Maternal exposure to heparin products and risk of birth defects in the National Birth Defects Prevention Study.
Maternal exposure to heparin products and risk of birth defects in the National Birth Defects Prevention Study.
复制标题
国家出生缺陷预防研究中母亲接触肝素产品和出生缺陷的风险。
DOI：
10.1002/bdr2.2074
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发表时间：
2023
影响因子：
2.1
通讯作者：
NationalBirthDefectsPreventionStudy
中科院分区：
文献类型：
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作者：
Howley,MeredithM;Fisher,SarahC;VanZutphen,AlissaR;Papadopoulos,EleniA;Patel,Jenil;Lin,AngelaE;Browne,MarilynL;NationalBirthDefectsPreventionStudy
背景：肝素和低分子量肝素是妊娠期间首选的抗凝血剂，因为它们不会穿过胎盘。虽然关于肝素产品安全性的研究令人放心，但以前的研究将出生缺陷视为单一结果或由更大的器官系统引起，并没有检查与特定出生缺陷的关系。方法：我们分析了1997年至2011年国家出生缺陷预防研究的数据，这是一项多地点、基于人群的病例对照研究。我们使用无条件逻辑回归与Firth的惩罚似然来计算至少有五个暴露病例的缺陷的调整优势比（ORs）和轮廓似然95%置信区间（CIs）。对于有3-4个暴露病例的缺陷，我们估计了粗ORs和精确的95% ci。在我们分析的42,743名妇女中，117名（0.4%）病例和44名（0.4%）对照母亲报告在妊娠早期使用肝素产品。调整后的OR值范围为0.9 - 3.9，对于肛肠闭锁（OR = 2.0, 95% CI = 0.8-4.3）、纵肢不足（3.5,1.3-7.8）、横肢不足（1.8,0.6-4.3）、房室间隔缺损（3.9,1.4-9.0）和第二房间隔缺损（2.2,1.2-3.8），OR值升高。结论：我们观察到肝素与一些出生缺陷的相关性升高，尽管肝素是罕见的暴露，这限制了我们评估许多相关性的能力。未来的研究可以探索特定的出生缺陷和充分控制的适应症混淆是必要的。考虑到在怀孕期间有肝素产品适应症的妇女通常需要服药，人们必须牢记无论使用何种药物都存在的先天缺陷的潜在风险。
BackgroundHeparin and low‐molecular‐weight heparin are the preferred anticoagulants during pregnancy as they do not cross the placenta. Although research on the safety of heparin products has been reassuring, previous studies have considered birth defects as a single outcome or by larger organ system and have not examined associations with specific birth defects.MethodsWe analyzed data from the National Birth Defects Prevention Study, a multisite, population‐based case–control study from 1997 to 2011. We used unconditional logistic regression with Firth's penalized likelihood to calculate adjusted odds ratios (ORs) and profile likelihood 95% confidence intervals (CIs) for defects with at least five exposed cases. For defects with 3–4 exposed cases, we estimated crude ORs and exact 95% CIs.ResultsOf the 42,743 women in our analysis, 117 (0.4%) case and 44 (0.4%) control mothers reported using a heparin product in early pregnancy. The adjusted ORs ranged from 0.9 to 3.9 and were elevated for anorectal atresia (OR = 2.0, 95% CI = 0.8–4.3), longitudinal limb deficiency (3.5, 1.3–7.8), transverse limb deficiency (1.8, 0.6–4.3), atrioventricular septal defect (3.9, 1.4–9.0), and secundum atrial septal defect (2.2, 1.2–3.8).ConclusionsWe observed elevated associations for some birth defects, although heparin is a rare exposure, which limited our ability to evaluate many associations. Future studies that can explore specific birth defects and adequately control for confounding by indication are needed. Given that women with an indication for heparin products during pregnancy often need to take medication, one must remain mindful of the underlying risk of a birth defect that exists regardless of medication use.