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Children are not born equal in their likelihood of survival. The risk of mortality is highest during and shortly after birth. In the immediate postnatal period and beyond, perinatal events, nutrition, infections, family and environmental exposures, and health services largely determine the risk of death. We argue that current public health programmes do not fully acknowledge this spectrum of risk or respond accordingly. As a result, opportunities to improve the care, survival, and development of children in resource-poor settings are overlooked. Children at high risk of mortality are underidentified and commonly treated using guidelines that do not differentiate care according to the magnitude or drivers of those risks. Children at low risk of mortality are often provided with more intensive care than needed, disproportionately using limited health-care resources with minimal or no benefits. Declines in newborn, infant, and child mortality rates globally are slowing, and further reductions are likely to be incrementally more difficult to achieve once simple, high impact interventions have been universally implemented. Currently, 63 countries have rates of neonatal mortality that are off track to meet the Sustainable Development Goal 2030 target of 12 deaths per 1000 livebirths or less, and 54 countries have rates of mortality in children younger than 5 years that are off track to meet the target of 25 deaths per 1000 livebirths or less. If these targets are to be met, a change of approach is needed to address infant and child mortality and for health-care systems to more efficiently address residual mortality., Competing Interests: Declaration of interests We decare no competing interests. The authors alone are responsible for the views expressed in this Viewpoint and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment., Methods: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk., Results: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097)., Conclusions: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings., Clinical Trial Registration: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044., Competing Interests: All other authors declare no competing interests. YBN and RB are WHO employees. The expressed views and opinions do not necessarily express the policies of the World Health Organization. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: ZAB is a member of the Editorial Board of PLOS Medicine. Remaining authors declared no competing interests.

Background: Use of uterotonics like oxytocin to induce or augment labor has been shown to reduce placental perfusion and oxygen supply to the fetus, and studies indicate that it may increase the risk of stillbirth and neonatal asphyxia. Antenatal use of uterotonics, even without the required fetal monitoring and prompt access to cesarean section, is widespread, yet no study has adequately estimated the risk of intrapartum stillbirth and early neonatal deaths ascribed to such use. We conducted a case-control study to estimate this risk., Methods: We conducted a population-based case-control study nested in a cluster-randomized trial. From 2008 to 2010, we followed pregnant women in rural Haryana, India, monthly until delivery. We visited all live-born infants on day 29 to ascertain whether they were alive. We conducted verbal autopsies for stillbirths and neonatal deaths. Cases (n = 2,076) were the intrapartum stillbirths and day-1 deaths (early deaths), and controls (n = 532) were live-born babies who died between day 8 and 28 (late deaths)., Results: Antenatal administration of uterotonics preceded 74% of early and 62% of late deaths, translating to an adjusted odds ratio (95% confidence interval [CI]) for early deaths of 1.7 (95% CI = 1.4, 2.1), and a population attributable risk of 31% (95% CI = 22%, 38%)., Conclusions: Antenatal administration of uterotonics was associated with a substantially increased risk of intrapartum stillbirth and day-1 death. See video abstract: http://links.lww.com/EDE/B707.

Introduction: Neonatal infections are a common cause of death in India, but many families cannot access appropriate hospitals for its treatment due to various reasons. We implemented the World Health Organization PSBI management guideline when referral is not feasible within the public health system in Pune, India to evaluate feasibility, barriers and facilitators for its implementation., Methods: A national-level consultative meeting between government officials and study partners resulted in a consensus on adaptation and implementation in four demonstration sites in selected states in India. At the state and district levels, similar meetings to plan the implementation strategy and roles were held between KEM Hospital Research Centre (KEMHRC) Pune and the public health system Pune, Maharashtra. The public health system was responsible for implementation of the intervention at eight tribal primary health centres (PHC) in Pune district, India, including delivering the intervention and ensuring supplies of all commodities while KEMHRC was responsible for technical support including training of health workers, assistance in PSBI identification and management, data collection and documentation of the implementation strategy., Results: A total of 175 young infants with PSBI were identified and managed. Of these, 34 had critical illness (CI), 46 had clinical severe infection (CSI) and 10 were infants aged 0-6 days with fast breathing (FB) while 85 infants aged 7-59 days had fast breathing. Assuming a 10% incidence of PSBI among all live births, with 3071 live births recorded, the actual incidence of PSBI found in the study was 5.7%, resulting in an actual coverage was of 57%. Among the 90 infants with CI, CSI and FB in 0-6 days, who were advised referral to government tertiary care centre as per the PSBI guideline algorithm, 81 (90%) accepted referral while 9 (10%) refused and were offered treatment at primary health centres (PHC) with a seven-day course of injectable gentamicin and oral amoxicillin. All infants with FB in 7-59 days were offered treatment at PHCs as per the PSBI guideline algorithm with a seven-day course of oral amoxicillin. All except six infants who died and one with FB in 7-59 days, who was lost to follow-up, were successfully cured. Of the six who died, five had CSI and one had CI. Among the 81 infants with CI, CSI and FB in 0-6 days who accepted referral; 48(53%) were successfully referred to government tertiary facility while 33 (36.6%) preferred to visit a private tertiary health facility. The implementation strategy demonstrated a relatively high fidelity, acceptance and intervention penetration. Lack of training and confidence of the public health staff were major challenges faced, which were resolved to a large extent through supportive supervision and re-trainings., Conclusion: Management of PSBI is feasible to implement in out-patient facilities in the public health system, but technical support to the health system is required to jump-start the process. Fast breathing in 7-59 days old infants can be managed with oral amoxicillin without referral. A sustainable adoption of this intervention by the health system can lead to decrease in neonatal mortality and morbidity., Competing Interests: The authors have declared that no competing interests exist.

Background: Coverage of kangaroo mother care remains very low despite WHO recommendations for its use for babies with low birthweight in health facilities for over a decade. Initiating kangaroo mother care at the community level is a promising strategy to increase coverage. However, knowledge of the efficacy of community-initiated kangaroo mother care is still lacking. We aimed to assess the effect of community-initiated kangaroo mother care provided to babies weighing 1500-2250 g on neonatal and infant survival., Methods: In this randomised controlled, superiority trial, undertaken in Haryana, India, we enrolled babies weighing 1500-2250 g at home within 72 h of birth, if not already initiated in kangaroo mother care, irrespective of place of birth (ie, home or health facility) and who were stable and feeding. The first eligible infants in households were randomly assigned (1:1) to the intervention (community-initiated kangaroo mother care) or control group by block randomisation using permuted blocks of variable size. Twins were allocated to the same group. For second eligible infants in the same household as an enrolled infant, if the first infant was assigned to the intervention group the second infant was also assigned to this group, whereas if the first infant was assigned to the control group the second infant was randomly assigned (1:1) to the intervention or control group. Mothers and infants in the intervention group were visited at home (days 1-3, 5, 7, 10, 14, 21, and 28) to support kangaroo mother care (ie, skin-to-skin contact and exclusive breastfeeding). The control group received routine care. The two primary outcomes were mortality between enrolment and 28 days and between enrolment and 180 days. Analysis was by intention to treat and adjusted for clustering within households. The effect of the intervention on mortality was assessed with person-time in the denominator using Cox proportional hazards model. This study is registered with ClinicalTrials.gov, NCT02653534 and NCT02631343, and is now closed to new participants., Findings: Between July 30, 2015, and Oct 31, 2018, 8402 babies were enrolled, of whom 4480 were assigned to the intervention group and 3922 to the control group. Most births (6837 [81·4%]) occurred at a health facility, 36·2% (n=3045) had initiated breastfeeding within 1 h of birth, and infants were enrolled at an average of about 30 h (SD 17) of age. Vital status was known for 4470 infants in the intervention group and 3914 in the control group at age 28 days, and for 3653 in the intervention group and 3331 in the control group at age 180 days. Between enrolment and 28 days, 73 infants died in 4423 periods of 28 days in the intervention group and 90 deaths in 3859 periods of 28 days in the control group (hazard ratio [HR] 0·70, 95% CI 0·51-0·96; p=0·027). Between enrolment and 180 days, 158 infants died in 3965 periods of 180 days in the intervention group and 184 infants died in 3514 periods of 180 days in the control group (HR 0·75, 0·60-0·93; p=0·010). The risk ratios for death were almost the same as the HRs (28-day mortality 0·71, 95% CI 0·52- 0·97; p=0·032; 180-day mortality 0·76, 0·60-0·95; p=0·017)., Interpretation: Community-initiated kangaroo mother care substantially improves newborn baby and infant survival. In low-income and middle-income countries, incorporation of kangaroo mother care for all infants with low birthweight, irrespective of place of birth, could substantially reduce neonatal and infant mortality., Funding: Research Council of Norway and University of Bergen., (Copyright © 2019 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy., Design: Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices., Setting: Rural Haryana, North India., Participants: Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life., Results: We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight <2000 g (RR 3.38; 95% CI 2.71 to 4.12). The risk of hospitalisation in the neonatal period and postneonatal period was (RR 1.86; 95% CI 1.64 to 2.11) and (RR 1.13; 95% CI 1.05 to 1.21), respectively. LBWs were at increased risk of breast feeding initiation 24 hours after birth (RR 1.64; 95% CI 1.45 to 1.81), no breast feeding at 6 months (RR 1.34; 95% CI 1.23 to 1.46) and at 12 months of age (RR 1.24; 95% CI 1.18 to 1.30)., Conclusions: LBW babies, especially those with birth weight of <2000 g, were at increased risk of mortality, hospitalisation and suboptimal breast feeding practices during entire infancy and therefore require additional care beyond the first 28 days of life., Trial Registration Number: NCT01138449., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries., Methods: We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality., Findings: Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality., Conclusion: Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings.

Aim: To synthesise the evidence for effects of optimal breastfeeding on all-cause and infection-related mortality in infants and children aged 0-23 months., Methods: We conducted a systematic review to compare the effect of predominant, partial or nonbreastfeeding versus exclusive breastfeeding on mortality rates in the first six months of life and effect of no versus any breastfeeding on mortality rates between 6 and 23 months of age. A systematic literature search was conducted in PubMed, Cochrane CENTRAL and CABI., Results: The risk of all-cause mortality was higher in predominantly (RR 1.5), partially (RR 4.8) and nonbreastfed (RR14.4) infants compared to exclusively breastfed infants 0-5 months of age. Children 6-11 and 12-23 months of age who were not breastfed had 1.8- and 2.0-fold higher risk of mortality, respectively, when compared to those who were breastfed. Risk of infection-related mortality in 0-5 months was higher in predominantly (RR 1.7), partially (RR 4.56) and nonbreastfed (RR 8.66) infants compared to exclusive breastfed infants. The risk was twofold higher in nonbreastfed children when compared to breastfed children aged 6-23 months., Conclusion: The findings underscore the importance of optimal breastfeeding practices during infancy and early childhood., (©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

The purpose of this study was to review the evidence on the effect of initiation of breastfeeding early after birth and of exclusive breastfeeding during the first month in reducing neonatal mortality and morbidity. We searched Cochrane and PubMed databases for all available papers addressing our review questions and identified eleven papers. Data were extracted using a standard abstraction form. Evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. Meta-analysis was done using STATA 11.0. Early initiation of breastfeeding was associated with a reduced risk of neonatal mortality. Initiating breastfeeding after the first hour doubled the risk of neonatal mortality. Exclusively breastfed neonates had a lower risk of mortality and infection-related deaths in the first month than partially breastfed neonates. Exclusively breastfed neonates also had a significantly lower risk of sepsis, diarrhea and respiratory infections compared with those partially breastfed. The pooled evidence indicates that substantial benefits in reducing neonatal mortality and morbidity can be achieved with effective promotion of early initiation of breastfeeding and exclusive breastfeeding during the first month of life.

Progress in newborn survival has been slow, and even more so for reductions in stillbirths. To meet Every Newborn targets of ten or fewer neonatal deaths and ten or fewer stillbirths per 1000 births in every country by 2035 will necessitate accelerated scale-up of the most effective care targeting major causes of newborn deaths. We have systematically reviewed interventions across the continuum of care and various delivery platforms, and then modelled the effect and cost of scale-up in the 75 high-burden Countdown countries. Closure of the quality gap through the provision of effective care for all women and newborn babies delivering in facilities could prevent an estimated 113,000 maternal deaths, 531,000 stillbirths, and 1·325 million neonatal deaths annually by 2020 at an estimated running cost of US$4·5 billion per year (US$0·9 per person). Increased coverage and quality of preconception, antenatal, intrapartum, and postnatal interventions by 2025 could avert 71% of neonatal deaths (1·9 million [range 1·6-2·1 million]), 33% of stillbirths (0·82 million [0·60-0·93 million]), and 54% of maternal deaths (0·16 million [0·14-0·17 million]) per year. These reductions can be achieved at an annual incremental running cost of US$5·65 billion (US$1·15 per person), which amounts to US$1928 for each life saved, including stillbirths, neonatal, and maternal deaths. Most (82%) of this effect is attributable to facility-based care which, although more expensive than community-based strategies, improves the likelihood of survival. Most of the running costs are also for facility-based care (US$3·66 billion or 64%), even without the cost of new hospitals and country-specific capital inputs being factored in. The maximum effect on neonatal deaths is through interventions delivered during labour and birth, including for obstetric complications (41%), followed by care of small and ill newborn babies (30%). To meet the unmet need for family planning with modern contraceptives would be synergistic, and would contribute to around a halving of births and therefore deaths. Our analysis also indicates that available interventions can reduce the three most common cause of neonatal mortality--preterm, intrapartum, and infection-related deaths--by 58%, 79%, and 84%, respectively., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo., Methods/design: The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation., Discussion: The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.

Objective: To determine the association of different feeding patterns for infants (exclusive breastfeeding, predominant breastfeeding, partial breastfeeding and no breastfeeding) with mortality and hospital admissions during the first half of infancy., Methods: This paper is based on a secondary analysis of data from a multicentre randomized controlled trial on immunization-linked vitamin A supplementation. Altogether, 9424 infants and their mothers (2919 in Ghana, 4000 in India and 2505 in Peru) were enrolled when infants were 18-42 days old in two urban slums in New Delhi, India, a periurban shanty town in Lima, Peru, and 37 villages in the Kintampo district of Ghana. Mother-infant pairs were visited at home every 4 weeks from the time the infant received the first dose of oral polio vaccine and diphtheria-pertussis-tetanus at the age of 6 weeks in Ghana and India and at the age of 10 weeks in Peru. At each visit, mothers were queried about what they had offered their infant to eat or drink during the past week. Information was also collected on hospital admissions and deaths occurring between the ages of 6 weeks and 6 months. The main outcome measures were all-cause mortality, diarrhoea-specific mortality, mortality caused by acute lower respiratory infections, and hospital admissions., Findings: There was no significant difference in the risk of death between children who were exclusively breastfed and those who were predominantly breastfed (adjusted hazard ratio (HR) = 1.46; 95% confidence interval (CI) = 0.75-2.86). Non-breastfed infants had a higher risk of dying when compared with those who had been predominantly breastfed (HR = 10.5; 95% CI = 5.0-22.0; P < 0.001) as did partially breastfed infants (HR = 2.46; 95% CI = 1.44-4.18; P = 0.001)., Conclusion: There are two major implications of these findings. First, the extremely high risks of infant mortality associated with not being breastfed need to be taken into account when informing HIV-infected mothers about options for feeding their infants. Second, our finding that the risks of death are similar for infants who are predominantly breastfed and those who are exclusively breastfed suggests that in settings where rates of predominant breastfeeding are already high, promotion efforts should focus on sustaining these high rates rather than on attempting to achieve a shift from predominant breastfeeding to exclusive breastfeeding.

To achieve the Millennium Development Goal for child survival (MDG-4), neonatal deaths need to be prevented. Previous papers in this series have presented the size of the problem, discussed cost-effective interventions, and outlined a systematic approach to overcoming health-system constraints to scaling up. We address issues related to improving neonatal survival. Countries should not wait to initiate action. Success is possible in low-income countries and without highly developed technology. Effective, low-cost interventions exist, but are not present in programmes. Specific efforts are needed by safe motherhood and child survival programmes. Improved availability of skilled care during childbirth and family/community-based care through postnatal home visits will benefit mothers and their newborn babies. Incorporation of management of neonatal illness into the integrated management of childhood illness initiative (IMCI) will improve child survival. Engagement of the community and promotion of demand for care are crucial. To halve neonatal mortality between 2000 and 2015 should be one of the targets of MDG-4. Development, implementation, and monitoring of national action plans for neonatal survival is a priority. We estimate the running costs of the selected packages at 90% coverage in the 75 countries with the highest mortality rates to be US4.1 billion dollars a year, in addition to current expenditures of 2.0 billion dollars. About 30% of this money would be for interventions that have specific benefit for the newborn child; the remaining 70% will also benefit mothers and older children, and substantially reduce rates of stillbirths. The cost per neonatal death averted is estimated at 2100 dollars (range 1700-3100 dollars). Maternal, neonatal, and child health receive little funding relative to the large numbers of deaths. International donors and leaders of developing countries should be held accountable for meeting their commitments and increasing resources.

The study aimed at obtaining insights into the processes underlying infant deaths to help identify preventive interventions which may bring down infant mortality rates further. Verbal autopsies were performed on 162 deaths of liveborn infants that occurred in a birth cohort in two urban slums of Delhi, India, between February 1995 and August 1996. A structured verbal autopsy form was used for ascertaining the cause of death. The narratives of caretakers on seeking of care and treatment received for illness were reviewed to identify the actions and behaviours that might have contributed to death. Seeking of care was less common (57%) for illnesses that led to death in the first week of life than at later ages. The first-week deaths commonly (61%) occurred within 24 hours of recognition of illness which might have been too a short time for effective interventions by care providers. Only six of 45 neonates who had features of sepsis, pneumonia or meningitis, major congenital malformations, birth asphyxia, or prematurity were advised by primary care providers for hospitalization. Similarly, only 25 (41%) of 61 older infants who had severe malnutrition and sepsis or meningitis, diarrhoea or pneumonia, or other illnesses were referred to hospital. Parenteral antibiotics were prescribed less often than warranted. Only two of 16 neonates with serious bacterial infections and eight of 19 postneonates with features of sepsis or meningitis received parenteral antibiotics. Inappropriate healthcare practices were common among the practitioners of modern and indigenous systems of medicine and registered medical practitioners. Forty percent of the neonates and a little over half of the older infants, advised for hospitalization, were taken to hospital. Fifteen percent of the infants taken to hospital were refused admission. Of 21 hospitalized infants discharged alive, five (23%) died within 48 hours and 13 (62%) within a week of returning home. A major effort is required to improve skills of healthcare providers of the biomedical and indigenous systems of medicine in caring for neonates and infants. Development of home-based treatment regimens for young infants and objective criteria for their hospitalization and discharge should receive a high priority.

BackgroundCOVID-19 is disrupting health services for mothers and newborns, particularly in low- and middle-income countries (LMIC). Preterm newborns are particularly vulnerable. We undertook analyses of the benefits of kangaroo mother care (KMC) on survival among neonates weighing ≤2000 g compared with the risk of SARS-CoV-2 acquired from infected mothers/caregivers.MethodsWe modelled two scenarios over 12 months. Scenario 1 compared the survival benefits of KMC with universal coverage (99%) and mortality risk due to COVID-19. Scenario 2 estimated incremental deaths from reduced coverage and complete disruption of KMC. Projections were based on the most recent data for 127 LMICs (~90% of global births), with results aggregated into five regions.FindingsOur worst-case scenario (100% transmission) could result in 1,950 neonatal deaths from COVID-19. Conversely, 125,680 neonatal lives could be saved with universal KMC coverage. Hence, the benefit of KMC is 65-fold higher than the mortality risk of COVID-19. If recent evidence of 10% transmission was applied, the ratio would be 630-fold. We estimated a 50% reduction in KMC coverage could result in 12,570 incremental deaths and full disruption could result in 25,140 incremental deaths, representing a 2·3-4·6% increase in neonatal mortality across the 127 countries.InterpretationThe survival benefit of KMC far outweighs the small risk of death due to COVID-19. Preterm newborns are at risk, especially in LMICs where the consequences of disruptions are substantial. Policymakers and healthcare professionals need to protect services and ensure clearer messaging to keep mothers and newborns together, even if the mother is SARS-CoV-2-positive.FundingEunice Kennedy Shriver National Institute of Child Health & Human Development; Bill & Melinda Gates Foundation; Elma Philanthropies; Wellcome Trust; and Joint Global Health Trials scheme of Department of Health and Social Care, Department for International Development, Medical Research Council, and Wellcome Trust.

BackgroundIn 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025.MethodsWe used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts.ResultsNine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour.ConclusionThese findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.

Background: Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival. Methods: In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant's sex, and religion. Results: Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu. Conclusions: We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival. Trial registration: ClinicalTrials.gov, NCT02653534. Registered January 12, 2016—Retrospectively registered. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal infections contribute substantially to infant mortality in Nigeria and globally. Management requires hospitalization, which is not accessible to many in low resource settings. World Health Organization developed a guideline to manage possible serious bacterial infection (PSBI) in young infants up to two months of age when a referral is not feasible. We evaluated the feasibility of implementing this guideline to achieve high coverage of treatment. Methods: This implementation research was conducted in out-patient settings of eight primary health care centres (PHC) in Lagelu Local Government Area (LGA) of Ibadan, Oyo State, Nigeria. We conducted policy dialogue with the Federal and State officials to adopt the WHO guideline within the existing programme setting and held orientation and sensitization meetings with communities. We established a Technical Support Unit (TSU), built the capacity of health care providers, supervised and mentored them, monitored the quality of services and collected data for management and outcomes of sick young infants with PSBI signs. The Primary Health Care Directorate of the state ministry and the local government led the implementation and provided technical support. The enablers and barriers to implementation were documented. Results: From 1 April 2016 to 31 July 2017 we identified 5278 live births and of these, 1214 had a sign of PSBI. Assuming 30% of births were missed due to temporary migration to maternal homes for delivery care and approximately 45% cases came from outside the catchment area due to free availability of medicines, the treatment coverage was 97.3% (668 cases/6861 expected births) with an expected 10% PSBI prevalence within the first 2 months of life. Of 1214 infants with PSBI, 392 (32%) infants 7–59 days had only fast breathing (pneumonia), 338 (27.8%) infants 0–6 days had only fast breathing (severe pneumonia), 462 (38%) presented with signs of clinical severe infection (CSI) and 22 (1.8%) with signs of critical illness. All but two, 7–59 days old infants with pneumonia were treated with oral amoxicillin without a referral; 80% (312/390) adhered to full treatment; 97.7% (381/390) were cured, and no deaths were reported. Referral to the hospital was not accepted by 87.7% (721/822) families of infants presenting with signs of PSBI needing hospitalization (critical illness 5/22; clinical severe infection; 399/462 and severe pneumonia 317/338). They were treated on an outpatient basis with two days of injectable gentamicin and seven days of oral amoxicillin. Among these 81% (584/721) completed treatment; 97% (700/721) were cured, and three deaths were reported (two with critical illness and one with clinical severe infection). We identified health system gaps including lack of staff motivation and work strikes, medicines stockouts, sub-optimal home visits that affected implementation. Conclusions: When a referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing programme structures in Nigeria with high coverage and low case fatality. To scale up this intervention successfully, government commitment is needed to strengthen the health system, motivate and train health workers, provide necessary commodities, establish technical support for implementation and strengthen linkages with communities. Registration: Trial is registered on Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369. [ABSTRACT FROM AUTHOR]

Background: Community-based data on the prevalence of clinical signs of possible serious bacterial infection (PSBI) and the mortality associated with them are scarce. The aim was to examine the prevalence for each sign of infection and mortality associated with infants in the first two months of life, using community surveillance through community health workers (CHW). Methods: We used population-based surveillance data of infants up to two months of age from the African Neonatal Sepsis Trial (AFRINEST). In this study, CHWs visited infants up to 10 times during the first two months of life at five sites in three sub-Saharan African countries. CHW assessed the infant for signs of infection (local or systemic) and referred infants who presented with any sign of infection to a health facility. We used a longitudinal analysis to calculate the risk of death associated with the presence of a sign of infection at the time of the visit until the subsequent visit. Results: During the first two months of their life, CHWs visited 84,759 live-born infants at least twice. In 11,089 infants (13.1%), one or more signs of infection were identified, of which 237 (2.1%) died. A sign of infection was detected at 2.1% of total visits. In 52% of visits, infants had one or more sign of systemic infection, while 25% had fast breathing in 7–59 days period and 23% had a local infection. All signs of infection, including multiple signs, were more frequently seen in the first week of life. The risk of mortality was very low (0.2%) for local infections and fast breathing in 7–59 days old, it was low for fast breathing 0–6 days old (0.6%), high body temperature (0.7%) and severe chest indrawing (1.0%), moderate for low body temperature (4.9%) and stopped feeding well/not able to feed at all (5.0%) and high for movement only when stimulated or no movement at all (10%) and multiple signs of systemic infection (15.5%). The risk of death associated with most clinical signs was higher (1.5 to 9 times) in the first week of life than at later age, except for low body temperature (4 times lower) as well as high body temperature (2 times lower). Conclusion: Signs of infections are common in the first two months of life. The mortality risk differs with clinical signs and can be grouped as very low (local infections, fast breathing 7–59 days), low (fever, severe chest indrawing and fast breathing 0–6 days), moderate (low body temperature and stopped feeding well/not able to feed at all) and high (for movements only on stimulation or no movements at all and multiple signs of infection). New treatment strategies that consider differential mortality risk could be developed and evaluated based on these findings. Clinical trial registration: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044. [ABSTRACT FROM AUTHOR]

Background: Around 70% neonatal deaths occur in low birth weight (LBW) babies. Globally, 15% of babies are born with LBW. Kangaroo Mother Care (KMC) appears to be an effective way to reduce mortality and morbidity among LBW babies. KMC comprises of early and continuous skin-to-skin contact between mother and baby as well as exclusive breastfeeding. Evidence derived from hospital-based studies shows that KMC results in a 40% relative reduction in mortality, a 58% relative reduction in the risk of nosocomial infections or sepsis, shorter hospital stay, and a lower risk of lower respiratory tract infections in babies with birth weight <2000 g. There has been considerable interest in KMC initiated outside health facilities for LBW babies born at home or discharged early. Currently, there is insufficient evidence to support initiation of KMC in the community (cKMC). Formative research in our study setting, where 24% of babies are born with LBW, demonstrated that KMC is feasible and acceptable when initiated at home for LBW babies. The aim of this trial is to determine the impact of cKMC on the survival of these babies.Methods/design: This randomized controlled trial is being undertaken in the Palwal and Faridabad districts in the State of Haryana, India. Neonates weighing 1500-2250 g identified within 3 days of birth and their mothers are being enrolled. Other inclusion criteria are that the family is likely to be available in the study area over the next 6 months, that KMC was not initiated in the delivery facility, and that the infant does not have an illness requiring hospitalization. Eligible neonates are randomized into intervention and control groups. The intervention is delivered through home visits during the first month of life by study workers with a background and education similar to that of workers in the government health system. An independent study team collects mortality and morbidity data as well as anthropometric measurements during periodic home visits. The primary outcomes of the study are postenrollment neonatal mortality and mortality between enrollment and 6 months of age. The secondary outcomes are breastfeeding practices; prevalence of illnesses and care-seeking practices for the same; hospitalizations; weight and length gain; and, in a subsample, neurodevelopment.Discussion: This efficacy trial will answer the question whether the benefits of KMC observed in hospital settings can also be observed when KMC is started in the community. The formative research used for intervention development suggests that the necessary high level of KMC adoption can be reached in the community, addressing a problem that seriously constrained conclusions in the only other trial in which researchers examined the benefits of cKMC.Trial Registration: ClinicalTrials.gov identifier: NCT02653534 . Registered on 26 December 2015 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Objectives: The AMANHI mortality study aims to use harmonized methods, across eleven sites in eight countries in South Asia and sub-Saharan Africa, to estimate the burden, timing and causes of maternal, fetal and neonatal deaths. It will generate data to help advance the science of cause of death (COD) assignment in developing country settings.Methods: This population-based, cohort study is being conducted in the eleven sites where approximately 2 million women of reproductive age are under surveillance to identify and follow-up pregnancies through to six weeks postpartum. All sites are implementing uniform protocols. Verbal autopsies (VAs) are conducted for deaths of pregnant women, newborns or stillbirths to confirm deaths, ascertain timing and collect data on the circumstances around the death to help assign causes. Physicians from the sites are selected and trained to use International Classification of Diseases (ICD) principles to assign CODs from a limited list of programmatically-relevant causes. Where the cause cannot be determined from the VA, physicians assign that option. Every physician who is trained to assign causes of deaths from any of the study countries is tested and accredited before they start COD assignment in AMANHI.Importance Of the Amanhi Mortality Study: It is one of the first to generate improved estimates of burden, timing and causes of maternal, fetal and neonatal deaths from empirical data systematically collected in a large prospective cohort of women of reproductive age. AMANHI makes a substantial contribution to global knowledge to inform policies, interventions and investment decisions to reduce these deaths. [ABSTRACT FROM AUTHOR]

Background: Most complications during labour and childbirth could be averted with timely interventions by skilled healthcare providers. Yet, the quality and outcomes of childbirth care remains suboptimal in many health facilities in low-resource settings. To accelerate the reduction of childbirth-related maternal, fetal and newborn mortality and morbidity, the World Health Organization has initiated the "Better Outcomes in Labour Difficulty" (BOLD) project to address weaknesses in labour care processes and better connect health systems and communities. The project seeks to develop a "Simplified, Effective, Labour Monitoring-to-Action" tool (SELMA) to assist healthcare providers to monitor labour and take decisive actions more efficiently; and by developing an innovative set of service prototypes and/or tools termed "Passport to Safer Birth", designed with communities and healthcare providers, to promote access to quality care for women during childbirth. This protocol describes the formative research activities to support the development of these tools. Methods/Design: We will employ qualitative research and service design methodologies in eight health facilities and their catchment communities in Nigeria and Uganda. In the health facilities, focus group discussions (FGD) and in-depth interviews (IDI) will be conducted among different cadres of healthcare providers and facility administrators. In the communities, FGDs and IDIs will be conducted among women who have delivered in a health facility. We will use service design methods to explore women's journey to access and receive childbirth care in order to innovate and design services around the needs and expectations of women, within the context of the health system. Discussion: This formative research will serve several roles. First, it will provide an in-depth understanding of healthcare providers and health system issues to be accounted for in the final design and implementation of SELMA. Second, it will help to identify key moments ("touch points") where women's experiences of childbirth care are shaped, and where the overall experience of quality care could be improved. The synthesis of findings from the qualitative and service design activities will help identify potential areas for behaviour change related to the provision and experience of childbirth care, and serve as the basis for the development of Passport to Safer Birth. Please see related articles 'http://dx.doi.org/10.1186/s12978-015-0027-6' and 'http://dx.doi.org/10.1186/s12978-015-0029-4'. [ABSTRACT FROM AUTHOR]

Background: The partograph is currently the main tool available to support decision-making of health professionals during labour. However, the rate of appropriate use of the partograph is disappointingly low. Apart from limitations that are associated with partograph use, evidence of positive impact on labour-related health outcomes is lacking. The main goal of this study is to develop a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool. The primary objectives are: to identify the essential elements of intrapartum monitoring that trigger the decision to use interventions aimed at preventing poor labour outcomes; to develop a simplified, monitoring-to-action algorithm for labour management; and to compare the diagnostic performance of SELMA and partograph algorithms as tools to identify women who are likely to develop poor labour-related outcomes. Methods/Design: A prospective cohort study will be conducted in eight health facilities in Nigeria and Uganda (four facilities from each country). All women admitted for vaginal birth will comprise the study population (estimated sample size: 7,812 women). Data will be collected on maternal characteristics on admission, labour events and pregnancy outcomes by trained research assistants at the participating health facilities. Prediction models will be developed to identify women at risk of intrapartum-related perinatal death or morbidity (primary outcomes) throughout the course of labour. These predictions models will be used to assemble a decision-support tool that will be able to suggest the best course of action to avert adverse outcomes during the course of labour. To develop this set of prediction models, we will use up-to-date techniques of prognostic research, including identification of important predictors, assigning of relative weights to each predictor, estimation of the predictive performance of the model through calibration and discrimination, and determination of its potential for application using internal validation techniques. Discussion: This research offers an opportunity to revisit the theoretical basis of the partograph. It is envisioned that the final product would help providers overcome the challenging tasks of promptly interpreting complex labour information and deriving appropriate clinical actions, and thus increase efficiency of the care process, enhance providers' competence and ultimately improve labour outcomes. [ABSTRACT FROM AUTHOR]

Objective To compare the estimated prevalence of malnutrition using the World Health Organization's (WHO) child growth standards versus the National Center for Health Statistics' (NCHS) growth reference, to examine the relationship between exclusive breastfeeding and malnutrition, and to determine the sensitivity and specificity of nutritional status indicators for predicting death during infancy. Methods A secondary analysis of data on 9424 mother-Infant pairs in Ghana, India and Peru was conducted. Mothers and infants were enrolled In a trial of vitamin A supplementation during which the Infants' weight, length and feeding practices were assessed regularly. Malnutrition Indicators were determined using WHO and NCHS growth standards. Findings The prevalence of stunting, wasting and underweight in infants aged < 6 months was higher with WHO than NCHS standards. However, the prevalence of underweight in Infants aged 6-12 months was much lower with WHO standards. The duration of exclusive breastfeeding was not associated with malnutrition in the first 6 months of life. In Infants aged < 6 months, severe underweight at the first immunization visit as determined using WHO standards had the highest sensitivity (70.2%) and specificity (85.8%) for predicting mortality In India. No indicator was a good predictor In Ghana or Peru. In infants aged 6-12 months, underweight at 6 months had the highest sensitivity and specificity for predicting mortality in Ghana (37.0% and 82.2%, respectively) and Peru (33.3% and 97.9% respectively), while wasting was the best predictor In India (sensitivity: 54.6%; specificity: 85.5%). - ' Conclusion Malnutrition Indicators determined using WHO standards were better predictors of mortality than those determined - using NCHS standards. No association was found between breastfeeding duration and malnutrition at 6 months. Use of WHO child growth standards highlighted the Importance of malnutrition In the first 6 months of life. [ABSTRACT FROM AUTHOR]