[Serious life events and congenital malformations. A national study with a complete follow-up]

Emotional stress during organogenesis could, in theory, cause congenital malformations by increasing the level of cortisone, but documentation is lacking. We undertook a follow-up study to test the hypothesis that psychosocial stress increases the prevalence of malformations, in particular malformations of the cranial neural crest.

We defined serious life events as the death or first hospital admission for cancer or acute myocardial infarction of partners or children. All women exposed to severe life events during and up to 16 months before pregnancy in the period 1980 to 1992 were identified by means of five national registers. We studied 3560 exposed pregnancies and randomly selected 20,299 "not-exposed" pregnancies as the control cohort.

Women exposed to severe life events gave birth to offspring with an increased prevalence of cranial neural crest malformations, at an adjusted odds ratio of 1.54; 95% CI (1.05-2.27). For other malformations the adjusted odds ratio was 1.14-95% CI (0.94-1.42). Women exposed in two consecutive pregnancies had a higher odds ratio for cranial neural crest malformations, with an adjusted odds ratio of 2.99; 95% CI (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 in the offspring of 4.75; 95% CI (1.63-13.78). Unexpected death of a child during the first trimester was associated with an adjusted odds ratio of 8.36 in the offspring, 95% CI (2.41-28.99) for cranial neural crest malformations and 3.64, 95% CI (1.29-10.32) for other kinds of malformations.

These findings support the hypothesis that severe emotional stress during pregnancy, especially stress related to the death of a child, may cause congenital malformations, particularly those of the cranial neural crest.