This paper provides a comprehensive overview of teratology — the scientific study of congenital developmental disorders (CDDs). It traces the historical origins of the field from early mystical theories to Josef Warkany's experimental work in the 1930s and 1940s. The paper examines how teratogens affect fetal development at different stages, outlines the core principles of human teratology including FDA drug classifications and placental transfer, and discusses hereditary causes of congenital malformations. It concludes with a review of prenatal diagnostic procedures, including maternal serum cfDNA analysis and traditional fetal karyotyping, used to identify congenital anomalies before birth.
Teratology is the scientific study of the causes and mechanisms of malformation during human development. Fetal diseases, mechanical effects, and retarded development of the embryo and fetus are among the causes of congenital developmental disorders (CDDs), according to various studies. Both mystical and scientific theories were developed in the past to explain the origin of teratology, with some attributing it to the position of the stars, maternal impressions, hybridization, and oligohydramnios, among others. Today, biological explanations of abnormalities carry considerably more weight than these unproven historical theories. Scientific studies have revealed that the real causes of congenital developmental disorders include mechanical effects, biological factors, physical factors, and chemical substances (Ujhazy, Mach, Navarova, Brucknerova, & Dubovicky, 2012).
The contemporary science of teratology began in the 1930s with the publication of a study conducted on pregnant pigs. During the experiment, the pigs were fed a diet lacking vitamin A. The results showed malformed piglets — particularly the absence of eyes — leading to the conclusion that a deficiency of this vitamin is central to the poor development of body parts such as the eyes. The father of experimental teratology is the physician Josef Warkany (Ujhazy et al., 2012). He was the first to provide evidence-based research demonstrating that congenital developmental disorders can be induced in mammals, through his experiments in the 1930s and 1940s. This work led to the definition of both genetically and environmentally provoked structural defects.
Congeners of biologically active molecules — for example, the amino acid-mimicking compound azaserine — were used experimentally in animals to demonstrate the vulnerability of mammalian fetuses and embryos to xenobiotic poisons. Subsequently, aminopterin was used in the 1950s on a human embryo to induce abortion. Low oxygen concentration, changes in temperature, radiation, hormones such as cortisone, androgens, and estrogens, as well as hypervitaminosis and hypovitaminosis, are among the physical factors utilized in further experiments. A variety of chemicals and drugs were also employed. Animal experiments culminated in a report published in the late 1940s, revealing that environmental and genetic effects — and their various combinations — are among the causes of defects and other malformations (Ujhazy et al., 2012).
Approximately 7% of congenital defects are of teratogenic origin. Fetal morphology or subsequent function can be altered by exposure to a physical factor, infectious agent, chemical, or nutritional deficiency. The crossing of these agents across the placenta results in teratogenicity. Substances with high molecular weight, such as heparin, cannot cross the placenta and are therefore not considered teratogenic. During embryonic development, embryos are most vulnerable to teratogens when rapid differentiation phases occur. This is also the most critical stage in the early development of any given organ. For instance, brain development occurs from week three to week sixteen, even though its differentiation continues into infancy (Chung, n.d.).
Any agent capable of provoking or hastening congenital malformation is known as a teratogen. Knowledge of human teratogens helps prevent exposure that may lead to congenital malformations during development. The teratogenicity of drugs, food additives, and pesticides is tested in order to reduce the exposure of pregnant women to these agents (Chung, n.d.).
The following principles govern the characterization and management of teratogenic exposure (Can, 2007):
1. To characterize teratogenic exposures, one must consider the particular agent involved, genetic susceptibility, the dose of the agent, and the developmental phase during which exposure occurs.
2. Both general and specific effects are used to characterize teratogenic outcomes. General effects include morphogenesis alterations, death, and carcinogenesis; specific effects include distinct syndromes, magnitude of risk, and prenatal diagnosis (using invasive and non-invasive techniques).
3. The United States Food and Drug Administration developed five categories (A, B, C, D, and X) that manufacturers must adhere to and label appropriately on pregnancy medications, in order to minimize fetal exposure to teratogens.
4. Any substance given to the mother whose molecular size is small enough to pass through the placenta — and that is not destroyed during placental passage — can cross the placenta. Transplacental transfer begins at the fifth week of embryonic development. The passage of substances with low molecular weight is concentration-dependent.
5. The correlation between teratogenic risks and outcomes in the fetus, infant, or child is difficult to identify, unlike fetal anatomical anomalies and malformations, which are more readily observable.
6. Use of prescription, non-prescription, and recreational medicines is common among pregnant women. A WHO study found that 86% of pregnant women took drugs during pregnancy.
7. Some fetal infections are associated with inflammation of fetal tissues, resulting in intrauterine growth restriction, congenital defects, death, and mental abnormalities.
8. Due to the high cost of uterine diagnosis, serological tests on both mother and infant are recommended when congenital infection is suspected, because TORCH screening alone has proved insufficient.
9. Fetal and neonatal abnormalities have no specific diagnostic signs and symptoms of infection. The time of exposure, the type of agent involved, and host interactions can produce different kinds of symptoms.
10. Rubella, syphilis, hepatitis B, human immunodeficiency virus (HIV), and varicella are the only diseases currently subject to routine teratogenic screening.
Those who suffer from teratological conditions are often emotionally affected. Genetic counseling for couples helps them prepare for future pregnancies. Reproductive problems affect the general population broadly, making it difficult to isolate environmental causes. About 3 in every 100 births in the United States involve severe congenital defects, meaning that approximately 120,000 infants per year are born with serious birth abnormalities (Agrawal, 2007).
"Genetic factors and perinatal complication categories"
"Techniques used to diagnose fetal genetic anomalies"
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