Long-term risk of autism and depression after exposure to infection in utero

29 Apr 2019

Several types of bacterial and viral pathogens are able to cross the placental barrier and studies have shown that maternal exposure to certain infections during pregnancy can lead to adverse effects on the health and development of the fetus, as well as fetal death.1,2 Other than neurodevelopmental abnormalities, there has been evidence to indicate that some infections are able to cause fetal brain injury and increase the risk of psychiatric disorders in children.1,3 For example, prenatal influenza has been associated with the development of schizophrenia and a five-fold risk of bipolar disease in the infants.4

A recent cohort study of a Swedish population analyzed 4,278,146 neonates’ records between January 1, 1973 and December 31, 2014, and their subsequent hospitalization records up to 41 years after birth.3 The primary outcome of the study was autism, bipolar disorder, depression, and psychosis (including schizophrenia) during impatient hospitalization.3 Overall, the study found evidence that irrespective of the infection, the risk of the child for hospital admission with autism was increased after fetal exposure and hospitalization of the mother, with an adjusted hazard ratio of 1.79 (95% CI: 1.34-2.40).3 For severe maternal infection, including sepsis, pneumonia and meningitis, and the adjusted hazard ratio for development of autism was increased to 1.81 (95% CI: 1.18-2.78).3

The study was unable to capture every record of diagnoses of depression as some patients may have never been admitted to hospital after birth, though data from the National Death Registry provided results which associated an increased risk of suicide in those adults who were exposed to infection in utero.3 The hazard ratio for depression was 1.24 in both exposure to any (95% CI: 1.08-1.42) and in severe (95% CI: 0.88-1.73) maternal infections.3 However, there was not sufficient evidence to conclude maternal infection can lead to lifetime risk of other psychosis or bipolar disorders.3

The investigators concluded that this cohort study provided evidence that exposure to maternal infections during fetal life increased risk of autism and likely depression in the child, and whilst individual risk was perceived as small, effect as a population was much larger.3 Professor Kristina Adams Waldorf, co-leader of the study and professor of obstetrics and gynecology at the University of Washington, Seattle, United States, said “Parts of the fetal brain are exquisitely vulnerable to damage from infection and inflammation, especially areas involving social and emotional function,” further adding that this could help explain the association of increased risk to autism and emotive disorders (such as depression) with infection and inflammation during pregnancy.5 Prof. Adams Waldorf stated, “We should aggressively act to prevent and treat infections during pregnancy when we can,” and expressed a growing concern of pregnant women avoiding the influenza vaccine, explaining that risk is not only to the mother but to their infants too.5 Indeed, the Centers for Disease Control and Prevention also advise that pregnant women should receive the nasal spray flu vaccine to protect both the mother and the baby as this can reduce the risk of hospitalization with influenza by 40%, and protect the baby from influenza for several months post-partum.6 It has also been suggested that an imperative strategy to maintain maternal and infant health is educating pregnant women on the importance of prevention, early identification and treatment of infectious diseases.3,7

  1. Loughran A, Tuomanen E. Blood borne: bacterial components in mother’s blood influence fetal development. Inflamm Cell Signal. 2016;3(4). pii:e1421.
  2. Adams Waldorf K, McAdams R. Influence of infection during pregnancy on fetal development. Reproduction. 2013;146(5):R151-62.
  3. al-Haddad B, Jacobsson B, Chabra S, et al. Long-term Risk of Neuropsychiatric Disease After Exposure to Infection in Utero. JAMA Psychiatry. 2019. [Epub ahead of print].
  4. Canetta S, Bao Y, Co M, et al. Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring. Am J Psychiatry. 2014;171(5):557-63.
  5. Pregnancy infection increases a child’s autism, suicide risk. University of Washington School of Medicine. 2019. (Accessed March 15, 2019, at
  6. Pregnancy Women & Influenza (Flu). Centers for Disease Control and Prevention. 2019. (Accessed March 14, 2019, at
  7. Kourtis A, Read J, Jamieson D. Pregnancy and Infection. N Engl J Med. 2014;370(23):2211-18.
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