Embryo Project Encyclopedia Articles

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Josef Warkany studied the environmental causes of birth defects in the United States in the twentieth century. Warkany was one of the first researchers to show that factors in the environment could cause birth defects, and he helped to develop guidelines for the field of teratology, the study of birth defects. Prior to Warkany’s work, scientists struggled to explain if or how environmental agents could cause birth defects. Warkany demonstrated that a deficiency or excess of vitamin A in maternal nutrition could cause birth defects. He also established that mercury in teething powders increased infant mortality rates. Warkany showed how substances outside the human body could adversely affect conception, growth, and development of the human fetus in utero.

The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects. Those principles included what species are convenient for conducting teratological research, what principles act in human embryological and fetal development, and what agents impact those processes. Wilson's article was one of the first attempts in the twentieth century to synthesize basic research conducted in the field of teratology. The article helped to establish teratology as a field in medicine during the twentieth century.

Sidney Q. Cohlan studied birth defects in the US during the twentieth century. Cohlan helped to discover that if a pregnant woman ate too much vitamin A her fetus faced a higher than normal risk of teratogenic effects, such as cleft palate. A teratogen is a substance that causes malformation of a developing organism. Cohlan also identified the teratogenic effects of several other substances including a lack of normal magnesium and prenatal exposure to the antibiotic tetracycline. Cohlan's experiments with vitamins and other chemicals brought attention to how nutrition and environmental agents adversely affect human pregnancy outcomes.

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

In 2017, Julie Carré, Nicolas Gatimel, Jessika Moreau, Jean Parinaud, and Roger Léandri published “Does Air Pollution Play a Role in Infertility?: a Systematic Review,” hereafter “Does Air Pollution Play a Role,” in the journal Environmental Health. The authors completed a systematic literature review to investigate the effects of air pollutants on fertility in exposed populations. Since air quality has an impact on overall health as well as on reproductive function, the authors sought to increase the awareness of the importance of environmental protection issues among the general public and the authorities. The article “Does Air Pollution Play a Role” provided the foundation for further research on how air pollution can contribute to low reproductive capacity in areas with high exposure.

In September 2003, Robert L. Goldenberg and Cortney Thompson published the article “The Infectious Origins of Stillbirth” in the American Journal of Obstetrics and Gynecology. In the article, the authors conducted a literature review of articles from the US National Library of Medicine database to review the relationship between perinatal infections, which are infections around the time of birth, and the occurrence of stillbirth. Stillbirth is the death of a fetus in the uterus after at least twenty weeks of pregnancy. Infectious disease can cause or increase the risk of stillbirth in several ways, by causing illness in the pregnant person, damaging the placenta, or directly infecting the fetus. Infectious agents can be viruses, bacteria, or protozoa. Rates of infectious disease and stillbirth are both higher in developing than in developed countries, and the authors state that stillbirth due to infectious disease is also higher. “The Infectious Origins of Stillbirth” provides a comprehensive review of the information available on how infections can lead to stillbirth, providing a foundation for further research.

In 2017, Laura Geer and colleagues published the results of a study investigating the effects of parabens and antimicrobial compounds on birth outcomes in the article “Association of Birth Outcomes with Fetal Exposure to Parabens, Triclosan and Triclocarban in an Immigrant Population in Brooklyn, New York” in the Journal of Hazardous Materials. Parabens are a class of preservatives found in cosmetic and pharmaceutical products and antimicrobial compounds are compounds that kill microorganisms such as bacteria. In the University Hospital of Brooklyn’s Prenatal Clinic in New York City, New York, the authors tested the concentration of parabens and certain antimicrobial substances in pregnant women’s urine and umbilical cord blood plasma, finding that the concentration of one of the substances, triclocarban, may affect many health outcomes for the developing fetus. The authors’ results demonstrate how some common consumer products, in large quantities, may have harmful reproductive effects and birth outcomes.

In 1994, the Eastern Virginia District court case Bailey v. Blue Cross Blue Shield of Virginia established that insurance companies could not deny coverage for experimental stem cell therapy treatments. The plaintiff, Mary Bailey, was diagnosed with advanced stage breast cancer and sought treatment involving high-dose chemotherapy and an advanced stem cell treatment, which was a novelty at the time. Stem cells are cells that have the potential to develop into several different types of cells in the body. The defendant was the health insurance company Blue Cross Blue Shield, which denied coverage for Bailey’s treatment. The district court sided with Bailey and ordered that BCBS could not deny coverage for her specific treatment. While Bailey v. Blue Cross Blue Shield of Virginia resulted in Bailey receiving compensation for her treatment, it also increased national awareness of stem cell therapy with chemotherapy.

In the early 2000s, Richard S. Legro, Mark V. Sauer, Gilbert L. Mottla, Kevin S. Richter, William C. Dodson, and Duanping Liao studied the relationship between air pollution and reproductive complications. In the United States, Legro’s team tracked thousands of women undergoing in vitro fertilization, or IVF, along with the air quality of both the IVF clinics and patients’ home locations. IVF is a reproductive technology during which a physician obtains mature eggs from a patient’s ovaries and fertilizes them with sperm in a lab setting outside of the body, after which the physician transfers the fertilized eggs into the patient’s uterus. As stated in Legro’s publication, Legro suspected that poor air quality would adversely affect live birth rates during IVF, so he compiled and analyzed the various types of pollutants that IVF patients were naturally exposed to in their homes and clinics. Legro’s experiment led to an increased awareness among patients about the dangers of conceiving via IVF in highly polluted areas.