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), Â 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
1.        Sidman, R. L. & Rakic, P. (1973) Brain Res 62, 1-35.
2.        Bourgeois, J. P. (1997) Acta Paediatr Suppl 422, 27-33.
3.        Hayashi, A., Nagaoka, M., Yamada, K., Ichitani, Y., Miake, Y. & Okado, N. (1998) Int J Dev Neurosci 16, 209-16.
4.        Peterson, B. S., Vohr, B., Staib, L. H., Cannistraci, C. J., Dolberg, A., Schneider, K. C., Katz, K. H., Westerveld, M., Sparrow, S., Anderson, A. W., Duncan, C. C., Makuch, R. W., Gore, J. C. & Ment, L. R. (2000) Jama 284, 1939-47.
5.        Buss, C., Davis, E. P., Muftuler, L. T., Head, K. & Sandman, C. A.  Psychoneuroendocrinology 35, 141-53.
6.        Rini, C. K., Dunkel-Schetter, C., Wadhwa, P. D. & Sandman, C. A. (1999) Health Psychol 18, 333-45.
7.        Glynn, L. M., Schetter, C. D., Hobel, C. J. & Sandman, C. A. (2008) Health Psychol 27, 43-51.
8.        Buitelaar, J. K., Huizink, A. C., Mulder, E. J., de Medina, P. G. & Visser, G. H. (2003) Neurobiol Aging 24 Suppl 1, S53-60; discussion S67-8.
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.
The offspring of only 35 women were followed, not >500, right?
I don’t know if this thank you will ever reach the appropriate people, but I was so glad to read this article and find that this study had been done. I have struggled with the choice of being medicated or not for my own extreme anxiety during 2 pregnancies, and this is an issue that I feel is not addressed enough with moms to be. Thank you to those who continue this work for those of us who truly need your knowledge and assistance.
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This is interesting. I’m in my fifties, and have struggled all my life with anxiety, depression and social “blindness”. It was recently suggested to me I might have ADD/ADHD. which was not on the radar when I was young. I’ve been looking into it,but found it tends to run in families, and both my older sibling have not problems. However, when my mother was pregnant with me, my dad lost his job, my parents lost their house, and they were forced to beg their family to take them in with 2 1/2 kids in tow. Maybe this has something to do with my problems? I know it does not really make a difference, but knowing a possible reason for being the black sheep of the family makes me feel a little better.