetoprotein (AFP) concentrations
AFP levels increase in amniotic fluid and maternal serum in cases of neural tube defects and several other abnormalities, including omphalocele, gastroschisis, bladder exstrophy, amniotic band syndrome, sacrococcygeal teratoma, and intestinal atresia,
AFP concentrations decrease, as, for example, in Down syndrome, trisomy 18, sex chromosome abnormalities, and triploidy. These conditions are also associated with lower serum concentrations of human chorionic gonadotropin (hCG) and unconjugated estriol.
Prenatal dignosis
3.Amniocentesis
The amniotic fluid itself is analyzed for
Prenatal diagnosis
4. Chorionic villus sampling (CVS)
Chorionic villus sampling (CVS)
Indications for prenatal diagnostic tests
Fetal Therapy
Fetal Transfusion
Is performed in cases of fetal anemia produced by maternal antibodies or other causes, Ultrasound is used to guide insertion of a needle into the umbilical cord vein, and blood is transfused directly into the fetus.
Fetal Medical Treatment
Fetal Surgery
Stem Cell Transplantation and Gene Therapy
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