Table 4 Impact of anti-platelet agents on stillbirth and perinatal mortality

Askie et al. 2007 [50]

USA, Zimbabwe, Italy, Brazil, Australia, Jamaica, Spain, UK, South Africa, China, Barbados, Israel, Japan, France, Belgium, Finland.

Meta-analysis (Lancet). 31 RCTs (N = 30 563 women) were included.

To assess the effectiveness and safety of anti-platelet drugs for prevention of pre-eclampsia and its consequences vs. placebo.

SBR+neonatal death before discharge (23 trials): RR = 0.91 (95% CI: 0.81–1.03) [NS]

[484/15412 vs. 524/15260 in intervention vs. control groups, respectively.]

Duley et al. 2007 [44], Duley et al. 2001 [190]

Australia, Austria, Barbados, Brazil, Finland, France, Israel, Italy, Netherlands, Russia, South Africa, UK, USA, Jamaica, Zimbabwe, China, Spain, India, Belgium.

Meta-analysis (Cochrane). 42 RCTs (N = 37,560 women) included.

To assess the effectiveness and safety of anti-platelet agents (intervention group) vs. placebo (controls) for women at risk of developing pre-eclampsia.

Fetal loss (miscarriage+SB): RR = 0.96 (95% CI: 0.78–1.18) [NS]

[169/9109 vs. 172/8960 in intervention vs. control groups, respectively.]

PMR: RR = 0.89 (95% CI: 0.74–1.08) [NS] [190/8294 vs. 212/8256 in intervention vs. control groups, respectively.]

2001 findings (30 RCTs): Fetal loss (miscarriage+SB): RR = 0.86 (95% CI: 0.75–0.98).

Intervention studies

Beaufils et al. 1991 [191]

France.

RCT. N = 323 women at 15–18 wks amenorrhea at 25 centres with prior history of FGR or placental abruption.

Compared impact of aspirin vs. placebo on birth weight, FGR, placental abruption, and stillbirth.

SBR: 1% vs. 5% in intervention vs. control groups, respectively.

Mean birth weight difference: 225 g (95% CI: 129–321 g, P = 0.029)

[mean birth weight 2751 (SD = 670) vs. 2526 (SD = 848) g in intervention vs. control groups, respectively.]

FGR: 13% (N = 20) vs. 26% (N = 19); P < 0.02).

Placental abruption: 5% vs. 8% in intervention vs. control groups, respectively.

Tempfer et al. 2006 [192]

Austria.

Prospective case-control study. N = 102 women, N = 50 intervention group, N = 52 controls, all with a history of idiopathic recurrent miscarriage, defined as ≥ 3 consecutive miscarriages < 20 wks gestation without associated anatomic, cytogenetic, hormonal, and infectious pathologies or anti-phospholipid syndrome.

To compare a combination treatment of prednisone (20 mg/d) and progesterone (20 mg/d) for the first 12 weeks of gestation, aspirin (100 mg/d) for 38 weeks of gestation, and folate (5 mg every second day) throughout their pregnancies (intervention group) with no treatment (controls).

Live birth rate: 77% (40/52) vs. 35% (18/52) in intervention vs. control groups, respectively (P = 0.04).

Observational studies

Backos et al. 1999 [193]

UK, tertiary referral clinic.

Prospective observational study. N = 150 women with history of recurrent miscarriage associated with persistently positive tests for anti-phospholipid antibodies.

Assessed impact of administration of low dose aspirin and low dose heparin.

Live births: 71% (107/150, 71%).

Miscarriage: 27%

SBR: 1%

NND: 1%

Pre-term: 24% (N = 26)

Deligiannidis et al. 2007 [66]

Greece.

Prospective study (N = 52 women, N = 29 intervention, N = 23 controls who declined intervention).

Anti-thrombotic therapy (low-dose aspirin and low molecular weight heparin) vs. controls.

Fetal death rate (miscarriage+SB): OR = 0.10 (95% CI: 0.002–0.98, Fisher exact test, 0.04)

[1/29 vs. 17/23 in intervention vs. control groups, respectively].

Leduc et al. 2007 [194]

Canada (hospital records).

Retrospective cohort study. N = 110 pregnancies (N = 50 intervention, N = 60 controls) among women (N = 43) with ≥ 1 pregnancy complicated by severe early-onset

pre-eclampsia, placental abruption, fetal growth restriction (FGR),

or fetal death.

Anti-coagulant prophylaxis was administered using dalteparin in 13 pregnancies, ASA with dalteparin in 26, and ASA alone in 11.

SB: No deaths occurred.