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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: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB)., Objectives: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations., Methods: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort., Results: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration., Conclusions: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB., (Copyright © 2023. Published by Elsevier Inc.)

Despite major achievements in child survival, the burden of neonatal mortality has remained high and even increased in some countries since 1990. Currently, most neonatal deaths are attributable to being born preterm, small for gestational age (SGA), or with low birthweight (LBW). Besides neonatal mortality, these conditions are associated with stillbirth and multiple morbidities, with short-term and long-term adverse consequences for the newborn, their families, and society, resulting in a major loss of human capital. Prevention of preterm birth, SGA, and LBW is thus critical for global child health and broader societal development. Progress has, however, been slow, largely because of the global community's failure to agree on the definition and magnitude of newborn vulnerability and best ways to address it, to frame the problem attractively, and to build a broad coalition of actors and a suitable governance structure to implement a change. We propose a new definition and a conceptual framework, bringing preterm birth, SGA, and LBW together under a broader umbrella term of the small vulnerable newborn (SVN). Adoption of the framework and the unified definition can facilitate improved problem definition and improved programming for SVN prevention. Interventions aiming at SVN prevention would result in a healthier start for live-born infants, while also reducing the number of stillbirths, improving maternal health, and contributing to a positive economic and social development in the society., Competing Interests: Declaration of interests PA reports a grant from Children's Investment Fund Foundation, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A large proportion of infants in low- and middle-income countries are stunted. These infants are often fed complementary foods that are low-quality, primarily in terms of protein and micronutrients., Objectives: We aimed to test 2 milk-cereal mixes supplemented with modest and high amounts of protein during 6-12 mo of age, compared with no supplementation, for their effect on length-for-age z score (LAZ) at 12 mo of age., Methods: Eligible infants (6 mo plus ≤29 d) were randomly assigned to either of the 2 interventions (modest- and high-protein) or a no supplement group. The milk-cereal mixes provided ∼125 kcal, 30%-45% energy from fats, and 80%-100% RDA of multiple micronutrients (MMN). The modest-protein group received 2.5 g protein [protein energy ratio (PER): 8%; 0.75 g from milk source] and the high-protein group received 5.6 g protein (PER: 18%, 1.68 g from milk source). One packet was given daily for 180 d. Counseling on continued breastfeeding and optimal infant-care practices was provided to all., Results: We enrolled 1548 infants (high-protein: n = 512; modest-protein: n = 519; and no supplement: n = 517). Compared with the no supplement group, there was an improvement in LAZ [adjusted mean difference (MD): 0.08; 95% CI: 0.01, 0.15], weight-for-age z score (MD: 0.12; 95% CI: 0.06, 0.19), weight-for-length z score (MD: 0.11; 95% CI: 0.02, 0.19), and midupper arm circumference z score (MD: 0.10; 95% CI: 0.02, 0.18) in the high-protein group at 12 mo of age. No significant differences for these anthropometric indicators were noted between the modest-protein and no supplement groups or between the high- and modest-protein groups., Conclusions: Cereal mixes with higher amounts of milk-based protein and MMN may lead to improvement in linear growth and other anthropometric indexes in infants, compared with no supplementation.This trial was registered at ctri.nic.in as CTRI/2018/04/012932., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: In lower-middle-income settings, growth faltering in the first 6 mo of life occurs despite exclusive breastfeeding., Objective: The aim was to test the efficacy of an approach to improve the dietary adequacy of mothers during lactation and thus improve the growth of their infants., Methods: Eligible mother-infant dyads (infants ≤7 d of age) were randomly assigned to either intervention or control groups. Mothers in the intervention group received snacks that were to be consumed daily, which provided 600 kcal of energy-with 25-30% of energy derived from fats (150-180 kcal) and 13% of energy from protein (80 kcal). Micronutrients were supplemented as daily tablets. We provided counseling on breastfeeding and infant-care practices to mothers in both groups. The primary outcome was attained infant length-for-age z scores (LAZ) at 6 mo of age. Secondary outcomes included exclusive breastfeeding proportion reported by the mother, maternal BMI and midupper arm circumference (MUAC), hemoglobin concentrations in mothers and infants, and the proportion of anemic infants at 6 mo of age., Results: We enrolled 816 mother-infant dyads. The intervention did not achieve a significant effect on LAZ at 6 mo (adjusted mean difference: 0.09; 95% CI: -0.03, 0.20). Exclusive breastfeeding at 5 mo was higher (45.1% vs. 34.5%; RR: 1.31; 95% CI: 1.04, 1.64) in the intervention group compared with the controls. There were no significant effects on mean hemoglobin concentration or the proportion of anemic infants at 6 mo of age compared with the control group. We noted significant effects on maternal nutritional status (BMI, MUAC, hemoglobin concentration, and proportion anemic)., Conclusions: Postnatal supplementation of 600 kcal energy, 20 g protein, and multiple micronutrients daily to lactating mothers did not affect infant LAZ at age 6 mo. Such supplementation may improve maternal nutritional status. This trial was registered at Clinical Trials Registry-India as CTRI/2018/04/013095., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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.)

Background: Improving breastfeeding rates is critical. In low- and middle-income countries (LMICs), only subtle improvements in breastfeeding rates have been observed over the past decade, which highlights the need for accelerating breastfeeding promotion interventions. Objective: The objective of this article is to update evidence on the effect of interventions on early initiation of and exclusive (<1 and 1-5 mo) and continued (6-23 mo) breastfeeding rates in LMICs when delivered in health systems, in the home or in community environments, or in a combination of settings. Methods: A systematic literature search was conducted in PubMed, Cochrane, and CABI databases to identify new articles relevant to our current review, which were published after the search date of our earlier meta-analysis (October 2014). Nine new articles were found to be relevant and were included, in addition to the other 52 studies that were identified in our earlier meta-analysis. We reported the pooled ORs and corresponding 95% CIs as our outcome estimates. In cases of high heterogeneity, random-effects models were used and causes were explored by subgroup analysis and meta-regression. Results: Early initiation of and exclusive (<1 and 1-5 mo) and continued (6-23 mo) breastfeeding rates in LMICs improved significantly as a result of interventions delivered in health systems, in the home or community, or a combination of these. Interventions delivered concurrently in a combination of settings were found to show the largest improvements in desired breastfeeding outcomes. Counseling provided in any setting and baby-friendly support in health systems appear to be the most effective interventions to improve breastfeeding. Conclusions: Improvements in breastfeeding practices are possible in LMICs with judicious use of tested interventions, particularly when delivered in a combination of settings concurrently. The findings can be considered for inclusion in the Lives Saved Tool model., Competing Interests: Author disclosures: BS, RC, RPU, ST, JM, RB, and MJS, no conflicts of interest., (© 2017 American Society for Nutrition.)

The importance of breastfeeding in low-income and middle-income countries is well recognised, but less consensus exists about its importance in high-income countries. In low-income and middle-income countries, only 37% of children younger than 6 months of age are exclusively breastfed. With few exceptions, breastfeeding duration is shorter in high-income countries than in those that are resource-poor. Our meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes. We did not find associations with allergic disorders such as asthma or with blood pressure or cholesterol, and we noted an increase in tooth decay with longer periods of breastfeeding. For nursing women, breastfeeding gave protection against breast cancer and it improved birth spacing, and it might also protect against ovarian cancer and type 2 diabetes. The scaling up of breastfeeding to a near universal level could prevent 823,000 annual deaths in children younger than 5 years and 20,000 annual deaths from breast cancer. Recent epidemiological and biological findings from during the past decade expand on the known benefits of breastfeeding for women and children, whether they are rich or poor., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Supplementation of vitamin A in children aged 6-59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months)., Methods: We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants' families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055., Findings: Between Aug 26, 2010, and March 3, 2013, 31,999 newborn babies were randomly assigned to receive vitamin A (n=15,995) or placebo (n=16,004; 15,428 and 15,464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95-1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90-1·29) and for girls was 1·12 (0·91-1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing., Interpretation: Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation., Funding: Bill & Melinda Gates Foundation to WHO., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

Background: Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age., Methods: We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220., Findings: Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32])., Interpretation: The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy., Funding: Bill & Melinda Gates Foundation to WHO., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

Background: Results of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana., Methods: This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055., Findings: We assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130)., Interpretation: The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana., Funding: Bill & Melinda Gates Foundation grant to the WHO., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

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: We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities., Methods: In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios., Results: From May 1, 2010, to Dec 31, 2011, we included 314,623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23,015 (7.3%) women had potentially life-threatening disorders and 3024 (1.0%) developed an SMO. 808 (26.7%) women with an SMO had post-partum haemorrhage and 784 (25.9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0.826 [95% CI 0.802-0.851])., Interpretation: High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy., Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects., (Copyright © 2013 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

Background: Micronutrient deficiencies can affect cognitive function. Many young children in low- and middle-income countries have inadequate cobalamin (vitamin B-12) status., Objective: The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo., Design: Bayley Scales of Infant Development II were used to assess cognition. In multiple regression models adjusted for several potential confounders, we measured the association between biomarkers for folate and cobalamin status and psychomotor or mental development scores on the day of blood sampling and 4 mo thereafter., Results: Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile. None of these markers was associated with psychomotor scores in the multiple regression models., Conclusions: Cobalamin and folate status showed a statistically significant association with cognitive performance. Given the high prevalence of deficiencies in these nutrients, folate and cobalamin supplementation trials are required to measure any beneficial effect on cognition.

Our objective in this trial was to assess the impact of daily zinc supplementation on growth in young children. A double-blind, randomized, placebo-controlled trial was conducted in New Delhi, India. We enrolled 2482 children aged 6-30 mo who were supplemented daily with placebo or zinc (10 mg elemental zinc to infants and 20 mg to older children) for 4 mo. At enrollment, all children also received a single dose of vitamin A (104.7 micromol for infants and 209.4 micromol for older children). Weight and length were measured at enrollment and 4 mo later. Weekly visits were conducted by field workers to ascertain morbidity in the previous 7 d. Change in length, weight, length-for-age Z-scores (LAZ), and weight-for-length Z-scores (WLZ) after 4 mo of supplementation were assessed in the zinc and placebo groups. After 4 mo of supplementation, the weight and length gains in the 2 groups did not differ and there was no impact on LAZ, weight-for-age, and WLZ in the 2 groups. There was no substantial effect in any of the subgroups defined for age, income, gender, zinc levels in the crude analysis nor after adjusting for age, gender, income, breast-feeding status, and baseline anthropometric status. Despite successful zinc supplementation reflected in increased plasma zinc concentration and a substantially reduced incidence of diarrhea and pneumonia in zinc-supplemented children, the intervention did not have a beneficial effect on growth.

Background: Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking., Objective: The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India., Design: Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial., Results: The median (interquartile range; IQR) cobalamin concentration in 6-11-mo-old children was substantially lower in breastfed (183; 120-263 pmol/L) than in nonbreastfed (334; 235-463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6-11-mo-old group were higher in breastfed (20.3; 11.7-34.4 nmol/L) than in nonbreastfed (5.3; 3.4-7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001)., Conclusions: In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered.

Background: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections., Objective: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity., Design: A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo., Results: We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31)., Conclusions: Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk.

Studies have found a substantial reduction in diarrhea and respiratory morbidity in young children receiving zinc supplementation. The impact of daily zinc supplementation administered with iron plus folic acid (IFA) in young children on all-cause hospitalizations and mortality in comparison with IFA alone was evaluated. In a double blind cluster-randomized controlled trial, 94,359 subjects aged 1-23 mo were administered a daily dose of zinc plus IFA or IFA alone for a duration of 12 mo after enrollment. The intervention group tablet contained 10 mg of elemental zinc, 12.5 mg of iron, and 50 microg of folic acid. The control group tablets were similar except that they contained a placebo for zinc. Infants aged <6 mo were administered half a tablet, and those older received 1 tablet dissolved in breast milk or water. Hospitalizations were captured by trained study physicians through the surveillance of 8 hospitals. Deaths and hospitalizations were ascertained through visits to households by study supervisors once every 2 mo. The overall death rates did not differ significantly between the 2 groups when adjusted for cluster randomization (hazard ratio = 1.02, 95% CI 0.87, 1.19). Zinc and IFA supplementation compared with IFA alone did not affect adjusted hospitalization rates (overall rate ratio = 1.08, 95% CI 0.98, 1.19; diarrhea-specific rate ratio = 1.15, 95% CI 0.99, 1.34; or pneumonia-specific rate ratio = 1.09, 95% CI 0.94, 1.25). The lack of impact of zinc on mortality and hospitalization rates in this study may have been due to the use of lower daily zinc dosing than used in some of the morbidity prevention trials or from an interaction between zinc and iron, where the addition of iron may have adversely affected potential effects of zinc on immune function and morbidity. Future research should address iron and zinc interaction effects on important functional outcomes.

Typhoid fever is estimated to have caused 21.6 million illnesses and 216,500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings.

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.

Complementary feeding practices are often inadequate in developing countries, resulting in a significant nutritional decline between 6 and 18 mo of age. We assessed the effectiveness of an educational intervention to promote adequate complementary feeding practices that would be feasible to sustain with existing resources. The study was a cluster randomized controlled trial in communities in the state of Haryana in India. We developed the intervention through formative research. Eight communities were pair matched on their baseline characteristics; one of each pair was randomly assigned to receive the intervention and the other to no specific feeding intervention. Health and nutrition workers in the intervention communities were trained to counsel on locally developed feeding recommendations. Newborns were enrolled in all of the communities (552 in the intervention and 473 in the control) and followed up every 3 mo to the age of 18 mo. The main outcome measures were weights and lengths at 6, 9, 12, and 18 mo and complementary feeding practices at 9 and 18 mo. All analyses were by intent to treat. In the overall analyses, there was a small but significant effect on length gain in the intervention group (difference in means 0.32 cm, 95% CI, 0.03, 0.61). The effect was greater in the subgroup of male infants (difference in mean length gain 0.51 cm, 95% CI 0.03, 0.98). Weight gain was not affected. Energy intakes from complementary foods overall were significantly higher in the intervention group children at 9 mo (mean +/- SD: 1556 +/- 1109 vs. 1025 +/- 866 kJ; P < 0.001) and 18 mo (3807 +/- 1527 vs. 2577 +/- 1058 kJ; P < 0.001). Improving complementary feeding practices through existing services is feasible but the effect on physical growth is limited. Factors that limit physical growth in such settings must be better understood to plan more effective nutrition programs.

Background: Exclusive breastfeeding is recommended until age 6 months. We assessed the feasibility, effectiveness, and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India., Methods: We developed the intervention through formative research, pair-matched eight communities on their baseline characteristics, and randomised one of each pair to receive the intervention and the other to no specific intervention. We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities. We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities. Feeding at age 3 months, and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed. All analyses were by intention to treat., Findings: We assessed 483 and 412 individuals at 3 months in the intervention and control groups, respectively, and 468 and 412 at 6 months. At 3 months, exclusive breastfeeding rates were 79% (381) in the intervention and 48% (197) in the control communities (odds ratio 4.02, 95% CI 3.01-5.38, p<0.0001). The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months (0.64, 0.44-0.95, p=0.028) and 6 months (0.85, 0.72-0.99, p=0.04). The mean weights and lengths, and the proportion with weight-for-height or height-for-age Z scores of 2 or less, at age 3 months and 6 months did not differ much between groups. Intervention effect on exclusive breastfeeding, diarrhoeal morbidity, and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births., Interpretation: Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering.

Vitamin A supplementation of lactating mothers and of infants at the time of diphtheria-pertussis-tetanus (DPT) and oral polio vaccine (OPV) immunizations have both been suggested as measures to prevent deficiency among infants. This multicenter randomized, double-blind, placebo-controlled trial was conducted in Ghana, India and Peru to determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status. Mothers in the intervention group received 60 mg vitamin A (as retinol palmitate) at 18-42 d postpartum; their infants were given 7.5 mg three times, i.e., at 6, 10 and 14 wk of age with DPT and OPV immunizations. Mothers and infants in the comparison group received a placebo. Maternal supplementation resulted in higher breast milk retinol at 2 mo postpartum [difference in means 7.1, 95% confidence interval (CI), 3.4, 10.8 nmol/g fat] and lower proportion of mothers with breast milk retinol < or = 28 nmol/g fat (15.2 vs. 26.6%, 95% CI of difference -16.6, -4.1%). At 6 and 9 mo, maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol. Vitamin A supplementation of the mothers and their infants reduced the proportion of infants with serum retinol < or = 0.7 micro mol/L (30.4 vs. 37%, 95% CI of difference -13.7, 0.6%) and that with low vitamin A stores as indicated by the modified relative dose response (MRDR) > 0.06 (44.2 vs. 52.9%, 95% CI of difference -16.6, -0.9%) at 6 mo. Supplementation had no effect at 9 mo. The beneficial effect of supplementation on breast milk retinol and infants' vitamin A status varied by site. It was greatest in India followed by Ghana and Peru. At the doses used, maternal supplementation improved breast milk retinol status at 2 mo (P < 0.001) and maternal and infant supplementation modestly increased (P = 0.03) infant vitamin A status at 6 mo of age. Additional strategies to improve vitamin A status of 6- to 9-mo-old infants must be considered.