Fetal Exposure to Infection Increases Risk of Autism, Depression

By Will Boggs MD

NEW YORK—Fetal exposure to infection is associated with an increased long-term risk of autism and depression, according to findings from Swedish registries.

"We were surprised that urinary tract infections (UTIs) conferred the same level of risk for autism and depression as severe infections," Dr. Benjamin J. S. al-Haddad from Seattle Children's Hospital and the University of Washington, in Seattle, told Reuters Health by email. "While there are many possible reasons for this finding, there is evidence from the literature that even seemingly small insults can change inflammatory cytokine and neurotransmitter secretion and alter neurodevelopment."

Several studies have linked particular infections to elevated lifelong risks for certain psychiatric disorders, but whether maternal infection and inflammation can alter fetal neurodevelopment in a way that increases the risk for a broad spectrum of psychopathological conditions across the child's lifetime is unknown.

Dr. al-Haddad and colleagues investigated whether fetal exposure to any maternal infection while hospitalized during pregnancy increases the risk of a later diagnosis of autism, depression, bipolar disorder, or psychosis among offspring.

Among 4.3 million neonates with records up to 41 years after birth, there was a 79% increased risk of an autism diagnosis and a 24% increased risk of a depression diagnosis among those exposed to any maternal infection during pregnancy, the researchers report in JAMA Psychiatry, online March 6.

In contrast, fetal exposure to any maternal infection was not associated with an increased risk of bipolar disorder or psychosis, including schizophrenia.

In a subanalysis by type of infection, the magnitude of increased risk for autism and depression was similar regardless of whether the exposure was a severe maternal infection or a UTI.

As external validation, the researchers found that the cumulative hazard for death by suicide among adults exposed to infection during fetal life was also significantly greater compared with unexposed individuals starting at age 21 years, which mirrored the results from the inpatient registry for depression.

"Infections during pregnancy may have long-term neuropsychiatric effects on the fetus," Dr. al-Haddad concluded. "Every pregnant woman should receive the influenza vaccine and be screened and treated for UTIs."

"These findings occurred in the healthy Swedish population with universal high-quality health care," he added. "If these findings are generalizable, they suggest that in populations with endemic prenatal malaria and lack of prenatal care, the resulting burden of neuropsychiatric disease may be dramatically higher."

Dr. Ole Koehler-Forsberg from Aarhus University Hospital, in Risskov, Denmark, who recently reported an association between treated infections and the subsequent risk of treated mental disorders in children and adolescents, told Reuters Health by email, "Interestingly, we find that infections during pregnancy were associated with an increased risk for mental disorders in the offspring - however, so were infections before and after pregnancy. So our findings do not indicate a causal effect per se but rather very important confounding factors. Our conclusion was that infections during pregnancy, in general, do not affect the risk of the offspring for developing a mental disorder - it may rather be explained by socioeconomic status, genetic aspects, etc."

"Basically, if you compare women who were hospitalized for an infection during pregnancy with women who did not experience this - this is not a comparable study population," he said. "Hence, I would be very cautious in claiming that the infection increased the risk of mental disorders."

"Pregnant women should not get anxious when having an infection during pregnancy," Dr. Koehler-Forsberg concluded. "40-50% of pregnant women receive antibiotics during pregnancy and several get hospitalized for an infection. So this is very normal, having an infection during pregnancy."

"Although, of course," he added, "infections can have detrimental impacts on the developing brain, so of course one should do everything to avoid unnecessary infections during pregnancy, in particular, regarding the severe infections."

Dr. Michael Eriksen Benros from Aarhus University and Copenhagen University Hospital, also in Denmark, co-authored the study with Dr. Koehler-Forsberg and has studied other possible associations between infectious and autoimmune diseases and mental health disorders. He told Reuters Health by email, "Both autism and psychosis have previously been associated with maternal infections; hence, it was a bit surprising that the association here was only found for autism and depression, but not for psychosis or bipolar disorders, in the offspring."

"Other studies have shown that the risk estimates are similarly increased for mental disorders in the child for overall infections outside of the pregnancy period, so there could also be genetic or socioeconomic factors influencing the shown associations," he said. "Nevertheless, there might be specific maternal infections or immune components that can have detrimental effects to the fetus, which need to be identified in order to identify at-risk pregnancies."

SOURCE: https://bit.ly/2F8gIJb

JAMA Psychiatry 2019.

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