Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Am J Ther. 2014 Jul-Aug;21(4):254-9. doi: 10.1097/MJT.0b013e3182456a8f.
Proton pump inhibitors (PPIs) are increasingly used in reflux disease treatment also among pregnant women. Hypospadias prevalence is increasing and the birth defect is diagnosed in 0.3%-0.8% of male births, but the association with maternal PPI use during pregnancy is virtually unknown. Therefore, we decided to estimate the hypospadias risk in male offspring after maternal PPI use during pregnancy. We used Danish nationwide registries to conduct a population-based prevalence study including all live-born boys from 1997 through 2009. Maternal PPI use was classified according to exposure time: early pregnancy (30 days before conception through the end of the first trimester) and entire pregnancy (30 days before and throughout pregnancy). Outcome was defined as a hospital hypospadias diagnosis recorded any time after delivery. We calculated prevalence ratios and 95% confidence intervals associating maternal PPI use with hypospadias in male offspring using Cox proportional hazard regression analysis and adjusted for confounding factors. We identified a total of 430,569 live-born boys of whom 2926 were exposed to maternal PPI use during early pregnancy. Among the exposed boys, 20 (0.7%) were diagnosed with hypospadias, whereas 2683 (0.6%) of the nonexposed had hypospadias (adjusted prevalence ratio = 1.1; 95% confidence interval, 0.7-1.7). A total of 5227 boys were exposed during the entire pregnancy, and 32 (0.6%) had hypospadias corresponding to a prevalence ratio of 1.0 (95% confidence interval, 0.7-1.4). The subanalysis restricted to omeprazole exposure showed similar results. We thus conclude that maternal PPI use during pregnancy was not associated with hypospadias in boy offspring.
质子泵抑制剂（PPIs）在反流疾病治疗中的应用越来越广泛，包括孕妇。尿道下裂的发病率正在增加，这种出生缺陷在 0.3%-0.8%的男性出生中被诊断出来，但与孕妇在怀孕期间使用 PPI 之间的关联实际上是未知的。因此，我们决定评估母亲在怀孕期间使用 PPI 后男性后代发生尿道下裂的风险。我们使用丹麦全国性登记处进行了一项基于人群的患病率研究，包括 1997 年至 2009 年所有活产男婴。根据暴露时间对母亲使用 PPI 进行分类：妊娠早期（受孕前 30 天至孕早期结束）和整个孕期（受孕前 30 天至整个孕期）。结果定义为分娩后任何时间记录的医院尿道下裂诊断。我们使用 Cox 比例风险回归分析计算了与男性后代中母亲使用 PPI 相关的尿道下裂的患病率比和 95%置信区间，并针对混杂因素进行了调整。我们总共确定了 430569 名活产男婴，其中 2926 名男婴在妊娠早期暴露于母亲的 PPI 使用中。在暴露的男婴中，有 20 名（0.7%）被诊断为尿道下裂，而在未暴露的男婴中，有 2683 名（0.6%）患有尿道下裂（调整后的患病率比=1.1；95%置信区间，0.7-1.7）。共有 5227 名男婴在整个孕期暴露于 PPI 中，其中 32 名（0.6%）患有尿道下裂，患病率比为 1.0（95%置信区间，0.7-1.4）。将亚分析限制在奥美拉唑暴露的情况下，得到了类似的结果。因此，我们得出结论，母亲在怀孕期间使用 PPI 与男婴后代的尿道下裂无关。
