Parental mental illness and fatal birth defects in a national birth cohort

Few large studies describe links between maternal mental illness and risk of major birth defect in offspring. Evidence is sparser still for how effects vary between maternal diagnoses and no previous study has assessed risk with paternal illnesses.

A population-based birth cohort was created by linking Danish national registers. We identified all singleton live births during 1973-1998 (n=1.45 m), all parental psychiatric admissions from 1969 onwards, and all fatal birth defects until 1 January 1999. Linkage and case ascertainment were almost complete. Relative risks were estimated using Poisson regression.

Risk of fatal birth defect was elevated in relation to history of 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 [relative risk (RR) 2.34, 95% confidence interval (CI) 1.45-3.77], which also represented a significant excess risk compared with 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 toxicity, and gene-environment interactions. Further research is needed to elucidate the causal mechanisms.