Meta-Analysis
doi: 10.1002/14651858.CD012203.pub2.
Care prior to and during subsequent pregnancies following stillbirth for improving outcomes
Affiliations
- PMID: 30556599
- PMCID: PMC6516997
- DOI: 10.1002/14651858.CD012203.pub2
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Meta-Analysis
Care prior to and during subsequent pregnancies following stillbirth for improving outcomes
Cochrane Database Syst Rev.
.
Abstract
Background: Stillbirth affects at least 2.6 million families worldwide every year and has enduring consequences for parents and health services. Parents entering a subsequent pregnancy following stillbirth face a risk of stillbirth recurrence, alongside increased risks of other adverse pregnancy outcomes and psychosocial challenges. These parents may benefit from a range of interventions to optimise their short- and longer-term medical health and psychosocial well-being.
Objectives: To assess the effects of different interventions or models of care prior to and during subsequent pregnancies following stillbirth on maternal, fetal, neonatal and family health outcomes, and health service utilisation.
Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 June 2018), along with ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (18 June 2018).
Selection criteria: We included randomised controlled trials (RCTs) and quasi-randomised controlled trials (qRCTs). Trials using a cluster-randomised design were eligible for inclusion, but we found no such reports. We included trials published as abstract only, provided sufficient information was available to allow assessment of trial eligibility and risk of bias. We excluded cross-over trials.
Data collection and analysis: Two review authors independently assessed trials for eligibility and undertook data extraction and 'Risk of bias' assessments. We extracted data from published reports, or sourced data directly from trialists. We checked the data for accuracy and resolved discrepancies by discussion or correspondence with trialists, or both. We conducted an assessment of the quality of the evidence using the GRADE approach.
Main results: We included nine RCTs and one qRCT, and judged them to be at low to moderate risk of bias. Trials were carried out between the years 1964 and 2015 and took place predominantly in high-income countries in Europe. All trials assessed medical interventions; no trials assessed psychosocial interventions or incorporated psychosocial aspects of care. Trials evaluated the use of antiplatelet agents (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH), or both), third-party leukocyte immunisation, intravenous immunoglobulin, and progestogen. Trial participants were women who were either pregnant or attempting to conceive following a pregnancy loss, fetal death, or adverse outcome in a previous pregnancy.We extracted data for 222 women who had experienced a previous stillbirth of 20 weeks' gestation or more from the broader trial data sets, and included them in this review. Our GRADE assessments of the quality of evidence ranged from very low to low, due largely to serious imprecision in effect estimates as a result of small sample sizes, low numbers of events, and wide confidence intervals (CIs) crossing the line of no effect. Most of the analyses in this review were not sufficiently powered to detect differences in the outcomes assessed. The results presented are therefore largely uncertain.Main comparisonsLMWH versus no treatment/standard care (three RCTs, 123 women, depending on the outcome)It was uncertain whether LMWH reduced the risk of stillbirth (risk ratio (RR) 2.58, 95% CI 0.40 to 16.62; 3 trials; 122 participants; low-quality evidence), adverse perinatal outcome (RR 0.81, 95% CI 0.20 to 3.32; 2 trials; 77 participants; low-quality evidence), adverse maternal psychological effects (RR 1.00, 95% CI 0.07 to 14.90; 1 trial; 40 participants; very low-quality evidence), perinatal mortality (RR 2.58, 95% CI 0.40 to 16.62; 3 trials; 122 participants; low-quality evidence), or any preterm birth (< 37 weeks) (RR 1.01, 0.58 to 1.74; 3 trials; 114 participants; low-quality evidence). No neonatal deaths were reported in the trials assessed and no data were available for maternal-infant attachment. There was no clear evidence of a difference between the groups among the remaining secondary outcomes.LDA versus placebo (one RCT, 24 women)It was uncertain whether LDA reduced the risk of stillbirth (RR 0.85, 95% CI 0.06 to 12.01), neonatal death (RR 0.29, 95% CI 0.01 to 6.38), adverse perinatal outcome (RR 0.28, 95% CI 0.03 to 2.34), perinatal mortality, or any preterm birth (< 37 weeks) (both of the latter RR 0.42, 95% CI 0.04 to 4.06; all very low-quality evidence). No data were available for adverse maternal psychological effects or maternal-infant attachment. LDA appeared to be associated with an increase in birthweight (mean difference (MD) 790.00 g, 95% CI 295.03 to 1284.97 g) when compared to placebo, but this result was very unstable due to the extremely small sample size. Whether LDA has any effect on the remaining secondary outcomes was also uncertain.Other comparisonsLDA appeared to be associated with an increase in birthweight when compared to LDA + LMWH (MD -650.00 g, 95% CI -1210.33 to -89.67 g; 1 trial; 29 infants), as did third-party leukocyte immunisation when compared to placebo (MD 1195.00 g, 95% CI 273.35 to 2116.65 g; 1 trial, 4 infants), but these results were again very unstable due to extremely small sample sizes. The effects of the interventions on the remaining outcomes were also uncertain.
Authors' conclusions: There is insufficient evidence in this review to inform clinical practice about the effectiveness of interventions to improve care prior to and during subsequent pregnancies following a stillbirth. There is a clear and urgent need for well-designed trials addressing this research question. The evaluation of medical interventions such as LDA, in the specific context of stillbirth prevention (and recurrent stillbirth prevention), is warranted. However, appropriate methodologies to evaluate such therapies need to be determined, particularly where clinical equipoise may be lacking. Careful trial design and multicentre collaboration is necessary to carry out trials that would be sufficiently large to detect differences in statistically rare outcomes such as stillbirth and neonatal death. The evaluation of psychosocial interventions addressing maternal-fetal attachment and parental anxiety and depression is also an urgent priority. In a randomised-trial context, such trials may allocate parents to different forms of support, to determine which have the greatest benefit with the least financial cost. Importantly, consistency in nomenclature and in data collection across all future trials (randomised and non-randomised) may be facilitated by a core outcomes data set for stillbirth research. All future trials should assess short- and longer-term psychosocial outcomes for parents and families, alongside economic costs of interventions.
Conflict of interest statement
Aleena M Wojcieszek: none known.
Emily Shepherd: none known.
Philippa Middleton: none known.
Zohra S Lassi: none known.
Trish Wilson: none known.
Margaret M Murphy: none known.
Alexander EP Heazell: Alexander EP Heazell's salary is funded by his National Institute of Health Research (NIHR) Clinician Scientist Award (CS‐2013‐13‐009) although this review is not directly funded by this award. He also receives salary support from Tommy's Charity as Director of the Tommy's Stillbirth Research Centre, University of Manchester. This review is part of this programme of work into improving care in pregnancies after stillbirth. Alexander E P Heazell is the Clinical Lead for a specialist antenatal service for women who have experienced a stillbirth in previous pregnancy.
David A Ellwood: David Ellwood has received sitting fees from the Australian Medical Council but this work is not related to this Cochrane Review. He has received payment for providing expert witness reviews for medico‐legal cases – these cases are in no way related to the topic under review. I am the co‐Director of an NHMRC Centre for Research Excellence ‐ the centre is related to stillbirth and will cover all aspects of research on this topic.
Robert M Silver: Robert M Silver has been awarded NIH grants unrelated to this work. He is a member of the International stillbirth Alliance Scientific Research Committee. He has carried out paid consultancy for Gestavision (a company developing a diagnostic for pre‐eclampsia) and has received payment for grand rounds at several universities.
Vicki Flenady: none known
Figures
PRISMA study flow diagram. GA: gestational age; ICTRP: WHO International Clinical Trials Registry Platform; PCG: Pregnancy and Childbirth Group
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 LMWH vs no treatment/standard care, Outcome 1 Stillbirth.
Comparison 1 LMWH vs no treatment/standard care, Outcome 2 Neonatal death.
Comparison 1 LMWH vs no treatment/standard care, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 1 LMWH vs no treatment/standard care, Outcome 4 Adverse maternal psychological effects (anxiety, depression or complicated grief).
Comparison 1 LMWH vs no treatment/standard care, Outcome 5 Perinatal mortality.
Comparison 1 LMWH vs no treatment/standard care, Outcome 6 Very preterm birth (28 to < 32 weeks).
Comparison 1 LMWH vs no treatment/standard care, Outcome 7 Late preterm birth (32 to < 37 weeks).
Comparison 1 LMWH vs no treatment/standard care, Outcome 8 Any preterm birth (birth < 37 weeks).
Comparison 1 LMWH vs no treatment/standard care, Outcome 9 Birthweight.
Comparison 1 LMWH vs no treatment/standard care, Outcome 10 Low birthweight.
Comparison 1 LMWH vs no treatment/standard care, Outcome 11 Small‐for‐gestational age.
Comparison 1 LMWH vs no treatment/standard care, Outcome 12 Apgar score less than seven at five minutes.
Comparison 1 LMWH vs no treatment/standard care, Outcome 13 Respiratory distress syndrome.
Comparison 1 LMWH vs no treatment/standard care, Outcome 14 Neonatal jaundice.
Comparison 1 LMWH vs no treatment/standard care, Outcome 15 Adherence to the intervention.
Comparison 1 LMWH vs no treatment/standard care, Outcome 16 Caesarean birth (elective).
Comparison 1 LMWH vs no treatment/standard care, Outcome 17 Caesarean birth (emergency).
Comparison 1 LMWH vs no treatment/standard care, Outcome 18 Induction of labour.
Comparison 1 LMWH vs no treatment/standard care, Outcome 19 Instrumental vaginal birth.
Comparison 1 LMWH vs no treatment/standard care, Outcome 20 Placental abruption.
Comparison 1 LMWH vs no treatment/standard care, Outcome 21 Pre‐eclampsia.
Comparison 1 LMWH vs no treatment/standard care, Outcome 22 Gestational diabetes.
Comparison 1 LMWH vs no treatment/standard care, Outcome 23 Chorioamnionitis.
Comparison 1 LMWH vs no treatment/standard care, Outcome 24 Postpartum haemorrhage.
Comparison 1 LMWH vs no treatment/standard care, Outcome 25 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 1 LMWH vs no treatment/standard care, Outcome 26 Maternal antenatal admission.
Comparison 1 LMWH vs no treatment/standard care, Outcome 27 Duration of maternal hospital stay.
Comparison 1 LMWH vs no treatment/standard care, Outcome 28 Duration of neonatal hospital stay.
Comparison 1 LMWH vs no treatment/standard care, Outcome 29 Admission to the neonatal intensive care unit.
Comparison 1 LMWH vs no treatment/standard care, Outcome 30 Duration of neonatal intensive care unit stay.
Comparison 2 LDA vs placebo, Outcome 1 Stillbirth.
Comparison 2 LDA vs placebo, Outcome 2 Neonatal death.
Comparison 2 LDA vs placebo, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 2 LDA vs placebo, Outcome 4 Perinatal mortality.
Comparison 2 LDA vs placebo, Outcome 5 Very preterm birth (28 to < 32 weeks).
Comparison 2 LDA vs placebo, Outcome 6 Late preterm birth (32 to < 37 weeks).
Comparison 2 LDA vs placebo, Outcome 7 Any preterm birth (birth < 37 weeks).
Comparison 2 LDA vs placebo, Outcome 8 Birthweight.
Comparison 2 LDA vs placebo, Outcome 9 Low birthweight.
Comparison 2 LDA vs placebo, Outcome 10 Small‐for‐gestational age.
Comparison 2 LDA vs placebo, Outcome 11 Respiratory distress syndrome.
Comparison 2 LDA vs placebo, Outcome 12 Adherence to the intervention.
Comparison 2 LDA vs placebo, Outcome 13 Caesarean birth (elective).
Comparison 2 LDA vs placebo, Outcome 14 Caesarean birth (emergency).
Comparison 2 LDA vs placebo, Outcome 15 Induction of labour.
Comparison 2 LDA vs placebo, Outcome 16 Instrumental vaginal birth.
Comparison 2 LDA vs placebo, Outcome 17 Placental abruption.
Comparison 2 LDA vs placebo, Outcome 18 Pre‐eclampsia.
Comparison 2 LDA vs placebo, Outcome 19 Gestational diabetes.
Comparison 2 LDA vs placebo, Outcome 20 Postpartum haemorrhage.
Comparison 2 LDA vs placebo, Outcome 21 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 2 LDA vs placebo, Outcome 22 Antenatal care attendance.
Comparison 2 LDA vs placebo, Outcome 23 Duration of maternal hospital stay.
Comparison 2 LDA vs placebo, Outcome 24 Duration of neonatal hospital stay.
Comparison 2 LDA vs placebo, Outcome 25 Admission to the neonatal intensive care unit.
Comparison 2 LDA vs placebo, Outcome 26 Duration of neonatal intensive care unit stay.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 1 Stillbirth.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 2 Neonatal death.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 4 Perinatal mortality.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 5 Very preterm birth (28 to < 32 weeks).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 6 Late preterm birth (32 to < 37 weeks).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 7 Any preterm birth (birth < 37 weeks).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 8 Birthweight.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 9 Low birthweight.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 10 Small‐for‐gestational age.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 11 Respiratory distress syndrome.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 12 Adherence to the intervention.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 13 Caesarean birth (elective).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 14 Caesarean birth (emergency).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 15 Induction of labour.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 16 Instrumental vaginal birth.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 17 Placental abruption.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 18 Pre‐eclampsia.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 19 Gestational diabetes.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 20 Postpartum haemorrhage.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 21 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 3 LDA + LMWH vs LDA alone, Outcome 22 Antenatal care attendance.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 23 Duration of maternal hospital stay.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 24 Duration of neonatal hospital stay.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 25 Admission to the neonatal intensive care unit.
Comparison 3 LDA + LMWH vs LDA alone, Outcome 26 Duration of neonatal intensive care unit stay.
Comparison 4 LDA + LMWH vs placebo, Outcome 1 Stillbirth.
Comparison 4 LDA + LMWH vs placebo, Outcome 2 Neonatal death.
Comparison 4 LDA + LMWH vs placebo, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 4 LDA + LMWH vs placebo, Outcome 4 Perinatal mortality.
Comparison 4 LDA + LMWH vs placebo, Outcome 5 Very preterm birth (28 to < 32 weeks).
Comparison 4 LDA + LMWH vs placebo, Outcome 6 Late preterm birth (32 to < 37 weeks).
Comparison 4 LDA + LMWH vs placebo, Outcome 7 Any preterm birth (birth < 37 weeks).
Comparison 4 LDA + LMWH vs placebo, Outcome 8 Birthweight.
Comparison 4 LDA + LMWH vs placebo, Outcome 9 Low birthweight.
Comparison 4 LDA + LMWH vs placebo, Outcome 10 Small‐for‐gestational age.
Comparison 4 LDA + LMWH vs placebo, Outcome 11 Respiratory distress syndrome.
Comparison 4 LDA + LMWH vs placebo, Outcome 12 Adherence to the intervention.
Comparison 4 LDA + LMWH vs placebo, Outcome 13 Caesarean birth (elective).
Comparison 4 LDA + LMWH vs placebo, Outcome 14 Caesarean birth (emergency).
Comparison 4 LDA + LMWH vs placebo, Outcome 15 Induction of labour.
Comparison 4 LDA + LMWH vs placebo, Outcome 16 Instrumental vaginal birth.
Comparison 4 LDA + LMWH vs placebo, Outcome 17 Placental abruption.
Comparison 4 LDA + LMWH vs placebo, Outcome 18 Pre‐eclampsia.
Comparison 4 LDA + LMWH vs placebo, Outcome 19 Gestational diabetes.
Comparison 4 LDA + LMWH vs placebo, Outcome 20 Postpartum haemorrhage.
Comparison 4 LDA + LMWH vs placebo, Outcome 21 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 4 LDA + LMWH vs placebo, Outcome 22 Antenatal care attendance.
Comparison 4 LDA + LMWH vs placebo, Outcome 23 Duration of maternal hospital stay.
Comparison 4 LDA + LMWH vs placebo, Outcome 24 Duration of neonatal hospital stay.
Comparison 4 LDA + LMWH vs placebo, Outcome 25 Admission to the neonatal intensive care unit.
Comparison 4 LDA + LMWH vs placebo, Outcome 26 Duration of neonatal intensive care unit stay.
Comparison 5 LMWH vs LDA, Outcome 1 Stillbirth.
Comparison 5 LMWH vs LDA, Outcome 2 Neonatal death.
Comparison 5 LMWH vs LDA, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 5 LMWH vs LDA, Outcome 4 Perinatal mortality.
Comparison 5 LMWH vs LDA, Outcome 5 Very preterm birth (28 to < 32 weeks).
Comparison 5 LMWH vs LDA, Outcome 6 Late preterm birth (32 to < 37 weeks).
Comparison 5 LMWH vs LDA, Outcome 7 Any preterm birth (birth < 37 weeks).
Comparison 5 LMWH vs LDA, Outcome 8 Birthweight.
Comparison 5 LMWH vs LDA, Outcome 9 Low birthweight.
Comparison 5 LMWH vs LDA, Outcome 10 Small‐for‐gestational age.
Comparison 5 LMWH vs LDA, Outcome 11 Apgar score less than seven at five minutes.
Comparison 5 LMWH vs LDA, Outcome 12 Respiratory distress syndrome.
Comparison 5 LMWH vs LDA, Outcome 13 Neonatal jaundice.
Comparison 5 LMWH vs LDA, Outcome 14 Caesarean birth (elective).
Comparison 5 LMWH vs LDA, Outcome 15 Caesarean birth (emergency).
Comparison 5 LMWH vs LDA, Outcome 16 Induction of labour.
Comparison 5 LMWH vs LDA, Outcome 17 Instrumental vaginal birth.
Comparison 5 LMWH vs LDA, Outcome 18 Placental abruption.
Comparison 5 LMWH vs LDA, Outcome 19 Pre‐eclampsia.
Comparison 5 LMWH vs LDA, Outcome 20 Gestational diabetes.
Comparison 5 LMWH vs LDA, Outcome 21 Postpartum haemorrhage.
Comparison 5 LMWH vs LDA, Outcome 22 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 5 LMWH vs LDA, Outcome 23 Breastfeeding.
Comparison 5 LMWH vs LDA, Outcome 24 Maternal antenatal admission.
Comparison 5 LMWH vs LDA, Outcome 25 Duration of maternal hospital stay.
Comparison 5 LMWH vs LDA, Outcome 26 Duration of neonatal hospital stay.
Comparison 5 LMWH vs LDA, Outcome 27 Admission to the neonatal intensive care unit.
Comparison 5 LMWH vs LDA, Outcome 28 Duration of neonatal intensive care unit stay.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 1 Stillbirth.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 2 Very preterm birth (28 to < 32 weeks).
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 3 Late preterm birth (32 to < 37 weeks).
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 4 Any preterm birth (birth < 37weeks).
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 5 Birthweight.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 6 Low birthweight.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 7 Small‐for‐gestational age.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 8 Apgar score less than seven at five minutes.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 9 Adherence to the intervention.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 10 Caesarean birth (elective).
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 11 Caesarean birth (emergency).
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 12 Induction of labour.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 13 Instrumental vaginal birth.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 14 Placental abruption.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 15 Pre‐eclampsia.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 16 Gestational diabetes.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 17 Chorioamnionitis.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 18 Postpartum haemorrhage.
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 19 Serious maternal outcome (death, cardiac arrest, respiratory arrest, admission to intensive care).
Comparison 6 LMWH (adjusted dose) vs LMWH (fixed dose), Outcome 20 Admission to neonatal intensive care unit.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 1 Stillbirth.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 2 Neonatal death.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 7 Leukocyte immunisation vs placebo, Outcome 4 Perinatal mortality.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 5 Very preterm birth (28 to < 32 weeks).
Comparison 7 Leukocyte immunisation vs placebo, Outcome 6 Late preterm birth (32 to < 37 weeks).
Comparison 7 Leukocyte immunisation vs placebo, Outcome 7 Any preterm birth (birth < 37 weeks).
Comparison 7 Leukocyte immunisation vs placebo, Outcome 8 Birthweight.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 9 Low birthweight.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 10 Small‐for‐gestational age.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 11 Apgar score less than seven at five minutes.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 12 Adherence to the intervention.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 13 Caesarean birth (elective).
Comparison 7 Leukocyte immunisation vs placebo, Outcome 14 Caesarean birth (emergency).
Comparison 7 Leukocyte immunisation vs placebo, Outcome 15 Induction of labour.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 16 Instrumental vaginal birth.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 17 Placental abruption.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 18 Pre‐eclampsia.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 19 Gestational diabetes.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 20 Chorioamnionitis.
Comparison 7 Leukocyte immunisation vs placebo, Outcome 21 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 8 Intravenous IgG vs placebo, Outcome 1 Stillbirth.
Comparison 8 Intravenous IgG vs placebo, Outcome 2 Neonatal death.
Comparison 8 Intravenous IgG vs placebo, Outcome 3 Adverse perinatal outcome (composite outcome including stillbirth, neonatal death, and major neonatal morbidity).
Comparison 8 Intravenous IgG vs placebo, Outcome 4 Perinatal mortality.
Comparison 8 Intravenous IgG vs placebo, Outcome 5 Very preterm birth (28 to < 32 weeks).
Comparison 8 Intravenous IgG vs placebo, Outcome 6 Late preterm birth (32 to < 37 weeks).
Comparison 8 Intravenous IgG vs placebo, Outcome 7 Any preterm birth (birth < 37 weeks).
Comparison 8 Intravenous IgG vs placebo, Outcome 8 Low birthweight.
Comparison 8 Intravenous IgG vs placebo, Outcome 9 Small‐for‐gestational age.
Comparison 8 Intravenous IgG vs placebo, Outcome 10 Apgar score less than seven at five minutes.
Comparison 8 Intravenous IgG vs placebo, Outcome 11 Respiratory distress syndrome.
Comparison 8 Intravenous IgG vs placebo, Outcome 12 Neonatal jaundice.
Comparison 8 Intravenous IgG vs placebo, Outcome 13 Adherence to the intervention.
Comparison 8 Intravenous IgG vs placebo, Outcome 14 Caesarean birth (elective).
Comparison 8 Intravenous IgG vs placebo, Outcome 15 Caesarean birth (emergency).
Comparison 8 Intravenous IgG vs placebo, Outcome 16 Induction of labour.
Comparison 8 Intravenous IgG vs placebo, Outcome 17 Instrumental vaginal birth.
Comparison 8 Intravenous IgG vs placebo, Outcome 18 Placental abruption.
Comparison 8 Intravenous IgG vs placebo, Outcome 19 Pre‐eclampsia.
Comparison 8 Intravenous IgG vs placebo, Outcome 20 Gestational diabetes.
Comparison 8 Intravenous IgG vs placebo, Outcome 21 Chorioamnionitis.
Comparison 8 Intravenous IgG vs placebo, Outcome 22 Postpartum haemorrhage.
Comparison 8 Intravenous IgG vs placebo, Outcome 23 Serious maternal outcome (death; cardiac arrest; respiratory arrest; admission to intensive care).
Comparison 8 Intravenous IgG vs placebo, Outcome 24 Admission to the neonatal intensive care unit.
Update of
- doi: 10.1002/14651858.CD012203
References
References to studies included in this review
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