Pregnancy, infection, and childhood psychiatric issues

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Results of a new study suggest that subtle changes in the fetal brain caused by some infections during pregnancy may be linked with autism and possibly depression. Although the findings point to limited individual risk for offspring the population effects are potentially large. The key message here for ob/gyns is to make every effort to prevent infections in pregnancy, according to co-author Kristina M. Adams Waldorf, MD, of the Center for Innate Immunity and Disease, Department of Obstetrics & Gynecology at the University of Washington, Seattle.

Published in JAMA Psychiatry, the data are from a study of nearly 1.8 million Swedish children born between January 1, 1973 and December 31, 2014. They were observed for up to 41 years using linked population-based registries. 

The authors used results of a systematic literature review they performed to create directed acyclic graphs. The graphs were used to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses, which were conducted from February 10 to October 17, 2018.

Looking at more than 32 million person-years of exposure with the graphs, the authors found that fetal exposure to any maternal infection increased risk of an inpatient diagnosis of autism in the child (hazard ratio [HR] 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a sever maternal infection (autism: HR, 1.81; 95% CI, 1.18-12.78; depression: HR, 1.24; 95% CI, 0.88-1.73 or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30: 95% CI, 1.04-1.61) and were robust to moderate unknown confounding.

The relationship between infection and depression was vulnerable to bias from loss to follow-up within the graph framework of assumptions but separate data from the Swedish Death Registry showed increased risk of suicide in individuals exposed to prenatal infection. No increased risk of bipolar disorder or psychosis was seen in children exposed to infection in utero.

The new findings are consistent with other epidemiologic and animal studies which suggest that inflammation during gestation alters brain architecture or transcriptional programs and point to an important possible biological basis for a fetal origin for depression and suicide.  

Speaking with Contemporary OB/GYN, Dr. Waldorf said, “Our results emphasize that development of the fetal brain is a fragile process. Although we recognize the devastating consequences of a severe Zika virus or cytomegalovirus infection on the fetal brain, the more subtle effects of other infections on fetal brain development are unknown.”

She went on to note that, “As obstetricians, we are limited in recognition of fetal brain injury to structural anomalies. However, inflammatory injury to parts of the fetal brain that are exquisitely vulnerable, like the neuroprogenitor cells in the hippocampus, can have a direct impact on socio-emotional control and mental health. A normal anatomy scan or reassuring fetal monitoring simply can’t detect these more subtle injuries to the fetal brain that may alter mental health.”

“However, we don’t want to frighten our patients,” Dr. Waldorf emphasized. “To put the study results into context, one could interpret a 79% increased risk of autism in children exposed to infection in utero as changing the autism risk from 1 in 59 (baseline, United States) to 1 in 33. Although the increased autism risk on a population level is large, the absolute risk to an individual patient Is still small.”