Table 4

Studies of low-dose aspirin (LDA) with heparin compared with LDA alone in women with ≥3 recurrent spontaneous miscarriages before the 10th week of gestation

ReferenceDesignComparisonPercentage with explicitly ≥3 early miscarriagesInterventionControlNumber of patients, interventionNumber of patients, controlEvents, interventionEvents, controlRelative effect (95% CI)Study quality
Live births
Rai et al 199765RCTDirect100LDA+UFHLDA454532 (71.1%)19 (42.2%)RR 1.68 (1.14 to 2.49)High risk of bias*
Lima et al 199666Retrospective cohortIndirectNRLDA+heparinLDA7286 (85.7%)20 (71.4%)Intermediate quality
Muñoz-Rodriguez et al 199932Retrospective cohortIndirectNRLDA+LMWHLDA121810 (83%)14 (78%)High quality
Franklin and Kutteh 200267Retrospective cohortIndirect88LDA+LMWHLDA252619 (76%)12 (46%)High quality
Laskin et al 200968RCTIndirect75LDA+LMWHLDA454335 (77.8%)34 (79.1%)High quality
Naru et al 201069Retrospective cohortIndirectNRLDA+LMWHLDA352935 (100%)29 (100%)High quality
Cohn et al 201070Retrospective cohortIndirectNRLDA+LMWHLDA629849 (79%)61 (62%)High quality
Mohamed and Saad 201471Retrospective cohortIndirectNRLDA+LMWHLDA472343 (91%)15 (65%)Intermediate quality
Ruffatti et al 201472Retrospective cohortIndirectNRLDA+LMWHLDA1041681 (77.8%)11 (68.7%)High quality
 TotalDirect and indirect382326310215RR 1.23 (1.12 to 1.35) I2=85%
Miscarriages
Rai et al 199765RCTDirect100LDA+UFHLDA454511 (24.4%)24 (53.3%)RR 0.46 (0.26 to 0.82)High risk of bias*
Cohn et al 201070Retrospective cohortIndirectNRLDA+LMWHLDA629811 (16%)38 (37%) –High quality
 TotalDirect and indirect1071432262RR 0.46 (0.30 to 0.70) I2=0%
Pre-term delivery
Rai et al 199765RCTDirect100LDA+UFHLDA45458 (8.8%)4 (4.4%)RR 2.00 (0.65 to 6.17)High risk of bias*
Lima et al 199666Retrospective cohortIndirectNRLDA+heparinLDA7282 (28.5%)5 (18%)Intermediate quality
Franklin and Kutteh 200267Retrospective cohortIndirect88LDA+LMWHLDA25262 (10.5%)0High quality
Naru et al 201069Retrospective cohortIndirectNRLDA+UFHLDA352912 (34.3%)9 (31%)High quality
 TotalDirect and indirect1121282418RR 1.51 (0.88 to 2.59) I2=0%
Pre-eclampsia
Rai et al 199765RCTDirect100LDA+UFHLDA454501 (2.2%)RR 0.33 (0.01 to 7.97)High risk of bias*
Lima et al 199666Retrospective cohortIndirectNRLDA+heparinLDA7283 (43%)3 (11%)Intermediate quality
Naru et al 201069Retrospective cohortIndirectNRLDA+UFHLDA352910 (28.6%)6 (20.7%)High quality
Mohamed and Saad 201471Retrospective cohortIndirectNRLDA+LMWHLDA47233 (7%)9 (40%)Intermediate quality
 TotalDirect and indirect1341251619RR 0.77 (0.45 to 1.31) I2=78%
Intrauterine growth retardation
Rai et al 199765RCTDirect100LDA+UFHLDA45454 (9%)2 (5%)RR 2.00 (0.39 to 10.38)High risk of bias*
Franklin and Kutteh 200267Retrospective cohortIndirect88LMWH+LDALDA25262 (10.5%)1 (8.3%)High quality
Naru et al 201069Retrospective cohortIndirectNRLDA+UFHLDA35298 (22.8%)5 (17.2%)High quality
Mohamed and Saad 201471Retrospective cohortIndirectNRLDA+LMWHLDA47236 (12%)8 (33%)Intermediate quality
 TotalDirect and indirect1521232016RR 0.90 (0.51 to 1.60) I2=46%
Maternal thrombosis
Rai et al 199765RCTDirectLDA+UFHLDA454500RR not estimable
Naru et al 201069Retrospective cohortIndirectLDA+UFHLDA352900NA
TotalDirect and indirect807400RR not estimable
  • *Risk of bias for randomised controlled trials using the Cochrane tool.

  • LMWH, low molecular weight heparin; NR, not reported; RCT, randomised controlled trial; RR, risk ratio; UFH, unfractionated heparin.