Table 1 Characteristics of the included reviews on pre-pregnancy and pregnancy interventions

Conde-Agudelo 2007[20]

To explore the association between birth spacing and risk of adverse maternal outcomes

Observational studies = 22

Non-Cochrane

Yes

Pre-eclampsia, maternal outcomes

Conde-Agudelo 2007[19]

To examine the association between birth spacing and relative risk of adverse perinatal outcomes.

Observational studies = 67

Non-Cochrane

Yes

preterm birth, low birth weight, and small for gestational age

Kozuki 2013[21]

To examine the association between short/long birth intervals and adverse neonatal outcomes by calculating and meta-analyzing associations using original data from cohort studies conducted in low-and middle-income countries.

Cohort =5

Non-cohrane

Yes

Small for gestational age, Infant mortality, Preterm births

Anglemyer 2013[23]

To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples.

Observational studies = 7

Cochrane

Yes

Episodes of HIV transmisison, index partner's CD4 cell count.

Ng 2011[24]

To determine the impact of population-based biomedical STI interventions on the incidence of HIV infection.

RCT: 4

Cochrane

Yes

incident HIV infection, prevalence of syphilis

Blencowe 2010[29]

To review the evidence for, and estimate the effect of, folic acid fortification/supplementation on neonatal mortality due to NTDs, especially in low-income countries.

RCT: 3

Observational studies: 8

Non-Cochrane

Yes

NTD recurrence, NTD incidence, congenital abnormalities, neonatal deaths

De-Regil 2010[30]

This review examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies.

RCTs: 5

Cochrane

Yes

Prevention of NTDs, incidence of NTDs, reoccurrence of NTDs, cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects.

Imdad 2011[31]

To evaluate the effectiveness of peri-conceptional folic acid supplementation in reducing neural tube defects (NTD), related stillbirths and balanced protein energy and multiple micronutrients supplementation during pregnancy in reducing all-cause stillbirths.

RCTs: 18

Non-Cochrane

Yes

NTDs, stillbirths

Carrolli 2001[33]

a systematic review of randomised trials assessing the effectiveness of different models of antenatal care.

RCTs: 7

Non-Cochrane

Yes

pre-eclampsia, urinary-tract infection, postpartum anaemia, maternal mortality, low birth weight

Dowswell 2010[34]

To compare the effects of antenatal care programmes with reduced visits for low-risk women with standard care.

RCTs: 7

Cochrane

Yes

Perinatal mortality, admission to neonatal intensive care

Homer 2012[35]

The first objective was to compare the effects of group antenatal care versus one-to-one care on outcomes for women and their babies.

RCTs and q-RCTs : 2

Cochrane

Yes

Preterm birth, low birth weight, small-for-gestational age and perinatal mortality.

Pena-Rosas 2012[41]

To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention.

RCTs and q-RCTs : 43

Cochrane

Yes

low birthweight, mean birth weight, maternal anaemia, iron deficiency at term, side effects, haemoglobin (Hb) concentrations

Yakoob 2011[42]

To address the impact of iron with and without folate supplementation on maternal anemia and provides outcome specific quality according to the Child Health Epidemiology Reference Group (CHERG) guidelines.

RCTs and q-RCTs : 31

Non-Cochrane

Yes

incidence of anemia at term, iron deficiency anemia at term

Lassi 2013[43]

To assess the effectiveness of oral folic acid supplementation alone or with other micronutrients versus no folic acid (placebo or same micronutrients but no folic acid) during pregnancy on haematological and biochemical parameters during pregnancy and on pregnancy outcomes.

RCTs and q-RCTs : 31

Cochrane

Yes

Preterm birth, stillbirths/neonatal deaths, mean birthweight, anaemia, mean pre-delivery haemoglobin level, mean pre-delivery serum folate levels, mean pre-delivery red cell folate levels, incidence of megaloblasticanaemia

Demicheli 2013[47]

To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus

RCTs: 2

Non-Cochrane

No

vaccine effectiveness was 43%

Blencowe 2010[48]

To review the evidence for and estimate the effect on neonatal tetanus mortality of immunization with tetanus toxoid of pregnant women, or women of childbearing age.

RCT: 1

CT: 1

Non-Cochrane

Yes

mortality from neonatal tetanus

Garner 2006[52]

To assess drugs given to prevent malaria infection and its consequences in pregnant women living in malarial areas. This includes prophylaxis and intermittent preventive treatment (IPT).

RCTs and q-RCTs : 16

Cochrane

Yes

antenatal parasitaemia, placental malaria, perinatal deaths

TerKuile 2007[53]

To determine the effect of increasing resistance to sulfadoxine-pyrimethamine on the efficacy of IPT during pregnancy in Africa.

RCTs: 4

Non-Cochrane

Yes

placental malaria, low birth weight, anemia

Lengeler 2004[54]

To assess the impact of insecticide-treated bed nets or curtains on mortality, malarial illness (life-threatening and mild), malaria parasitaemia, anaemia, and spleen rates.

RCTs: 22

Cochrane

Yes

protective efficacy, severe malaria, parasite prevalence, high parasitaemia, splenomegaly (30% PE), haemoglobin

Gamble 2007[55]

To compare the impact of ITNs with no nets or untreated nets on preventing malaria in pregnancy

RCTs: 5

Non-Cochrane

Yes

low birthweight, stillbirths/abortions in the first to fourth pregnancy

Gamble 2006[56]

To compare the impact of ITNs with no nets or untreated nets on preventing malaria in pregnancy.

RCTS: 6

Cochrane

Yes

low birthweight, stillbirths/abortions in the first to fourth pregnancy

Eisele 2010[57]

To estimate the effect of ITNs and IRS on preventing malaria-attributable mortality in children 1–59 months, and to estimate the effect of ITNs and IPTp on preventing neonatal and child mortality through improvements in birth outcomes.

RCTs: 14

Non-Cochrane

Yes

rotective efficacy, malaria-attributable mortality 1–59 months, prevention interventions in pregnancy

Lumley 2009[58]

To assess the effects of smoking cessation interventions during pregnancy on smoking behaviour and perinatal health outcomes.

RCTs: 72

Cochrane

Yes

reduction in smoking in late pregnancy, relapse

Coleman 2012[59]

To determine the efficacy and safety of smoking cessation pharmacotherapies, including NRT, varenicline and bupropion (or any other medications) when used to support smoking cessation in pregnancy.

RCTs: 6

Cochrane

Yes

smoking cessation in later pregnancy

Blencowe 2011[61]

This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality.

Observational studies: 25

Non-Cochrane

Yes

Stillbirth, preterm delivery, neonatal deaths

Walker 2001[62]

To identify the most effective antibiotic treatment regimen (in terms of dose, length of course and mode of administration) of syphilis with and without concomitant infection with HIV for pregnant women infected with syphilis.

RCTs and q-RCTs : 26

Cochrane

No

None matched predetermined criteria for comparison

Wiysonge 2011[65]

To assess the effects of antenatal and intrapartum vitamin A supplementation on the risk of MTCT of HIV infection and infant and maternal mortality and morbidity, and the tolerability of vitamin A supplementation.

RCTs: 4

Cochrane

Yes

MTCT of HIV infection, birth weight, stillbirths, preterm births, death by 24 months among live births

Shey 2002[66]

To estimate the effect of vaginal lavage on the risk of MTCT of HIV and infant and maternal mortality and morbidity, as well as tolerability of vaginal lavage in HIV infected women.

RCT: 1

Cochrane

No

vaginal disinfection on MTCT of HIV

Kesho Bora 2009[64]

Triple-antiretroviral (ARV) prophylaxis during pregnancy and breastfeeding compared to short-ARV prophylaxis to prevent mother-to-child transmission of HIV-1 (PMTCT): the Kesho Bora randomized controlled clinical trial in five sites in Burkina Faso, Kenya

1 study in five different location

Non Cochrane

No

Extended triple ARV regimen consisting of the anti-HIV drugs zidovudine, lamivudine andlopinavir/ritonavir, from the last trimester of pregnancy and continued during breastfeeding up to the age of six months.

Imdad 2011[78]

To evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries.

RCTs: 10

Non-Cochrane

Yes

gestational hypertension, pre-eclampsia, neonatal mortality

Hofmeyr 2010[79]

To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes.

RCTs: 13

Cochrane

Yes

high blood pressure, pre-eclampsia, preterm birth, stillbirth or death before discharge from hospital, maternal death or serious morbidity

Jabeen 2011[81]

To review the effect of aspirin, calcium supplementation, antihypertensive agents and magnesium sulphate on risk stillbirths.

RCTs: 82

Non-Cochrane

Yes

stillbirths

Duley 2013[83]

To assess the effectiveness and safety of antiplatelet agents for women at risk of developing pre-eclampsia.

RCTs: 59

Cochrane yes

Yes

pre-eclampsia, maternal risk, preterm birth, fetal or neonatal deaths, small-for-gestational age babies

Askie 2007[84]

to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most.

RCTs: 31

Non-Cochrane

Yes

pre-eclampsia, of delivering before 34 weeks,serious adverse outcome

Duley 2013[88]

To compare different antihypertensive drugs for very high blood pressure during pregnancy.

RCTs: 24

Cochrane

Yes

persistent high blood, risk of HELLP, risk of hypotension, eclampsia, respiratory difficulties, but fewer side-effects, less postpartum haemorrhage

Magee 2003[89]

to assess whether oral beta-blockers are overall better than placebo, or no beta-blocker, for women with mild-moderate hypertension during pregnancy, and to assess whether oral beta-blockers have any advantages over other antihypertensive agents for women with mild-moderate hypertension during pregnancy.

RCTs; 27

Cochrane

Yes

Both maternal outcomes (e.g., the incidence of severe hypertension) and perinatal outcomes

Duley 2010[90]

The objective of this review was to assess the effects of magnesium sulphate compared with diazepam when used for the care of women with eclampsia. Magnesium sulphate is compared with phenytoin and with lytic cocktail in other Cochrane reviews.

RCTs: 7

Cochrane

Yes

Recurrence of seizures, maternal morbidity, perinatal mortality, neonatal mortality, Apgar score

Duley 2010[91]

The objective of this review was to assess the effects of magnesium sulphate compared with phenytoin when used for the care of women with eclampsia.

RCTs: 7

Cochrane

Yes

Recurrence of seizures, maternal morbidity, perinatal mortality, neonatal mortality, Apgar score

Duley 2010[92]

To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia.

RCTs: 15

Cochrane

Yes

Eclampsia, maternal death, serious maternal morbidity, placental abruption, caesarean section, stillbirths

Duley 2010[93]

To assess the effects of magnesium sulphate compared with lytic cocktail (usually chlorpromazine, promethazine and pethidine) when used for the care of women with eclampsia

RCTs: 3

Cochrane

Yes

maternal deaths, seizures, respiratory depression , coma, pneumonia

Cluver 2012[95]

To assess interventions such as tocolysis, fetal acoustic stimulation, regional analgesia, transabdominalamnioinfusion or systemic opioids on ECV for a breech baby at term.

RCTs and qRCTs: 25

Cochrane

Yes

cephalic presentations in labour, caesarean sections

Hutton 2006[96]

To assess the effectiveness of a policy of beginning ECV before term (before 37 weeks' gestation) for breech presentation on fetal presentation at birth, method of delivery, and the rate of preterm birth, perinatal morbidity, stillbirth or neonatal mortality.

RCTs: 3

Cochrane

No

non-cephalic presentation at birth

Hofmeyr 2012[97]

The objective of this review was to assess the effects of postural management of breech presentation on measures of pregnancyoutcome.We evaluated procedures in which the motherrests with herpelvis elevated. These include the knee-chestposition, and a supin e position with the pelvis elevated with a wedge-shaped cushion

RCTs: 6

Cochrane

Yes

non-cephalic births, Cesarean section and Apgar scores below 7 at one minute, r

Hofmeyr 2012[98]

The objective of this review was to assess the effects of ECV at or near term on measures of pregnancy outcome. Methods of facilitatingECV, and ECV before term are reviewed separately

RCTs: 7

Cochrane

Yes

non-cephalic presentation at birth, Cesarean section

Hofmeyr 2003[99]

To assess the effects of planned caesarean section for singleton breech presentation at term on measures of pregnancy outcome.

RCTs: 3

Cochrane

Yes

Caesarean delivery, perinatal or neonatal death or serious neonatal morbidity, urinary incontinence, abdominal pain , perineal pain

Coyle 2012[100]

To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality for breech presentation.

RCTs: 3

Cochrane

Yes

need for ECV, use of oxytocin before or during

Buchanan 2010[102]

To assess the effect of planned early birth compared with expectant management for pregnancies complicated with PPROM prior to 37 weeks' gestation.

RCTs: 7

Cochrane

Yes

neonatal sepsis, respiratory distress, incidence of caesarean section

Kenyon 2010[103]

To evaluate the immediate and long-term effects of administering antibiotics to women with pROM before 37 weeks, on maternal infectious morbidity, fetal and neonatal morbidity and mortality, and longer term childhood development.

RCTs: 19

Cochrane

Yes

Chorioamnionitis, neonatal morbidity, neonatal infection, use of surfactant

Cousens 2010[104]

To review the evidence for and estimate the effect on neonatal mortality due to pre-term birth complications or infection, of administration of antibiotics to women with pPROM, in low and middle-income countries.

RCTs: 18

Non-Cochrane

Yes

respiratory distress syndrome , early onset postnatal infection, neonatal mortality

Roberts 2006[105]

To assess the effects on fetal and neonatal morbidity and mortality, on maternal mortality and morbidity, and on the child in later life of administering corticosteroids to the mother before anticipated preterm birth.

RCTs: 22

Cochrane

Yes

chorioamnionitis or puerperal sepsis, neonatal death, RDS, cerebroventricularhaemorrhage, necrotisingenterocolitis

Mwansa-Kambafwile 2010[108]

To review the evidence for and estimate the effect on cause-specific neonatal mortality of administration of antenatal steroids to women with anticipated preterm labour, with additional analysis for the effect in low- and middle-income countries.

Studies: 44

RCTs: 18

Non-Cochrane

Yes

neonatal mortality among preterm infant

Brownfoot 2008[109]

To assess the effects of different corticosteroid regimens for women at risk of preterm birth.

RCTs: 10

Cochrane

Yes

Incidence of intraventricularhaemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricularhaemorrhage, periventricular leukomalacia, perinatal death, or mean birthweight.

WHO 2003[113]

evidence profiles related to the prioritized questions were prepared, based upon recent systematic reviews, most of which are included in the Cochrane Database of Systematic Reviews

-

-

-

-

Kidney 2009[116]

The objective was to provide a systematic review of the effectiveness of community-level interventions to reduce maternal mortality.

RCTs: 5

Cohort: 8

Non-Cochrane

Yes

Maternal mortality

Lassi 2010[117]

To assess the effectiveness of community-based intervention packages in reducing maternal and neonatal morbidity and mortality; and improving neonatal outcomes.

RCTs and qRCTs: 18

Cochrane

Yes

Maternal mortality, neonatal mortality, perinatal morality, stillbirths, newborn care practices

Gogia 2010[118]

To determine whether home visits for neonatal care by community health workers can reduce infant and neonatal deaths and stillbirths in resource-limited settings.

RCTs: 5

Non-Cochrane

Yes

Neonatal death and stillbirth, and a significant improvement in antenatal and neonatal practice indicators (> 1 antenatal check-up, 2 doses of maternal tetanus toxoid, clean umbilical cord care, early breastfeeding and delayed bathing).

Bhutta 2009[115]

examines the evidence for community and health systems approaches to improve uptake and quality of antenatal and intrapartum care,

RCTs: 9

Non-Cochrane

Yes

Stillbirths