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Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study.

ABSTRACT: OBJECTIVE: To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage. DESIGN: Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview. SETTING: Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States. PARTICIPANTS: 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days. MAIN OUTCOME MEASURES: Pregnancy outcomes up to 20 weeks of gestation. RESULTS: 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use. CONCLUSION: Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.

SUBMITTER: Li DK

PROVIDER: S-EPMC175811 | biostudies-literature | 2003 Aug

REPOSITORIES: biostudies-literature

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Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study.

Li De-Kun DK Liu Liyan L Odouli Roxana R

BMJ (Clinical research ed.) 20030801 7411

<h4>Objective</h4>To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage.<h4>Design</h4>Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview.<h4>Setting</h4>Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States.<h4>Participants</h4>1055 pregnant women recruited and interviewed imme ...[more]

PMID: 12919986

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Project description:BackgroundHeavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.ObjectivesTo determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.Search methodsWe searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.Selection criteriaThe inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.Data collection and analysisWe identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.Main resultsAs a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.Authors' conclusionsNSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.

Project description: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.

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Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study.

Publications

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study.

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