Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes.

A package of care for all pregnant women within eight scheduled antenatal care contacts is recommended by WHO. Some interventions for reducing and managing the outcomes for small vulnerable newborns (SVNs) exist within the WHO package and need to be more fully implemented, but additional effective measures are needed. We summarise evidence-based antenatal and intrapartum interventions (up to and including clamping the umbilical cord) to prevent vulnerable births or improve outcomes, informed by systematic reviews. We estimate, using the Lives Saved Tool, that eight proven preventive interventions (multiple micronutrient supplementation, balanced protein and energy supplementation, low-dose aspirin, progesterone provided vaginally, education for smoking cessation, malaria prevention, treatment of asymptomatic bacteriuria, and treatment of syphilis), if fully implemented in 81 low-income and middle-income countries, could prevent 5·202 million SVN births (sensitivity bounds 2·398-7·903) and 0·566 million stillbirths (0·208-0·754) per year. These interventions, along with two that can reduce the complications of preterm (<37 weeks' gestation) births (antenatal corticosteroids and delayed cord clamping), could avert 0·476 million neonatal deaths (0·181-0·676) per year. If further research substantiates the preventive effect of three additional interventions (supplementation with omega-3 fatty acids, calcium, and zinc) on SVN births, about 8·369 million SVN births (2·398-13·857) and 0·652 million neonatal deaths (0·181-0·917) could be avoided per year. Scaling up the eight proven interventions and two intrapartum interventions would cost about US$1·1 billion in 2030 and the potential interventions would cost an additional $3·0 billion. Implementation of antenatal care recommendations is urgent and should include all interventions that have proven effects on SVN babies, within the context of access to family planning services and addressing social determinants of health. Attaining high effective coverage with these interventions will be necessary to achieve global targets for the reduction of low birthweight births and neonatal mortality, and long-term benefits on growth and human capital.

Small vulnerable newborns-big potential for impact.

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.

Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting.

Small newborns are vulnerable to mortality and lifelong loss of human capital. Measures of vulnerability previously focused on liveborn low-birthweight (LBW) babies, yet LBW reduction targets are off-track. There are two pathways to LBW, preterm birth and fetal growth restriction (FGR), with the FGR pathway resulting in the baby being small for gestational age (SGA). Data on LBW babies are available from 158 (81%) of 194 WHO member states and the occupied Palestinian territory, including east Jerusalem, with 113 (58%) having national administrative data, whereas data on preterm births are available from 103 (53%) of 195 countries and areas, with only 64 (33%) providing national administrative data. National administrative data on SGA are available for only eight countries. Global estimates for 2020 suggest 13·4 million livebirths were preterm, with rates over the past decade remaining static, and 23·4 million were SGA. In this Series paper, we estimated prevalence in 2020 for three mutually exclusive types of small vulnerable newborns (SVNs; preterm non-SGA, term SGA, and preterm SGA) using individual-level data (2010-20) from 23 national datasets (∼110 million livebirths) and 31 studies in 18 countries (∼0·4 million livebirths). We found 11·9 million (50% credible interval [Crl] 9·1-12·2 million; 8·8%, 50% Crl 6·8-9·0%) of global livebirths were preterm non-SGA, 21·9 million (50% Crl 20·1-25·5 million; 16·3%, 14·9-18·9%) were term SGA, and 1·5 million (50% Crl 1·2-4·2 million; 1·1%, 50% Crl 0·9-3·1%) were preterm SGA. Over half (55·3%) of the 2·4 million neonatal deaths worldwide in 2020 were attributed to one of the SVN types, of which 73·4% were preterm and the remainder were term SGA. Analyses from 12 of the 23 countries with national data (0·6 million stillbirths at ≥22 weeks gestation) showed around 74% of stillbirths were preterm, including 16·0% preterm SGA and approximately one-fifth of term stillbirths were SGA. There are an estimated 1·9 million stillbirths per year associated with similar vulnerability pathways; hence integrating stillbirths to burden assessments and relevant indicators is crucial. Data can be improved by counting, weighing, and assessing the gestational age of every newborn, whether liveborn or stillborn, and classifying small newborns by the three vulnerability types. The use of these more specific types could accelerate prevention and help target care for the most vulnerable babies.

Seasonal Variation in Birth Rates: Physiology versus Family Planning.

Seasonal variation in birth rates is a ubiquitous property of human populations. Although the general birth rate is dependent on relatively few parameters-sexual behavior, zygote survival, and the number of ova released-the quantitative influence of the effects of each is difficult to estimate. Research has been directed more towards seasonal variation in physiology and less towards behavioral effects such as preferences for birthing in particular seasons. This may be because alongside seasonal variation in birth rate there is also seasonal variation in the multiple birth rate, which necessarily depends on the same physiological factors as the birth rate, suggestive of a link. Here we use a simulation that follows females through their reproductive lives, replicating the incidence of singleton and twin births that arise from single and double ovulations. We use the simulation to quantify the impact of seasonal variation in the physiological variables that affect birth rate. We can generate the seasonal variation in twinning rates observed in European populations, but this does not generate the magnitude of the observed seasonal variation in birth rate. Our simulation shows that, despite correlations between twinning rate and general birth rate, seasonal changes in sexual behavior are necessary to explain the magnitude of the seasonal variation in the general birth rate in humans.

What can work and how? An overview of evidence-based interventions and delivery strategies to support health and human development from before conception to 20 years.

Progress has been made globally in improving the coverage of key maternal, newborn, and early childhood interventions in low-income and middle-income countries, which has contributed to a decrease in child mortality and morbidity. However, inequities remain, and many children and adolescents are still not covered by life-saving and nurturing care interventions, despite their relatively low costs and high cost-effectiveness. This Series paper builds on a large body of work from the past two decades on evidence-based interventions and packages of care for survival, strategies for delivery, and platforms to reach the most vulnerable. We review the current evidence base on the effectiveness of a variety of essential and emerging interventions that can be delivered from before conception until age 20 years to help children and adolescents not only survive into adulthood, but also to grow and develop optimally, support their wellbeing, and help them reach their full developmental potential. Although scaling up evidence-based interventions in children younger than 5 years might have the greatest effect on reducing child mortality rates, we highlight interventions and evidence gaps for school-age children (5-9 years) and the transition from childhood to adolescence (10-19 years), including interventions to support mental health and positive development, and address unintentional injuries, neglected tropical diseases, and non-communicable diseases.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Maternal interventions to decrease stillbirths and neonatal mortality in Tanzania: evidence from the 2017-18 cross-sectional Tanzania verbal and social autopsy study.

BACKGROUND: Reduction of Tanzania's neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We conducted a national verbal and social autopsy (VASA) study to estimate the causes and social determinants of stillbirths and neonatal deaths with the aim of identifying relevant health care and social interventions. METHODS: A VASA interview was conducted of all stillbirths and neonatal deaths in the prior 5 years identified by the 2015-16 Tanzania Demographic and Health Survey. We evaluated associations of maternal complications with antepartum and intrapartum stillbirth and leading causes of neonatal death; conducted descriptive analyses of antenatal (ANC) and delivery care and mothers' careseeking for complications; and developed logistic regression models to examine factors associated with delivery place and mode. RESULTS: There were 204 stillbirths, with 185 able to be classified as antepartum (88 [47.5%]) or intrapartum (97 [52.5%]), and 228 neonatal deaths. Women with an intrapartum stillbirth were 6.5% (adjusted odds ratio (aOR) = 1.065, 95% confidence interval (CI) 1.002, 1.132) more likely to have a C-section for every additional hour before delivery after reaching the birth attendant. Antepartum hemorrhage (APH), maternal anemia, and premature rupture of membranes (PROM) were significantly positively associated with early neonatal mortality due to preterm delivery, intrapartum-related events and serious infection, respectively. While half to two-thirds of mothers made four or more ANC visits (ANC4+), a third or fewer received quality ANC (Q-ANC). Women with a complication were more likely to deliver at hospital only if they received Q-ANC (neonates: aOR = 4.5, 95% CI 1.6, 12.3) or ANC4+ (stillbirths: aOR = 11.8, 95% CI 3.6, 38.0). Nevertheless, urban residence was the strongest predictor of hospital delivery. CONCLUSIONS: While Q-ANC and ANC4 + boosted hospital delivery among women with a complication, attendance was low and the quality of care is critical. Quality improvement efforts in urban and rural areas should focus on early detection and management of APH, maternal anemia, PROM, and prolonged labor, and on newborn resuscitation.

Prognostic value of different anthropometric indices over different measurement intervals to predict mortality in 6-59-month-old children.

OBJECTIVE: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. DESIGN: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. SETTING: Community-based, prospective studies from twelve countries in Africa and Asia. PARTICIPANTS: Children aged 6-59 months living in the study areas. RESULTS: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. CONCLUSIONS: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.

Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts.

OBJECTIVE: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. DESIGN: A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. SETTING: Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. PARTICIPANTS: Children aged 6 to 59 months. RESULTS: Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height Z-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. CONCLUSIONS: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

How do children with severe underweight and wasting respond to treatment? A pooled secondary data analysis to inform future intervention studies.

Children with weight-for-age z-score (WAZ) <-3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6-59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <-3 versus children with WAZ ≥-3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <-3 and WAZ ≥-3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥-2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <-3. Children admitted with WAZ <-3 compared to those with WAZ ≥-3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <-3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥-3. If moderately wasted children with WAZ <-3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <-3 are an especially vulnerable group and those with moderate wasting and WAZ <-3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.

Revisiting maternal and child undernutrition in low-income and middle-income countries: variable progress towards an unfinished agenda.

13 years after the first Lancet Series on maternal and child undernutrition, we reviewed the progress achieved on the basis of global estimates and new analyses of 50 low-income and middle-income countries with national surveys from around 2000 and 2015. The prevalence of childhood stunting has fallen, and linear growth faltering in early life has become less pronounced over time, markedly in middle-income countries but less so in low-income countries. Stunting and wasting remain public health problems in low-income countries, where 4·7% of children are simultaneously affected by both, a condition associated with a 4·8-times increase in mortality. New evidence shows that stunting and wasting might already be present at birth, and that the incidence of both conditions peaks in the first 6 months of life. Global low birthweight prevalence declined slowly at about 1·0% a year. Knowledge has accumulated on the short-term and long-term consequences of child undernutrition and on its adverse effect on adult human capital. Existing data on vitamin A deficiency among children suggest persisting high prevalence in Africa and south Asia. Zinc deficiency affects close to half of all children in the few countries with data. New evidence on the causes of poor growth points towards subclinical inflammation and environmental enteric dysfunction. Among women of reproductive age, the prevalence of low body-mass index has been reduced by half in middle-income countries, but trends in short stature prevalence are less evident. Both conditions are associated with poor outcomes for mothers and their children, whereas data on gestational weight gain are scarce. Data on the micronutrient status of women are conspicuously scarce, which constitutes an unacceptable data gap. Prevalence of anaemia in women remains high and unabated in many countries. Social inequalities are evident for many forms of undernutrition in women and children, suggesting a key role for poverty and low education, and reinforcing the need for multisectoral actions to accelerate progress. Despite little progress in some areas, maternal and child undernutrition remains a major global health concern, particularly as improvements since 2000 might be offset by the COVID-19 pandemic.

The effects of armed conflict on the health of women and children.

Women and children bear substantial morbidity and mortality as a result of armed conflicts. This Series paper focuses on the direct (due to violence) and indirect health effects of armed conflict on women and children (including adolescents) worldwide. We estimate that nearly 36 million children and 16 million women were displaced in 2017, on the basis of international databases of refugees and internally displaced populations. From geospatial analyses we estimate that the number of non-displaced women and children living dangerously close to armed conflict (within 50 km) increased from 185 million women and 250 million children in 2000, to 265 million women and 368 million children in 2017. Women's and children's mortality risk from non-violent causes increases substantially in response to nearby conflict, with more intense and more chronic conflicts leading to greater mortality increases. More than 10 million deaths in children younger than 5 years can be attributed to conflict between 1995 and 2015 globally. Women of reproductive ages living near high intensity conflicts have three times higher mortality than do women in peaceful settings. Current research provides fragmentary evidence about how armed conflict indirectly affects the survival chances of women and children through malnutrition, physical injuries, infectious diseases, poor mental health, and poor sexual and reproductive health, but major systematic evidence is sparse, hampering the design and implementation of essential interventions for mitigating the harms of armed conflicts.

Delivering health and nutrition interventions for women and children in different conflict contexts: a framework for decision making on what, when, and how.

Existing global guidance for addressing women's and children's health and nutrition in humanitarian crises is not sufficiently contextualised for conflict settings specifically, reflecting the still-limited evidence that is available from such settings. As a preliminary step towards filling this guidance gap, we propose a conflict-specific framework that aims to guide decision makers focused on the health and nutrition of women and children affected by conflict to prioritise interventions that would address the major causes of mortality and morbidity among women and children in their particular settings and that could also be feasibly delivered in those settings. Assessing local needs, identifying relevant interventions from among those already recommended for humanitarian settings or universally, and assessing the contextual feasibility of delivery for each candidate intervention are key steps in the framework. We illustratively apply the proposed decision making framework to show what a framework-guided selection of priority interventions might look like in three hypothetical conflict contexts that differ in terms of levels of insecurity and patterns of population displacement. In doing so, we aim to catalyse further iteration and eventual field-testing of such a decision making framework by local, national, and international organisations and agencies involved in the humanitarian health response for women and children affected by conflict.

The political and security dimensions of the humanitarian health response to violent conflict.

The nature of armed conflict throughout the world is intensely dynamic. Consequently, the protection of non-combatants and the provision of humanitarian services must continually adapt to this changing conflict environment. Complex political affiliations, the systematic use of explosive weapons and sexual violence, and the use of new communication technology, including social media, have created new challenges for humanitarian actors in negotiating access to affected populations and security for their own personnel. The nature of combatants has also evolved as armed, non-state actors might have varying motivations, use different forms of violence, and engage in a variety of criminal activities to generate requisite funds. New health threats, such as the COVID-19 pandemic, and new capabilities, such as modern trauma care, have also created new challenges and opportunities for humanitarian health provision. In response, humanitarian policies and practices must develop negotiation and safety capabilities, informed by political and security realities on the ground, and guidance from affected communities. More fundamentally, humanitarian policies will need to confront a changing geopolitical environment, in which traditional humanitarian norms and protections might encounter wavering support in the years to come.

Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

BACKGROUND: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences. OBJECTIVES: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children. METHODS: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA. RESULTS: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05). CONCLUSIONS: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Demographic, socio-economic, obstetric, and behavioral factors associated with small-and large-for-gestational-age from a prospective, population-based pregnancy cohort in rural Nepal: a secondary data analysis.

BACKGROUND: In South Asia, a third of babies are born small-for-gestational age (SGA). The risk factors are well described in the literature, but many studies are in high-and-middle income countries or measure SGA on facility births only. There are fewer studies that describe the prevalence of risk factors for large-for-gestational age (LGA) in low-income countries. We aim to describe the factors associated with SGA and LGA in a population-based cohort of pregnant women in rural Nepal. METHODS: This is a secondary data analysis of community-based trial on neonatal oil massage (22,545 women contributing 39,479 pregnancies). Demographic, socio-economic status (SES), medical/obstetric history, and timing of last menstruation were collected at enrollment. Vital signs, illness symptoms, and antenatal care (ANC) attendance were collected throughout the pregnancy and neonatal weight was measured for live births. We conducted multivariate analysis using multinomial, multilevel logistic regression, reporting the odds ratio (OR) with 95% confidence intervals (CIs). Outcomes were SGA, LGA compared to appropriate-for-gestational age (AGA) and were multiply imputed using birthweight recalibrated to time at delivery. RESULTS: SGA was associated with nulligravida (OR: 2.12 95% CI: 1.93-2.34), gravida/nulliparous (OR: 1.86, 95% CI: 1.26-2.74), interpregnancy intervals less than 18 months (OR: 1.16, 95% CI: 1.07-1.27), and poor appetite/vomiting in the second trimester, (OR: 1.27, 95% CI: 1.19-1.35). Greater wealth (OR: 0.78, 95% CI: 0.69-0.88), swelling of hands/face in the third trimester (OR: 0.81, 95% CI: 0.69-0.94) parity greater than five (OR: 0.77, 95% CI: 0.65-0.92), male fetal sex (OR: 0.91, 95% CI: 0.86-0.98), and increased weight gain (OR: 0.93 per weight kilogram difference between 2nd and 3rd trimester, 95% CI: 0.92-0.95) were protective for SGA. Four or more ANC visits (OR: 0.53, 95% CI: 0.41-0.68) and respiratory symptoms in the third trimester (OR: 0.67, 95% CI: 0.54-0.84) were negatively associated with LGA, and maternal age < 18 years (OR: 1.39, 95% CI: 1.03-1.87) and respiratory symptoms in the second trimester (OR: 1.27, 95% CI: 1.07-1.51) were positively associated with LGA. CONCLUSIONS: Our findings are in line with known risk factors for SGA. Because the prevalence and mortality risk of LGA babies is low in this population, it is likely LGA status does not indicate underlaying illness. Improved and equitable access to high quality antenatal care, monitoring for appropriate gestational weight gain and increased monitoring of women with high-risk pregnancies may reduce prevalence and improve outcomes of SGA babies. TRIAL REGISTRATION: The study used in this secondary data analysis was registered at Clinicaltrials.gov NCT01177111.