Recurrent pregnancy loss as an indicator for increased risk of birth defects: a population-based case-control study

Stillbirths and spontaneous abortuses have higher rates of birth defects than liveborn infants. The relationship between a woman's previous pregnancy loss and the risk of birth defects in the offspring has not been adequately examined, however. Using data from a population-based case-control study, we assessed whether one or more previous pregnancy loss was associated with increased birth defect risks. Case subjects were 4918 infants with serious births defects diagnosed in the first year of life and ascertained by the Metropolitan Atlanta Congenital Defects Program from 1968 to 1980. Control subjects were 3028 normal liveborn infants frequency-matched to case infants by race, hospital and period of birth. Among case and control infants whose mothers had already had at least one previous pregnancy, reported pregnancy losses (stillbirths and miscarriages) were associated with elevated risks of birth defects (odds ratios for one pregnancy loss of 1.24, two pregnancy losses of 1.49, and three or more pregnancy losses of 1.62, P < 0.0001 for trend). This association held after considering several potential confounders using logistic regression analysis. When specific defects were examined, many exhibited this association, notably hydrocephalus, and some cardiovascular, genital and limb defects. We estimate that the risk of serious birth defects increases from 2.5% for infants of women with no prior pregnancy loss to 4.2% for infants of women with three or more pregnancy losses. This finding has both clinical implications for pregnancy counselling and pathogenetic implications related to birth defect aetiology.