Background: Calcium supplementation reduces the risk of pre‐eclampsia, but questions remain about the dosage to prescribe and who would benefit most.Objectives: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre‐eclampsia prevention, according to baseline dietary calcium, pre‐eclampsia risk and co‐interventions, and intervention timing.Search strategy: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239).Selection criteria: Randomised controlled trials of calcium supplementation for pre‐eclampsia prevention, for women before or during pregnancy. Network meta‐analysis (NMA) also included trials of different calcium doses.Data collection and analysis: Two independent reviewers extracted published data. The meta‐analysis employed random‐effects models and the NMA, a Bayesian random‐effects model, to obtain direct and indirect effect estimates.Main results: The meta‐analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre‐eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36–0.66) or a low dose (RR 0.49, 95% CI 0.36–0.65). By NMA, high‐dose (vs low‐dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43–1.40). Calcium was similarly effective regardless of baseline pre‐eclampsia risk, vitamin D co‐administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake.Conclusions: Low‐ and high‐dose calcium supplementation are effective for pre‐eclampsia prevention in women with low calcium intake. This has implications for population‐level implementation where dietary calcium is low, and targeted implementation where average intake is adequate.Tweetable A network meta‐analysis of 25 trials found that low‐dose calcium supplementation (<1 g/day) is as effective as high‐dose calcium supplementation (≥1 g/day) in halving the risk of pre‐eclampsia when baseline calcium intake is low.

Objective: To compare pre‐eclampsia risk factors identified by clinical practice guidelines (CPGs) with risk factors from hierarchical evidence review, to guide pre‐eclampsia prevention.Design: Our search strategy provided hierarchical evidence of relationships between risk factors and pre‐eclampsia using Medline (Ovid), searched from January 2010 to January 2021.Setting: Published studies and CPGs.Population: Pregnant women.Methods: We evaluated the strength of association and quality of evidence (GRADE). CPGs (n = 15) were taken from a previous systematic review.Main outcome measure: Pre‐eclampsia.Results: Of 78 pre‐eclampsia risk factors, 13 (16.5%) arise only during pregnancy. Strength of association was usually ‘probable’ (n = 40, 51.3%) and the quality of evidence was low (n = 35, 44.9%). The ‘major’ and ‘moderate’ risk factors proposed by 8/15 CPGs were not well aligned with the evidence; of the ten ‘major’ risk factors (alone warranting aspirin prophylaxis), associations with pre‐eclampsia were definite (n = 4), probable (n = 5) or possible (n = 1), based on moderate (n = 4), low (n = 5) or very low (n = 1) quality evidence. Obesity (‘moderate’ risk factor) was definitely associated with pre‐eclampsia (high‐quality evidence). The other ten ‘moderate’ risk factors had probable (n = 8), possible (n = 1) or no (n = 1) association with pre‐eclampsia, based on evidence of moderate (n = 1), low (n = 5) or very low (n = 4) quality. Three risk factors not identified by the CPGs had probable associations (high quality): being overweight; ‘prehypertension’ at booking; and blood pressure of 130–139/80–89 mmHg in early pregnancy.Conclusions: Pre‐eclampsia risk factors in CPGs are poorly aligned with evidence, particularly for the strongest risk factor of obesity. There is a lack of distinction between risk factors identifiable in early pregnancy and those arising later. A refresh of the strategies advocated by CPGs is needed.

Background: While breast milk is widely accepted as the best source of nutrients for almost all newborns, breastfeeding can be especially challenging for preterm and low birth weight (LBW) infants. With increased risk of admission to neonatal intensive care units (NICUs) and separation from parents, this population experiences significant barriers to successful breastfeeding. Thus, it is crucial to identify interventions that can optimize breastfeeding for preterm and LBW infants that is continued from birth and admission, through to hospital discharge and beyond. Objectives: To identify and analyze evidence-based interventions that promote any and exclusive breastfeeding among preterm and LBW neonates at discharge and/or postdischarge from hospital. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Searches were performed in the following databases: MEDLINE Ovid, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health (CINAHL). Results: From the 42 studies included, 6 groups of intervention types were identified: educational and breastfeeding support programs, early discharge, oral stimulation, artificial teats and cups, kangaroo mother care (KMC), and supportive policies within NICUs. All groupings of interventions were associated with significantly increased rates of any breastfeeding at discharge. All types of interventions except artificial teats/cups and oral stimulation showed statistically significant increases in exclusive breastfeeding at discharge. KMC demonstrated the highest increased odds of breastfeeding at discharge among preterm and LBW infants. Conclusions: A variety of effective interventions exist to promote breastfeeding among hospitalized preterm and LBW infants. Hospital settings hold unique opportunities for successful breastfeeding promotion. PROSPERO registration: CRD42021252610

Bubble continuous positive airway pressure (CPAP) has been shown to be effective in supporting breathing in newborns with respiratory distress. The factors that influence implementation in resource-constrained settings remain unclear. The objective of this review is to evaluate the barriers and facilitators of CPAP implementation for newborn care at sub-Saharan African health facilities and how different facility levels and types of bubble CPAP systems may impact utilization. A systematic search (database inception to July 2019) was performed on MEDLINE Ovid, EMBASE, CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the WHO Regional Database for Africa, African Index Medicus (AIM), African Journals Online, grey literature and the references of relevant articles. Studies that met the inclusion criteria (primary research, bubble CPAP implementation with neonates ≤ 28 days old at a health facility in sub-Saharan Africa) were included in the review and assessed with National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) quality assessment tools. The review protocol was published to PROSPERO (CRD42018116082). Seventeen studies were included in the review. Reliable availability of equipment, effectively informing and engaging caregivers and staffing shortages were frequently mentioned barriers to the implementation of bubble CPAP. Understaffed neonatal units and high turnover of nurses and doctors compromised effective training. Provider-to-provider clinical mentorship models as well as affordability and cost-effectiveness of innovative bubble CPAP systems were identified as frequently mentioned facilitators of implementation. With a strong recommendation by the World Health Organization for its use with premature infants with respiratory distress, it is important to understand the barriers and facilitators that can inform the implementation of bubble CPAP. More research is needed into health system factors that can support or impede the use of this potentially promising intervention.

Preterm birth complications are the leading cause of neonatal deaths. Malawi has high rates of preterm birth, with 18.1 preterm births per 100 live births. More than 50% of preterm neonates develop respiratory distress which if left untreated, can lead to respiratory failure and death. Term and preterm neonates with respiratory distress can often be effectively managed with Continuous Positive Airway Pressure (CPAP) and this is considered an essential intervention for the management of preterm neonates by the World Health Organization. Bubble CPAP may represent a safe and cost-effective method for delivering CPAP in low-income settings. The study explored the factors that influence the implementation of bubble CPAP among health care professionals in secondary and tertiary hospitals in Malawi. This was a qualitative study conducted in three district hospitals and a tertiary hospital in southern Malawi. We conducted 46 in-depth interviews with nurses, clinicians and clinical supervisors, from June to August 2018. All data were digitally recorded, transcribed verbatim and thematically analyzed. Factors that influenced implementation of bubble CPAP occurred in an interconnected manner and included: inadequate healthcare provider training in preparation for use, rigid division of roles and responsibilities among providers, lack of effective communication among providers and between providers and newborn’s caregivers, human resource constraints, and inadequate equipment and infrastructure. There are provider, caregiver and health system level factors that influence the implementation of bubble CPAP among neonates in Malawian health facilities. Ensuring adequate staffing in the nurseries, combined with ongoing training for providers, team cohesion, improved communication with caregivers, and improved hospital infrastructure would ensure optimal utilization of bubble CPAP and avoid inadvertent harm from inappropriate use.

The placenta is a vital, multi-functional organ that acts as an interface between maternal and fetal circulation during pregnancy. Nutritional deficiencies during pregnancy alter placental development and function, leading to adverse pregnancy outcomes, such as pre-eclampsia, infants with small for gestational age and low birthweight, preterm birth, stillbirths and maternal mortality. Maternal nutritional supplementation may help to mitigate the risks, but the evidence base is difficult to navigate. The primary purpose of this umbrella review is to map the evidence on the effects of maternal nutritional supplements and dietary interventions on pregnancy outcomes related to placental disorders and maternal mortality. A systematic search was performed on seven electronic databases, the PROSPERO register and references lists of identified papers. The results were screened in a three-stage process based on title, abstract and full-text by two independent reviewers. Randomized controlled trial meta-analyses on the efficacy of maternal nutritional supplements or dietary interventions were included. There were 91 meta-analyses included, covering 23 types of supplements and three types of dietary interventions. We found evidence that supports supplementary vitamin D and/or calcium, omega-3, multiple micronutrients, lipid-based nutrients, and balanced protein energy in reducing the risks of adverse maternal and fetal health outcomes. However, these findings are limited by poor quality of evidence. Nutrient combinations show promise and support a paradigm shift to maternal dietary balance, rather than single micronutrient deficiencies, to improve maternal and fetal health. The review is registered at PROSPERO (CRD42020160887).