Target product profile: aerosolized surfactant for neonatal respiratory distress.

Treatment with surfactant has been found to improve the survival rate of neonates with respiratory distress syndrome, particularly preterm infants. However, surfactant is usually administered by endotracheal intubation and generally only in level-3 neonatal intensive care units. Recent improvements in aerosolization technology have raised the possibility that aerosolized surfactant could now be given in wider range of settings, including resource-poor settings. Consequently, the World Health Organization has developed a target product profile for product developers that describes the optimal and minimal characteristics of an aerosolized surfactant for treating neonates with respiratory distress syndrome in low- and middle-income countries. Development of the target product profile involved a scoping review of systematic reviews and target product profiles of aerosolized surfactant, the constitution of an international expert advisory group, consultations with medical professionals from a wide range of countries and a public consultation. The resulting target product profile specifies that the surfactant and its associated aerosolization device should ideally, among other characteristics: (i) be at least as safe and effective as current intratracheal surfactant; (ii) produce a rapid clinical improvement; (iii) be easy to transport and use (e.g. by nurses in level-2 health-care facilities in low- and middle-income countries); (iv) be affordable for low- and middle-income countries; and (v) be stable when stored in hot and humid conditions. In addition, the aerosolization device should be capable of daily use for many years. The introduction of an effective aerosolized surfactant globally could substantially reduce neonatal mortality due to respiratory distress syndrome.

Le traitement par surfactant permet d'améliorer le taux de survie des nouveau-nés souffrant d'un syndrome de détresse respiratoire, en particulier les nourrissons prématurés. Pourtant, ce surfactant est généralement administré par intubation endotrachéale et, la plupart du temps, uniquement dans les unités de soins intensifs néonatals de niveau 3. Les récents progrès réalisés dans le domaine des technologies d'aérosolisation laissent entrevoir la possibilité d'administrer dorénavant un surfactant en aérosol dans d'autres cadres, y compris dans des lieux où les ressources sont limitées. L'Organisation mondiale de la Santé a donc développé un profil de produit cible à l'attention des laboratoires, qui détaille les caractéristiques minimales et optimales d'un surfactant en aérosol destiné à la prise en charge des nouveau-nés souffrant d'un syndrome de détresse respiratoire dans les pays à revenu faible et intermédiaire. Ce document est le fruit d'une analyse exploratoire de revues systématiques et de profils de surfactants en aérosol; un groupe consultatif d'experts internationaux a été constitué, des professionnels de la santé originaires de nombreux pays ont été sollicités, et une consultation publique a été organisée. Le profil de produit cible qui en résulte précise que le surfactant et son dispositif d'aérosolisation doivent idéalement présenter une série de caractéristiques, notamment: (i) être au moins aussi sûrs et efficaces que le surfactant intratrachéal actuel; (ii) entraîner une amélioration clinique rapide; (iii) être faciles à transporter et à utiliser (par exemple par le personnel infirmier de niveau 2, au sein d'établissements de santé dans des pays à revenu faible et intermédiaire); (iv) être abordables pour les pays à revenu faible et intermédiaire; et enfin, (v) demeurer stables quand ils sont stockés dans un environnement chaud et humide. En outre, le dispositif d'aérosolisation doit pouvoir être employé au quotidien pendant plusieurs années. Le lancement d'un surfactant en aérosol à l'échelle mondiale pourrait réduire considérablement la mortalité néonatale due au syndrome de détresse respiratoire.

Se ha observado que el tratamiento con sustancias tensioactivas mejora la tasa de supervivencia de los neonatos con síndrome de dificultad respiratoria, especialmente los prematuros. Sin embargo, la sustancia tensioactiva suele administrarse mediante intubación endotraqueal y, por lo general, solo en unidades de cuidados intensivos neonatales de nivel 3. Las mejoras recientes en la tecnología de aerosolización han planteado la posibilidad de que la sustancia tensioactiva en aerosol se pueda administrar ahora en más entornos, incluidos los de escasos recursos. En consecuencia, la Organización Mundial de la Salud ha desarrollado un perfil de producto específico para los desarrolladores de productos que describe las características óptimas y mínimas de una sustancia tensioactiva en aerosol para el tratamiento de neonatos con síndrome de dificultad respiratoria en países de ingresos bajos y medios. El desarrollo del perfil de producto específico implicó una revisión del alcance de las revisiones sistemáticas y los perfiles de producto específicos de la sustancia tensioactiva en aerosol, la constitución de un grupo asesor internacional de expertos, consultas con profesionales médicos de diversos países y una consulta pública. El perfil de producto específico obtenido indica que lo ideal sería que la sustancia tensioactiva y su dispositivo de aerosolización asociado tuvieran, entre otras, las siguientes características: (i) ser al menos tan seguros y eficaces como la sustancia tensioactiva intratraqueal actual; (ii) producir una mejora clínica rápida; (iii) ser fáciles de transportar y utilizar (p. ej. por el personal de enfermería de los centros sanitarios de nivel 2 de los países de ingresos bajos y medios); (iv) ser asequibles para los países de ingresos bajos y medios; y (v) ser estables cuando se almacenan en condiciones de calor y humedad. Además, el dispositivo de aerosolización se debería poder utilizar a diario durante muchos años. La introducción de una sustancia tensioactiva en aerosol eficaz a nivel mundial podría reducir de manera sustancial la mortalidad neonatal causada por el síndrome de dificultad respiratoria.

Effect of early childhood development interventions delivered by healthcare providers to improve cognitive outcomes in children at 0-36 months: a systematic review and meta-analysis.

OBJECTIVE: To determine the effect of early childhood development interventions delivered by healthcare providers (HCP-ECD) on child cognition and maternal mental health. DESIGN: Systematic review, meta-analysis. SETTING: Healthcare setting or home. PARTICIPANTS: Infants under 1 month of age. INTERVENTIONS: HCP-ECD interventions that supported responsive caregiving, early learning and motor stimulation. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects and Cochrane Database of Systematic Reviews were searched until 15 November 2021. Studies reporting prespecified outcomes were pooled using standard meta-analytical methods. MAIN OUTCOME MEASURES: Cognitive development in children at 0-36 months. RESULTS: Forty-two randomised controlled trials with 15 557 infants were included in the narrative synthesis. Twenty-seven trials were included in the meta-analyses. Pooled data from 13 trials suggest that HCP-ECD interventions may improve cognitive outcomes in children between 0 and 36 months (Bayley Scales of Infant Development version IIII (BSID-III) mean difference (MD) 2.65; 95% CI 0.61 to 4.70; 2482 participants; low certainty of evidence). Pooled data from nine trials suggest improvements in motor development (BSID-III MD 4.01; 95% CI 1.54 to 6.48; 1437 participants; low certainty of evidence). There was no evidence of improvement in maternal mental health (standardised MD -0.13; 95% CI -0.28 to 0.03; 2806 participants; 11 trials; low certainty of evidence). CONCLUSIONS: We report promising evidence, particularly for cognitive and motor outcomes, of the effect of HCP-ECD interventions. However, effect sizes were small, and the certainty of evidence ranged from very low to moderate. Additional high-quality research is required. PROSPERO REGISTRATION NUMBER: CRD42019122021.

Perspectives of health service providers in delivering best-practice care for Aboriginal mothers and their babies during the postnatal period.

BACKGROUND: Evidence suggests that Aboriginal babies in Western Australia are not receiving adequate primary health care in their first 3 months of life, leading to questions about enablers and constraints to delivering such care. This paper presents findings from a qualitative research project investigating health providers' perceptions and experiences of best and current practice in discharge planning, postnatal care and health education for Aboriginal mothers and their newborn babies. METHODS: Constructivist grounded theory guided this research involving 58 semi-structured interviews conducted with health providers who deliver care to Aboriginal mothers and infants. Participants were recruited from hospital-based and primary health sites in metropolitan Perth, and regional and remote locations in Western Australia. RESULTS: Structural factors enabling best practice in discharge planning, postnatal care, and health education for mothers included health providers following best practice guidelines and adequate staffing levels. Organisational enablers included continuity of care throughout pregnancy, birth and postnatally. In particular, good communication between services around discharge planning, birth notifications, and training in culturally respectful care. Structural and organisational constraints to delivering best practice and compromising continuity of care were identified as beyond individual control. These included poor communication between different health and social services, insufficient hospital staffing levels leading to early discharge, inadequate cultural training, delayed receipt of birth notifications and discharge summaries received by Aboriginal primary health services. CONCLUSION: Findings highlight the importance of examining current policies and practices to promote best practice in postnatal care to improve health outcomes for mothers and their Aboriginal babies.

Family-centred interventions for Indigenous early childhood well-being by primary healthcare services.

BACKGROUND: Primary healthcare, particularly Indigenous-led services, are well placed to deliver services that reflect the needs of Indigenous children and their families. Important characteristics identified by families for primary health care include services that support families, accommodate sociocultural needs, recognise extended family child-rearing practices, and Indigenous ways of knowing and doing business. Indigenous family-centred care interventions have been developed and implemented within primary healthcare services to plan, implement, and support the care of children, immediate and extended family and the home environment. The delivery of family-centred interventions can be through environmental, communication, educational, counselling, and family support approaches. OBJECTIVES: To evaluate the benefits and harms of family-centred interventions delivered by primary healthcare services in Canada, Australia, New Zealand, and the USA on a range of physical, psychosocial, and behavioural outcomes of Indigenous children (aged from conception to less than five years), parents, and families. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 22 September 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster RCTs, quasi-RCTs, controlled before-after studies, and interrupted time series of family-centred care interventions that included Indigenous children aged less than five years from Canada, Australia, New Zealand, and the USA. Interventions were included if they met the assessment criteria for family-centred interventions and were delivered in primary health care. Comparison interventions could include usual maternal and child health care or one form of family-centred intervention versus another. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall health and well-being, 2. psychological health and emotional behaviour of children, 3. physical health and developmental health outcomes of children, 4. family health-enhancing lifestyle or behaviour outcomes, 5. psychological health of parent/carer. 6. adverse events or harms. Our secondary outcomes were 7. parenting knowledge and awareness, 8. family evaluation of care, 9. service access and utilisation, 10. family-centredness of consultation processes, and 11. economic costs and outcomes associated with the interventions. We used GRADE to assess the certainty of the evidence for our primary outcomes. MAIN RESULTS: We included nine RCTs and two cluster-RCTs that investigated the effect of family-centred care interventions delivered by primary healthcare services for Indigenous early child well-being. There were 1270 mother-child dyads and 1924 children aged less than five years recruited. Seven studies were from the USA, two from New Zealand, one from Canada, and one delivered in both Australia and New Zealand. The focus of interventions varied and included three studies focused on early childhood caries; three on childhood obesity; two on child behavioural problems; and one each on negative parenting patterns, child acute respiratory illness, and sudden unexpected death in infancy. Family-centred education was the most common type of intervention delivered. Three studies compared family-centred care to usual care and seven studies provided some 'minimal' intervention to families such as education in the form of pamphlets or newsletters. One study provided a minimal intervention during the child's first 24 months and then the family-centred care intervention for one year. No studies had low or unclear risk of bias across all domains. All studies had a high risk of bias for the blinding of participants and personnel domain. Family-centred care may improve overall health and well-being of Indigenous children and their families, but the evidence was very uncertain. The pooled effect estimate from 11 studies suggests that family-centred care improved the overall health and well-being of Indigenous children and their families compared no family-centred care (standardised mean difference (SMD) 0.14, 95% confidence interval (CI) 0.03 to 0.24; 2386 participants). We are very uncertain whether family-centred care compared to no family-centred care improves the psychological health and emotional behaviour of children as measured by the Infant Toddler Social Emotional Assessment (ITSEA) (Competence domain) (mean difference (MD) 0.04, 95% CI -0.03 to 0.11; 2 studies, 384 participants). We assessed the evidence as being very uncertain about the effect of family-centred care on physical health and developmental health outcomes of children. Pooled data from eight trials on physical health and developmental outcomes found there was little to no difference between the intervention and the control groups (SMD 0.13, 95% CI -0.00 to 0.26; 1961 participants). The evidence is also very unclear whether family-centred care improved family-enhancing lifestyle and behaviours outcomes. Nine studies measured family health-enhancing lifestyle and behaviours and pooled analysis found there was little to no difference between groups (SMD 0.16, 95% CI -0.06 to 0.39; 1969 participants; very low-certainty evidence). There was very low-certainty evidence of little to no difference for the psychological health of parents and carers when they participated in family-centred care compared to any control group (SMD 0.10, 95% CI -0.03 to 0.22; 5 studies, 975 parents/carers). Two studies stated that there were no adverse events as a result of the intervention. No additional data were provided. No studies reported from the health service providers perspective or on outcomes for family's evaluation of care or family-centredness of consultation processes. AUTHORS' CONCLUSIONS: There is some evidence to suggest that family-centred care delivered by primary healthcare services improves the overall health and well-being of Indigenous children, parents, and families. However, due to lack of data, there was not enough evidence to determine whether specific outcomes such as child health and development improved as a result of family-centred interventions. Seven of the 11 studies delivered family-centred education interventions. Seven studies were from the USA and centred on two particular trials, the 'Healthy Children, Strong Families' and 'Family Spirit' trials. As the evidence is very low certainty for all outcomes, further high-quality trials are needed to provide robust evidence for the use of family-centred care interventions for Indigenous children aged less than five years.

Effectiveness of universal newborn hearing screening: A systematic review and meta-analysis.

Background: Permanent bilateral hearing loss (PBHL) is a serious condition in newborns, with a prevalence of at least one per 1000 live births. However, there has been no recent systematic review and meta-analysis of the effectiveness of universal newborn hearing screening programs (UNHS). Methods: We registered our study protocol on PROSPERO CRD42020175451. Primary outcomes were any identification of PBHL (ie, PBHL diagnosed at any time), age of identification of PBHL, and neurodevelopment. Two reviewers searched standard databases to March 2022 and extracted data. We used fixed and random effects meta-analysis to pool data and graded the certainty of evidence using standard methods. Results: The search retrieved 2834 records. We identified five studies reporting on the effects of UNHS vs no UNHS in 1 023 610 newborns. The relative risk of being identified with PBHL before nine months in infants with UNHS compared to infants without UNHS was 3.28 (95% confidence interval (95% CI) = 1.84, 5.85, one study, 1 023 497 newborns, low certainty evidence). The mean difference in the age of identification of PBHL in infants with UNHS compared to infants without UNHS was 13.2 months earlier (95% CI = -26.3, -0.01, two studies, 197 newborns, very low certainty evidence). The relative risk of infants eventually being identified with PBHL in infants with UNHS compared to infants without UNHS was 1.01 (95% CI = 0.89, 1.14, three studies, 1 023 497 newborns, low certainty evidence). At the latest follow-up at 3-8 years, the standardised mean difference (SMD) in receptive language development between infants with UNHS compared to infants without UNHS was 0.60 z scores (95% CI = 0.07, 1.13, one study, 101 children, low certainty evidence) and the mean difference in developmental quotients was 7.72 (95% CI = -0.03, 15.47, three studies, 334 children, very low certainty evidence). The SMD in expressive language development was 0.39 z scores (95% CI = -0.20, 0.97, one study, 87 children, low certainty evidence) and the mean difference in developmental quotients was 10.10 scores (95% CI = 1.47, 18.73, 3 studies, 334 children, very low certainty evidence). Conclusions: UNHS programs result in earlier identification of PBHL and may improve neurodevelopment. UNHS should be implemented across high-, middle-, and low-income countries. Registration: PROSPERO (CRD42020175451).

Enteral Multiple Micronutrient Supplementation in Preterm and Low Birth Weight Infants: A Systematic Review and Meta-analysis.

OBJECTIVES: To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS: Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS: Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.

Family Involvement in the Routine Care of Hospitalized Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Preterm and low birth weight (LBW) infants are often separated from parents during hospitalization. Our objective was to assess effects of interventions to increase family involvement in the routine newborn care of preterm or LBW infants compared with standard NICU care on infant and parental outcomes. METHODS: Data sources include Medline, Embase, CINAHL, and World Health Organization Global Index Medicus to August 2021. The study selection included randomized controlled trials (RCTs) of family involvement intervention packages. Data were extracted and pooled with random-effects models. RESULTS: We included 15 RCTs with 5240 participants. All interventions included direct parental bedside care; packages varied with respect to additional components. Family involvement interventions decreased retinopathy of prematurity (odds ratio 0.52, 95% confidence interval [CI]: 0.34, 0.80; 8 RCTs), length of hospital stay (mean difference [MD] -2.91 days; 95% CI: -5.15,-0.82; 11 RCTs), and parental stress and anxiety (Parental Stress Scale: MD -0.29 points, 95% CI: -0.56,-0.01, 2 RCTs; Anxiety State-Trait scale: MD -1.79, 95% CI: -3.11,-0.48; 2 RCTs). Family involvement increased weight gain velocity (MD 2.09 g/day; 95% CI: 1.27, 2.91; 3 RCTs), neurobehavioral exam scores (MD: 1.11; 95% CI: 0.21, 2.01; 2 RCTs) and predominant or exclusive breastmilk intake (odds ratio 1.34; 95% CI: 1.01, 1.65; 3 RCTs). It may decrease rates of bronchopulmonary dysplasia, infection, and intraventricular hemorrhage. There were no effects on mortality or necrotizing enterocolitis. Certainty of evidence ranged from low to moderate. CONCLUSIONS: Family involvement has a beneficial role on several infant and parental outcomes.

Early Enteral Feeding for Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis.

CONTEXT: Early enteral feeding has been associated with adverse outcomes such as necrotizing enterocolitis in preterm and low birth weight infants. OBJECTIVES: To assess effects of early enteral feeding initiation within the first days after birth compared to delayed initiation. DATA SOURCES: Medline, Scopus, Web of Science, CINAHL from inception to June 30, 2021. STUDY SELECTION: Randomized trials (RCTs) were included. Primary outcomes were mortality, morbidity, growth, neurodevelopment, feed intolerance, and duration of hospitalization. DATA EXTRACTION: Data were extracted and pooled with random-effects models. RESULTS: We included 14 randomized controlled trials with 1505 participants in our primary analysis comparing early (<72 hours) to delayed (≥72 hours) enteral feeding initiation. Early initiation likely decreased mortality at discharge and 28 days (1292 participants, 12 trials, relative risk 0.69, 95% confidence interval [95% CI] 0.48-0.99, moderate certainty evidence) and duration of hospitalization (1100 participants, 10 trials, mean difference -3.20 days, 95%CI -5.74 to -0.66, moderate certainty evidence). The intervention may also decrease sepsis and weight at discharge. Based on low certainty evidence, early feeding may have little to no effect on necrotizing enterocolitis, feed intolerance, and days to regain birth weight. The evidence is very uncertain regarding the effect of initiation time on intraventricular hemorrhage, length, and head circumference at discharge. CONCLUSIONS: Enteral feeding within 72 hours after birth likely reduces the risk of mortality and length of hospital stay, may reduce the risk of sepsis, and may reduce weight at discharge.

Mother's Own Milk Compared With Formula Milk for Feeding Preterm or Low Birth Weight Infants: Systematic Review and Meta-analysis.

OBJECTIVES: We assessed the effect of feeding preterm or low birth weight infants with infant formula compared with mother's own milk on mortality, morbidity, growth, neurodevelopment, and disability. METHODS: We searched Medline (Ovid), Embase (Ovid), and Cochrane Central Register of Controlled Studies to October 1, 2021. RESULTS: Forty-two studies enrolling 89 638 infants fulfilled the inclusion criteria. We did not find evidence of an effect on mortality (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.91-1.76), infection (OR 1.52, 95% CI 0.98-2.37), cognitive neurodevelopment (standardized mean difference -1.30, 95% CI -3.53 to 0.93), or on growth parameters. Formula milk feeding increased the risk of necrotizing enterocolitis (OR 2.99, 95% CI 1.75-5.11). The Grading of Recommendations Assessment, Development, and Evaluation certainty of evidence was low for mortality and necrotizing enterocolitis, and very low for neurodevelopment and growth outcomes. CONCLUSIONS: In preterm and low birth weight infants, low to very low-certainty evidence indicates that feeding with infant formula compared with mother's own milk has little effect on all-cause mortality, infection, growth, or neurodevelopment, and a higher risk of developing necrotizing enterocolitis.

Evidence for Global Health Care Interventions for Preterm or Low Birth Weight Infants: An Overview of Systematic Reviews.

CONTEXT: Twenty-four research questions (framed as population, intervention, comparator, and outcomes) for global health care interventions for preterm and low birth weight (LBW) infants were identified at a World Health Organization guideline development group expert meeting in December 2020. OBJECTIVE: To describe which systematic reviews had addressed these research questions in the last 3 years. DATA SOURCES: Medline (Ovid); the Cochrane Database of Systematic Reviews; the Cochrane Database of Systematic Review Protocols; and the PROSPERO International prospective register of systematic reviews databases from January 1, 2019 to December 31, 2021 were used.Randomized controlled trials or observational studies. Two reviewers independently extracted data. RESULTS: We found 9 systematic reviews. Eight reviews of 121 studies and 25 465 preterm or LBW infants published in the last 36 months "fully" addressed 8 of our 24 research questions (donor human milk, multicomponent fortifier, formula milk, probiotics, emollients, continuous positive airways pressure [CPAP] any, CPAP early, CPAP prophylactic); and 1 systematic review found no trials (mother's own milk). All received a "high" AMSTAR quality rating. Fifteen research questions (kangaroo mother care, early initiation, responsive feeding, advancement, exclusive breastfeeding duration, iron, zinc, vitamin D, vitamin A, calcium and phosphorous, multiple micronutrients, CPAP pressure source, methyl xanthines, family involvement, and family support) had no systematic review. Limitations include that we restricted our search to those interventions identified as a priority at a World Health Organization scoping meeting. Other interventions that may be of importance to preterm or LBW infants were not able to be considered. CONCLUSIONS: Almost a third of our research questions were addressed by high quality systematic reviews. We found gaps in thermal care, feeding, and familysupport interventions, which need to be addressed.

Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania.

BACKGROUND: Vaccines may induce non-specific effects on survival and health outcomes, in addition to protection against targeted pathogens or disease. Observational evidence suggests that infant Baccillus Calmette-Guérin (BCG) vaccination may provide non-specific survival benefits, while diphtheria-tetanus-pertussis (DTP) vaccination may increase the risk of mortality. Non-specific vaccine effects have been hypothesized to modify the effect of neonatal vitamin A supplementation (NVAS) on mortality. METHODS: 22,955 newborns in Ghana and 31,999 newborns in Tanzania were enrolled in two parallel, randomized, double-blind, placebo-controlled trials of neonatal vitamin A supplementation from 2010 to 2014 and followed until 1-year of age. Cox proportional hazard models were used to estimate associations of BCG and DTP vaccination with infant survival. RESULTS: BCG vaccination was associated with a decreased risk of infant mortality after controlling for confounders in both countries (Ghana adjusted hazard ratio (aHR): 0.51, 95% CI: 0.38-0.68; Tanzania aHR: 0.08, 95% CI: 0.07-0.10). Receiving a DTP vaccination was associated with a decreased risk of death (Ghana aHR: 0.39, 95% CI: 0.26-0.59; Tanzania aHR: 0.19, 95% CI: 0.16-0.22). There was no evidence of interaction between BCG or DTP vaccination status and infant sex or NVAS. CONCLUSION: We demonstrated that BCG and DTP vaccination were associated with decreased risk of infant mortality in Ghana and Tanzania with no evidence of interaction between DTP or BCG vaccination, NVAS, and infant sex. Our study supports global recommendations on BCG and DTP vaccination and programmatic efforts to ensure all children have access to timely vaccination. CLINICAL TRIALS REGISTRATION: Ghana (Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000582055) and Tanzania (ANZCTR: ACTRN12610000636055).

Implementing effective community-based surveillance in research studies of maternal, newborn and infant outcomes in low resource settings.

BACKGROUND: Globally adopted health and development milestones have not only encouraged improvements in the health and wellbeing of women and infants worldwide, but also a better understanding of the epidemiology of key outcomes and the development of effective interventions in these vulnerable groups. Monitoring of maternal and child health outcomes for milestone tracking requires the collection of good quality data over the long term, which can be particularly challenging in poorly-resourced settings. Despite the wealth of general advice on conducting field trials, there is a lack of specific guidance on designing and implementing studies on mothers and infants. Additional considerations are required when establishing surveillance systems to capture real-time information at scale on pregnancies, pregnancy outcomes, and maternal and infant health outcomes. MAIN BODY: Based on two decades of collaborative research experience between the Kintampo Health Research Centre in Ghana and the London School of Hygiene and Tropical Medicine, we propose a checklist of key items to consider when designing and implementing systems for pregnancy surveillance and the identification and classification of maternal and infant outcomes in research studies. These are summarised under four key headings: understanding your population; planning data collection cycles; enhancing routine surveillance with additional data collection methods; and designing data collection and management systems that are adaptable in real-time. CONCLUSION: High-quality population-based research studies in low resource communities are essential to ensure continued improvement in health metrics and a reduction in inequalities in maternal and infant outcomes. We hope that the lessons learnt described in this paper will help researchers when planning and implementing their studies.

Community health worker service delivery for maternal and child health: an observational study from Afghanistan.

OBJECTIVE: To understand the reach of the community health worker (CHW) programme in remote and non-remote districts of Afghanistan. METHODS: Using data collected from the Ministry of Public Health's National Health Management Information System, we conducted a population-based study from 2018 to 2019 in 401 districts across 34 provinces of Afghanistan. We assessed the availability of CHWs, antenatal visits (ANV) and postnatal visits (PNV) conducted by the CHWs, and the availability of CHW supplies. Districts were classified as remote if the district centre was >2 hours by any form of transport from provincial capital, and non-remote if <2 hours. Data were analysed using multivariable regression models. RESULTS: 15 562 CHWs were working in the districts of Afghanistan, 13 482 (87%) in remote and 2080 (13%) in non-remote districts. The mean of the proportion of CHWs per pregnant woman was higher in remote (0.019 (SD 0.011)) compared with non-remote (0.012 (SD 0.006)) districts (adjusted mean difference (AMD) 0.008, 95% CI 0.004 to 0.01). The mean of the proportion of ANVs received from a CHW per pregnant women was higher in remote (0.88 (SD 0.82)) compared with non-remote (0.62 (SD 0.50)) districts (AMD 0.28, 95% CI 0.02 to 0.54). The mean of the proportion of PNVs received from a CHW per pregnant women was higher in remote (0.54 (SD 0.53)) compared with non-remote (0.36 (SD 0.25)) districts (AMD 0.19, 95% CI 0.02 to 0.36). The mean of the proportion of CHWs who reported that they had stocks of cotrimoxazole and oral contraceptives in the previous month per district was higher in remote compared with non-remote districts. CONCLUSIONS: In Afghanistan, the CHW programme appears to be effective and proportionate to need in remote regions.

Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.

BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa. METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes. CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths. TRIAL REGISTRATION: The study is not a clinical trial.

Understanding an Aboriginal and Torres Strait Islander child's journey through paediatric care in Western Australia.

OBJECTIVE: To explore caregiver perspectives of their children's journey through the specialist paediatric service, the Aboriginal Ambulatory Care Coordination Program (AACC), and non-AACC services at the Perth Children's Hospital. METHODS: Eighteen semi-structured interviews with families of Aboriginal children were completed. Indigenous research methodology and a phenomenological approach guided data collection and analysis. RESULTS: Four key themes were identified from interviews: hospital admissions, discharge and follow-up outpatient appointments; communication; financial burden; and cultural issues. Our findings suggest Aboriginal children and their caregivers using the AACC program had more positive and culturally secure experiences than those using non-AACC services. However, barriers relating to health providers' understanding of Aboriginal cultural issues and lived experience were commonly discussed, regardless of which service families received. CONCLUSIONS: Australian Aboriginal children have an increased use of tertiary hospital care compared to non-Indigenous children. Healthcare programs specifically designed for Aboriginal children and their families can improve their experience of care in hospital. However, improvements in cultural awareness for other hospital staff is still needed. Implications for public health: Dedicated Aboriginal programs in mainstream services can successfully improve cultural care to their clients, which is fundamental to improving service delivery for families.

Acknowledging the gap: a systematic review of micronutrient supplementation in infants under six months of age.

Background: Micronutrient deficiencies remain common worldwide, but the consequences to growth and development in early infancy (under six months of age) are not fully understood. We present a systematic review of micronutrient interventions in term infants under six months of age, with a specific focus on iron supplementation. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) from January 1980 through December 2019. Interventions included iron or multiple micronutrients (MMNs). Results: Of 11,109 records identified, 33 publications from 24 trials were included (19 iron and five MMN supplementation trials). All but one trial (evaluating only morbidity and mortality) evaluated the effect of supplementation on biochemical outcomes, ten reported on growth, 15 on morbidity and/or mortality and six on neuro-behavioural development. Low- and middle- income countries made up 88% (22/25) of the total trial locations. Meta-analysis was not possible due to extensive heterogeneity in both exposure and outcome measures.  However, these trials indicated that infants less than six months of age benefit biochemically from early supplementation with iron, but the effect of additional nutrients or MMNs, along with the impacts on growth, morbidity and/or mortality, and neuro-behavioural outcomes remain unclear. Conclusions: Infants less than six months of age appear to benefit biochemically from micronutrient supplementation. However, well-powered randomised controlled trials are required to determine whether routine supplementation with iron or MMNs containing iron should commence before six months of life in exclusively breast-fed infants in low-resource settings.