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.

Edward Donnall Thomas, an American physician and scientist, gained recognition in the scientific community for conducting the first bone marrow transplant, a pioneering form of hematopoietic stem cell transplantation (HSCT). Bone marrow transplants are considered to be the first successful example of tissue engineering, a field within regenerative medicine that uses hematopoietic stem cells (HSCs) as a vehicle for treatment. Prior to Thomas's groundbreaking work, most blood-borne diseases, including certain inherited and autoimmune diseases, were considered lethal.

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.

Otto Rank studied how birth impacts individuals’ psychology and creates anxiety throughout their lives in Europe and the US during the nineteenth century. In his book The Trauma of Birth, Rank stated that birth was extremely traumatic and that one spent his or her whole life trying to recover from the experience of being born and harshly separated from the peaceful womb. He argued that the trauma experienced at birth is the source of all human suffering and the key to understanding anxiety later in life. He stated that the experience of birth was one’s earliest experience of anxiety, which served as the blueprint for all other anxiety related experiences in life. Through his work, Rank prompted studies in developmental embryology analyzing early mother-child relationships and problems in early psychological development.

Tissue engineering is a field of regenerative medicine that integrates the knowledge of scientists, physicians, and engineers into the construction or reconstruction of human tissue. Practitioners of tissue engineering seek to repair, replace, maintain, and enhance the abilities of a specific tissue or organ by means of living cells. More often than not stem cells are the form of living cells used in this technology. Tissue engineering is one of the disciplines involved in translating knowledge of developmental biology into the clinical setting. One focus that this field has taken is the understanding of tissue and organ development during embryogenesis, as this knowledge will open avenues to new applications of this technology.

In 2011, fetal researcher Vivette Glover published “Annual Research Review: Prenatal Stress and the Origins of Psychopathology: An Evolutionary Perspective,” hereafter, “Prenatal Stress and the Origins of Psychopathology,” in the Journal of Child Psychology and Psychiatry. In that article, Glover explained how an evolutionary perspective may be useful in understanding the effects of fetal programming. Fetal programming is a hypothesis that attempts to explain how factors during pregnancy can affect fetuses after birth. Researchers associate exposure to prenatal stress, or stress experienced before birth, with an increased likelihood of some mental disorders. Glover states that such outcomes may be traced back to a fetus’s response to stress during pregnancy, and that those outcomes may have been beneficial in the past. By taking an evolutionary approach toward understanding mental disorders, Glover provided insights for studying the lasting effects of maternal stress during pregnancy on children’s mental health.

In 2009, A. John Henderson and colleagues published “Mothers’ Anxiety During Pregnancy Is Associated with Asthma in Their Children,” hereafter, “Mothers’ Anxiety,” in The Journal of Allergy and Clinical Immunology. Previous studies had shown that maternal stress during pregnancy affects children’s health during childhood. The researchers explored the association of asthma in children with maternal anxiety during pregnancy. The cause of asthma is often unknown. Thus, the researchers tested the possibility that maternal anxiety may increase disease risk in the children, particularly the development of asthma. The authors reported a positive association between maternal anxiety during pregnancy and asthma in offspring, indicating the possibility of a causal relationship. The authors’ findings demonstrated the health effects of maternal stress during pregnancy on children’s physiological and immune development.

The purpose of regenerative medicine, especially tissue engineering, is to replace damaged tissue with new tissue that will allow the body to resume normal function. The uniqueness of tissue engineering is that it can restore normal structure in addition to repairing tissue function, and is often accomplished using stem cells. The first type of tissue engineering using stem cells was hematopoietic stem cell transplantation (HSCT), a surgical procedure in which hematopoietic stem cells (HSCs) are infused into a host to treat a variety of blood diseases, cancers, and immunodeficiencies. While there is a standard procedure for the infusion of these cells into a donor, variations in the sources of hematopoietic stem cells, and in the relationship between donor and recipient, do produce some variability in the procedure.

In 2004, Amanda J. Drake and Brian R. Walker published “The Intergenerational Effects of Fetal Programming: Non-genomic Mechanisms for the Inheritance of Low Birth Weight and Cardiovascular Risk,” hereafter, “The Intergenerational Effects,” in the Journal of Endocrinology. In their article, the authors assert that cardiovascular disease may develop via fetal programming, which is when a certain event occurring during a critical point of pregnancy affects the fetus long after birth. Drake and Walker were among the first to show that the programming effects of cardiovascular disease could be sustained across generations through non-genetic means. In “The Intergenerational Effects,” the authors identify how non-genetic mechanisms may perpetuate fetal programming influences over generations, highlighting the importance for further research on fetal programming.