Population-based evidence is lacking for risk of major birth defect with parental psychopathology, and how effects vary by maternal and paternal diagnosis. We aimed to investigate this risk in offspring of parents admitted for psychiatric treatment in a 26-year national birth cohort.

The study cohort was created using several linked Danish national registers. We identified all singleton live births during 1973-98 (N=1.45m), all parental psychiatric admissions from 1969 onwards, and all fatal birth defects until 1st Jan. 1999. Linkage and case ascertainment were virtually complete. Relative risks were estimated by Poisson regression.

Fatal birth defect risk was elevated with any maternal admission and also with affective disorders specifically, although the strongest effect found was with maternal schizophrenia. The rate was more than doubled in this group compared to the general population (RR 2.34, 95% CI 1.45-3.77); this also represented a significant excess risk versus all other admitted maternal disorders (P=0.018). Risk of death from causes other than birth defect was no higher with schizophrenia than with other maternal conditions. There was no elevation in risk of fatal birth defect if the father was admitted with schizophrenia or any other psychiatric diagnosis.

There are many possible explanations for a higher risk of fatal birth defect with maternal schizophrenia and affective disorder. These include genetic effects directly linked with maternal illness, lifestyle factors (diet, smoking, alcohol and drugs), poor antenatal care, psychotropic medication, and gene-environment interactions. Further research is needed to elucidate the causal mechanisms.