Introduction
Methods
Prevention and management of problems during pregnancy |
Management of chronic and pregnancy-induced hypertension and prevention of pre-eclampsia |
• Calcium supplementation to prevent pregnancy-induced hypertension and pre-eclampsia |
• Anti-hypertensives for chronic maternal hypertension |
Anti-platelet agents |
Heparin and other anti-coagulants |
Anti-oxidants |
Management of intrahepatic cholestasis |
Maternal plasma exchange |
Cervical cerclage |
Infection control and treatment
|
Syphilis screening and treatment |
Antibiotics and antisepsis in high-risk pregnancies (BV, asymptomatic bacteriuria, and GBS colonisation) |
Antibiotics for preterm premature rupture of membranes |
Anti-helminthics during pregnancy |
Prophylactic anti-malarials |
Insecticide-treated nets during pregnancy |
Prevention of mother-to-child transmission of HIV |
Periodontal care |
Results
Prevention and management of problems in pregnancy
Calcium supplementation to prevent pregnancy-induced hypertension (PIH) and pre-eclampsia
Background
Literature-based evidence
Source | Location and Type of Trial | Intervention | Stillbirths and perinatal outcomes |
---|---|---|---|
Reviews & meta-analyses
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Argentina, USA, Australia, Ecuador, India, Egypt, Peru, South Africa, Vietnam. Meta-analysis (Cochrane) 10 RCTs included, N = 15,103 women. | To assess the effects of calcium supplementation during pregnancy vs. placebo on hypertensive disorders of pregnancy and related maternal and child outcomes. | SB or death before discharge from hospital: RR = 0.89 (95% CI: 0.73–1.09) [NS] | |
Trumbo et al. 2007 [16] | Argentina, USA, Guatemala, Austrália. Review (FDA). 7 RCTs included, N = 6542 women. | To assess the effects of calcium supplementation during pregnancy vs. placebo on hypertensive disorders of pregnancy. | PIH: 3 of 7 RCTs showed reduction in PIH with 2 g/day dose, 4 RCTs showed no impact. Pre-eclampsia: 2 of 5 RCTs showed reduction in pre-eclampsia with 1.8 or 2 g/day dose, 3 RCTs showed no impact. |
Intervention studies
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Kumar et al. 2009 [19] | India (New Delhi). Lok Nayak Hospital. RCT. N = 524 healthy primigravidas with a blood pressure of less than 140/90 mm Hg between the 12th and 25th weeks of gestation. | Compared the impact of 2 g of elemental calcium (intervention) vs. placebo (controls) from the time of enrollment to delivery. | SBR: 5/251 (2.0%) vs. 6/273 (2.2%) in intervention and control groups, respectively; P = 0.62. |
Conclusion
Anti-hypertensives for chronic maternal hypertension
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
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Abalos et al. 2007 [29] | Brazil, Caribbean Islands, Ireland, Israel, Italy, South Africa, Sweden, UK, USA, Sudan, Argentina, Australia, France, India, Venezuela. Meta-analysis (Cochrane). 43 RCTs included. | To assess the effects of anti-hypertensive drug treatments for women with mild to moderate hypertension during pregnancy on pregnancy outcomes. | SBR: RR = 1.14 (95% CI: 0.60, 2.17) [NS] PMR: RR = 0.96 (95% CI: 0.60–1.54) [NS] |
Duley et al. 2006 [21] | UK (Northern Ireland, England), South Africa, USA, Brazil, The Netherlands, Germany, Australia. Meta-analysis (Cochrane). 13 RCTs included. | To compare the impact of different anti-hypertensive drugs for very high blood pressure during pregnancy on pregnancy outcomes. | PMR: RR = 0.50 (95% CI: 0.05–4.94) [NS] in labetalol vs. hydralazine groups, respectively. PMR: RR = 1.36 (95% CI: 0.42–4.41) [NS] in calcium channel blockers vs. hydralazine groups, respectively. |
King et al. 2003 [36] | USA, Spain, France, Israel, The Netherlands, Thailand. Meta-analysis. 10 RCTs included (N = 810 participants). | To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in pre-term labour. | PMR: RR = 1.65 (95% CI: 0.74–3.64). |
Magee and Duley 2003 [35] | England, Caribbean Islands, Israel, France, Scotland, Sweden, USA, Argentina, Australia, India, Venezuela. Meta-analysis (Cochrane). 27 RCTs included. | To assess whether oral beta-blockers are better than placebo, or no beta-blocker, and have advantages over other anti-hypertensives, for women with mild to moderate pregnancy hypertension. | PMR: RR = 1.01 (95% CI: 0.46–2.22) [NS] in beta-blocker vs. placebo/no beta-blocker groups, respectively. |
Meher et al. 2007 [41] | Italy. Meta-analysis. 4 RCTs included. | Compared the impact of nitric oxide vs. placebo/no intervention in treatment of hypertension in pregnancy. | PMR + NMR: RR = 0.25 (95% CI: 0.03–2.34) [NS] [0/65 vs. 2/49 in the nitric oxide group vs. the placebo group, respectively.] |
Say et al. 1996 [37] | The Netherlands. 1 RCT included (N = 100 participants). | Assessed the effects of calcium channel blockers on fetal growth and neonatal morbidity and mortality in pregnancies where impaired fetal growth was suspected. | PMR: OR = 0.14 (95% CI: 0.00–6.82). |
Intervention studies
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Hennessy et al. 2007 [40] | Australia, Sydney, tertiary referral maternity hospital. RCT. N = 124 hypertensive women. | Compared the impact of IV hydralazine (5 mg doses) to mini-bolus diazoxide (15 mg doses) on pregnancy outcomes. | PMR: 3 vs. 1 perinatal deaths in hydralazine vs. diazoxide groups, respectively. No statistical significance data given. |
Observational studies
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Kanner et al. 1980 [189] | Israel, Tel Aviv University Medical School. Prospective cohort study. N = 13 patients with longstanding hypertension during 15 pregnancies. | Measured pregnancy outcomes after administering a combination of propranolol and hydralazine to subjects with essential hypertension in pregnancy. | SB: 1/15 in subjects given propranolol+hydralazine. No controls. |
Conclusion
Anti-platelet agents
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
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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.] |
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
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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
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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. |
Conclusion
Heparin and other anti-coagulants in high-risk pregnancies
Background
Literature-based evidence
Source | Location and Type of Trial | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
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Anti-phospholipid antibodies | |||
Empson et al. 2005 [51] | UK, USA, Italy, New Zealand, Finland. Meta-analysis (Cochrane). Aspirin: 13 RCTs (N = 849 women) included. Heparin: 8 RCTs included (Women with prior miscarriage and anti-phospholipid antibody-positive). N = 98 in trial of LMWH; N = 140 in trial of unfractionated heparin. | To assess the impact on pregnancy loss of: 1. LMWH plus aspirin (intervention) vs. aspirin alone (controls). 2. Unfractionated heparin plus aspirin (intervention) vs. aspirin (controls). 3. Aspirin (intervention) vs. placebo or standard care (control) | 1. Pregnancy loss: RR = 0.78 (95% CI: 0.39–1.57) [NS] [11/51 vs. 13/47 in intervention vs. control groups, respectively]. 2. Pregnancy loss: RR = 0.46 (95% CI: 0.29–0.71). [18/70 vs. 40/70 in intervention vs. control groups, respectively]. 3. Fetal loss (miscarriage+SB): RR = 1.05 (95% CI: 0.66–1.68) [NS] in intervention vs. control groups, respectively. |
Thrombophilias
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Di Nisio et al. 2005 [60] | Finland, France. Meta-analysis (Cochrane). 1 quasi-RCT included (N = 20 women). 2 RCTs and quasi-RCTs (N = 74 women) included. | To evaluate the efficacy and safety of anti-coagulant agents, such as aspirin compared to placebo and enoxaparin vs. aspirin, in women with a history of ≥ 2 spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias. 1. Assessed the impact of aspirin vs. no treatment on live birth rate. 2. Assessed the effects on live birth rate of subcutaneous enoxaparin (40 mg/daily) vs. aspirin (100 mg/daily) from the 8th week of amenorrhoea after positive pregnancy test. | 1. Live-birth rate: RR = 1.00 (95% CI: 0.78–1.29) [NS] in intervention (aspirin) vs. control groups (placebo), respectively. 2. Live-birth rate: RR = 10.00 (95% CI: 1.56–64.20). [10/10 vs. 1/10 in enoxaparin vs. aspirin groups, respectively]. |
Gates et al. 2002 [62] | UK, Finland. Meta-analysis (Cochrane). 3 RCTs included (N = 40 women). | To assess the effects of unfractionated heparin (intervention) vs. no treatment (controls) on the incidence of venous thromboembolic disease. | Fetal death (miscarriage + SB): RR = 1.00 (95% CI: 0.07–14.90) [NS] [1/20 vs. 1/20 in both groups]. |
Intervention studies
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Anti-phospholipid antibodies
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Bar et al. 2000 [54] | Israel. High Risk Pregnancy Clinic, tertiary hospital. Case series. Pregnant women (N = 46) with a history of recurrent abortions, intrauterine fetal death or IUGR and severe early-onset pre-eclampsia. | Compared the impact of LMWH (enoxaparin sodium, 40 mg daily) in combination with low-dose aspirin (100 mg daily) in the first trimester (intervention group 1, n = 14) vs. the second trimester (intervention group 2, n = 17) vs. low-dose aspirin alone (controls). | Abortions: 14% vs. 0% vs. 0% in intervention group 1, intervention group 2, and controls, respectively [NS] |
Glasnovic et al. 2007 [55] | Croatia. Case series with non-pregnant controls. Pregnant women (N = 62) with suspected anti-phospholipid syndrome (N = 36) vs. non-pregnant women (N = 26) with secondary anti-phospholipid syndrome and previous bad reproductive anamnesis. | Studied the impact of treatment with LMWH plus low-dose aspirin during pregnancy. | Fetal deaths: 0 in all groups. |
Goel et al. 2006 [52] | India (New Delhi). RCT. Pregnant women (N = 550) with poor obstetric history and raised anti-cardiolipin antibodies IgG. | Compared the impact of a combination of low-dose aspirin (80 mg/day) and 5000 IU of unfractionated heparin subcutaneously every 12 hrs under hospital surveillance (intervention) vs. low-dose aspirin (80 mg/day; controls) on pregnancy outcomes. | Live birth rate: 28/33 (84.8%) vs. 24/39 (61.5%) in intervention vs. control groups, respectively (P < 0.05). |
Malinowski et al. 2003 [56] | Poland (Lodz). RCT. Pregnant women (N = 148) suffering from recurrent abortion with presence of lupus anti-coagulant antibodies and/or high moderate concentration of anti-cardiolipin antibodies. | Compared the impact of low-dose aspirin + LMWH simultaneously (Group 1) vs. LMWH 20 g daily (Group 2) vs. low-dose aspirin 75 mg daily (Group 3). | Live birth (%): 92.5% vs. 81.1% vs. 89.3% in Groups 1, 2 and 3, respectively. |
Noble et al. 2005 [57] | USA. Academically based reproductive health centers. Prospective, controlled pilot study. Pregnant women (N = 50) with ≥ 3 pregnancy losses and positive anti-phospholipid antibody. | Compared the impact of LMWH plus low-dose aspirin (Group 1) vs. unfractionated heparin plus low-dose aspirin (Group 2). | Miscarriage: 4/25 (16%) vs. 5/25 (20%) in Group 1 and Group 2, respectively. P = 1.00) [NS] Live births: 21/25 (84%) vs. 20/25 (80%) in Group 1 and Group 2, respectively. (P = 1.00) [NS] |
Stephenson et al. 2004 [53] | Vancouver. Tertiary referral centre. RCT. Pregnant women (N = 28) with anti-phospholipid syndrome. | Compared the impact of LMWH (dalteparin; intervention) vs. unfractionated heparin (control) preconceptionally or early in pregnancy on live birth rate. All women also received low-dose aspirin, initiated preconceptionally. | Live birth rate: 9/13 (69%) vs. 4/13 (31%) in intervention vs. control groups, respectively. |
Thrombophilias
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Brenner, LIVE-ENOX Investigators 2005. [195] | Israel. Multicentre. RCT. Pregnant women (N = 180) with thrombophilia and a history of recurrent pregnancy loss. | Compared the impact of enoxaparin 80 mg/day (40 mg 2× daily; intervention) vs. enoxaparin 40 mg/day (40 mg 1× daily; controls). | Live birth rate: 65/83 (78.3%) vs. 70/83 (84.3%) vs. in the intervention vs. comparison groups, respectively. |
Dendrinos et al. 2007 [65] | Greece (Athens). RCT. Women (N = 62) with a history of recurrent pregnancy loss and at least one factor of thrombophilic disorder. | Compared the impact of 50 IU/kg of tinzaparin sodium daily (intervention) vs. 100 mg of aspirin daily (controls). | New abortions: 6/31 vs. 11/31 in intervention vs. control groups, respectively; (P = 0.04). |
Sarig et al. 2005 [196] | Israel. Non-matched case-control study. Pregnant women (N = 87; N = 47 intervention, N = 40 controls with normal pregnancies) with thrombophilia and recurrent pregnancy loss. | Compared the impact of LMWH (enoxaparin) 40 mg daily (intervention group 1) vs. 40 mg 2× daily (intervention group 2) vs. no treatment (controls). | Live birth: 38/48 (79%) vs. 32/39 (82%) in groups 1 and 2, respectively [NS] |
Unexplained prior losses
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Dolitzky et al. 2006 [70] | Israel. University hospitals, general hospital, and community health clinic. Multi-centre randomised comparative cohort. Pregnant women (N = 107) with ≥ 3 consecutive 1st trimester miscarriages or ≥ 2 consecutive 2nd trimester miscarriages | Compared the impact of LMWH enoxaparin (intervention) vs. aspirin (controls) on the live birth rate. | Live birth rate: RR = 0.92 (95% CI: 0.58–1.46) [NS] [44/54 (81.5%) vs. 42/50 (84%) in intervention vs. control groups, respectively]. Live birth rate in primary aborters: [17/18 (94%) vs. 18/22 (81%) in intervention vs. control groups, respectively]. |
Cardiac indications
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Lee et al. 2007 [68] | Korea (Daegu). Retrospective study. Pregnant women (N = 25) with mechanical heart valve replacement between 1997 and 2005. | Compared the impact of LMWH nadroparin (7,500 U 2× daily) 6–12 wks of gestation and close-to-term only, and coumarin derivatives were used with aspirin at other times (exposed) vs. coumarin derivatives throughout pregnancy (unexposed). | Fetal death (miscarriage + SB): 2/23 (8.7%) vs. 4/8 (50%) in the exposed and unexposed groups, respectively (P = 0.011). |
Source | Location and Type of Trial | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Observational studies
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Antiphospholipid antibodies | |||
Carp et al. 2003 [58] | Israel. Cohort study. Pregnant women (N = 85) with ≥ 3 consecutive pregnancy losses and a hereditary thrombophilia who conceived (N = 85 delivered; N = 38 miscarried). | Compared the impact of enoxaparin 40 mg (intervention) vs. no treatment (controls) on pregnancy outcomes. | Live births: OR = 3.03 (95% CI: 1.12–8.36); P < 0.02. [26/37 (70.2%) vs. 21/48 (43.8%) in intervention vs. control groups, respectively]. (Among primary aborters) Live birth rate: OR = 9.75 (95% CI: 1.59–52.48; P < 0.008). (Among primary aborters ≥ 5 miscarriages) Live birth rate: 61.6% vs. 18.2% in intervention vs. control groups, respectively [NS]. |
Franklin and Kutteh 2002 [197] | USA. 2 centres. Prospective cohort study. Pregnant women (N = 79) with ≥ 2 consecutive pregnancy losses and anti-phospholipid antibodies (2 intervention groups: group 1 had recurrent pregnancy loss + anti-phospolipid antibodies; group 2 had other positive anti-phospholipid antibodies). | Compared the impact of heparin and aspirin (intervention) vs. aspirin alone (group 3; controls). Intervention group 1 was treated with heparin and aspirin; intervention group 2 was treated with heparin or aspirin; group 3 received aspirin alone. | Viable infants: 19/25 (76%) vs. 18/28 (64%) vs. 12/26 (46%) in groups 1, 2 and 3, respectively (P = 0.03 for group 1 vs. group 3). |
Ruffatti et al. 1997 [59] | Italy (Padova). Prospective cohort study. Pregnant women (N = 53) with ≥ 2 consecutive miscarriages during first trimester and/or 1 fetal death during last two trimesters. | Compared the pregnancy success rate with calcium heparin alone, self-administered subcutaneously 3× daily at dosages 15,000–37,500 IU vs. rate prior to therapy. | Live birth: 100% vs. 24.52% in the calcium heparin vs. prior to therapy (P < 0.0001). Malformations: 0/53 30/37 examined placentas (81.08%) showed signs of thrombotic events. |
Thrombophilias
| |||
Deligiannidis et al. 2007 [66] | Greece. Cohort study. Pregnant women (N = 52) with thrombophilia. | Compared the impact of LMWH plus low-dose aspirin (intervention) vs. no treatment (controls). | Fetal death (miscarriage+SB): OR = 0.10 (95% CI: 0.002–0.98). [1/29 vs. 17/23 in intervention vs. control groups, respectively]. |
Folkeringa et al. 2007 [63] | Netherlands. Prospective, family cohort study. Pregnant women (N = 376) with (N = 37) and without (N = 18) hereditary deficiencies of antithrombin protein C or protein S. | Compared the impact of thromboprophylaxis with unfractionated or LMWH < 16 wks and > 36 wks of gestation, and a vitamin K antagonist from 16–36 wks and after delivery (intervention #1) vs. no treatment (controls). Additionally compared same treatment in women deficient for antithrombin protein C or protein S (intervention #2) vs. no treatment in non-deficient women (controls). | Fetal death (miscarriage + SB): adj. RR = 0.07 (95% CI: 0.001–0.7, P = 0.02) in intervention #1 group vs. controls, respectively. Fetal death (miscarriage+SB): 0% in deficient women with thromboprophylaxis versus 45% in deficient women without (P = 0.001) and 7% in non-deficient women without thromboprophylaxis (P = 0.37). |
Cardiac indications
| |||
Kawamata et al. 2007 [69] | Japan. Retrospective study. Women (N = 12; N = 16 pregnancies) with mechanical heart valve replacement. | Assessed the impact of changing warfarin treatment to heparin at 6–13 wks of gestational age; administration continuously adjusted according to the activated partial thromboplastin time level up to the time of delivery. | Fetal death (miscarriage + SB): 1/16 (at 30 wks). |
Kim et al. 2007 [67] | South Korea (Seoul). Retrospective study. Women (N = 27; N = 41 pregnancies) with a mechanical valve replacement. | Compared the impact among three groups: group 1 (N = 5) took warfarin throughout the pregnancy, group 2 (N = 18) took heparin throughout the pregnancy, and group 3 (N = 18) took heparin in the 1st trimester and warfarin from 12–20 wks gestation. | SBR: 2/5 (40%) vs. 1/18 (5.6%) vs. 8/18 (44.4%) in groups 1, 2, and 3, respectively. |
Safety
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Sorensen et al. 2000 [71] | Denmark. Population-based. Retrospective cohort study using national databases. Pregnant women receiving LMWH (N = 66) or no drugs (N = 17,259) between 1991–98. | Compared the impact of LMWH (exposed) vs. no prescriptive drugs (unexposed). | SBR: 0/66 (0%) vs. 204/17,259 (1.2%) in the exposed vs. unexposed groups, respectively. Pre-term: OR = 2.11 (95% CI: 0.96–4.65) [NS] LBW and malformations: no increased risk. |
New meta-analyses
Conclusion
Anti-oxidant treatment to prevent or treat pre-eclampsia
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Rumbold et al. 2008 [77] | UK, Australia, South Africa. Meta-analysis (Cochrane). 4 RCTs included. | Compared impact of supplementation with any anti-oxidants vs. control/placebo. | Fetal death rate (miscarriage+SB): RR = 1.32 (95% CI: 0.92–1.90) [NS] [66/2569 vs. 50/2575 in intervention vs. control groups, respectively.] |
Rumbold et al. 2005 [78] | UK, South Africa Meta-analysis (Cochrane). 3 RCTs included | Compared impact of supplementation with Vitamin C vs. control/placebo. | SBR: RR = 0.87 (95% CI: 0.41–1.87) [NS] [9/268 vs. 11/271 in intervention vs. control groups, respectively.] |
Rumbold et al. 2005 [79] | UK, South Africa Meta-analysis (Cochrane). 2 RCTs included. | Compared impact of supplementation with Vitamin E vs. control/placebo. | SBR: RR = 0.77 (95% CI: 0.35–1.71) [8/168 vs. 11/171 in intervention vs. control groups, respectively.] |
Intervention studies
| |||
Roberts et al. 2008 [80] | USA. RCT. N = 9969 low-risk nulliparous women 9–16 weeks gestation at enrolment. | Compared impact of supplementation with Vitamin C (1000 mg/day) plus Vitamin E (400 IU/day) vs. placebo. | Severe hypertension or pregnancy-related hypertension with at least one of the following: SGA, hepatic or renal dysfunction, eclampsia, stillbirth, or neonatal death before discharge: 6.1% vs. 5.8% in antioxidant vs. placebo groups, respectively/ Pre-eclampsia (7.2% vs. 6.7% in antioxidant vs. placebo groups, respectively). |
Conclusion
Management of intrahepatic cholestasis in pregnancy
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Intervention studies
| |||
Binder et al. 2006 [82] | Czech Republic. RCT. Singleton pregnancies (N = 78) < 36 wks with a moderate or severe form of cholestasis recruited 1999–2004. | Compared the impact among three groups [SAMe (S-adenosyl-L-methionine) monotherapy (group 1), UDCA (ursodeoxycholic acid) (group 2), and combined therapy (group 3)] on PMR. | PMR: 0/25 vs. 0/26 vs. 0/27 in groups 1, 2 and 3, respectively [NS] |
Glantz et al. 2005 [83] | Sweden. Double-blind, placebo-controlled RCT. Pregnant women (N = 130; N = 47 UDCA, N = 36 dexamethasone, N = 47 placebo) with cholestasis. | Compared the impact on perinatal outcomes of treatment of cholestasis with UDCA (intervention #1), or dexamethasone (intervention #2), vs. placebo (controls). | Fetal death (miscarriage + SB): 0/47 vs. 0/36 vs. 1/47 in intervention group #1, intervention group #2, and controls, respectively. |
Palma et al. 1997 [84] | Chile. Secondary case-referral center. RCT. Pregnant women (N = 15) with early-onset obstetric cholestasis. | Compared the impact on perinatal outcomes of treatment with UDCA (intervention) vs. placebo (controls). | SBR: 0/8 vs. 1/7 in intervention vs. control groups, respectively. |
Roncaglia et al. 2002 [85] | Italy (Milan). University hospital. Intervention trial using prospective cases. Pregnant women (N = 218) with obstetric cholestasis and historical series data. | Compared the effect of a management protocol for cholestasis incorporating transcervical amnioscopy, standard monitoring of fetal well-being with 2× weekly non-stress testing and AFI indices, and induction of labour at 37 weeks if high-risk (intervention) vs. historical controls on obstetric outcome. | SBR: 0/218 vs. 14/888 in intervention vs. control groups, respectively (P = 0.045). |
Conclusion
Maternal plasma exchange
Background
Literature-based evidence
Conclusion
Cervical cerclage
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Drakeley et al. 2003 [92] | Netherlands, France, UK, South Africa. Meta-analysis (Cochrane). 6 RCTs included (N = 2059 women). | Assessed the effects of cervical cerclage (intervention) vs. no cerclage (controls). | PMR: RR = 0.80 (95% CI: 0.48–1.36) [NS] [24/1035 vs. 31/1024 in intervention vs. control groups, respectively. |
Jorgensen et al. 2007 [100] | Netherlands, USA, Nigeria, UK, France, Hungary, Norway, Italy, Belgium, Zimbabwe, South Africa, Iceland, Ireland, Canada, Brazil Slovenia, Greece and Chile. Meta-analysis. 7 RCTs included (N = 2091 women). | Assessed the effects of cervical cerclage (intervention) vs. no cerclage (controls). | (Singleton gestations) Pregnancy loss or death before hospital discharge: OR = 0.81 (95% CI: 0.60–1.10) [NS] (Multiple gestations) Pregnancy loss or death before hospital discharge: OR = 5.88 (95% CI: 1.14–30.19). |
Intervention studies
| |||
Blair et al. 2002 [101] | West Indies. RCT. Pregnant women (N = 50) with cervical incompetence. | Compared the impact of cervical cerclage between inpatient care for 3 days post-procedure, spending 3 days in hospital post-procedure (intervention) vs. outpatient bed rest (controls). Both groups given salbutamol tablets postoperatively for tocolysis. | Live birth rate: 20/23 vs. 18/23 (86.9% vs. 78.3%) in intervention vs. control groups, respectively [NS] |
Jaswal et al. 2006 [198] | India. Quasi-RCT. Pregnant women (N = 37) being expectantly managed for placenta previa. | Compared the impact of cervical cerclage (intervention) versus no cerclage (controls). | PMR: 0/18 vs. 8/19 in intervention vs. control groups, respectively (P < 0.01). |
Observational studies
| |||
Debbs et al. 2007 [104] | USA. Retrospective case series. Pregnant women (N = 75) with negative evaluation for recurrent pregnancy loss and ≥ 1 previous unsuccessful transvaginal cerclage. | Assessed the impact of transabdominal cerclage on birth outcomes. | Live birth rate: 96% after transabdominal cerclage. |
Fick et al. 2007 [102] | USA. A cohort study. Pregnant women (N = 88 women; N = 9 pregnancies) with transabdominal cerclage. | Compared the live birth rate before and after transabdominal cerclage. | Live birth rate: 93% vs. 18% after vs. cerclage, respectively; P < 0.001). |
Gesson-Paute et al. 2007 [103] | France. Retrospective study. Transabdominal cerclages (N = 12) performed from 1988–2005. | Compared the live birth rate during the period where transabdominal cerclage was performed vs. the pre-cerclage period. | Live birth rate: 93% vs. 17% after vs. before cerclage, respectively. |
Conclusion
Infection control and treatment
Anti-helminthics during pregnancy in hookworm-endemic regions
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirth/Perinatal mortality outcomes |
---|---|---|---|
Intervention study
| |||
Gyorkos et al. 2006 [113] | Peru (Amazon region). RCT. Data on adverse birth outcomes (N = 1042 births). | To compare of the impact of antenatal mebendazole (500 mg single dose; intervention) plus iron supplement vs. placebo plus iron supplement (controls) on the occurrence of adverse birth outcomes. | SBR: 8 vs. 4 in intervention vs. control groups, respectively. [NS] ENND: 3 vs. 6 in intervention vs. control groups, respectively. [NS] PMR: 22/1000 vs. 20.2/1000 in intervention and control groups, respectively (P = 0.840). [NS] Pre-term: 28 vs. 31 respectively (P = 0.664). [NS] |
Christian et al. 2004 [117] | Nepal (Sarlahi). RCT. | Compared the impact of two doses of albendazole in pregnancy (intervention) vs. no treatment (controls) on birth outcomes. | NMR: OR = 0.54 (95% CI: 0.37–0.78) [unpublished data] |
Observational Study
| |||
De Silva et al. 1999 [116] | Sri Lanka, hospital based. Cross-sectional survey. | Compared impact on major congenital defects, stillbirth, perinatal death, and LBW among babies of mothers who had taken mebendazole during pregnancy (intervention) with those whose mothers had not taken an anti-helmintic (controls). | PMR: OR = 0.55 (95% CI: 0.4–0.77) [19/1000 vs 33/1000 in intervention vs. control groups, respectively]. LBW: OR = 0.47 (95% CI: 0.32–0.71) [1.1 vs 2.3% in intervention vs. control groups, respectively]. Major congenital malformations: OR = 1.24 (95% CI: 0.8–1.91, P = 0.39) [NS] [97/5275 vs 26/1737 in intervention vs. control groups, respectively]. |
Conclusion
Syphilis screening and treatment
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Walker et al. 2001 [124] | None. Meta-analysis (Cochrane). 29 RCTs and quasi-RCTs reviewed, 0 studies included. | Assessed the impact of antibiotic treatment for syphilis during pregnancy. | No data, 0 eligible studies. |
Intervention studies
| |||
Bique et al. 2000 [130] | Mozambique, ANC clinics. Case-control study. 4 suburban ANC clinics (2 intervention clinics, 2 control clinics). Pregnant women (N = 929; N = 453 intervention, N = 476 controls) with positive RPR. | Compared the impact of an intervention offering RPR testing with immediate on-site treatment of seropositive cases with 2.4 million IU benzathine penicillin by specially trained nurse-midwives. The study offered to treat partners of intervention group as well. Controls were offered routine syphilis screening protocol requiring testing at a separate lab, return visits, and payment for treatment (< 50% compliance), with no partner treatment option. | PMR: 13/1000 vs 34/1000 in intervention vs. control groups, respectively (P = 0.03). Fetal death (miscarriage+SB): 13/1000 vs. 26/1000 (P = 0.159) [NS] |
Donders et al. 1997 [128] | South Africa (Pretoria), hospital-based. Prospective cohort study. HIV-, RPR+ black urban pregnant women (N = 212; N = 135 received ≥ 1 injection) | Assessed dosage impact of 0–3 weekly IM injections of benzathine penicillin G on perinatal outcomes. | PMR secondary to congenital syphilis: RR = 20.5 (95% CI: 2.3–184, P = 0.0015). [0 injections: 7/55 (13%) 1 injection: 2/19 (11%) 2 injections: 1/24 (4.2%) 3 injections: 2/82 (2.4%)] Adjusted when Treponemicidal coverage was < 3 wks |
Myer et al. 2003 [123] | South Africa (Hlabisa district, rural KwaZulu Natal), PHC clinics. Cluster RCT. 7 pairs of clinics. Pregnant women (N = 549). | Compared the impact of on-site syphilis testing complemented by laboratory confirmation vs. laboratory testing alone. | PMR: adj. RD: -0.9%; 95% CI: (-) 4.4-2.7, P = 0.31) [NS] [33/1000 (18/549) vs. 51/1000 (8/157) in intervention clinics vs. control clinics, respectively.] |
Rotchford et al. 2000 [129] | South Africa (Hlabisa district, rural KwaZulu Natal), ANC clinics. Cluster RCT. 12 clinics. Pregnant women (N = 1783) screened for syphilis (N = 158 RPR+; 9% prevalence) at first ANC visit (mean: 24 wks); RPR+ women followed for pregnancy outcome (data available for N = 142 (90%); N = 30 had no treatment; N = 96 had all 3 doses penicillin) | Assessed impact on PMR of inadequate maternal syphilis treatment in presence of adequate screening. | PMR: 15/142 [0 or 1 dose penicillin: 11/43 (260/1000) ≥ 2 doses penicillin: 4/99 (40/1000)] Dose-response relationship observed. (P = 0.0001) PMR risk reduction: 1 dose: 41% reduction 2 doses: 65% reduction 3 doses: 79% reduction |
Watson Jones et al. 2002 [127] | Tanzania (Mwanza), ANC clinic. Case-control study. Pregnant women (N = 1688; N = 133 high-titre [RPR titre ≥ 1:8, TPHA/FTA+]; N = 249 low-titre [RPR titre < 1:8, TPHA/FTA+], N = 950 seronegative controls). | To examine the effectiveness of treatment for maternal syphilis with single-dose IM benzathine penicillin (2.4 million units). | Birth outcomes were compared SBR: 23/1000 vs. 25/1000 in treated high-titer women vs. seronegative women. LBW: 6.3% vs. 9.2% in treated high-titer women vs. seronegative women. Adverse pregnancy outcome (combined SBR+LBW): OR = 0.76 (95% CI: 0.4–1.4) [NS]. |
Observational studies
| |||
Delport et al. 1993 [199] | South Africa (Pretoria), ANC clinic. Descriptive study. Kalafong Hospital. Pregnant women (N = 1237) attending ANC. | Assessed the sensitivity, specificity, negative and positive predictive values of the RPR test at ANC compared with gold-standard laboratory Treponema pallidum haemagglutination test. | RPR test: Sensitivity: 92.8% Specificity: 96.3% Negative predictive value: 99.5% Positive predictive value: 64.7%. |
Guinness et al. 1988 [125] | Swaziland (Mbabane), Public health unit Prospective cohort study. Pregnant women (N = 283) tested at ANC enrollment: N = 37 (13.1%) TPHA+ and RPR+; N = 87 (30.7%) TPHA+ and RPR-. | Assessed the impact of antenatal screening on perinatal mortality attributable to syphilis. Mothers were tested prenatally and again at delivery; prenatal test found to have sensitivity = 36% and predictive accuracy = 48%. | PMR (untreated active syphilis): 219/1000 (7/32). 12/172 seronegative women had active syphilis (late seroconversion or false negative prenatal test results): 4/12 experienced perinatal death. PMR: 46/1000 (4/87) vs. 28/1000 (4/415) in TPHA+/RPR- vs. syphilis-seronegative women. Screening reduced expected syphilis-attributable PMR from 3.5% to 2.3% (65% of mothers with active syphilis missed treatment; sexual partners were not treated). |
Temmerman et al. 2000 [126] | Kenya (Nairobi), maternity hospital. Prospective case control study. Women (N = 12414) delivering at Pumwani Hospital were RPR tested (3%, N = 377 were RPR-positive). TPHA testing confirmed syphilis infection (N = 296). Equal numbers of seronegative women also enrolled; records examined for syphilis testing and treatment during pregnancy. | Assessed the impact of an antenatal syphilis control programme on pregnancy outcome. | Adverse obstetric outcome (LBW or SB): OR = 4.1 (95% CI: 2.3–7.5, P < 0.001). [22.5% vs. 6.6% in untreated syphilis-positive vs. uninfected mothers, respectively.] LBW: OR = 4.0 (P < 0.0001) in untreated syphilis-seropositive mothers vs. uninfected mothers, respectively. SBR: OR = 3.3 (P = 0.028) in untreated syphilis-seropositive mothers vs. uninfected mothers, respectively. OR = 2.5 in treated syphilis-seropositive mothers vs. uninfected mothers, respectively (P < 0.05). |
Conclusion
Antibiotics and antisepsis for urinary and reproductive tract infections (bacterial vaginosis, asymptomatic bacteriuria, and Group B streptococcus)
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
King and Flenady 2002 [140] | Chile, Denmark, USA, South Africa, UK. Meta-analysis (Cochrane). 9 RCTs included. | Assessed the impact of any antibiotic (intervention) vs. no antibiotic (controls) in women in pre-term labour with intact membranes. | PMR: RR = 1.22 (95% CI: 0.88–1.70) [NS] |
Lumbiganon et al. 2004 [142] | USA. Meta-analysis (Cochrane). 2 RCTs included. | Assessed the impact of chlorhexidine vaginal wash (intervention) vs. placebo (controls) in preventing maternal and neonatal infections including chorioamnionitis and sepsis. | PMR: RR = 1.00 (0.17–5.79) [NS] |
Thinkhamrop et al. 2002 [146] | Kenya, Belgium, USA, The Netherlands. Meta-analysis (Cochrane). 3 RCTs included. | Assessed the impact of prophylactic antibiotic administration in the second and third trimester (intervention) vs. no antibiotic (controls), particularly in reference to women with prior pre-term birth and women with BV. | PMR: OR = 0.5 (95% CI: 0.16–1.71) [NS] PROM: OR = 0.32 (95% CI: 0.14–0.73) LBW: OR = 0.48 (95% CI: 0.27–0.84) in women with a previous pre-term birth Pre-term: OR = 1.06 (95% CI: 0.68–1.64) [NS] Pre-term: OR = 0.48 (95% CI: 0.28–0.81) in women with confirmed BV. |
Goldenberg et al. 2006 [143] | Malawi, Egypt. Review. 2 non-randomised, non-blinded trials included. N = 11,380 women. | Assessed the impact of chlorhexidine vaginal wash (intervention) vs. placebo (controls) in preventing maternal and neonatal infections and neonatal death. | No pooled estimates given. ENND [Malawi]: RR = 0.78 [29/1000 vs 37/1000 in intervention vs. control groups, respectively], RR = 0.78) NM due to infections [Malawi]: OR = 0.5 (95% CI: 0.29–0.88, P < 0.005) [2.4 vs. 7.3 per 1000 in intervention vs. control groups, respectively]. Infant death [Egypt]: 2.8 vs. 4.2% in intervention vs. control groups, respectively (P = 0.01) Infant death due to infection: 0.22% vs. 0.84% in intervention vs. control groups, respectively (P = 0.004) |
McDonald et al. 2007 [141] | Australia, UK, USA, South Africa. Meta-analysis (Cochrane). 5 RCTs included. | Assessed the impact of oral antibiotics (intervention) vs. placebo/no treatment (controls). | PMR: OR = 0.94 (95% CI: 0.52–1.70) [NS] |
Observational studies
| |||
Watson-Jones et al. 2007 [187] . | Tanzania (Mwanza). Prospective cohort study. Women (N = 1688) attending ANC. | As part of a study of the effectiveness of syphilis screening and treatment, assessed the impact of screening and treatment for reproductive tract infections (RTIs) during pregnancy on SB, IUGR, LBW, and pre-term birth. | SBR: 27/1000. No statistical significance data. Pre-term: 12% LBW: 8% SB risk factors: past history of stillbirth, short maternal stature and anaemia. No association between treated RTIs and adverse pregnancy outcomes. |
Tita et al. 2007 [200] | USA (Alabama). RCT, subgroup analysis. Center for Women's Reproductive Health, University of Alabama at Birmingham. N = 241 nonpregnant women with reproductive tract infections; N = 124 conceived with birth outcome data (N = 59 intervention; N = 65 controls). | Compared impact of 2 doses of azithromycin 1.0 g given 4 days apart plus sustained-release metronidazole 750 mg daily for 7 days (intervention) vs. placebo (controls). Treatment was repeated 3x/yr until conception or until study termination. Reevaluation after randomisation with cultures and histopathology. Followed up 5 years. | Adverse pregnancy outcome (pre-term birth or fetal death): 66.1% (39/59) vs. 61.5% (40/65) [NS] in intervention vs. control groups, respectively. RR = 1.25 (99% CI: 0.42–3.7) [NS] in women colonised with any microbe at baseline vs. women without any colonisation. [62.7% vs 50%, respectively]. RR = 0.87 (0.50–1.5) [NS] in women with plasma cell endometritis vs. women without. [61.9% vs. 70.8%, respectively]. RR = 0.60 (95% CI = 0.3–1.2) [NS] in women without Gardnerella vaginalis colonisation vs. women with colonisation RR = 0.66 (95% CI = 0.4–1.2) [NS] in women without Gram-negative rod colonisation vs women with colonisation. RR = 1.5 (95% CI: 1.1–2.0) in intervention vs. control groups, respectively, in the presence of Gardnerella vaginalis (crossover interaction). RR = 1.5 (95% CI: 1.1–2.1) in intervention vs. control groups, respectively, in the presence of Gram-negative rod colonisation (crossover interaction). |
Conclusion
Antibiotics for pre-term premature rupture of membranes (PPROM) and premature rupture of membranes (PROM) in high-risk pregnancies
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Flenady and King 2002 [151] . | Spain. Meta-analysis (Cochrane). 2 RCTs included (N = 838 women). | Compared the impact of any antibiotic (intervention) vs. no antibiotic (controls) in cases of PROM ≥ 36 wks' gestation. | PMR: RR = 0.98 (95% CI: 0.14 – 6.89) [NS] [2/426 vs. 2/412 in intervention vs. control groups, respectively]. |
Kenyon et al. 2003 [150] | Mozambique, Norway, Sweden, USA, Spain, UK, Finland, Chile, Denmark. Meta-analysis (Cochrane). 19 RCTs included (N = 6411). | Compared the impact of any antibiotic (intervention) vs. placebo (controls) in cases of PPROM. | PMR/death before hospital discharge: RR = 0.90 (95% CI: 0.74–1.10) [NS] [data from 13 RCTs]. [281/4374 vs. 148/2037 in intervention vs. control groups, respectively]. |
Intervention studies
| |||
Kenyon et al. 2002 [201] | UK and other international sites. Multicentre. RCT. Pregnant women (N = 4826) with PPROM. | Assessed the effects of co-amoxiclav and erythromycin singly and in combination: 325 mg co-amoxiclav plus 250 mg erythromycin (group 1), co-amoxiclav plus erythromycin placebo (group 2), erythromycin plus co-amoxiclav placebo (group 3), or co-amoxiclav placebo plus erythromycin placebo (group 4). Antibiotics given 4× daily for 10 d or until delivery. | NMR: 5.2% vs. 5.7% vs. 6.2% in erythromycin (group 3), co-amoxiclav (group 2) and placebo (group 4), respectively. Major neonatal cerebral abnormality lower with erythromycin vs. placebo or co-amoxiclav. |
Conclusion
Anti-malarials in malaria-endemic areas
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Garner et al. 2006 [155] | Burkina Faso, Cameroon, Gambia, Nigeria, Uganda, Thailand, Kenya. Meta-analysis (Cochrane). 9 RCTs included. | Assessed 1) the impact of treating malaria with any anti-malarial drug (intervention #1) vs. no drug (control #1), and 2) preventing malaria with any anti-malarial drug (intervention #2) vs. no drug (control #2). | PMR (treatment): RR = 1.02 (95% CI: 0.73–1.43) [NS] in intervention group #1 vs. control group #1, respectively. PMR (prevention): RR = 0.73 (95% CI: 0.53–0.99) in intervention group #2 vs. control group #2, respectively. |
Intervention studies
| |||
Hamer et al. 2007 [156] | Zambia (Ndola), urban setting. Cluster RCT. N = 456 HIV-positive mothers (N = 224 intervention group, N = 232 controls). | Compared 2 dosing schedules for malaria prevention: 1 treatment course of SP per month (intervention) vs. 1 course of SP per trimester (controls). | SBR: RR = 0.43 (95% CI: 0.1–2.2) [NS] [2/191 vs. 5/203 in intervention vs. control groups, respectively.] |
Observational studies
| |||
Verhoeff et al. 1999 [202] | Malawi (Chikwawa district), rural setting. Prospective cohort study. N = 1523 women. | Assessed the impact of antenatal screening and treatment for malaria and anaemia. | SBR: 3.7% ENND (< 48 h postpartum): 1.7% |
Conclusion
Use of insecticide-treated nets (ITNs) during pregnancy
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Kenya. Meta-analysis (Cochrane). 5 RCTs included. | To compare the impact of ITNs (permethrin 500 g/m2 except in one trial that used cyfluthrin; intervention) vs. untreated nets or no nets (control) in preventing malaria in pregnancy. All African trials gave double- or family-sized nets to each household, vs. single-sized nets in Thailand. | Fetal death (3 RCTs): RR = 0.68 (95% CI: 0.48–0.98, P = 0.04) in all gravidae RR = 0.67 (95% CI: 0.47–0.97, P = 0.03) in low gravidae (1–2 pregnancies) RR = 1.02 (95% CI: 0.17–6.23, P = 0.98) [NS] in high gravidae (> 4 pregnancies) Birth weight: Mean increase: 50 g (95% CI: 20–90 g) in women with 1–2 prior pregnancies. LBW (1 RCT): RR = 0.77, 95% CI: 0.61–0.98) in women with 1–2 prior pregnancies Placental malaria: RR = 0.79, 95% CI: 0.63–0.98). Fetal death (with untreated nets as control group, 1 RCT): RR = 0.21 (95% CI: 0.05–0.92) in all gravidae [2/102 vs. 10/97 in intervention vs. control groups, respectively.] |
Conclusion
Prevention of mother-to-child transmission of HIV
Background
Literature-based evidence
Source | Location and Type of Trial | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses | |||
Suksomboon et al. 2007 [167] | USA, France, Côte d'Ivoire, Burkina Faso, Thailand, Bahamas, Brazil. Meta-analysis (Cochrane). 15 trials, 5 reporting SBR. | Assessed a variety of regimens and dosing schedules for PMTCT for efficacy in preventing vertical transmission, infant death, and adverse pregnancy outcomes. |
Zidovudine vs. placebo:
Vertical transmission: Pooled RR = 0.57 (95% CI: 0.45–0.71) LBW: Pooled RR = 0.75 (95% CI: 0.57–0.99, P = 0.039) SBR: [NS] Pre-term: [NS] 2-dose maternal+infant nevirapine therapy vs. nevirapine placebo (both given zidovudine)[1 RCT]: Infant death: RR = 0.20 (95% CI: 0.05–0.90) SBR: RR = 1.11 (95% CI: 0.48–2.56) [NS] [10/826 vs.9/835 in intervention vs. control groups, respectively (pooled)]. |
Volmink et al. 2007 [166] | Thailand, Côte d'Ivoire, Burkina Faso, Uganda, Kenya, USA, France, Brazil, Bahamas, Tanzania, Zimbabwe. Meta-analysis (Cochrane). 13 RCTs included that reported stillbirth rates. | Assessed the impact of zidovudine alone (intervention #1), nevirapine alone (intervention #2), and combination zidovudine-nevirapine therapy (intervention #3) vs. placebo (controls) on MTCT. Subgroups also analyzed according to breastfeeding. | Pooled analysis not given for SBR.
ARV vs. placebo:
Vertical transmission: RR = 0.46 (95% CI: 0.35–0.60) SBR: RR = 0.14 (95% CI: 0.02–1.17); RR = 0.33 (95% CI: 0.01–8.11); RR = 0.40 (95% CI: 0.07–2.15); RR = 0.80 (95% CI: 0.20–3.18); RR = 3.02 (95% CI: 0.12–73.57); RR = 3.50 (95% CI: 0.74–16.55) for the 6 trials, respectively.
Long vs. short-course zidovudine:
SBR: RR = 0.25, 95% CI: 0.05–1.17; RR = 0.33, 95% CI: 0.11–1.01; RR = 0.55, 95% CI: 0.23–1.33, for the 3 trials, respectively |
Wiysonge et al. 2005 [173] | Tanzania, Zimbabwe, South Africa, and Malawi. Meta-analysis (Cochrane). 4 RCTs included (N = 2855 participants). | Assessed the impact of vitamin A supplementation (intervention) vs. placebo (controls) on MTCT. | SBR: OR = 0.99 (95% CI: 0.67–1.46) [NS] |
Intervention studies
| |||
Bussmann et al. 2007 [169] | Botswana. RCT. | Assessed the impact of 6 HAART regimens, 3 of which contained efavirenz (intervention), vs. non-efavirenz regimens (controls). | SBR: No difference between efavirenz and non-efavirenz-exposed pregnancies (P = 0.7). |
Sharma et al. 2007 [172] | USA (New York). Prospective cohort study (before-after design). Women's Interagency HIV study, data collected pre-HAART (1994–95) and during HAART (2001–02). | Assessed the impact of HAART on live birth rates among HIV-positive women (intervention) compared to HIV-negative women (comparison). | Live birth rate: 150% vs. 5% higher in intervention vs. comparison groups after introduction of HAART (P = 0.001). |
Sperling et al. 1996 [204] | USA. RCT. Mother-infant pairs (N = 402). | Compared the impact of maternal zidovudine treatment (intervention) vs. placebo (controls). | Rate of HIV-1 transmission: 7.6% (95% CI: 4.3–12.3%) vs. 22.6% (95% CI: 17.0–29.0%) in intervention vs. control groups, respectively (P < 0.001). Transmission occurred at a wide range of maternal plasma HIV-1 RNA levels. No SBR reported. |
Stiehm et al. 1999 [205] | USA, Puerto Rico. RCT. Women (N = 501) at 53 centers. | Assessed the impact of HIV immunoglobulin 200 mg/kg IV infusion every 4 wks beginning between 20 – 30 wks gestation and during delivery plus 200 mg/kg IV infusion to baby within 12 hours of birth, plus maternal+infant zidovudine standard course (intervention) vs. standard polyvalent HIV antibody-negative IVIG to mother and baby as above, plus maternal+infant zidovudine standard course (controls). | SBR: RR = 0.33 (95% CI: 0.01–8.03) [NS] [0/231 vs. 1/228 in intervention vs. control groups, respectively.] |
Tonwe-Gold et al. 2007 [171] | Cote d'Ivoire (Abidjan). Observational cohort study. | Assessed the impact of HAART vs. short-course anti-retroviral (scARV) PMTCT regimens to which women were allocated according to their clinical and immunological status. | SBR: [NS] [4 (3.9%) vs. 6 (4.3%) in HAART vs. scARV for PMTCT groups, respectively (P = 1.00)]. |
Townsend et al. 2007 [170] | UK, Ireland. Retrospective study. Pregnancies in women notified to the National Study of HIV in Pregnancy and Childhood (NSHPC). | Compared women on HAART (intervention) to women on mono/dual therapy (controls). | SBR: adj. OR = 2.27 (95% CI: 0.96–5.41; P = 0.063) [NS] [12.7/1000 births (43/3384) vs. 5.7/1000 (6/1061) in HAART vs. mono/dual therapy groups]. |
Tuomala et al. 2002 [168] | USA (Miami, Florida & Southern California). Case control study. 2 multisite studies + 3 single site studies. | Compared impact of combination ART (cases) vs. no ART (controls) | SBR: 12/2123 (1%) vs.7/1143 (1%) in intervention vs. control groups, respectively. Adjusted rate (for CD4, tobacco, alcohol, illicit drug use): 1% (P = 0.92) [NS] |
Onah et al. 2007 [206] | Nigeria (Enugu). Retrospective case-control study. Pregnant women (N = 162; N = 62 HIV-positive women, N = 100 HIV-negative controls) delivering in the University of Nigeria Teaching Hospital from 2002–2004. | Compared incidence of stillbirth in untreated HIV-positive women (cases) vs. HIV-negative women (controls). | SBR: No difference (P > 0.05). 4.8/1000 vs. 1.0/1000 in cases vs. controls, respectively. Maternal and fetal morbidities: higher in HIV-positive group. |
Conclusion
Periodontal care during pregnancy
Background
Literature-based evidence
Source | Location and Type of Study | Intervention | Stillbirths/Perinatal Outcomes |
---|---|---|---|
Reviews and meta-analyses
| |||
Xiong et al. 2007 [179] | UK. Review. 2 cohort studies included. | Assessed the association of periodontal disease with fetal death. | Fetal death (miscarriage or SB): Effect size ranged from 2.54–3.84. |
Xiong et al. 2006 [176] | UK. Review. 1 cohort study included (N = 3738 participants). | Assessed any association between periodontal disease and adverse pregnancy outcome. | Fetal death (Miscarriage+SB): adj OR = 2.54 (95% CI: 1.20–5.39) |
Intervention studies
| |||
Michalowicz et al. 2006 [184] | USA. RCT. Women (N = 823 women; N = 413 intervention, N = 410 controls) at 13–17 wks' gestation | Used competing-risks analysis to assess the impact of scaling and root planing before 21 wks' gestation, plus monthly tooth polishing and oral hygiene instruction (intervention) vs. scaling and root planing after delivery (controls). | SBR (20–37 wks): [3/413 vs. 10/410 in intervention vs. control groups, respectively, P = 0.04 [NS]] Pre-term: P = 0.51 [NS] Fetal death (miscarriage+SB): [5/413 vs. 14/410 in intervention vs. control groups, respectively, P = 0.08]. |
Macones et al. 2008 [182] | USA. RCT. Multicentre. Women (N = 757; N = 378 intervention, N = 379 controls) < 20 weeks' gestation with periodontal disease identified through screening. | Assessed the impact of periodontal care (scaling and root planing; intervention) vs. tooth polishing (controls) on pre-term birth and its complications. | Major neonatal morbidity/mortality: RR = 1.30 (95% CI; 0.83–2.03) [NS] [10.6% vs. 8.2% in intervention vs. control groups, respectively] Pre-term (< 35 wks): RR = 1.55 (95% CI: 0.90–2.67) [NS] [8.6% vs. 5.6% in intervention vs. control groups, respectively] |
Observational studies
| |||
Oittinen et al. 2005 [207] | Finland. Observational study. Women who became pregnant (N = 130) out of a total cohort of women who had discontinued contraception in order to become pregnant. | Assessed the association between maternal disease status, including periodontal disease and BV, with and adverse pregnancy outcome. | Adverse pregnancy outcome (pre-term birth or fetal death): OR = 5.5 (95% CI: 1.4–21.2, P = 0.014). [26/130 (20%) of sample. Univariate analysis also showed significant association of periodontal disease with adverse outcome (P = 0.012)]. Fetal death (miscarriage+SB): 17/130. Pre-term: N = 9. |
Mobeen et al. 2008 [181] | Pakistan. Community setting. Prospective cohort study. Pregnant women enrolled at 20–26 weeks gestation and given dental exam, then followed until delivery. | Assessed the association between maternal periodontal disease severity with adverse pregnancy outcomes. | SBR: 19/1000 vs. 41/1000 (P = 0.069) between the first and the fourth periodontal quartiles (least severe disease vs. most severe disease). 26/1000 vs. 42/1000 (P = 0.131 [NS]) with increasing severity of the clinical attachment measures. 22/1000 vs. 50/1000 stillbirths (P = .033) with increasing severity of plaque index measures, 24/1000 vs. 51/1000 (P = 0.019) with increasing severity of the gingival index measures. |
Conclusion
Summary
Evidence of no or negative impact (leave out of programs) | Uncertain evidence (need for additional research before including in programs) | Some evidence (may include in programs, but further evaluation is warranted) | Clear evidence (merits inclusion in programs) | |
---|---|---|---|---|
Calcium supplementation for pregnancy-induced hypertension | X1 | |||
Anti-hypertensives | X | |||
Anti-platelet agents | X | |||
Anti-oxidants | X | |||
Heparin | X (for certain conditions) | |||
Management of intrahepatic cholestasis | X | |||
Plasma exchange | X | |||
Cervical cerclage | X | |||
Anti-helminthics | X | |||
Syphilis screening and treatment | X | |||
Antibiotics for BV, asymptomatic bacteriuria, and GBS | X | |||
Antibiotics for PROM/PPROM | X | |||
Anti-malarials | X2 | |||
ITNs | X | |||
PMTCT for HIV | X2 | |||
Periodontal care | X |
Research gaps
Basic science and physiological studies
|
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• Mechanisms of causation of hypertensive disorders of pregnancy and how these cause stillbirths* |
• Auto-immune pathophysiology in stillbirth causation |
• Association of periodontal disease with pre-eclampsia and pathophysiology of subsequent stillbirth* |
• Dynamics of stillbirth causation in intrahepatic cholestasis |
• Drug safety and efficacy studies: |
◦ Anti-malarials in pregnancy |
◦ Drugs for intrahepatic cholestasis |
◦ Non-penicillin treatments for syphilis |
◦ Antibiotic use in pregnancy |
• Identification of other unknown risk factors |
• Prevalence of uterine abnormalities in low-/middle-income countries |
Pilot/cohort studies of interventions
|
• New approaches for PIH and chronic hypertension management in community settings* |
• Management protocols for HIV and syphilis co-infection |
• Management of penicillin drug allergy in community settings |
• Diagnosis and surgical repair of uterine abnormalities in women with recurrent fetal loss |
• Intravenous immunoglobulin treatment (compared to heparin, aspirin, or other anti-coagulants) in selected populations with recurrent pregnancy loss and antiphospholipid antibodies |
Well-designed large RCTs of interventions powered to detect stillbirths
|
• Periodontal care studies powered to detect impact on stillbirth rates* |
• Calcium supplementation to prevent PIH and pre-eclampsia in deficient populations |
• Anti-oxidant supplementation in deficient populations |
• Management of intrahepatic cholestasis including nonstress test, amniotic fluid index, meconium screening and early delivery |
• Calcium supplementation in high-risk pregnancies* |
• Antibiotics for pPROM* |
Effectiveness trials in large populations/at scale
|
• Maternal anti-helminthic treatment: impact on maternal anaemia and stillbirth* |
• On-site syphilis testing and treatment |
• ITNs for Plasmodium vivax and in lower-transmission settings (Asia and Latin America) |