Reference | Design | Comparison | Percentage with explicitly ≥3 early miscarriages | Intervention | Control | Number of patients, intervention | Number of patients, control | Events, intervention | Events, control | Relative effect (95% CI) | Study quality |
Live births | |||||||||||
Rai et al 199765 | RCT | Direct | 100 | LDA+UFH | LDA | 45 | 45 | 32 (71.1%) | 19 (42.2%) | RR 1.68 (1.14 to 2.49) | High risk of bias* |
Lima et al 199666 | Retrospective cohort | Indirect | NR | LDA+heparin | LDA | 7 | 28 | 6 (85.7%) | 20 (71.4%) | – | Intermediate quality |
Muñoz-Rodriguez et al 199932 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 12 | 18 | 10 (83%) | 14 (78%) | – | High quality |
Franklin and Kutteh 200267 | Retrospective cohort | Indirect | 88 | LDA+LMWH | LDA | 25 | 26 | 19 (76%) | 12 (46%) | – | High quality |
Laskin et al 200968 | RCT | Indirect | 75 | LDA+LMWH | LDA | 45 | 43 | 35 (77.8%) | 34 (79.1%) | – | High quality |
Naru et al 201069 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 35 | 29 | 35 (100%) | 29 (100%) | – | High quality |
Cohn et al 201070 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 62 | 98 | 49 (79%) | 61 (62%) | High quality | |
Mohamed and Saad 201471 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 47 | 23 | 43 (91%) | 15 (65%) | – | Intermediate quality |
Ruffatti et al 201472 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 104 | 16 | 81 (77.8%) | 11 (68.7%) | – | High quality |
Total | Direct and indirect | 382 | 326 | 310 | 215 | RR 1.23 (1.12 to 1.35) I2=85% | |||||
Miscarriages | |||||||||||
Rai et al 199765 | RCT | Direct | 100 | LDA+UFH | LDA | 45 | 45 | 11 (24.4%) | 24 (53.3%) | RR 0.46 (0.26 to 0.82) | High risk of bias* |
Cohn et al 201070 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 62 | 98 | 11 (16%) | 38 (37%) | – | High quality |
Total | Direct and indirect | 107 | 143 | 22 | 62 | RR 0.46 (0.30 to 0.70) I2=0% | |||||
Pre-term delivery | |||||||||||
Rai et al 199765 | RCT | Direct | 100 | LDA+UFH | LDA | 45 | 45 | 8 (8.8%) | 4 (4.4%) | RR 2.00 (0.65 to 6.17) | High risk of bias* |
Lima et al 199666 | Retrospective cohort | Indirect | NR | LDA+heparin | LDA | 7 | 28 | 2 (28.5%) | 5 (18%) | – | Intermediate quality |
Franklin and Kutteh 200267 | Retrospective cohort | Indirect | 88 | LDA+LMWH | LDA | 25 | 26 | 2 (10.5%) | 0 | – | High quality |
Naru et al 201069 | Retrospective cohort | Indirect | NR | LDA+UFH | LDA | 35 | 29 | 12 (34.3%) | 9 (31%) | – | High quality |
Total | Direct and indirect | 112 | 128 | 24 | 18 | RR 1.51 (0.88 to 2.59) I2=0% | |||||
Pre-eclampsia | |||||||||||
Rai et al 199765 | RCT | Direct | 100 | LDA+UFH | LDA | 45 | 45 | 0 | 1 (2.2%) | RR 0.33 (0.01 to 7.97) | High risk of bias* |
Lima et al 199666 | Retrospective cohort | Indirect | NR | LDA+heparin | LDA | 7 | 28 | 3 (43%) | 3 (11%) | – | Intermediate quality |
Naru et al 201069 | Retrospective cohort | Indirect | NR | LDA+UFH | LDA | 35 | 29 | 10 (28.6%) | 6 (20.7%) | – | High quality |
Mohamed and Saad 201471 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 47 | 23 | 3 (7%) | 9 (40%) | – | Intermediate quality |
Total | Direct and indirect | 134 | 125 | 16 | 19 | RR 0.77 (0.45 to 1.31) I2=78% | |||||
Intrauterine growth retardation | |||||||||||
Rai e t al 199765 | RCT | Direct | 100 | LDA+UFH | LDA | 45 | 45 | 4 (9%) | 2 (5%) | RR 2.00 (0.39 to 10.38) | High risk of bias* |
Franklin and Kutteh 200267 | Retrospective cohort | Indirect | 88 | LMWH+LDA | LDA | 25 | 26 | 2 (10.5%) | 1 (8.3%) | – | High quality |
Naru et al 201069 | Retrospective cohort | Indirect | NR | LDA+UFH | LDA | 35 | 29 | 8 (22.8%) | 5 (17.2%) | – | High quality |
Mohamed and Saad 201471 | Retrospective cohort | Indirect | NR | LDA+LMWH | LDA | 47 | 23 | 6 (12%) | 8 (33%) | – | Intermediate quality |
Total | Direct and indirect | 152 | 123 | 20 | 16 | RR 0.90 (0.51 to 1.60) I2=46% | |||||
Maternal thrombosis | |||||||||||
Rai e t al 199765 | RCT | Direct | LDA+UFH | LDA | 45 | 45 | 0 | 0 | RR not estimable | ||
Naru e t al 201069 | Retrospective cohort | Indirect | LDA+UFH | LDA | 35 | 29 | 0 | 0 | NA | ||
Total | Direct and indirect | 80 | 74 | 0 | 0 | RR 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.