Heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome, a systematic review and meta-analysis

Abstract

Background: We performed a systematic review and meta-analysis to assess the efficacy and safety of heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome (APS).

Methods: We reviewed randomized controlled trials from CENTRAL, EMBASE, MEDLINE, and Web of science (inception to November 5th 2019), and relevant article reference lists. Two reviewers independently screened and extracted data from trials investigating heparin, including Low Molecular Weight Heparin (LMWH) and unfractionated heparin (UFH) at any dose, associated or not with aspirin, compared to any comparator group in pregnant women with APS. Internal validity was assessed in duplicate using the Cochrane Risk of Bias tool. The strength of evidence was assessed in duplicate using the Grading of Recommendations Assessment, Development and Evaluation framework. Our primary outcome was live birth rate. Secondary outcomes included preeclampsia, preterm birth, intra-uterine growth restriction (IUGR) and thromboembolism. Safety outcomes included maternal or neonatal bleedings, heparin-induced thrombocytopenia and allergy. Subgroup analyses were conducted to explore heterogeneity.

Results: From 2395 identified citations, 13 trials (1916 patients) met inclusion criteria. Heparin, associated or not with aspirin, significantly increased the rate of live birth compared to any comparator (RR 1.20; 95 % CI 1.09-1.33, I² = 67 %, 1916 patients, low-certainty evidence). In subgroup analyses, LMWH and UFH were independently associated with greater rates of live birth: RR 1.15 (95 % CI 1.04-1.28, I² = 71 %, 1684 patients, 9 trials) and RR 1.45 (95 % CI 1.16-1.81, I² = 19 %, 149 patients, 4 trials) respectively. Heparin associated or not to aspirin, significantly decreased the rate of preeclampsia compared to any comparator (RR 0.32; 95 % CI 0.12-0.87, I² = 0%, 465 patients, 8 trials) but was not associated with differential rates of preterm birth nor IUGR. Heparin was associated with minor bleeding (bruises, epistaxis): RR 2.58 (95 % CI 1.03-6.43, I² = 16 %, 653 patients, 9 trials). No serious maternal or neonatal adverse events were reported in the included studies.

Conclusions: In pregnant women with APS, heparin, associated or not to aspirin, significantly improved the live birth rate compared to any comparator and decreased the risk of preeclampsia, without increasing maternal and neonatal severe morbidity.

Keywords: Anticoagulation; Antiphospholipid syndrome; Heparin; Pregnancy.