Infection in Pregnancy Ups Child’s Autism, Depression Risk

Exposure to severe and non-severe maternal infections in the womb increased a child’s later risk of autism and depression, a Swedish population-based study found.

Children of mothers hospitalized for any infection during pregnancy had a higher risk for diagnoses of autism by age 7 (HR 1.79, 95% CI 1.34-2.40) and depression by age 21 (HR 1.24 95% CI 1.08-1.42) compared to those of mothers with no such infection history, reported Kristina Adams Waldorf, MD, of the University of Washington in Seattle, and colleagues.

For autism, the association did not appear to be affected by the severity of maternal infection, they wrote in JAMA Psychiatry.

Risk of receiving an autism diagnosis was similar in magnitude whether a child had been exposed to urinary tract infections (UTI; HR 1.89, 95% CI 1.23-2.90) or a composite of severe infections (HR 1.81, 95% CI 1.18-2.78), which consisted of chorioamnionitis, influenza, sepsis, pneumonia, pyelonephritis, and meningitis or encephalitis.

For depression, the levels of increased risk were similar across levels of severity:

• Severe infections: HR 1.24, 95% CI 0.88-1.73
• UTIs: HR 1.30, 95% CI 1.04-1.61

Adjustments in all analyses were made for maternal age, tobacco use, asthma, diabetes, and premature rupture of membranes.

“As an obstetrician, I’m very concerned about my patients that refuse an influenza vaccination because they’re worried it might harm the baby,” Adams Waldorf told MedPage Today. “This is the result of misinformation, and in fact, an influenza viral infection can harm the fetal brain and result in an elevated risk of autism and depression in their child across their lifetime.”

Infections can injure the fetal brain directly, Adams Waldorf said, or indirectly — a body’s inflammatory response when trying to clear a virus could have a negative impact on in utero development, for example. Certain infections like Zika have been shown to cause a number of injuries to developing fetal organs, but how strongly other maternal infections might affect brain development and mental health post-utero is less clear, she added.

For their study, the researchers used linked data from the Swedish population-based birth registry and hospital inpatient and death registries. Through Swedish International Classification of Diseases hospitalization codes, they identified three groups of maternal infections — any, severe, and UTIs.

The primary analysis included 2,138,012 neonates born from 1973 to 2014 who had hospitalization records up to 41 years. There were 2,108,156 mothers without infections and 29,856 with infections during pregnancy. Those without a history of infections tended to be a bit older (28.7 vs 27.6 years), were less often tobacco users (15.4% vs 19%), and had lower rates of asthma, seizures, and hypertension. The infants in the sample were similar in terms of sex and birth weight.

Along with autism and depression, the researchers also examined bipolar disorder and psychosis, but found no association with exposure to infection in the womb:

• Bipolar disorder: HR 0.99, 95% CI 0.71-1.38
• Psychosis, including schizophrenia: HR 1.14, 95% CI 0.83-1.57

Adams Waldorf and colleagues conducted two bias analyses. In a sensitivity analysis that examined the risk of misdiagnosed or miscoded infection, they reported that the “measures of effect remained significant and only slightly decreased for all statistically significant results for the development of autism or depression.”

The second explored the effect of misclassification of outcome bias from loss to follow-up. Here they found no increased risk of depression among those exposed to infections when assuming a depression prevalence of 5%. However, pulling in data from the Swedish National Death Registry revealed that starting at age 21, “death by suicide among adults exposed to infection during fetal life was significantly greater” compared with unexposed individuals.

“Suicides were much more common in children that had been exposed to a mother’s infection in pregnancy than those unexposed,” Adams Waldorf said. “This provided evidence from a completely different source that suicide was much more common in children exposed, so this kind of corroborated our depression data.”

Limitations of the study included the fact that the data only involves Swedish women and was collected from inpatient hospitalization records; therefore, it may not be generalizable to other populations or patients treated in outpatient settings, they added. The authors did not adjust for socioeconomic status either.