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Maternal Stress Affects Fetal Development

A preliminary study of pre- and postpartum women and their infants suggests that prenatal stress may cause adverse effects on neonatal development.

The study by Pathik Wadhwa, M.D., Ph.D., an assistant professor of behavioral science at the University of Kentucky College of Medicine in Lexington, and colleagues, assessed prenatal stress and related psychosocial variables in women participating in a large study of stress and birth outcomes funded by the National Institutes of Health (NIH).

The study asked 47 mothers of 6-week-old infants to complete a questionnaire on their babies' temperaments, and 49 mothers of 3-year-olds to complete an assessment of their children's activity levels and propensities for anger and social fearfulness. In addition, scientists directly assessed 24

4-month-olds for motor and cry reactivity to a series of visual and auditory challenges.

After adjusting for a variety of confounding factors, including maternal affect and prematurity, scientists found evidence suggesting that higher levels of prenatal stress and associated stress hormones correlated with temperamental and behavioral problems in the evaluated children. Lead author Wadhwa cautioned that the results, "although very interesting, are preliminary" and require larger samples, longer follow-up, and more comprehensive evaluations before a firm conclusion can be drawn.

The as yet unpublished research is an extension of earlier published research by Wadhwa and colleagues. It was reported at the annual meeting of the Society of Behavioral Medicine this March in New Orleans.

"It is becoming increasingly clear that the early environment, including the biochemical environment of the mother during pregnancy, plays a critical role in interacting with the genetic material of the developing fetus to shape the developmental trajectory over the entire life span," Wadhwa commented.

Environment is "a double-edged sword," he added. Optimal environments play a key role in enhanced brain development, while hostile environments, including those produced by maternal stress, adversely impact brain development.

Some of these effects may be subtle and not evident at birth, he added. But there is increasing evidence from both animal and human studies that maternal stress "may play a significant role" in the etiology of intellectual deficits and psychiatric and behavioral disorders, he remarked. The mechanisms underlying these effects are partially mediated by maternal stress hormones and consequent changes in "the set points of developing neurotransmitter systems in the fetus," said Wadhwa.

David Fassler, M.D., chairs the APA Council on Children, Adolescents, and Their Families. "I think these are interesting and useful results that contribute to our understanding of the effects of maternal stress and hormones on fetal development and early personality traits," said Fassler. "However, they are preliminary, and significant additional research will be needed, in particular, research looking more closely at and controlling for the full range of maternal personality and environmental factors that may influence such results."

The research began several years ago with an NIH-funded prospective, longitudinal study of 260 pregnant women recruited in the second trimester of pregnancy and followed through delivery. (The three sets of mother-infant pairs in the current, preliminary study were drawn from this sample.) The original, 260-subject study employed both psychological questionnaires and physiological markers to assess maternal stress levels during pregnancy. Levels of corticotropin-releasing hormone, cortisol, and beta-endorphin were among the physiological markers assessed.

That study found that maternal stress levels were directly related to prematurity outcomes, that is, length of gestation and birth weight. Pregnant women reporting high stress levels were at "significantly greater risk" of delivering preterm and low birth-weight infants than women reporting low stress, even after adjusting for known demographic and medical risk factors, according to Wadhwa.

Wadhwa and colleagues gathered further, now published data from the 260-subject study confirming the interplay of maternal stress and social support on maternal pituitary-adrenal stress hormones and prematurity outcomes. These findings led Wadhwa to wonder whether maternal stress during pregnancy might also impact infant neurodevelopment.

Stanley Greenspan, M.D., is a clinical professor of psychiatry, behavioral sciences, and pediatrics at George Washington University Medical Center in Washington, D.C.

"It is a good solid, study," remarked Greenspan. The study's preliminary findings linking maternal stress, stress hormones, and perinatal development are consistent with both neurodevelopmental theory and animal studies.

The idea of "looking at [the impact of] stress factors on postnatal development makes a lot of sense." If stress is going to affect the ability of mothers to conceive properly, it is also likely to affect the developing child's nervous system, he added.

It stands to reason that some of the subtle, neurodevelopmental effects of stress could place children at risk for a variety of emotional, attentional, and intellectual problems, Greenspan said.

One methodological issue that should be addressed in future research is the study's absence of controls on nonpsychosocial maternal stressors, such as exposure to toxic substances and poor diet, observed Greenspan.

NIH recently provided grants for Wadhwa and colleagues to conduct two new studies of stress in pregnant women, he told Psychiatric News. The studies will be conducted over five years at both the University of Kentucky and the University of California at Irvine. Researchers will track approximately 850 women and their fetuses through pregnancy, with a follow-up of neurodevelopment among a subset of infants for the first three years of life. The lead investigator for the California arm will be psychologist Curt Sandman, Ph.D.