Table 2.

Main Sources of Bias and Possible Cures in Studies of Environmental Impacts on Fetal Loss^a

Source of Bias	Description of Potential Bias	Possible Approaches to Limit Bias
Study design	Gestational age at start of follow-up or at pregnancy detection varies between women and may be associated with exposure (54).	Assess date of pregnancy recognition and gestational age at start of follow-up and analyze data with a survival model with delayed entry (54, 56).
	Study is based on the recall of the last pregnancy only, leading to an underestimation of fetal loss rate (109).	Alternatives include collecting information on all past pregnancies or using a prospective design.
Outcome assessment	Elective or therapeutic abortions may be described as spontaneous abortions.	Design study questionnaire with great care to distinguish pregnancy outcomes. Collect medical records.
	The fetal loss may occur several weeks after the death of the fetus.	Identify the gestational age and results of all ultrasound examinations. Consider using a discrete-time (interval-censored) survival approach allowing consideration that the fetal death occurred in a time window rather than during a specific week.
Exposure assessment	Exposure window varies with outcome. Exposure varies during pregnancy (or probability of exposure depends on pregnancy duration), leading to noncausal differences in exposure between pregnancies with short (fetal losses) and longer (livebirths) durations.	Assess temporal variations in exposure and analyze data with a survival model with time-varying covariates. Consider only very early exposures (e.g., during first month of pregnancy), if there is a biological relevance.
Statistical analysis	Previous history of fetal loss is adjusted for in the model, whereas a previous fetal loss may be due to the exposure under study.	Build a directed acyclic graph to discuss relevance of adjustment for previous reproductive history (41, 57).
	Pregnancies ending as an induced abortion or medical termination may have otherwise ended as a spontaneous abortion; these pregnancies are not considered in the denominator when assessing the frequency of fetal loss.	Use a survival analysis; treat induced abortions and medical terminations of pregnancy as competing events.

^a Early fetal losses are not considered.