The association between malnutrition and childhood disability in low- and middle- income countries: systematic review and meta-analysis of observational studies.

OBJECTIVE: The aim of this study was to evaluate the association between childhood disability and malnutrition in low- and middle- income countries (LMICs). METHODS: Articles were identified from 1990 to August 2017 by searching nine electronic databases. Epidemiological studies, undertaken in LMICs that compared the prevalence of malnutrition in children with disabilities to children without disabilities were eligible for inclusion. Titles, abstracts, and full texts were screened by two reviewers, and data were extracted using a structured table for eligible papers. Meta-analyses for the association between childhood disability and undernutrition were performed. RESULTS: The search generated 4678 results, from which 17 articles were eligible. Fifty-three per cent of these studies showed a positive association between childhood disability and undernutrition. Results varied when disaggregated by type of disability, with positive associations identified for 44% of studies focussed on neurodevelopmental disability, 60% of general disability studies and 67% of studies on hearing impairment. Only four studies were identified that considered overnutrition outcomes, and these showed variable results. Eighteen per cent of eligible studies were considered at low risk of bias, 53% had a medium risk, and 29% had a high risk of bias. Pooled ORs showed that children with disabilities were almost three times more likely to be underweight (OR 2.97, 95% CI 2.33, 3.79), and nearly twice as likely to experience stunting and wasting (Stunting: 1.82, 1.40, 2.36; Wasting: 1.90, 1.32-2.75), compared to controls. CONCLUSIONS: Children with disabilities may be a vulnerable group for undernutrition in LMICs, which should be reflected in disability and nutritional programming and policy-making.

Review of the role of additional treatments including oseltamivir, oral steroids, macrolides, and vitamin supplementation for children with severe pneumonia in low- and middle-income countries.

Background: Pneumonia is a major cause of death in children aged under five years. As children with severe pneumonia have the highest risk of morbidity and mortality, previous studies have evaluated the additional benefit of adjunctive treatments such as oseltamivir, oral steroids, macrolides, and vitamin supplementation that can be added to standard antibiotic management to improve clinical outcomes. The study reviewed the evidence for the role of these additional treatments for children with severe pneumonia in low- and middle-income countries (LMICs). Methods: Four electronic databases were searched for English-language articles between 2000 to 2020. Systematic reviews (SRs) with meta-analyses, comparative cohort studies, and randomised controlled trials (RCTs) from LMICs that reported clinical outcomes for children with severe pneumonia aged between one month to 9 years who received adjunct treatment in addition to standard care were included. Risk of bias of included SRs was assessed using AMSTAR 2, and of individual studies using the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies. Results: Overall, the search identified 2147 articles, 32 of which were eligible, including 7 SRs and 25 RCTs. These studies evaluated zinc (4 SRs, 17 RCTs), Vitamin D (1 SR, 4 RCTs), Vitamin A (3 SRs, 1 RCT), Vitamin C (1 SR, 2 RCTs) and micronutrients (1 RCT). Most studies reported clinical outcomes of time to improvement, length of stay, and treatment failure (including mortality). No studies of oseltamivir, steroids, or macrolides fulfilling the inclusion criteria were identified. For zinc, pooled analyses from SRs showed no evidence of benefit. Similarly, a Cochrane review and one RCT found that Vitamin A did not improve clinical outcomes. For Vitamin D, an RCT evaluating a single high dose of 100 000 international units (IU) of vitamin D found a reduction in time to improvement, with 38%-40% documented vitamin D deficiency at baseline. However, two other studies of 1000 IU daily did not show any effect, but vitamin D status was not measured. For vitamin C, two studies found a reduction in time to symptom resolution in those with severe disease, with one reporting a shorter length of hospital stay. However, both studies were of weak quality. Most studies excluded malnourished children, and studies which included these children did not report specifically on the effect of micronutrients. Conclusions: This review found that adjunctive zinc and vitamin A, in addition to standard care, does not improve clinical outcomes in children with severe pneumonia in LMICs (strong evidence). However, a reduction in time to symptom resolution was reported with high dose vitamin D supplementation in children with documented vitamin D deficiency (strong evidence from one study) and vitamin C (weak evidence), although further research is needed, especially in underweight children.

Systematic review of the clinical outcomes of pneumonia with a penicillin-group resistant pneumococcus in respiratory and blood culture specimens in children in low- and middle-income countries.

Background: Streptococcus pneumoniae is one of the most common bacteria causing pneumonia and the World Health Organization (WHO) recommends first-line treatment of pneumonia with penicillins. Due to increases in the frequency of penicillin resistance, this systematic review aimed to determine the clinical outcomes of children with pneumonia in low- and middle-income countries (LMICs), with penicillin-group resistant pneumococci in respiratory and/or blood cultures specimens. Methods: English-language articles from January 2000 to November 2020 were identified by searching four databases. Systematic reviews and epidemiological studies from LMICs that included children aged one month to 9 years and reported outcomes of pneumonia with a penicillin-resistant pneumococcus in respiratory and blood culture specimens with or without comparison groups were included. Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. A narrative synthesis of findings based on the results of included studies was performed. Results: We included 7 articles involving 2864 children. One strong- and four medium-quality studies showed no difference in clinical outcomes (duration of symptoms, length of hospital stay and mortality) between those children with penicillin non-susceptible compared to susceptible pneumococci. Two weak quality studies suggested better outcomes in the penicillin-susceptible group. Conclusions: Current evidence suggests no difference in clinical outcomes of child pneumonia due to a penicillin-resistant S. pneumoniae and as such, there is no evidence to support a change in current WHO antibiotic guidelines.

Prevention of young infant infections using oral azithromycin in labour in Fiji (Bulabula MaPei): study protocol of a randomised control trial.

INTRODUCTION: Infections are a leading cause of neonatal mortality globally and can be transmitted from mother-to-child vertically or horizontally. Fiji has higher rates of serious neonatal infections and infant skin and soft tissue infections (SSTIs) than high-income countries. Research from the Gambia found that a single dose of oral azithromycin in labour decreased bacterial carriage and infections in mothers and infants, particularly infant skin infections. The Bulabula MaPei clinical trial evaluates the safety and efficacy of a single dose of azithromycin in labour in reducing the incidence of maternal and infant SSTIs and other infections and the impact on bacterial carriage. It will also describe the effect of azithromycin on antimicrobial (AMR) resistance, the maternal and infant microbiome, and infant dysbiosis. METHODS AND ANALYSIS: We are conducting a blinded, placebo-controlled randomised clinical trial administering 2 g of oral azithromycin, or placebo, given to healthy, pregnant women (≥18 years) in labour in Suva, Fiji. The primary outcome is the cumulative incidence of SSTIs in infants by 3 months of age. Secondary outcomes include the incidence of other infant and maternal infections, and safety and tolerability of azithromycin in mother and infant. Following informed consent, 2110 pregnant women will be randomised in a 1:1 ratio, with all study staff and participants masked to group allocation. Mother/infant pairs will be followed up for 12 months over six visits collecting clinical data on infections, antimicrobial use, safety and anthropometrics, in addition to nasopharyngeal, oropharyngeal, rectovaginal and vaginal swabs, maternal breastmilk and infant stool samples, in order to compare bacterial carriage, AMR rates and microbiome. Recruitment for Bulabula MaPei started in June 2019. ETHICS AND DISSEMINATION: This trial was approved and is being conducted according to the protocol approved by The Royal Children's Hospital Human Research Ethics Committee, Australia, and the Fiji National Health Research and Ethics Review Committee. The findings of this study will be disseminated in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT03925480.

A Systematic Review and meta-analysis of the effect of administration of azithromycin during pregnancy on perinatal and neonatal outcomes.

BACKGROUND: Currently there are trials in Africa and Asia investigating whether prophylactic azithromycin during pregnancy reduces infection-related neonatal morbidity and mortality. We undertook a systematic review and meta-analysis to determine the effect of azithromycin during pregnancy on perinatal and neonatal outcomes. METHODS: We identified articles between January 1990 and 13th June 2021 by searching five electronic databases. Randomised control trials (RCTs) that included pregnant women administered azithromycin alone or in combination with other medications, and that reported outcomes of low birthweight (LBW), prematurity, stillbirth, and neonatal deaths, infections, and admissions, were eligible. Fixed effects meta-analyses were used for primary analysis. Quality appraisal was performed using Cochrane's Risk of Bias 2 tool. This review was registered with PROSPERO, CRD42019127099. FINDINGS: The search generated 5777 studies, of which 14 studies were included involving 17,594 participants. Most studies investigated azithromycin as Intermittent Preventive Treatment in Pregnancy (IPTp) for malaria. More than 50% of the studies had low risk of bias for all outcomes, except for LBW and neonatal admissions. Fixed-effects meta-analyses found that azithromycin reduced the risk of LBW (seven studies, Pooled RR 0·79; 95% CI 0·68-0·93; I2 = 0·00%), and prematurity compared to controls (eight studies, Pooled RR 0·87; 95% CI 0·78-0·98; I2 = 23·28%). There was no strong evidence of any effect on neonatal mortality, infections and admissions. There was an increase in stillbirth but the 95% CI crossed the null value (seven studies, Pooled RR 1·39; 95% CI 0·94 - 2.07; I2=0·00%). However this review was limited by differences in the types of intervention and study populations, and inconsistency in outcome reporting between studies. INTERPRETATION: Prophylactic azithromycin during pregnancy reduces LBW and prematurity. However, as azithromycin has been investigated as part of IPTp, it is unclear whether it would improve perinatal and neonatal outcomes in non-malaria endemic settings. The potential harm on stillbirth rates needs further investigation. FUNDING: None.