Potential sources of bias and confounding in environmental epidemiologic studies of pregnancy outcomes

Biases familiar to all epidemiologists take on new importance when studying spontaneous abortion because of the significance of the timing of exposure during gestation, and because the gestational age at which the pregnancy is recognized may be related to risk factors under study. In this paper, we systematically review the principal biases that might affect epidemiologic studies of pregnancy loss, in the context of a series of studies that found associations between adverse reproductive outcomes and prenatal use of tap or bottled water. These biases relate to availability of subjects for study, exposure opportunity, recall of exposure, recall of disease, and confounding. In one of the studies, the rate of bottled water use changed dramatically over the course of the study period, providing an opportunity to test indirectly for biased recall of exposure. We conclude that a less complete recall of water intake among women with normal pregnancies, as compared with those with spontaneous abortions, may have produced, or increased the magnitude of, the associations seen in these studies.