Embryo Project Encyclopedia Articles

Fetal programming, or prenatal programming, is a concept that suggests certain events occurring during critical points of pregnancy may cause permanent effects on the fetus and the infant long after birth. The concept of fetal programming stemmed from the fetal origins hypothesis, also known as Barker’s hypothesis, that David Barker proposed in 1995 at the University of Southampton in Southampton, England. The fetal origins hypothesis states that undernutrition in the womb during middle to late pregnancy causes improper fetal growth, which in turn, causes a predisposition to certain diseases in adulthood. In addition to nutritional impacts, researchers have studied the fetal programming effects of many factors, such as maternal anxiety or violence during pregnancy. Researchers proposing the concept of fetal programming established a new area of research into the developmental causes of disease, pointing towards the in utero environment and its critical role in healthy human development.

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 2011, Sarah McMahon and colleagues published “The Impact of Emotional and Physical Violence During Pregnancy on Maternal and Child Health at One Year Post-partum,” hereafter, “The Impact,” in the journal, Child and Youth Services Review. While existing studies had indicated negative chronic effects resulting from intimate partner violence, or IPV, such as miscarriage and premature labor, there was little research specifically analyzing the separate and joint effects of psychological and physical abuse on pregnant women and fetuses. The authors reported that both physical and emotional IPV had negative impacts on the woman and child at one-year after birth, including worse overall health and increased likelihood of depression. In “The Impact,” the researchers analyzed the effects of partner abuse during pregnancy, distinguishing between the effects of emotional abuse and physical abuse on health outcomes for a pregnant woman and her offspring.

In 2001, Kevin M. Godfrey and David J.P. Barker published the article “Fetal Programming and Adult Health” in Public Health Nutrition, where they identified the significance of maternal nutrition during pregnancy to healthy offspring development. The authors describe the effects of maternal nutrition on fetal programming of cardiovascular disease. Fetal programming is when a specific event during pregnancy has effects on the fetus long after birth. The authors argue that fetuses may adapt to varying shifts in their environment in utero, such as slowed fetal growth in response to malnutrition. While those adaptations can be helpful in utero, the authors assert they may persist into adolescence and adulthood, causing conditions such as high blood pressure or diabetes. Godfrey and Barker assert that fetal adaptations to maternal malnutrition may be implicated in the development of cardiovascular disease in adulthood, and called for future research investigating additional fetal programming variables.

This project focuses on the history of how teratogens, or agents which have the potential to cause birth defects, have been understood and tested for teratogenic potential in the US over the twentieth century. Prior to this time, teratogen studies were primarily concerned with cataloguing defects rather than exploring possible causes. At the turn of the twentieth century, experimental teratogen studies with the aim of elucidating mechanisms commenced. However, these early studies did not aim to discover human pregnancy outcomes and ways to prevent them, but simply focused on the results of exposing pregnant mammals to various physical and chemical insults.

Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances. Exposure to the teratogen affects the fetus or embryo in a variety of ways, such as the duration of exposure, the amount of teratogenic substance, and the stage of development the embryo or fetus is in during the exposure. Teratogens may affect the embryo or fetus in a number of ways, causing physical malformations, problems in the behavioral or emotional development of the child, and decreased intellectual quotient IQ in the child. Additionally, teratogens may also affect pregnancies and cause complications such as preterm labors, spontaneous abortions, or miscarriages. Teratogens are classified into four types: physical agents, metabolic conditions, infection, and finally, drugs and chemicals.