Boston University School of Public Health, Slone Epidemiology Center at Boston University, and Massachusetts Center for Birth Defects Research and Prevention, Boston, Massachusetts.
Obstet Gynecol. 2018 Aug;132(2):385-394. doi: 10.1097/AOG.0000000000002679.
To use data from two large studies of birth defects to describe time trends in ondansetron use for the treatment of first-trimester nausea and vomiting of pregnancy and to investigate associations, either previously reported or undescribed, between first-trimester ondansetron use and major birth defects.
We used data from two case-control studies, the National Birth Defects Prevention Study (1997-2011) and the Slone Birth Defects Study (1997-2014). The prevalence of ondansetron use for the treatment of first-trimester nausea and vomiting of pregnancy among control patients was calculated in 2-year intervals. Using women with untreated first-trimester nausea and vomiting of pregnancy as the reference, we calculated adjusted odds ratios (ORs) and 95% CIs for associations between first-trimester ondansetron use for treatment of nausea and vomiting of pregnancy and specific birth defects. A secondary exposure group of other prescription antiemetics was used to address confounding by indication.
In the National Birth Defects Prevention Study and Slone Birth Defects Study, respectively, 6,751 and 5,873 control mothers and 14,667 and 8,533 case mothers who reported first-trimester nausea and vomiting of pregnancy were included in the analysis. Among women in the control group, ondansetron exposure increased from less than 1% before 2000 to 13% in 2013-2014. Ondansetron use was not associated with an increased risk for most of the 51 defect groups analyzed. Modest increases in risk were observed for cleft palate (adjusted OR 1.6, 95% CI 1.1-2.3) in the National Birth Defects Prevention Study and renal agenesis-dysgenesis (adjusted OR 1.8, 95% CI 1.1-3.0) in the Birth Defects Study, although these findings may be the result of chance.
Off-label use of ondansetron for the treatment of nausea and vomiting of pregnancy increased to 13% by the end of the study period. For the majority of specific birth defects investigated, there was no increased risk associated with first-trimester use of ondansetron for treatment of nausea and vomiting of pregnancy compared with no treatment, although modest associations with cleft palate and renal agenesis-dysgenesis warrant further study.
利用两项大型出生缺陷研究的数据，描述孕早期恶心呕吐治疗中昂丹司琼使用的时间趋势，并调查孕早期使用昂丹司琼与主要出生缺陷之间的关联，这些关联既有先前报道的，也有未报道的。
我们使用了两项病例对照研究的数据，即国家出生缺陷预防研究（1997-2011 年）和斯隆出生缺陷研究（1997-2014 年）。计算了对照组中治疗孕早期恶心呕吐的昂丹司琼使用率，每隔两年计算一次。以未经治疗的孕早期恶心呕吐的女性为参照，我们计算了孕早期使用昂丹司琼治疗恶心呕吐与特定出生缺陷之间的调整比值比（OR）和 95%置信区间（CI）。另一个暴露组为其他处方止吐药，用于解决混杂因素的影响。
在国家出生缺陷预防研究和斯隆出生缺陷研究中，分别有 6751 名和 5873 名对照组母亲和 14667 名和 8533 名报告孕早期恶心呕吐的病例母亲被纳入分析。在对照组中，昂丹司琼的暴露率从 2000 年之前的不到 1%增加到 2013-2014 年的 13%。在分析的 51 个缺陷组中，昂丹司琼的使用与大多数缺陷的风险增加无关。在国家出生缺陷预防研究中，唇裂（调整 OR 1.6，95%CI 1.1-2.3）和斯隆出生缺陷研究中的肾发育不全-发育不良（调整 OR 1.8，95%CI 1.1-3.0）的风险略有增加，但这些发现可能是偶然的结果。
在研究结束时，昂丹司琼的非适应证用于治疗恶心呕吐的使用率增加到 13%。与未治疗相比，在孕早期使用昂丹司琼治疗恶心呕吐与大多数特定的出生缺陷无关，尽管与唇裂和肾发育不全-发育不良的适度关联需要进一步研究。
