Summary: Risks for autism and depression are higher if one’s mother was in hospital with an infection during pregnancy. This is shown by a major Swedish observational study of nearly 1.8 million children.
Source: University of Gothenburg
“The results indicate that safeguarding against and preventing infection during pregnancy as far as possible by, for instance, following flu vaccination recommendations, may be called for,” says Verena Sengpiel, Associate Professor of Obstetrics and Gynecology at Sahlgrenska Academy, University of Gothenburg, and last author of the study, published in the journal JAMA Psychiatry.
Maternal infection with certain infectious agents, such as cytomegalovirus (CMV) or the herpes virus, are already known to be capable of harming fetal brain development and boosting the risk of certain psychiatric disorders.
The findings of the current study, however, also show that infection in general during pregnancy, too — including when the actual infectious agent does not reach the fetal brain — is related to elevated risk of the child developing autism or depression later in life.
More autism and depression
The study is based on data on all children, totaling almost 1.8 million, born in Sweden during the years 1973–2014. The particulars from the Swedish Medical Birth Register were linked to the national inpatient register, which records whether the mother was treated in hospital with an infection diagnosis during the pregnancy concerned.
Using the inpatient register, the researchers also monitored these children’s mental health until 2014, when the oldest were aged 41.
It was found that if, during pregnancy, a mother with an infection diagnosis received hospital treatment, there was a marked rise in the risk of her child needing hospital care later in life, with a diagnosis of either autism or depression. The increase in risk was 79 percent for autism and 24 percent for depression.
In contrast, there was no association between the mothers being in hospital with an infection diagnosis during pregnancy and two other psychiatric diagnoses studied in their children: bipolar disorder and psychosis, including schizophrenia.
Increased risk even after mild infection
The pregnant women in the study may have been hospitalized with diagnoses other than infections, but then had infections diagnosed during their stay as well. The elevated risk of mental ill-health in the child was also evident after infections in the pregnant women that are usually considered mild, such as a common urinary tract infection.
The study, which was observational, provides no answer on how maternal infection during pregnancy affects fetal brain development. However, other studies have shown that an infection in the mother leads to an inflammatory reaction, and that some inflammatory proteins can affect gene expression in fetal brain cells.
Other research shows that inflammation in the mother boosts production of the neurotransmitter serotonin in the placenta, which may conceivably affect the unborn child’s brain development.
The study was carried out in collaboration between researchers at Sahlgrenska Academy and colleagues at the UW (University of Washington) School of Medicine in Seattle, Washington, US.
University of Gothenburg
Associate Professor Verena Sengpiel
Professor Bo Jacobsson
Image is in the public domain.
al-Haddad BJS, Jacobsson B, Chabra S, et al. Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero. JAMA Psychiatry. Published online March 06, 2019. doi: 10.1001/jamapsychiatry.2019.0029
Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero
The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero.
To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy.
Design, Setting, and Participants
A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018.
Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection.
Main Outcomes and Measures
Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring.
A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (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 severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; 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. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero.
Conclusions and Relevance
These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child’s life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.