Safety of non‐steroidal anti‐inflammatory drugs in postpartum period in women with hypertensive disorders of pregnancy: systematic review and meta‐analysis

Abstract

Objective To assess the effect of non‐steroidal anti‐inflammatory drugs (NSAIDs) on blood pressure when administered for postpartum analgesia in women with hypertensive disorders of pregnancy. Methods MEDLINE, Scopus, CENTRAL, http://Clinicaltrials.gov and Google Scholar databases were searched systematically from inception to 5 December 2019 for studies evaluating the safety of postpartum NSAIDs in women with any gestational hypertensive disorder. Randomized controlled trials (RCTs) and cohort studies were eligible for inclusion. Case–control studies, case series and case reports were excluded. The primary outcomes of interest were the incidence of severe hypertension and systolic, diastolic and mean arterial blood pressure. Pooled estimates were obtained by fitting a random‐effects statistical model. The quality of evidence was assessed according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. Results Ten studies were included, comprising five RCTs and five retrospective cohort studies and involving a total of 1647 women. All studies were evaluated qualitatively and eight of them were included in the quantitative meta‐analysis. Administration of NSAIDs was not associated with a significantly higher risk of severe postpartum hypertension (odds ratio, 1.52 (95% CI, 0.77–3.01)). Similarly, no significant differences were found in postpartum systolic blood pressure (mean difference (MD), –3.03 mmHg (95% CI, –6.21 to 0.15 mmHg)) and mean arterial pressure (MD, –0.38 mmHg (95% CI, –1.88 to 1.11 mmHg)) between women who received NSAIDs and those who did not, whereas postpartum diastolic blood pressure was marginally lower in women treated with NSAIDs (MD, –2.28 mmHg (95% CI, –4.44 to –0.13 mmHg)). The same effects were observed when studies with a large sample size, RCTs, women with severe pre‐eclampsia and studies using ibuprofen as the study drug and acetaminophen as the control treatment were examined separately. The credibility of evidence was judged to be very low according to GRADE, owing to concerns about study limitations, inconsistency and imprecision. Conclusions This meta‐analysis suggests that postpartum administration of NSAIDs is not associated with elevated blood pressure in women with hypertensive disorders of pregnancy. However, the existing evidence is of very low quality, thus future large‐scale RCTs are warranted to verify the safety of postpartum NSAIDs in this population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association

“…[133][134][135] A recent systematic review and meta-analysis that included 5 randomized controlled trials and 5 retrospective cohorts concluded that compared with acetaminophen, nonsteroidal antiinflammatory drugs were not associated with increased BPs up to discharge (2-4 days postpartum). 136 The authors considered the quality of evidence to be low because of the small sample sizes, imprecise results, and short duration of follow-up. Additional investigation is needed to address the impact of longer duration of postpartum nonsteroidal anti-inflammatory drug use in older women with chronic hypertension and additional renal and cardiovascular risk factors.…”

Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review

“…Published between 2000 and 2020, the SRs included a total of 740 studies (not accounting for some overlap across SRs), with a median of 15 studies per SR (interquartile range 10–37). All 26 SRs assessed pharmacologic interventions: eight assessed NSAIDs, 38–45 two antiepileptics, 46–48 two β‐blockers, 49–51 two calcium channel blockers, 50,52 two antiemetics (5‐HT3 receptor antagonists), 53,54 two antipsychotics, 55,56 two antihistamines, 57,58 and one each assessed serotonin and norepinephrine reuptake inhibitors (SNRIs), 59,60 tricyclic antidepressants, 59,60 benzodiazepines, 61,62 corticosteroids, 63 oral magnesium, 64 triptans (5‐HT1B/1D receptor agonists), 65 analgesics/antipyretics, 66 and intravenous magnesium 67 . Twelve SRs reported maternal adverse effects and 23 reported fetal/child adverse effects.…”

“…NSAIDs, [38][39][40][41][42][43][44][45] two antiepileptics, [46][47][48] two β-blockers, [49][50][51] two calcium channel blockers, 50,52 two antiemetics (5-HT3 receptor antagonists), 53,54 two antipsychotics, 55,56 two antihistamines, 57,58 and one each assessed serotonin and norepinephrine reuptake inhibitors (SNRIs), 59,60 tricyclic antidepressants, 59,60 benzodiazepines, 61,62 corticosteroids, 63 oral magnesium, 64 triptans (5-HT1B/1D receptor agonists), 65 analgesics/antipyretics, 66 and intravenous magnesium. 67 Twelve SRs reported maternal adverse effects and 23 reported fetal/child adverse effects.…”

GRADE Use in Evidence Syntheses Published in High-Impact-Factor Gynecology and Obstetrics Journals: A Methodological Survey

“…The characteristics of these SRs are summarized in Table 2 , Table 3 and Table 4 . Furthermore, from the 8 SRs including both RCTs and NRSs, 4 SRs [ 103 , 105 , 108 , 109 ] rated the certainty of evidence derived from RCTs and NRSs separately (in separate rows within a single Summary of Findings table, or in separate Summary of Findings tables), 2 SR [ 102 , 104 ] pooled RCTs and NRSs rated the combined evidence (in the same rows within a single Summary of Findings table), 2 SRs [ 106 , 107 ] rated only evidence from NRSs.…”