Conference Coverage

More research needed on how fetal exposure affects later development



The number of genes in humans seems inadequate to account for the diversity seen in people. While maternal and paternal factors do play a role in the development of offspring, increased attention is being paid to the forces that express these genes and the impact they have on the health of a person, including development of psychiatric conditions, according to Dolores Malaspina, MD.

Epigenetics, or changes that occur in a fetal phenotype that do not involve changes to the genotype, involve factors such as DNA methylation to control gene expression, histone modification or the wrapping of genes, or the silencing and activation of certain genes with noncoding RNA-associated factors, said Dr. Malaspina of the Icahn School of Medicine at Mount Sinai, New York.

When this occurs during pregnancy, “the fetus does not simply develop from a genetic blueprint of the genes from its father and mother. Instead, signals are received throughout the pregnancy as to the health of the mother and signals about the environment,” she said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

There is an evolutionary advantage to this so-called survival phenotype. “If, during the pregnancy, there’s a deficit of available nutrition, that may be a signal to the fetus that food will be scarce. In the setting of food scarcity, certain physiological adaptations during development can make the fetus more likely to survive to adulthood,” Dr. Malaspina said at the meeting, presented by Global Academy for Medical Education. But a fetus programmed to adapt to scarcity of food may also develop cardiovascular disease, metabolic disease, or mortality later in life if the prediction of scarce nutrition proved incorrect.

This approach to thinking about the developmental origins of health and disease, which examines how prenatal and perinatal exposure to environmental factors affect disease in adulthood, has also found a link between some exposures and psychiatric disorders. The most famous example, the Dutch Hunger Winter Families Study, found an increased risk of schizophrenia among children born during the height of the famine (Int J Epidemiol. 2007 Dec;36[6]:1196-204). During the Arab-Israeli war of 1967 (the Six-Day War), which took place in June, the fetuses of mothers who were pregnant during that month had a higher risk of schizophrenia if the fetus was in the second month (relative risk, 2.3; 95% confidence interval, 1.1-4.7) or third month (RR, 2.5; 95% CI, 1.2-5.2) of fetal life during June 1967, Dr. Malaspina and associates wrote (BMC Psychiatry. 2008 Aug 21;8:71).

“The key aspect is the ascertainment of individuals during a circumscribed period, the assessment and then the longitudinal follow-up,” she said. “Obviously, these are not easy studies to do, but enough of them have been done such that for the last decade at least, the general population should be aware of the developmental origins of health and disease.”

Maternal depression is another psychiatric condition that can serve as a prenatal exposure to adversity. A recent review found that children of women with untreated depression were 56% more likely to be born preterm and 96% more likely to have a low birth weight (Pediatr Res. 2019 Jan;85[2]:134-45). “Preterm birth and early birth along with low birth weight, these have ramifying effects throughout life, not only on neonatal and infant mortality, but on developmental disorders and lifetime morbidity,” she said. “These effects of maternal depression withstand all sorts of accounting for other correlated exposures, including maternal age and her medical complications or substance use.”

Maternal stress and depression can also harm neurocognitive development and effective functioning of the children, Dr. Malaspina noted. “The modulation of mood and affect can affect temperament and affect mental health. Studies exist linking maternal depression to autism, attention-deficit disorder, developmental delay, behavioral problems, sleep problems, externalizing behavior and depression, showing a very large effect of maternal depression on offspring well-being.”

To complicate matters, at least 15% of women will experience major depression during pregnancy, but of these, major depression is not being addressed in about half. Nonpharmacologic interventions can include cognitive-behavioral therapy and relaxation practices, but medication should be considered as well. “There’s an ongoing debate about whether antidepressant medications are harmful for the offspring,” she said. However, reviews conducted by Dr. Malaspina’s group have found low evidence of serious harm.

“My summary would be the depression itself holds much more evidence for disrupting offspring health and development than medications,” Dr. Malaspina said. “Most studies find no adverse birth effects when they properly controlled accounting for maternal age and the other conditions and other medications.”

Global Academy and this news organization are owned by the same parent company. Dr. Malaspina reported no relevant conflicts of interest.

Next Article: