Teratology is the scientific study of causes and mechanisms of malformation during the human development. Fetal diseases, mechanical effects and retarded development of the embryo and the fetus are some of the causes of CDDs (congenital developmental disorders) according to various studies. Both mystical and scientific theories were developed in the past to explain the origin of Teratology; some theories stating that it originated from the position of the stars, maternal impressions, hybridization, and oligohy dramnios, among others. Today, biological assumptions on abnormalities seem to have more weight than the unproven theories given in the past. 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).
Fig. 1. 1. The Birth of Modern Teratology (McCormick, 2012)
The contemporary science of teratology started in the 1930s with the release of a study that was done on expectant pigs. During the experiment, the pigs were given food lacking vitamin A. The results showed malformed piglets, especially lack of eyes, leading to a summary that, lack of the vitamins is central to the poor development of the body parts like the eyes. The father of experimental teratology is the physicist Josef Warkany (Ujhazy, Mach, Navarova, Brucknerova, & Dubovicky, 2012). He was the first to provide evidence-based research that congenital developmental disorders can be induced in mammals, through his experiments in the 1930s and 40s. This led to the definition of both the genetically and environmentally provoked structural defects. Congeners of biologically active molecules, e.g. amino acid mimicking azaserine, were used experimentally with animals to show the vulnerability of mammalian fetus and embryos to xenobiotic poisons. Consequently, amino-protein was utilized in the 1950s on a human embryo to induce abortion. Low oxygen concentration, changes in temperature, radiation, hormones such as cortisone, androgens, estrogens, hypervitaminosis and hypovitaminosis are some of the physical factors that were utilized in further experiments. A variety of chemicals and drugs were also used. Experiments with animals led to a report that was published during the late 40s, revealing the environmental and genetic effects and their related combinations, as some of the causes of defects and other malformations in animals (Ujhazy, Mach, Navarova, Brucknerova, & Dubovicky, 2012).
Describe the effects of various teratogens during different periods of development
About 7% of congenital defects are of teratogenic origins. Fetal morphology or its subsequent functions can be altered by exposure to a physical factor, infectious agent, chemical, or deficiency. The crossing of these agents into the placenta results in teratogenicity. Substances with high molecular weight like the heparin, cannot cross the placenta, and hence not considered teratogenic. During the embryonic development, the embryos are most vulnerable to teratogens when the rapid differentiation phases occur. This is also the most crucial stage of the early development or growth of any organ as illustrated for each organ in the picture below. For instance, the growth and development of the brain are from week three to week sixteen, even though its differentiation stretches into infancy (Chung, n.d.).
Any agent that is capable of provoking or hastening congenital malformation is known as a teratogen. The knowledge of these human teratogens helps in preventing one from its exposure that may lead to congenital malformations during the human development. The teratogenicity of drugs, food additives, and pesticides are tested to reduce exposure of expectant women to these agents (Chung, n.d.).
Fig. 1. 2. Effects of teratogens at different stages of development (HoRC, n.d.)Describe the Principles of Teratology
1. To Characterize teratogenic exposures, one must consider, the particular agent, genetic susceptibility, the dose of the agent, and the development phase (Can, 2007).
2. Both general and specific effects like morphogenesis alterations, death, and carcinogenesis and specific syndromes, magnitude of risk, and prenatal diagnosis, respectively, are used to characterize teratogenic effects (invasive and non-invasive techniques) (Can, 2007).
3. The United States Food and Drug Administration (A, B, C, D, X) developed 5 categories that manufacturers have to adhere to and label appropriately on their pregnancy medication to minimize fetal exposure to teratogens (Can, 2007).
4. The placenta can be crossed by any substance given to the mother, whose molecular size is small enough to pass through the placenta, or it’s not destroyed during the placental passage. The transplacental transfer starts at the fifth week of embryo development. The passage of substances with low molecular weight depends on concentration (Can, 2007).
5. The correlation between teratogenic risks and the fetus, infants or child, is difficult to identify, unlike fetal anatomical anomalies and malformations (Can, 2007).
6. Use of prescription, non-prescribed and recreational medicine is common among expectant mothers, according to a WHO research, which found that 86% of them took drugs (Can, 2007).
7. Some of the fetal infections that are related to inflammation of fetal tissues, resulting in intrauterine growth restriction, congenital defects, death, and mental abnormalities (Can, 2007).
8. Due to the high cost of diagnosis of the uterus, serological tests on the mother and infant are recommended where the congenital infection is suspected. This is because TORCH screening alone has proved to be insufficient (Can, 2007).
9. Fetal/neonatal abnormalities have no specific diagnostic signs and symptoms of infection. Time of exposure, type of agent exposed to and interactions in the host can bring about different kinds of symptoms (Can, 2007).
10. Rubella, syphilis, hepatitis B, human immunodeficiency virus, and varicella are the only diseases subject to regular teratogenic screening (Can, 2007).
Describe Hereditary Causes of Congenital Malformations
Fig. 1.3.Congenital anomalies as a proportion of 2013 neonatal deaths worldwide (WHO, 2015)
Those who suffer from teratology are emotionally stressed up. Genetic counseling for couples help them prepare for the next pregnancy. Reproductive problems affect the general population, making it difficult to substantiate the environmental causes. About 3 in every 100 births in the U.S. have severe congenital defects, meaning that about 120,000 infants per year are born with severe birth abnormalities (Agrawal, 2007).
Preterm Birth Complications:
Premature birth can cause a lot of short- and long-term complications like heart and breathing problems, temperature control problems and brain problems. Long-term complications might include: impaired cognitive skills, psychological problems or even chronic health problems (Mayo Clinic Staff, 2014).
Birth Asphyxia:
When a new born lacks oxygen during or after birth, it can develop birth asphyxia, which can result in cell damage after delivery, or reperfusion injury. This can result in permanent injury of the child’s organs, bowels, kidneys, lungs, heart etc. (Seattle Children’s, n.d.).
Neonatal Sepsis
This can be caused by the infection in a mother’s cervix, resulting in either early or late onset sepsis within two to three days (Medscape, 2014).
Describe the Prenatal Diagnostic Procedures used in Identifying Congenital Anomalies
Genetic analysis is done to obtain the traditional gold standard prenatal diagnostic results for the fetus, utilizing pregnancy-related tissues from cordo centesis, AC, or CVS. Nowadays, maternal serum cfDNA and traditional prenatal diagnostic procedures are used together for genetic screening, if the initial test is positive. Conversely, maternal serum cfDNA can also be utilized for fetal diagnosis only. In most cases, fetal karyotype abnormalities are used for prenatal genetic diagnosis, yet other analysis of specific genetic mutations can be done using fetal blood, chorionic villus, or amniocytes. Maternal serum cfDNA has shown other forms of mutations through case-by-case genetic differential diagnosis (Wilson, Gagnon, Audibert, Campagnolo, & Carroll, 2015).
Medical history, obstetrical history, surgical history, ethnicity, patient’s family history, and genetic background are some of the information collected before prenatal diagnostic counseling. This helps to detect undiagnosed syndrome in parents (Wilson, Gagnon, Audibert, Campagnolo, & Carroll, 2015).
Bibliography
Agrawal, S. (2007). Genetic Causes of Congenital Malformation. Anthropologist Special, 425-434 .
Can, O. G. (2007). Principles of Human Teratology: Drug, Chemical, and Infectious Exposure. JOGC, 911-917.
Chung, W. (n.d.). TERATOGENS AND THEIR EFFECTS. 1-8. Retrieved from: http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt23-Teratogens.pdf
HoRC. (n.d.). FASD and alcohol consumption patterns. Retrieved from Parliament of Australia: http://www.aph.gov.au/parliamentary_Business/Committees/House_of_Representatives_Committees?url=spla/fasd/report/chapter2.htm
Mayo Clinic Staff.(2014). Premature Birth. Retrieved from: http://www.mayoclinic.org/diseases-conditions/prematurebirth/basics/complications/con-20020050
McCormick, I. (2012, March 21). The Birth of Modern Teratology. Retrieved from grotesqueobservatory.com: http://grotesque-observatory.blogspot.com/2012/03/birth-of-modern-teratology.html
Medscape.(2014). Neonatal Sepsis. Emedicine.medscape.com. Retrieved from: http://emedicine.medscape.com/article/978352-overview#a4
Seattle Children’s.(n.d.).Birth Asphyxia. Retrieved from: http://www.seattlechildrens.org/medical-conditions/airway/birth-asphyxia/
Ujhazy, E., Mach, M., Navarova, J., Brucknerova, I., & Dubovicky, M. (2012). Teratology — past, present and future. NCBI, 163-168. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600518/
WHO. (2015, April). Congenital anomalies. Retrieved from World Health Organization: http://www.who.int/mediacentre/factsheets/fs370/en/
Wilson, D., Gagnon, A., Audibert, F., Campagnolo, C., & Carroll, J. (2015). Prenatal Diagnosis Procedures and Techniques to Obtain a Diagnostic Fetal Specimen or Tissue: Maternal and Fetal Risks and Benefits. JOGC, 656-668.
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