Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

Shepherd ES ，Goldsmith S ，Doyle LW ，Middleton P ，Marret S ，Rouse DJ ，Pryde P ，Wolf HT ，Crowther CA ... -  《Cochrane Database of Systematic Reviews》

Treatment for women with postpartum iron deficiency anaemia.

Postpartum iron deficiency anaemia is caused by antenatal iron deficiency or excessive blood loss at delivery and might affect up to 50% of labouring women in low- and middle-income countries. Effective and safe treatment during early motherhood is important for maternal well-being and newborn care. Treatment options include oral iron supplementation, intravenous iron, erythropoietin, and red blood cell transfusion. To assess the benefits and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. These include intravenous iron, oral iron supplementation, red blood cell transfusion, and erythropoietin. A Cochrane Information Specialist searched for all published, unpublished, and ongoing trials, without language or publication status restrictions. We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, LILACS, WHO ICTRP, and ClinicalTrials.gov, together with reference checking, citation searching, and contact with study authors to identify eligible studies. We applied date limits to retrieve new records since the last search on 9 April 2015 until 11 April 2024. We included published, unpublished, and ongoing randomised controlled trials (RCTs) that compared treatments for postpartum iron deficiency anaemia with placebo, no treatment, or alternative treatments. Cluster-randomised trials were eligible for inclusion. We included RCTs regardless of blinding. Participants were women with postpartum haemoglobin ≤ 12 g/dL, treated within six weeks after childbirth. We excluded non-randomised, quasi-randomised, and cross-over trials. The critical outcomes of this review were maternal mortality and fatigue. The important outcomes included persistent anaemia symptoms, persistent postpartum anaemia, psychological well-being, infections, compliance with treatment, breastfeeding, length of hospital stay, serious adverse events, anaphylaxis or evidence of hypersensitivity, flushing/Fishbane reaction, injection discomfort/reaction, constipation, gastrointestinal pain, number of red blood cell transfusions, and haemoglobin levels. We assessed risk of bias in the included studies using the Cochrane RoB 1 tool. Two review authors independently performed study screening, risk of bias assessment, and data extraction. We contacted trial authors for supplementary data when necessary. We screened all trials for trustworthiness and scientific integrity using the Cochrane Trustworthiness Screening Tool. We conducted meta-analyses using a fixed-effect model whenever feasible to synthesise outcomes. In cases where data were not suitable for meta-analysis, we provided a narrative summary of important findings. We evaluated the overall certainty of the evidence using GRADE. We included 33 RCTs with a total of 4558 postpartum women. Most trials were at high risk of bias for several risk of bias domains. Most of the evidence was of low or very low certainty. Imprecision due to few events and risk of bias due to lack of blinding were the most important factors. Intravenous iron versus oral iron supplementation The evidence is very uncertain about the effect of intravenous iron on mortality (risk ratio (RR) 2.95, 95% confidence interval (CI) 0.12 to 71.96; P = 0.51; I² = not applicable; 3 RCTs; 1 event; 572 women; very low-certainty evidence). One woman died of cardiomyopathy, and another developed arrhythmia, both in the groups treated with intravenous iron. Intravenous iron probably results in a slight reduction in fatigue within 8 to 28 days (standardised mean difference -0.25, 95% CI -0.42 to -0.07; P = 0.006; I² = 47%; 2 RCTs; 515 women; moderate-certainty evidence). Breastfeeding was not reported. Oral iron probably increases the risk of constipation compared to intravenous iron (RR 0.12, 95% CI 0.06 to 0.21; P < 0.001; I² = 0%; 10 RCTs; 1798 women; moderate-certainty evidence). The evidence is very uncertain about the effect of intravenous iron on anaphylaxis or hypersensitivity (RR 2.77, 95% CI 0.31 to 24.86; P = 0.36; I² = 0%; 12 RCTs; 2195 women; very low-certainty evidence). Three women treated with intravenous iron experienced anaphylaxis or hypersensitivity. The trials that reported on haemoglobin at 8 to 28 days were too heterogeneous to pool. However, 5 of 6 RCTs favoured intravenous iron, with mean changes in haemoglobin ranging from 0.73 to 2.10 g/dL (low-certainty evidence). Red blood cell transfusion versus intravenous iron No women died in the only trial that reported on mortality (1 RCT; 7 women; very low-certainty evidence). The evidence is very uncertain about the effect of red blood cell transfusion on fatigue at 8 to 28 days (mean difference (MD) 1.20, 95% CI -2.41 to 4.81; P = 0.51; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence) and breastfeeding more than six weeks postpartum (RR 0.43, 95% CI 0.12 to 1.57; P = 0.20; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence). Constipation and anaphylaxis were not reported. Red blood cell transfusion may result in little to no difference in haemoglobin within 8 to 28 days (MD -1.00, 95% CI -2.02 to 0.02; P = 0.05; I² = not applicable; 1 RCT; 12 women; low-certainty evidence). Intravenous iron and oral iron supplementation versus oral iron supplementation Mortality and breastfeeding were not reported. One trial reported a greater improvement in fatigue in the intravenous and oral iron group, but the effect size could not be calculated (1 RCT; 128 women; very low-certainty evidence). Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone (RR 0.21, 95% CI 0.07 to 0.69; P = 0.01; I² = not applicable; 1 RCT; 128 women; low-certainty evidence). There were no anaphylaxis or hypersensitivity events in the trials (2 RCTs; 168 women; very low-certainty evidence). Intravenous iron and oral iron may result in little to no difference in haemoglobin (g/dL) at 8 to 28 days (MD 0.00, 95% CI -0.48 to 0.48; P = 1.00; I² = not applicable; 1 RCT; 60 women; low-certainty evidence). Red blood cell transfusion versus no transfusion Mortality, fatigue at day 8 to 28, constipation, anaphylaxis, and haemoglobin were not reported. Red blood cell transfusion may result in little to no difference in breastfeeding more than six weeks postpartum (RR 0.91, 95% CI 0.78 to 1.07; P = 0.24; I² = not applicable; 1 RCT; 297 women; low-certainty evidence). Oral iron supplementation versus placebo or no treatment Mortality, fatigue, breastfeeding, constipation, anaphylaxis, and haemoglobin were not reported. Two trials reported on gastrointestinal symptoms, but did not report results by study arm. Intravenous iron probably reduces fatigue slightly in the early postpartum weeks (8 to 28 days) compared to oral iron tablets, but probably results in little to no difference after four weeks. It is very uncertain if intravenous iron has an effect on mortality and anaphylaxis/hypersensitivity. Breastfeeding was not reported. Intravenous iron may increase haemoglobin slightly more than iron tablets, but the data were too heterogeneous to pool. However, changes in haemoglobin levels are a surrogate outcome, and treatment decisions should preferentially be based on patient-relevant outcomes. Iron tablets probably result in a large increase in constipation compared to intravenous iron. The effect of red blood cell transfusion compared to intravenous iron on mortality, fatigue, and breastfeeding is very uncertain. No studies reported on constipation or anaphylaxis/hypersensitivity. Red blood cell transfusion may result in little to no difference in haemoglobin at 8 to 28 days. The effect of intravenous iron and oral iron supplementation on mortality, fatigue, breastfeeding, and anaphylaxis/hypersensitivity is very uncertain or unreported. Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone, and in little to no difference in haemoglobin. The effect of red blood cell transfusion compared to non-transfusion on mortality, fatigue, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. Red blood cell transfusion may result in little to no difference in breastfeeding. The effect of oral iron supplementation on mortality, fatigue, breastfeeding, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. This Cochrane review had no dedicated funding. Protocol and previous versions are available: Protocol (2013) [DOI: 10.1002/14651858.CD010861] Original review (2004) [DOI: 10.1002/14651858.CD004222.pub2] Review update (2015) [DOI: 10.1002/14651858.CD010861.pub2].

Jensen MCH ，Holm C ，Jørgensen KJ ，Schroll JB ... -  《Cochrane Database of Systematic Reviews》

Effect and safety of intravenous iron compared to oral iron for treatment of iron deficiency anaemia in pregnancy.

Intravenous iron is increasingly used to treat iron-deficient anaemia (IDA) in pregnancy. A previous network meta-analysis suggested that intravenous irons have a greater effect on haematological parameters than oral irons; however, the impact on serious pregnancy complications such as postpartum haemorrhage (PPH) or the need for blood transfusion was unclear. Since then, several new randomised controlled trials (RCTs) have been conducted. To evaluate the effect and safety of intravenous versus oral iron preparations for treating IDA in pregnancy. We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and the WHO ICTRP) for eligible studies. The latest search was performed on 19 March 2024. We included RCTs in pregnant women with confirmed IDA (haemoglobin (Hb) level < 11 g/dL as per World Health Organization (WHO) criteria) comparing intravenous (iron sucrose, ferric carboxymaltose, ferric derisomaltose, ferumoxytol) and oral (ferrous sulfate, ferrous fumarate, ferrous gluconate) iron preparations. Our outcomes were antenatal and postnatal Hb levels, antenatal and postnatal anaemia status, PPH, blood transfusion, maternal satisfaction, maternal well-being, breastfeeding, maternal mortality, maternal morbidity, and adverse events (AEs). We used the Cochrane RoB 1 tool to assess risk of bias in the included RCTs. We followed standard Cochrane methods. Two review authors independently assessed studies for eligibility and scientific rigour, evaluated the risk of bias of included studies, and extracted data. Where appropriate, we pooled data using a fixed-effect model in the first instance. We reported dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean differences (MDs) with 95% CIs. We assessed the certainty of the evidence using the GRADE approach. We included 13 RCTs (3939 participants) mainly conducted in India and Africa (8/13). Gestational age at baseline ranged from 13 to 37 weeks, and Hb levels ranged from 5.0 to just below 11.0 g/dL. The most frequently compared preparations were intravenous iron sucrose versus oral ferrous sulfate (5/13). Most RCTs were at low risk of bias, and the certainty of evidence ranged from moderate to very low, mainly due to concerns over attrition bias, imprecision, and inconsistency. Antenatal outcomes Compared with oral iron, intravenous iron likely slightly increases Hb level three to six weeks after treatment start (MD 0.49, 95% CI 0.28 to 0.69; 11 RCTs; 2935 participants; moderate-certainty evidence) and likely reduces anaemia status three to six weeks after treatment start (RR 0.81, 95% CI 0.77 to 0.86; 5 RCTs; 2189 participants; moderate-certainty evidence). Compared with oral iron, intravenous iron likely slightly increases Hb level around birth (MD 0.55, 95% CI 0.33 to 0.77; 6 RCTs; 1574 participants; moderate-certainty evidence) and likely reduces anaemia status around birth (RR 0.85, 95% CI 0.77 to 0.93; 4 RCTs; 1240 participants; moderate-certainty evidence). Postpartum outcomes Compared with oral iron, intravenous iron may slightly increase Hb level postpartum (MD 0.54, 95% CI 0.41 to 0.68; 3 RCTs; 1950 participants; low-certainty evidence). It may also reduce anaemia status (RR 0.66, 95% CI 0.59 to 0.73; 3 RCTs; 1950 participants; low-certainty evidence) and severe anaemia postpartum (RR 0.16, 95% CI 0.03 to 0.84; 2 RCTs; 1581 participants; very low-certainty evidence), although the evidence for the latter outcome is very uncertain. Compared with oral iron, intravenous iron may result in little to no difference in PPH (RR 1.44, 95% CI 0.50 to 4.20; 3 RCTs; 2251 participants; low-certainty evidence) and likely results in little to no difference in the need for blood transfusion (RR 0.97, 95% CI 0.58 to 1.60; 6 RCTs; 2592 participants; moderate-certainty evidence) or rates of breastfeeding (RR 1.04, 95% CI 0.97 to 1.12; 1 RCT; 404 participants; moderate-certainty evidence). No trials reported on maternal satisfaction or maternal well-being. Adverse outcomes Compared with oral iron, intravenous iron may have little to no effect on maternal mortality, but the evidence is very uncertain (RR 0.91, 95% CI 0.13 to 6.39; 4 RCTs; 2152 participants; very low-certainty evidence). Compared with oral iron, intravenous iron likely does not increase maternal morbidity: severe infections (RR 1.01, 95% CI 0.47 to 2.18; 1 RCT; 1881 participants; moderate-certainty evidence) and prolonged hospital stay (RR 0.86, 95% CI 0.62 to 1.21; 1 RCT; 1764 participants; moderate-certainty evidence) and may not increase admissions to the intensive care unit (ICU) (RR 1.99, 95% CI 0.18 to 21.87; 2 RCTs; 2069 participants; low-certainty evidence). Compared with oral iron, intravenous iron likely does not increase AEs (RR 1.05, 95% CI 0.82 to 1.35; 1 RCT; 349 participants; moderate-certainty evidence) and may not increase serious AEs (RR 1.25, 95% CI 0.61 to 2.59; 1 RCT; 1934 participants; low-certainty evidence). However, individual AEs were inconsistently reported across trials. Intravenous iron likely slightly increases Hb levels and likely reduces anaemia in pregnancy compared to oral iron. Hb levels postpartum may be slightly increased with intravenous iron, but the effect on postpartum severe anaemia status is very uncertain. Intravenous iron may result in little to no difference in PPH, and blood transfusion rates are likely unaffected by route of administration. Synthesis of adverse outcomes proved challenging due to their rarity and suboptimal reporting. The effects of intravenous iron on maternal mortality and admissions to the ICU are very uncertain, and there is likely little to no difference between groups in severe infections and prolonged hospital stay. Intravenous iron likely does not increase AEs and may not increase serious AEs; however, the 95% CIs in both cases include potential harm. Furthermore, this finding should be treated cautiously due to the varied adverse event profiles of both types of iron preparations. Data from the ongoing multicentre trials may address some of the identified evidence gaps. However, there is a clear need to strengthen the co-ordination of research efforts around clinically important time points of outcome measure, homogeneity of their definition, and safety reporting. This Cochrane Review was partially funded by the WHO and was supported by the UK Medical Research Council funding. Registration (2024): PROSPERO, CRD42024523791 via www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024523791.

Nicholson L ，Axon E ，Daru J ，Rogozińska E ... -  《Cochrane Database of Systematic Reviews》

Vitamin D supplementation for women during pregnancy.

Vitamin D supplementation during pregnancy may help improve maternal and neonatal health outcomes (such as fewer preterm birth and low birthweight babies) and reduce the risk of adverse pregnancy outcomes (such as severe postpartum haemorrhage). To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve certain maternal and neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and relevant conference proceedings) (3 December 2022). We also searched the reference lists of retrieved studies. Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention. Two review authors independently i) assessed the eligibility of studies against the inclusion criteria, ii) assessed trustworthiness based on pre-defined criteria of scientific integrity, iii) extracted data from included studies, and iv) assessed the risk of bias of the included studies. We assessed the certainty of the evidence using the GRADE approach. The previous version of this review included 30 studies; in this update, we have removed 20 of these studies to 'awaiting classification' following assessments of trustworthiness, one study has been excluded, and one new study included. This current review has a total of 10 included studies, 117 excluded studies, 34 studies in awaiting assessment, and seven ongoing studies. We used the GRADE approach to assess the certainty of the evidence. This removal of the studies resulted in evidence that was downgraded to low-certainty or very low-certainty due to study design limitations, inconsistency between studies, and imprecision. Supplementation with vitamin D compared to no intervention or a placebo A total of eight studies involving 2313 pregnant women were included in this comparison. We assessed four studies as having a low risk of bias for most domains and four studies as having high risk or unclear risk of bias for most domains. The evidence is very uncertain about the effect of supplementation with vitamin D during pregnancy compared to placebo or no intervention on pre-eclampsia (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.21 to 1.33; 1 study, 165 women), gestational diabetes (RR 0.53, 95% CI 0.03 to 8.28; 1 study, 165 women), preterm birth (< 37 weeks) (RR 0.76, 95% CI 0.25 to 2.33; 3 studies, 1368 women), nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 study, 135 women), or hypercalcaemia (1 study; no cases reported). Supplementation with vitamin D during pregnancy may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome (RR 0.68, 95% CI 0.51 to 0.91; 1 study, 1134 women; low-certainty evidence) and may reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out (RR 0.69, 95% CI 0.44 to 1.08; 3 studies, 371 infants; low-certainty evidence). Supplementation with vitamin D + calcium compared to no intervention or a placebo One study involving 84 pregnant women was included in this comparison. Overall, this study was at moderate to high risk of bias. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported. The evidence is very uncertain about the effect of supplementation with vitamin D and calcium on preterm birth (RR not estimable; very low-certainty evidence) or for low birthweight (RR 1.45, 95% CI 0.14 to 14.94; very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) One study involving 1298 pregnant women was included in this comparison. We assessed this study as having a low risk of bias in all domains. Pre-eclampsia was not reported. The evidence is very uncertain about the effect of supplementation with vitamin D, calcium, and other vitamins and minerals during pregnancy compared to no vitamin D on gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73; very low-certainty evidence), maternal adverse events (hypercalcaemia no events and hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; very low-certainty evidence), preterm birth (RR 1.04, 95% CI 0.68 to 1.59; low-certainty evidence), or low birthweight (RR 1.12, 95% CI 0.82 to 1.51; low-certainty evidence). This updated review using the trustworthy assessment tool removed 21 studies from the previous update and added one new study for a total of 10 included studies. In this setting, supplementation with vitamin D alone compared to no intervention or a placebo resulted in very uncertain evidence on pre-eclampsia, gestational diabetes, preterm birth, or nephritic syndrome. It may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome. It may also reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out. Supplementation with vitamin D and calcium versus placebo or no intervention resulted in very uncertain evidence on preterm birth and low birthweight. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported in the only study included in this comparison. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) resulted in very uncertain evidence on gestational diabetes and maternal adverse events (hypercalciuria) and uncertain evidence on preterm birth and low birthweight. Pre-eclampsia was not reported in the only study included in this comparison. All findings warrant further research. Additional rigorous, high-quality, and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.

Palacios C ，Kostiuk LL ，Cuthbert A ，Weeks J ... -  《Cochrane Database of Systematic Reviews》

Maternal postures for fetal malposition in labour for improving the health of mothers and their infants.

Fetal malposition (occipito-posterior and persistent occipito-transverse) in labour is associated with adverse maternal and infant outcomes. Whether use of maternal postures can improve these outcomes is unclear. This Cochrane Review of maternal posture in labour is one of two new reviews replacing a 2007 review of maternal postures in pregnancy and labour. To assess the effect of specified maternal postures for women with fetal malposition in labour on maternal and infant morbidity compared to other postures.  SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (13 July 2021), and reference lists of retrieved studies. We included randomised controlled trials (RCTs) or cluster-RCTs conducted among labouring women with a fetal malposition confirmed by ultrasound or clinical examination, comparing a specified maternal posture with another posture. Quasi-RCTs and cross-over trials were not eligible for inclusion. Two review authors independently assessed trials for inclusion, risk of bias, and performed data extraction. We used mean difference (MD) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. We included eight eligible studies with 1766 women.  All studies reported some form of random sequence generation but were at high risk of performance bias due to lack of blinding. There was a high risk of selection bias in one study, detection bias in two studies, attrition bias in two studies, and reporting bias in two studies. Hands and knees The use of hands and knees posture may have little to no effect on operative birth (average RR 1.14, 95% CI 0.87 to 1.50; 3 trials, 721 women; low-certainty evidence) and caesarean section (RR 1.34, 95% CI 0.96 to 1.87; 3 trials, 721 women; low-certainty evidence) but the evidence is uncertain; and very uncertain for epidural use (average RR 0.74, 95% CI 0.41 to 1.31; 2 trials, 282 women; very low-certainty evidence), instrumental vaginal birth (average RR 1.04, 95% CI 0.57 to 1.90; 3 trials, 721 women; very low-certainty evidence), severe perineal tears (average RR 0.88, 95% CI 0.03 to 22.30; 2 trials, 586 women; very low-certainty evidence), maternal satisfaction (average RR 1.02, 95% CI 0.68 to 1.54; 3 trials, 350 women; very low-certainty evidence), and Apgar scores less than seven at five minutes (RR 0.71, 95% CI 0.21 to 2.34; 2 trials, 586 babies; very low-certainty evidence).  No data were reported for the hands and knees comparisons for postpartum haemorrhage, serious neonatal morbidity, death (stillbirth or death of liveborn infant), admission to neonatal intensive care, neonatal encephalopathy, need for respiratory support, and neonatal jaundice requiring phototherapy.  Lateral postures The use of lateral postures may have little to no effect on reducing operative birth (average RR 0.72, 95% CI 0.43 to 1.19; 4 trials, 871 women; low-certainty evidence), caesarean section (average RR 0.78, 95% CI 0.44 to 1.39; 4 trials, 871 women; low-certainty evidence), instrumental vaginal birth (average RR 0.73, 95% CI 0.39 to 1.36; 4 trials, 871 women; low-certainty evidence), and maternal satisfaction (RR 0.96, 95% CI 0.84 to 1.09; 2 trials, 451 women; low-certainty evidence), but the evidence is uncertain. The evidence is very uncertain about the effect of lateral postures on severe perineal tears (RR 0.66, 95% CI 0.17 to 2.48; 3 trials, 609 women; very low-certainty evidence), postpartum haemorrhage (RR 0.90, 95% CI 0.48 to 1.70; 1 trial, 322 women; very low-certainty evidence), serious neonatal morbidity (RR 1.41, 95% CI 0.64 to 3.12; 3 trials, 752 babies; very low-certainty evidence), Apgar scores less than seven at five minutes (RR 0.25, 95% CI 0.03 to 2.24; 1 trial, 322 babies; very low-certainty evidence), admissions to neonatal intensive care (RR 1.41, 95% CI 0.64 to 3.12; 2 trials, 542 babies; very low-certainty evidence) and neonatal death (stillbirth or death of liveborn) (1 trial, 210 women and their babies; no events).  For the lateral posture comparisons, no data were reported for epidural use, neonatal encephalopathy, need for respiratory support, and neonatal jaundice requiring phototherapy. We were not able to estimate the outcome death (stillbirth or death of liveborn infant) due to no events (1 trial, 210 participants).  AUTHORS' CONCLUSIONS: We found low- and very low-certainty evidence which indicated that the use of hands and knees posture or lateral postures in women in labour with a fetal malposition may have little or no effect on health outcomes of the mother or her infant. If a woman finds the use of hands and knees or lateral postures in labour comfortable there is no reason why they should not choose to use them. Further research is needed on the use of hands and knees and lateral postures for women with a malposition in labour. Trials should include further assessment of semi-prone postures, same-side-as-fetus lateral postures with or without hip hyperflexion, or both, and consider interventions of longer duration or that involve the early second stage of labour.

Barrowclough JA ，Lin L ，Kool B ，Hofmeyr GJ ，Crowther CA ... -  《Cochrane Database of Systematic Reviews》