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Quantification of selection bias in studies of risk factors for birth defects among live births
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11 2020
Source: Paediatr Perinat Epidemiol. 34(6):655-664 -
Alternative Title:Paediatr Perinat Epidemiol
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Personal Author:
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Description:Background
Risk factors for birth defects are frequently investigated using data limited to liveborn infants. By conditioning on survival, results of such studies may be distorted by selection bias, also described as “live birth bias”. However, the implications of live birth bias on risk estimation remain poorly understood.
Objectives
We sought to quantify live birth bias and to investigate the conditions under which it arose.
Methods
We used data on 3,994 birth defects cases and 11,829 controls enrolled in the National Birth Defects Prevention Study to compare odds ratio (OR) estimates of the relationship between three established risk factors (antiepileptic drug use, smoking, and multifetal pregnancy) and four birth defects (anencephaly, spina bifida, omphalocele, and cleft palate) when restricted to live births as compared to among live births, stillbirths, and elective terminations. Exposures and birth defects represented varying strengths of association with live birth; all controls were liveborn. We performed a quantitative bias analysis to evaluate the sensitivity of our results to excluding terminated and stillborn controls.
Results
Cases ranged from 33% live born (anencephaly) to 99% (cleft palate). Smoking and multifetal pregnancy were associated with live birth among anencephaly (crude OR [cOR] 0.61 and cOR 3.15, respectively) and omphalocele cases (cOR 2.22 and cOR 5.22, respectively). For analyses of the association between exposures and birth defects, restricting to live births produced negligible differences in estimates except for anencephaly and multifetal pregnancy, which was two-fold higher among live births (adjusted OR [aOR] 4.93) as among all pregnancy outcomes (aOR 2.44). Within tested scenarios, bias analyses suggested that results were not sensitive to the restriction to liveborn controls.
Conclusions
Selection bias was generally limited except for high mortality defects in the context of exposures strongly associated with livebirth. Findings indicate that substantial live birth bias is unlikely to affect studies of risk factors for most birth defects.
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Pubmed ID:32249969
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Pubmed Central ID:PMC7541428
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