Higher Risk of Offspring Schizophrenia Following Antenatal Maternal Exposure to Severe Adverse Life Events

TLDR

Maternal psychological stress during pregnancy, especially in the first trimester, has been linked to adverse outcomes such as low birth weight, prematurity, and congenital malformations. The study aimed to evaluate whether antenatal maternal exposure to severe stress increases offspring risk of schizophrenia. Using a Danish population‑based cohort of 1.38 million births, mothers were considered exposed if a close relative died or had a severe illness up to six months before conception or during pregnancy, and offspring were followed from age ten via psychiatric registry linkage. Offspring whose mothers experienced a relative’s death during the first trimester had a 67 % higher risk of schizophrenia (adjusted RR = 1.67), whereas exposure in other trimesters or before conception was not associated with increased risk, supporting a first‑trimester stress effect on neurodevelopment.

Abstract

Most societies believe that a mother's psychological state can influence her unborn baby. Severe adverse life events during pregnancy have been consistently associated with an elevated risk of low birth weight and prematurity. Such events during the first trimester have also been associated with risk of congenital malformations.To assess the effect in offspring of antenatal maternal exposure to an objective measure of stress on risk of adverse neurodevelopment, specifically schizophrenia. We hypothesized that the strongest relationship would be to maternal exposures during the first trimester.Population-based study.Denmark.In a cohort of 1.38 million Danish births from 1973 to 1995, mothers were considered exposed if 1 (or more) of their close relatives died or was diagnosed with cancer, acute myocardial infarction, or stroke syndrome up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of schizophrenia, or June 30, 2005; admissions were identified by linkage to the Central Psychiatric Register. Main Outcome Measure Schizophrenia.The risk of schizophrenia and related disorders was raised in offspring whose mothers were exposed to death of a relative during the first trimester (adjusted relative risk, 1.67 [95% confidence interval, 1.02-2.73]). Death of a relative during other trimesters or up to 6 months before pregnancy were not linked with a higher risk of schizophrenia.Our population-based study suggests that severe stress to a mother during the first trimester may alter the risk of schizophrenia in offspring. This finding is consistent with ecological evidence from whole populations exposed to severe stressors and suggests that environment may influence neurodevelopment at the feto-placental-maternal interface.