Table 3.

Main Sources of Bias and Possible Cures in Studies of Environmental Impacts on Congenital Anomalies

Source of Bias	Description of Potential Bias	Possible Approaches to Limit Bias
Study design	The overall prevalence of anomalies is conditioned by the duration of observation (from conception up to a few years after birth).	Ascertain anomalies in therapeutic, spontaneous abortions and stillbirths; collect information on anomalies diagnosed during the first year of life.
Outcome assessment	Definition, diagnosis, and reporting of minor anomalies vary across registries (62–65).	Review individual medical records. Study with particular caution observations with multiple anomalies (62).
	Prevalence of specific anomalies such as cryptorchidism decreases with gestational age (64).	Take into account gestational duration in analysis.
	Identification of minor anomalies may vary between clinicians and between malformation registers.	Use a standardized protocol to assess and report the anomalies of interest.
	Sensitivity and specificity of identification of a given anomaly may vary with the classification used (66).	Use fine classifications; review individual medical records. Study with particular caution observations with multiple anomalies (62).
Medical interventions	Access to prenatal diagnosis may vary with couples' characteristics and possibly exposures (110).	Assess if access to prenatal diagnosis is associated with exposure in controls. In studies in large areas, identify differences in screening policies (110).
Exposure assessment	The biological window of sensitivity to environmental factors may be early in pregnancy and narrow for many anomalies.	Identify the a priori relevant time window from biological and toxicological knowledge; finely assess exposure in this time period.