High-Dimensional Biostatistics for Drug Safety and Genomics, Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, CESP, Villejuif, France.
Biostatistics and Bioinformatics (DIM), University Hospital, Dijon, France.
BJOG. 2021 Sep;128(10):1575-1584. doi: 10.1111/1471-0528.16670. Epub 2021 Mar 22.
To assess the risk of preterm birth associated with nonsteroidal anti-inflammatory drugs (NSAIDs), focusing on early exposure in the period from conception to 22 weeks of gestation (WG).
National population-based retrospective cohort study.
The French National Health Insurance Database that includes hospital discharge data and health claims data.
Singleton pregnancies (2012-2014) with a live birth occurring after 22WG from women between 15 and 45 years old and insured the year before the first day of gestation and during pregnancy were included. We excluded pregnancies for which anti-inflammatory medications were dispensed after 22WG.
The association between exposure and risk of preterm birth was evaluated with GEE models, adjusting on a large number of covariables, socio-demographic variables, maternal comorbidities, prescription drugs and pregnancy complications.
Prematurity, defined as a birth that occurred before 37WG.
Among our 1 598 330 singleton pregnancies, early exposure to non-selective NSAIDs was associated with a significantly increased risk of preterm birth, regardless of the severity of prematurity: adjusted odds ratio (aOR) = 1.76 (95% CI 1.54-2.00) for extreme prematurity (95% CI 22-27WG), 1.28 (95% CI 1.17-1.40) for moderate prematurity (28-31WG) and 1.08 (95% CI 1.05-1.11) for late prematurity (32-36WG), with non-overlapping confidence intervals. We identified five NSAIDs for which the risk of premature birth was significantly increased: ketoprofen, flurbiprofen, nabumetone, etodolac and indomethacin: for the latter, aOR = 1.92 (95% CI 1.37-2.70) with aOR = 9.33 (95% CI 3.75-23.22) for extreme prematurity.
Overall, non-selective NSAID use (delivered outside hospitals) during the first 22WG was found to be associated with an increased risk of prematurity. However, the association differs among NSAIDs.
French study for which early exposure to non-selective NSAIDs was associated with increased risk of prematurity.
评估非甾体抗炎药（NSAIDs）与早产相关的风险，重点关注妊娠 22 周前（WG）的早期暴露。
全国基于人群的回顾性队列研究。
法国国家健康保险数据库，包含医院出院数据和健康索赔数据。
纳入 2012-2014 年年龄在 15 至 45 岁之间、受孕前一年和孕期有医保的单胎活产妊娠，并排除了妊娠 22 WG 后开具抗炎药物的妊娠。
使用广义估计方程模型评估暴露与早产风险之间的关联，并对大量协变量、社会人口学变量、母体合并症、处方药和妊娠并发症进行了调整。
早产定义为发生在 37 WG 前的分娩。
在我们的 1598330 例单胎妊娠中，早期暴露于非选择性 NSAIDs 与早产风险显著增加相关，无论早产的严重程度如何：极早产（95%CI 22-27 WG）的调整比值比（aOR）为 1.76（95%CI 1.54-2.00），中度早产（95%CI 28-31 WG）为 1.28（95%CI 1.17-1.40），晚期早产（95%CI 32-36 WG）为 1.08（95%CI 1.05-1.11），置信区间无重叠。我们确定了五种 NSAIDs 的早产风险显著增加：酮洛芬、氟比洛芬、萘布美酮、依托度酸和吲哚美辛：对于后者，aOR=1.92（95%CI 1.37-2.70），aOR=9.33（95%CI 3.75-23.22），极早产。
总体而言，妊娠 22 WG 前使用非选择性 NSAIDs（非医院开具）与早产风险增加相关。然而，不同 NSAIDs 之间的关联存在差异。
法国研究表明，早期暴露于非选择性 NSAIDs 与早产风险增加相关。
