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Case-control studies of birth defects might be subject to selection bias when there is incomplete ascertainment of cases among pregnancies that are terminated after a prenatal diagnosis of the defect. We propose a simple method to estimate inverse probability of selection weights (IPSWs) for cases ascertained from both pregnancies that end in termination and those that do not end in termination using data directly available from the National Birth Defects Prevention Study and other published information. The IPSWs can then be used to adjust for selection bias analytically. We can also allow for uncertainty in the selection probabilities through probabilistic bias analysis. We provide an illustrative example using data from National Birth Defects Prevention Study (1997-2009) to examine the association between prepregnancy obesity (body mass index, measured as weight in kilograms divided by height in meters squared, of ≥30 vs. &lt;30) and spina bifida. The unadjusted odds ratio for the association between prepregnancy obesity and spina bifida was 1.48 (95% confidence interval: 1.26, 1.73), and the simple selection bias-adjusted odds ratio was 1.26 (95% confidence interval: 1.04, 1.53). The probabilistic bias analysis resulted in a median adjusted odds ratio of 1.22 (95% simulation interval: 0.97, 1.47). The proposed method provides a quantitative estimate of the IPSWs and the bias introduced by incomplete ascertainment of cases among terminated pregnancies conditional on a set of assumptions.

Adjusting for Bias Due to Incomplete Case Ascertainment in Case-Control Studies of Birth Defects