Serious life events and congenital malformations: a national study with complete follow-up

Background Emotional stress during organogenesis could, in theory, cause congenital malformations. We undertook a follow-up study to test the hypothesis that psychosocial stress increases the prevalence of malformations, particularly of the cranial neural crest. Methods We defined severe life events as death or first hospital admission for cancer or acute myocardial infarction in partners or children. From 1980 to 1992 all women exposed to severe life events during pregnancy and up to 16 months previously were identified by means of five national registers. We included 3560 exposed pregnancies and 20 299 pregnancies without such exposures randomly selected as a control cohort. Findings The frequency of cranial-neural-crest malformations was higher in pregnancies with exposure to severe life events than in those without such exposure (42 [1.18%] vs 131[0.65%]; adjusted odds ratio 1.54 [95% CI 1.05-2.27]). For other malformations, the frequencies were 3.04% and 3.26% (1.14 [0.94-1.42]). Women exposed in two consecutive pregnancies had a higher risk of cranial-neural-crest malformations (2.99 [1.06-8.43]). Death of an older child during the first trimester was associated with an adjusted odds ratio of cranial-neural-crest malformations of 4.75 (1.63-13.8). Unexpected death of a child during the first trimester was associated with adjusted odds ratios of 8.36 (2.41-29.0) for cranial-neural-crest malformations and 3.64 (1.29-10.3) for other malformations. Interpretation These findings support the hypothesis that severe emotional stress during pregnancy, especially that related to death of a child, may cause congenital malformations, particularly those of the cranial neural crest.