Fetal programming
Fetal programming, also known as prenatal programming, is the theory that environmental cues experienced during fetal development play a seminal role in determining health trajectories across the lifespan.
Three main forms of programming that occur due to changes in the maternal environment are:
- Changes in development that lead to greater disease risk;
- Genetic changes that alter disease risk;
- Epigenetic changes which alter disease risk of not only the child but also that of the next generation - i.e., after a famine, grandchildren of women who were pregnant during the famine, are born smaller than the normal size, despite nutritional deficiencies having been fulfilled.
History
Dutch famine 1944–45
In 1944–45, the German blockade of the Netherlands led to a lack of food supplies, causing the Dutch famine of 1944–45. The famine caused severe malnutrition among the population, including women in various stages of pregnancy. The Dutch Famine Birth Cohort Study examined the impact of lack of nutrition on children born during or after this famine. It showed that throughout their life, these children were at greater risk of diabetes, cardiovascular disease, obesity, and other non-communicable diseases.Barker hypothesis
In the 1980s, David Barker began a research study on this topic. The Barker Hypothesis, or Thrifty phenotype, forms the basis for much of the research conducted on fetal programming. This hypothesis states that if the fetus is exposed to low nutrition, it will adapt to that environment. Nutrients are diverted towards the developing heart, brain, and other essential fetal organs. The body also undergoes metabolic alterations that ensure survival despite low nutrition but may cause problems with normal or high nutrition. This leads to increased risk of metabolic syndrome.Nutritional status
The developing fetus forms an impression of the world into which it will be born via its mother's nutritional status. Its development is thus modulated to create the best chance of survival. However, excessive or insufficient nutrition in the mother can provoke maladaptive developmental responses in the fetus, which in turn manifest in the form of post-natal diseases. This may have such a profound effect on the fetus’s adult life that it can even outweigh lifestyle factors.Excessive nutrition
Body mass index before pregnancy and weight gain during pregnancy are linked to high blood pressure in the offspring during adulthood. Mouse models suggest that this is due to high levels of the fetal hormone leptin, which is present in the blood of individuals who are overweight or obese. There is a theory that this hormone hurts the regulatory systems of the fetus, and renders it impossible to maintain normal blood pressure levels.Insufficient nutrition
Pre-eclampsia, involving oxygen deprivation and death of trophoblastic cells that make up most of the placenta, is a disease which is often associated with maladaptive long-term consequences of inappropriate fetal programming. Here, an inadequately developed and poorly functioning placenta fails to meet the fetus’s nutritional needs during gestation, either by altering its selection for nutrients that can cross into fetal blood or restricting total volume thereof. Consequences of this for the fetus in adult life include cardiovascular and metabolic conditions.Hormonal influence
A delicate balance of hormones during pregnancy is regarded as highly relevant to fetal programming and may significantly influence the outcome of the offspring. Placental endocrine transfer from the mother to the developing fetus could be altered by the mental state of the mother, due to affected glucocorticoid transfer that takes place across the placenta.Thyroid
Thyroid hormones play an instrumental role during the early development of the fetus's brain. Therefore, mothers suffering from thyroid-related issues and altered thyroid hormone levels may inadvertently trigger structural and functional changes in the fetal brain. The fetus can produce its thyroid hormones from the onset of the second trimester; however, maternal thyroid hormones are important for brain development before and after the baby can synthesize the hormones while still in the uterus. Due to this, the baby may experience an increased risk of neurological or psychiatric diseases later in life.Cortisol
Cortisol is the most well-studied hormonal mechanism that may have prenatal programming effects. Although cortisol has normative developmental effects during prenatal development, excess cortisol exposure has deleterious effects on fetal growth, the postnatal function of physiological systems such as the hypothalamic-pituitary-adrenal axis and brain structure or connectivity.During gestation, cortisol concentrations in maternal circulation are up to ten times higher than cortisol concentrations in fetal circulation. The maternal-to-fetal cortisol gradient is maintained by the placenta, which forms a structural and enzymatic barrier to cortisol. During the first two trimesters of gestation intrauterine cortisol is primarily produced by the maternal adrenal glands. However, during the third trimester the fetal adrenal glands begin to endogenously produce cortisol and become responsible for most intrauterine cortisol by the time the fetus reaches term.