During fetal life, neurons proliferate, migrate and form connections, providing the structure of the developing brain. Neurons reach their final destinations by the 16th week of gestation, while branching and making appropriate connections occur even before that time (1). The brain continues to develop during the entire pregnancy, with most of the synapse formation in the developing brain happens during the third trimester (2).

During these complex neurodevelopmental events, the fetal brain is particularly vulnerable.  Many factors may affect fetal brain development, including infectious agents, alcohol, various illicit drugs, medications, and environmental toxins, but there is accumulating evidence to indicate that exposure to psychiatric illness in the mother may also affect development of the fetal brain.

In animal models, the offspring of mothers who experience stress during pregnancy show changes in the morphology of the brain (3) and alteration in the regulation of the stress axis.  In humans, high levels of anxiety during pregnancy have been associated with an increased risk of developing preeclampsia, premature birth and low birth weight. It has been demonstrated that low birth weight in premature infants has been associated with  changes in brain morphology (4). In this population, it has been difficult to parse out the effects of maternal anxiety from the perinatal complications when assessing the brain morphology changes that are present in premature infants.

A recently published prospective study (5),  recruited 557 pregnant women, none treated for any psychiatric disorder, and collected data on levels of anxiety at weeks 19, 25 and 31. A 10-item anxiety scale was used, which was developed specifically for pregnancy research (6, 7). So far, 52 offspring (between the ages of 6 and 9) have undergone brain scanning (MRI).

The researchers observed that anxiety during pregnancy had no effect on the global gray matter volume (estimate of the total neuronal body volume). However, high levels of anxiety at 19 weeks of pregnancy were correlated with the volume reductions in several regions of the brain, including the prefrontal, lateral temporal and premotor cortex, medial temporal lobe and cerebellum.  High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume.  There was no correlation between pregnancy anxiety and sociodemographic status or postpartum stress.

This is the first prospective study to show that pregnancy anxiety is related to specific changes in brain morphology.  The regions most affected by high levels of anxiety are important for cognitive performance, social and emotional processing and auditory language processing. These findings are consistent with the body of literature which demonstrates that prenatal stress and associated anxiety may lead to delays in infant development, lower academic achievement, greater emotional reactivity and emotional/behavioral problems persisting through the adolescence (8-12).

While many women are understandably cautious about taking medications during pregnancy, this study, as well as others, indicated that anxiety during pregnancy is not a benign event.  It is essential to address anxiety that emerges during pregnancy, and we must help to educate pregnant women about the long-term developmental risks of untreated anxiety.

Snezana Milanovic, MD

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9.         Davis, E. P., Glynn, L. M., Schetter, C. D., Hobel, C., Chicz-Demet, A. & Sandman, C. A. (2007) J Am Acad Child Adolesc Psychiatry 46, 737-46.

10.       O’Connor, T. G., Heron, J., Golding, J., Beveridge, M. & Glover, V. (2002) Br J Psychiatry 180, 502-8.

11.       Van den Bergh, B. R., Mennes, M., Oosterlaan, J., Stevens, V., Stiers, P., Marcoen, A. & Lagae, L. (2005) Neurosci Biobehav Rev 29, 259-69.

12.       Van den Bergh, B. R., Van Calster, B., Smits, T., Van Huffel, S. & Lagae, L. (2008) Neuropsychopharmacology 33, 536-45.