Center for Birth Defects Research and Prevention, Massachusetts Department of Public Health, Boston, Massachusetts.
Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts.
Paediatr Perinat Epidemiol. 2020 Nov;34(6):655-664. doi: 10.1111/ppe.12650. Epub 2020 Apr 6.
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 "livebirth bias." However, the implications of livebirth bias on risk estimation remain poorly understood. OBJECTIVES: We sought to quantify livebirth bias and to investigate the conditions under which it arose. METHODS: We used data on 3994 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 livebirths as compared to among livebirths, stillbirths, and elective terminations. Exposures and birth defects represented varying strengths of association with livebirth; 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% liveborn (anencephaly) to 99% (cleft palate). Smoking and multifetal pregnancy were associated with livebirth 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 livebirths produced negligible differences in estimates except for anencephaly and multifetal pregnancy, which was twofold higher among livebirths (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 livebirth bias is unlikely to affect studies of risk factors for most birth defects.
背景：出生缺陷的风险因素经常通过仅限于活产婴儿的数据进行研究。通过对存活情况进行条件限制，此类研究的结果可能会受到选择偏差的影响，这种偏差也被称为“活产偏倚”。然而，活产偏倚对风险估计的影响仍知之甚少。
目的：我们旨在量化活产偏倚，并探讨其产生的条件。
方法：我们使用了国家出生缺陷预防研究中纳入的 3994 例出生缺陷病例和 11829 例对照的数据，比较了三种已确立的风险因素（抗癫痫药物使用、吸烟和多胎妊娠）与四种出生缺陷（无脑畸形、脊柱裂、脐膨出和腭裂）之间的关系，当局限于活产儿时，与活产儿、死产儿和选择性终止妊娠时的比值比（OR）估计值进行了比较。暴露和出生缺陷与活产儿的关联程度各不相同；所有对照均为活产儿。我们进行了定量偏倚分析，以评估排除终止妊娠和死产儿对照对我们结果的敏感性。
结果：病例范围从无脑畸形的 33%（活产）到腭裂的 99%（活产）。吸烟和多胎妊娠与无脑畸形（粗 OR [cOR]0.61 和 cOR3.15）和脐膨出病例（cOR2.22 和 cOR5.22）的活产相关。对于暴露与出生缺陷之间的关联分析，除了无脑畸形和多胎妊娠之外，将活产儿限定为活产儿几乎不会对估计值产生差异，在活产儿中，这两种情况的比值比（aOR）分别是所有妊娠结局（aOR2.44）的两倍（aOR4.93）。在测试的场景中，偏差分析表明，结果对限制活产儿对照并不敏感。
结论：除了暴露与活产强烈相关的高死亡率缺陷外，选择偏差通常是有限的。研究结果表明，对于大多数出生缺陷的风险因素研究，大量的活产偏倚不太可能产生影响。
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