In the Journals

Infection exposure in utero increases risk for depression, autism

Maternal infection during pregnancy significantly increased the risk for depression and autism spectrum disorder in offspring, according to a Swedish population-based cohort study published in JAMA Psychiatry.

“Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” Benjamin J. S. al-Haddad, MD, PhD, from the department of pediatrics, Seattle Children’s Hospital and University of Washington, and colleagues wrote.

In their study, researchers estimated the long-term risk for neuropsychiatric disease after fetal exposure to infection in mothers hospitalized during pregnancy. The cohort included more than 1.7 million Swedish children observed for up to 41 years using data from population-based registries.

The investigators examined hospitalization during pregnancy with any maternal infection, severe maternal infection — including sepsis, pneumonia, pyelonephritis, meningitis or encephalitis, influenza and chorioamnionitis — and urinary tract infection (UTI) and measured inpatient diagnosis of autism, depression, bipolar disorder or psychosis in offspring.

Analyses demonstrated that fetal exposure to any maternal infection increased the risk for a diagnosis of depression (HR = 1.24; 95% CI, 1.08-1.42) or autism (HR = 1.79; 95% CI, 1.34-2.4) in offspring. The risk for autism and depression were also increased in offspring exposed to severe maternal infection (autism HR = 1.81; 95% CI, 1.18-2.78; depression HR = 1.24; 95% CI, 0.88-1.73) and maternal UTI (autism HR = 1.89; 95% CI, 1.23-2.9; depression HR = 1.3; 95% CI, 1.04-1.61).

However, al-Haddad and colleagues found that in utero maternal infection exposure did not increase the risk for bipolar disorder or psychosis.

In addition, the results showed that the risk for death by suicide among adults exposed to infection in the womb was significantly greater compared with unexposed adults beginning at age 21 years, mirroring the results from the inpatient registry for depression.

“Although the Cox proportional hazards regression models for depression using inpatient data were vulnerable to a misclassification of outcome bias, descriptive suicide data supported the results and were not subject to the same bias,” the researchers explained.

While the individual risk seems minor, the population effects could be significant, al-Haddad and colleagues concluded.

“Our findings amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (eg, influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they wrote. – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.

Maternal infection during pregnancy significantly increased the risk for depression and autism spectrum disorder in offspring, according to a Swedish population-based cohort study published in JAMA Psychiatry.

“Whether maternal infection and inflammation can alter fetal neurodevelopment to a degree that imparts risk for a broad spectrum of psychopathologic conditions across the child’s lifetime is unknown,” Benjamin J. S. al-Haddad, MD, PhD, from the department of pediatrics, Seattle Children’s Hospital and University of Washington, and colleagues wrote.

In their study, researchers estimated the long-term risk for neuropsychiatric disease after fetal exposure to infection in mothers hospitalized during pregnancy. The cohort included more than 1.7 million Swedish children observed for up to 41 years using data from population-based registries.

The investigators examined hospitalization during pregnancy with any maternal infection, severe maternal infection — including sepsis, pneumonia, pyelonephritis, meningitis or encephalitis, influenza and chorioamnionitis — and urinary tract infection (UTI) and measured inpatient diagnosis of autism, depression, bipolar disorder or psychosis in offspring.

Analyses demonstrated that fetal exposure to any maternal infection increased the risk for a diagnosis of depression (HR = 1.24; 95% CI, 1.08-1.42) or autism (HR = 1.79; 95% CI, 1.34-2.4) in offspring. The risk for autism and depression were also increased in offspring exposed to severe maternal infection (autism HR = 1.81; 95% CI, 1.18-2.78; depression HR = 1.24; 95% CI, 0.88-1.73) and maternal UTI (autism HR = 1.89; 95% CI, 1.23-2.9; depression HR = 1.3; 95% CI, 1.04-1.61).

However, al-Haddad and colleagues found that in utero maternal infection exposure did not increase the risk for bipolar disorder or psychosis.

In addition, the results showed that the risk for death by suicide among adults exposed to infection in the womb was significantly greater compared with unexposed adults beginning at age 21 years, mirroring the results from the inpatient registry for depression.

“Although the Cox proportional hazards regression models for depression using inpatient data were vulnerable to a misclassification of outcome bias, descriptive suicide data supported the results and were not subject to the same bias,” the researchers explained.

While the individual risk seems minor, the population effects could be significant, al-Haddad and colleagues concluded.

“Our findings amplify the urgency to better understand the role of maternal infection during pregnancy on fetal brain development and suggest that prevention of infection (eg, influenza vaccination) or anti-inflammatory therapies may be important strategies for the primary prevention of some portion of autism and depression,” they wrote. – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.