Abstract
ObjectiveTo 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).DesignNational population‐based retrospective cohort study.SettingThe French National Health Insurance Database that includes hospital discharge data and health claims data.PopulationSingleton 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.MethodsThe 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.Main outcome measuresPrematurity, defined as a birth that occurred before 37WG.ResultsAmong 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.ConclusionOverall, 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.Tweetable abstractFrench study for which early exposure to non‐selective NSAIDs was associated with increased risk of prematurity.
Highlights
Exposure to medication during pregnancy has been shown to be frequent, in France.[1]
In the sensitivity analysis for the chronic and the episodic use of Non-steroidal antiinflammatory drugs (NSAIDs), we found that the risk of prematurity was the same whatever the use of non-selective NSAIDs: Adjusted odds ratios (aORs) = 1.08 for chronic use and aOR = 1.08
Non-selective NSAID use during the first 22 weeks of pregnancy was found to be associated with an increased risk of prematurity, and extreme prematurity
Summary
Exposure to medication during pregnancy has been shown to be frequent, in France.[1] Non-steroidal antiinflammatory drugs (NSAIDs) are widely used in the general population and are prescribed to pregnant women who may need them to treat chronic illnesses or relieve pain (chronic or acute). The fetal consequences of late exposure to NSAIDs have been documented, for premature closure of the ductus arteriosus. The safety of early exposure to NSAIDs in pregnant women has not been fully established, with regard to prematurity. This seems relevant, as prematurity is a frequent and serious condition,[6] but very few studies have examined early exposure to NSAIDs7–10 and most did not analyse the effect on prematurity as the main study outcome. In early studies where the exposure period was defined as the entire pregnancy, no risk of prematurity was associated with the prescription of NSAIDs (including COX-2 inhibitors).[7,8] In contrast, Berard et al.[9] recently identified an increased risk of prematurity after exposure to COX2 inhibitors in the 3 months prior to delivery, but the authors found no association with exposure during pregnancy up to 3 months prior to delivery
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