Interventions to reduce preterm birth and stillbirth, and improve outcomes for babies born preterm in low- and middle-income countries: A systematic review.

BACKGROUND: Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required. METHODS: A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted. RESULTS: 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions. CONCLUSIONS: Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts.

The global burden of sickle cell disease in children under five years of age: a systematic review and meta-analysis.

BACKGROUND: Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes. METHODOLOGY: We performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region. RESULTS: 67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe. CONCLUSION: There were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood.