Impact of topical applications of sunflower seed oil on neonatal mortality and morbidity in southern Nepal: a community-based, cluster-randomised trial.

INTRODUCTION: Hospital-based studies have demonstrated topical applications of sunflower seed oil (SSO) to skin of preterm infants can reduce nosocomial infections and improve survival. In South Asia, replacing traditional mustard with SSO might have similar benefits. METHODS: 340 communities in Sarlahi, Nepal were randomised to use mustard oil (MO) or SSO for community practice of daily newborn massage. Women were provided oil in late pregnancy and the first month post partum, and visited daily through the first week of life to encourage massage practice. A separate data collection team visited on days 1, 3, 7, 10, 14, 21 and 28 to record vital status and assess serious bacterial infection. RESULTS: Between November 2010 and January 2017, we enrolled 39 479 pregnancies. 32 114 live births were analysed. Neonatal mortality rates (NMRs) were 31.8/1000 (520 deaths, 16 327 births) and 30.5/1000 (478 deaths, 15 676 births) in control and intervention, respectively (relative risk (RR)=0.95, 95% CI: 0.84, 1.08). Among preterm births, NMR was 90.4/1000 (229 deaths, 2533 births) and 79.2/1000 (188 deaths, 2373 births) in control and intervention, respectively (RR=0.88; 95% CI: 0.74, 1.05). Among preterm births <34 weeks, the RR was 0.83 (95% CI: 0.67, 1.02). No statistically significant differences were observed in incidence of serious bacterial infection. CONCLUSIONS: We did not find any neonatal mortality or morbidity benefit of using SSO instead of MO as emollient therapy in the early neonatal period. Further studies examining whether very preterm babies may benefit are warranted. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01177111).

Supplementation with fortified balanced energy-protein during pregnancy and lactation and its effects on birth outcomes and infant growth in southern Nepal: protocol of a 2×2 factorial randomised trial.

INTRODUCTION: Many women in low and middle-income countries enter pregnancy with low nutritional reserves with increased risk of fetal growth restriction and poor birth outcomes, including small-for-gestational-age (SGA) and preterm birth. Balanced energy-protein (BEP) supplements have shown reductions in risk of stillbirth and SGA, yet variations in intervention format and composition and limited evidence on the impact of BEP during lactation on growth outcomes warrant further study. This paper describes the protocol of the Maternal Infant Nutrition Trial (MINT) Study, which aims to evaluate the impact of a fortified BEP supplement during pregnancy and lactation on birth outcomes and infant growth in rural Nepal. METHODS AND ANALYSIS: MINT is a 2×2 factorial, household randomised, unblinded, efficacy trial conducted in a subarea of Sarlahi District, Nepal. The study area covers six rural municipalities with about 27 000 households and a population of approximately 100 000. Married women (15-30 years) who become pregnant are eligible for participation in the trial and are randomly assigned at enrolment to supplementation with fortified BEP or not and at birth to fortified BEP supplementation or not until 6 months post partum. The primary pregnancy outcome is incidence of SGA, using the INTERGROWTH-21st standard, among live born infants with birth weight measured within 72 hours of delivery. The primary infant growth outcome is mean length-for-age z-score at 6 months using the WHO international growth reference. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board (IRB) at Johns Hopkins Bloomberg School of Public Health, Baltimore, USA (IRB00009714), the Committee on Human Research IRB at The George Washington University, Washington, DC, USA (081739), and the Ethical Review Board of the Nepal Health Research Council, Kathmandu, Nepal (174/2018). TRIAL REGISTRATION NUMBER: NCT03668977.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Cognitive testing of questions about antenatal care and nutrition interventions in southern Nepal.

Large scale surveys such as the Demographic and Health Surveys (DHS) are used to measure the coverage and quality of antenatal care (ANC)-related services. Studies have increasingly validated questions from these surveys, though few have explored respondent comprehension or associated thought processes. This study aimed to use cognitive testing and validation approaches to understand how survey respondents understand questions related to ANC-related nutrition services. The study was nested within a larger validation study in southern Nepal. Pregnant women's receipt of ANC related services was directly observed at five health posts followed by a recall interview at 6 months postpartum. A week later, a survey module was re-administered to 30 women containing 15 questions about receipt of ANC care and specifically nutrition-related services. Detailed probing was used to identify cognitive challenges related to comprehension, retrieval, judgement, and response. Respondents accurately recalled the four specific ANC visits recommended by the government of Nepal but those with more visits struggled to estimate the total number of ANC visits they had made. A number of terms including "antenatal care, "nutrition" and "breastfeeding" were challenging for many respondents to understand. Visits to private providers including for ultrasounds were inconsistently included in ANC visit counts suggesting that question wording could better specify the type of care. Many respondents over-estimated the number of iron folic acid (IFA) supplements taken during pregnancy, and recall was challenging. Calculations were based on estimating the number of months between first ANC visit to delivery, and only sometimes factored in missed tablets. Opportunities exist to improve questions to facilitate better comprehension by respondents through a combination of using local terms and explanations, reordering some questions, and adapting questions to better match respondents' approaches to estimating numeric responses.

Acceptability of 11 fortified balanced energy-protein supplements for pregnant women in Nepal.

Evidence suggests that multiple micronutrient and balanced energy protein (BEP) supplementation during pregnancy can decrease the risk of stillbirth and small-for-gestational-age births and increase birth weight. We conducted a mixed-methods formative research study to identify the most acceptable among a range of 11 candidates fortified BEP supplements for use in pregnancy and lactation in a rural district in Nepal. Forty pregnant women aged 15-40 years participated in a test meal tasting of 11 different sweet and savoury candidate BEP supplements. Each participant rated the products on organoleptic properties using a 7-point hedonic scale (1 = Dislike it very much to 7 = Like it very much), ranked her 'top 3' most liked supplements, and subsequently discussed each product with peers in focus group discussions (FGDs). Five supplements (sweet lipid-based nutrient supplement (LNS), savoury LNS, sweet vanilla biscuits, vanilla instant drinks and seasoned pillows) achieved the maximum overall median hedonic score of 7, with sweet LNS and seasoned pillows ranking as the top 2. This was consistent with the assessments in FGDs. Women in the FGDs expressed dislike of the smell and taste of the cocoa drink, savoury masala bar, sweet mango bar and savoury curry biscuit, which was consistent with the hedonic scale scores. This study provides valuable insights into our understanding of women's acceptance of different BEP supplements during pregnancy in rural Nepal and has helped identify the two most accepted BEP supplements to be used in a two-month home trial to assess utilisation and compliance in this setting.

Compliance with and acceptability of two fortified balanced energy protein supplements among pregnant women in rural Nepal.

Some evidence suggests that balanced energy protein (BEP) supplements taken during pregnancy and lactation can have positive effects on birth outcomes such as small-for-gestational age and birthweight, but more evidence is needed on the long-term use and acceptability of such supplements. We conducted a mixed-methods formative research study to assess and compare compliance with and acceptability of two BEP supplements, a lipid-based peanut paste and a biscuit, to identify BEP supplements for subsequent inclusion in an efficacy trial. We conducted an 8-week feeding trial of daily supplementation among two groups of 40 pregnant women each in rural Nepal. Compliance data were collected and supplements distributed at the weekly visits. Sensory properties of the supplements were assessed using a 7-point Likert scale. In addition, in-depth interviews with women (n = 16), family members (n = 6) and health workers (n = 6) and focus group discussions (FGDs) (n = 4) were conducted to explore themes related to general use and intention of future use of the supplement. Overall self-reported compliance was high: medians of 91.1% in the lipid-based peanut paste group and 96.4% in the biscuit group. Both supplements were rated highly on overall likability (median score 6/7) and sensory properties. Qualitative findings showed that sustained use of the supplements was attributed to expected health benefits, favourable sensory attributes, and family support. The FGDs suggested providing the option to choose between more than one type/flavour of supplements to improve compliance. Sharing was mostly evident in the first week with higher sharing reported in the biscuit group.

Validation of Maternal Report of Receipt of Iron-Folic Acid Supplementation during Antenatal Care in Rural Southern Nepal.

BACKGROUND: Coverage of iron-folic acid (IFA) supplementation is a key indicator for tracking programmatic progress within and across countries. However, the validity of maternal report of this information during household surveys has yet to be determined. OBJECTIVES: This study aimed to examine the validity of maternal recall of receipt of IFA supplementation during antenatal care (ANC) and factors associated with accuracy of maternal recall. METHODS: A longitudinal cohort design was employed. The direct observation of the IFA received during all ANC visits at the 5 study health posts served as the "gold standard" to the maternal report of IFA received during the postpartum interview. Individual-level validity was assessed by calculating indicator sensitivity, specificity, and AUC. The inflation factor (IF) measured population-level bias. A multivariable log-binomial model was used to assess factors associated with accurate recall. RESULTS: The majority (95.8%) of women were observed receiving IFA during pregnancy. Women overreported the number of IFA tablets received compared with what was observed during ANC visits (mean difference: 45 tablets). Maternal report of any IFA receipt was moderate (AUC = 0.60; 95% CI: 0.50, 0.71), and population bias was low (IF = 1.01). However, the individual-level validity was poor across the 7 IFA tablet count categories; the AUC for categories ranged from misleading to moderate. Driven by the trend of maternal overreport, the IF indicated that maternal report drastically underestimated the coverage of lower tablet categories and overestimated the coverage of higher tablet counts. Accuracy of maternal report was not associated with months since last ANC observation nor any maternal characteristics. CONCLUSIONS: Maternal report of the amount of IFA supplementation received during pregnancy produced extremely biased population coverage and performed poorly to moderately for individual-level validity. It is imperative to improve this indicator because it is used in global frameworks and national program planning.

Impact of sunflower seed oil versus mustard seed oil on skin barrier function in newborns: a community-based, cluster-randomized trial.

BACKGROUND: Natural vegetable oils are widely used for newborn massage in many low resource settings. Animal models indicated that sunflower seed oil (SSO) can accelerate skin barrier recovery following damage, while other oils, including mustard oil (MO), may cause further skin barrier damage. The objective was to compare the effects of two SSO and MO used for routine massage on skin integrity in premature and full-term neonates. METHODS: This community-based cluster randomized controlled trial included 995 neonates assigned to full body massage with sunflower seed oil (SSO, intervention) or mustard seed oil (MO, standard practice) from July 2012-May 2014 in Sarlahi, Nepal. Skin integrity measures were evaluated over 28 days, including skin condition (erythema, rash, dryness), skin surface pH, stratum corneum (SC) cohesion/protein concentration, and transepidermal water loss (TEWL). Overall means and rates of change in these skin measures were compared between oil groups using bivariate random-effects models. RESULTS: 500 and 495 live born neonates received repeated massage with MO and SSO, respectively. Skin pH decreased more quickly for SSO than MO in the first week of life, with a difference in mean daily reductions of 0.02 (95% CI: 0.002-0.040). Erythema, rash and dryness increased (worsened) over days 1-14 then decreased by day 28, with no significant oil group differences. TEWL increased over time, with no significant oil group differences. Gestational age did not modify the effect; the slightly faster decrease in skin pH among SSO infants was similar in magnitude between term and preterm infants. CONCLUSIONS: Oil type may contribute to differences in skin integrity when neonates are massaged regularly. The more rapid acid mantle development observed for SSO may be protective for neonates in lower resource settings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01177111); registered August 6th, 2010.

Validity of self-reported receipt of iron supplements during pregnancy: implications for coverage measurement.

BACKGROUND: Iron-deficiency anemia during pregnancy is an underlying cause of maternal deaths, and reducing risk through routine iron supplementation is a key component of antenatal care (ANC) programs in most low- and middle income countries. Supplementation coverage during pregnancy is estimated from maternal self-reports in population-based household surveys, yet recall bias and social desirability bias lead to errors of unknown magnitude. METHODS: We linked data from household and health facility surveys from 16 countries to estimate input-adjusted coverage of iron supplementation during pregnancy. We assessed the validity of reported receipt of iron supplements in client exit interviews using direct observation as the gold standard across 9 countries with a recent Service Provision Assessment (SPA). Using a sample of 227 women who participated in the Nepal Oil Massage Study (NOMS), we also assessed the validity of self-reported receipt of iron folic acid (IFA) supplements. We used Poisson regression models to explore the association between client and health facility characteristics and agreement of self-reported receipt of iron supplements compared to direct observation. RESULTS: Across the 16 countries, iron supplements were in supply at most of the 9215 sampled health facilities offering ANC services (91%). We estimated that between 48 and 93% of women attended at least one ANC visit at a health facility with iron supplements available. The specificity of recall of receipt of iron supplementation immediately following a visit was 79.3% and the sensitivity was 88.7% for the entire sample. Individual-level accuracy was high (Area under the curve > 0.7) and population bias low (0.75 < inflation factor < 1.25) across all countries. By contrast, in the NOMS sub-study, the accuracy of self-reported receipt of IFA supplements after 1-2 years was poor (sensitivity 86.1%, specificity 34.3%). Adjusted regression analyses indicated that older age and higher level of education were associated with poorer agreement between self-reports and direct observation. CONCLUSIONS: These findings suggest the need for caution when using self-reported measures with an extended recall period. Further validation studies using conditions similar to widely used population-based household surveys are warranted.

Illness recognition, decision-making, and care-seeking for maternal and newborn complications: a qualitative study in Sarlahi District, Nepal.

BACKGROUND: Identification of maternal and newborn illness and the decision-making and subsequent care-seeking patterns are poorly understood in Nepal. We aimed to characterize the process and factors influencing recognition of complications, the decision-making process, and care-seeking behavior among families and communities who experienced a maternal complication, death, neonatal illness, or death in a rural setting of Nepal. METHODS: Thirty-two event narratives (six maternal/newborn deaths each and 10 maternal/newborn illnesses each) were collected using in-depth interviews and small group interviews. We purposively sampled across specific illness and complication definitions, using data collected prospectively from a cohort of women and newborns followed from pregnancy through the first 28 days postpartum. The event narratives were coded and analyzed for common themes corresponding to three main domains of illness recognition, decision-making, and care-seeking; detailed event timelines were created for each. RESULTS: While signs were typically recognized early, delays in perceiving the severity of illness compromised prompt care-seeking in both maternal and newborn cases. Further, care was often sought initially from informal health providers such as traditional birth attendants, traditional healers, and village doctors. Key decision-makers were usually female family members; husbands played limited roles in decisions related to care-seeking, with broader family involvement in decision-making for newborns. Barriers to seeking care at any type of health facility included transport problems, lack of money, night-time illness events, low perceived severity, and distance to facility. Facility care was often sought only after referral or following treatment failure from an informal provider and private facilities were sought for newborn care. Respondents characterized government facility-based care as low quality and reported staff rudeness and drug type and/or supply stock shortages. CONCLUSION: Delaying the decision to seek skilled care was common in both newborn and maternal cases. Among maternal cases, delays in receiving appropriate care when at a facility were also seen. Improved recognition of danger signs and increased demand for skilled care, motivated through community level interventions and health worker mobilization, needs to be encouraged. Engaging informal providers through training in improved danger sign identification and prompt referral, especially for newborn illnesses, is recommended.

Nutrition and maternal, neonatal, and child health.

This article reviews the central role of nutrition in advancing the maternal, newborn, and child health agenda with a focus on evidence for effective interventions generated using randomized controlled trials in low- and middle-income countries (LMIC). The 1000 days spanning from conception to 2 years of life are a critical period of time when nutritional needs must be ensured; failure to do so can lead to adverse impacts on short-term survival as well as long-term health and development [corrected]. The burden of maternal mortality continues to be high in many under-resourced settings; prenatal calcium supplementation in populations with low intakes can reduce the risk of pre-eclampsia and eclampsia morbidity and mortality and is recommended, and antenatal iron-folic acid use in many countries may reduce anemia, a condition that may be an underlying factor in postpartum hemorrhage. Sufficient evidence exists to promote multiple micronutrient supplementation during pregnancy to reduce fetal growth restriction and low birth weight. Early initiation of breastfeeding (within an hour), exclusive breastfeeding in the first 6 months of life, and vitamin A supplementation in the first few days of life in Asia (but not in Africa) reduce infant mortality. Biannual large-dose vitamin A supplements to children 6-59 months of age and zinc for treatment of diarrhea continue to be important strategies for improving child health and survival. Early nutrition and micronutrient status can influence child development but should be integrated with early responsive learning interventions. Future research is needed that goes beyond the 1000 days to ensure adequate preconceptional nutrition and health, with special emphasis on adolescents who contribute to a large proportion of first births in many LMIC. Thus, we make the case for integrating proven nutrition interventions with those for health in pregnant women, and with those for health and child development in neonates, infants, and young children to help advance the global MNCH agenda.

The role of zinc and iron-folic acid supplementation on early child temperament and eating behaviors in rural Nepal: a randomized controlled trial.

UNLABELLED: Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4-17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (ß = -0.03, 95% CI -0.3, 0.2) or iron-folic acid and non-iron-folic acid (ß = 0.08, 95% CI -0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (ß = -0.14, 95% CI -0.3, 0.04) or between iron and non-iron eating behavior scores (ß = -0.11, 95% CI -0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (ß = -0.3, 95% CI -0.6, -0.01), Ultimately, this effect of zinc on eating behaviors was the only effect we observed after approximately one year of micronutrient supplementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109551.

Deaths due to injury, including violence among married Nepali women of childbearing age: a qualitative analysis of verbal autopsy narratives.

OBJECTIVES: Self-harm and interpersonal violence are important causes of death among women in Nepal. We analysed prospectively collected data to investigate the extent and nature of injury-related deaths among married women aged 15-49 years, recorded through verbal autopsy in rural Sarlahi District, Nepal. METHODS: Verbal autopsies were systematically collected on all deaths of married women of reproductive age (15-49 years) over a 3-year period (1994-1997) as part of a randomised community-based trial of maternal vitamin A and ß-carotene supplementation. This analysis included a three-way comparison of verbal autopsy data: qualitative free-response narratives, closed-ended responses, and physician-assigned consensus cause of death. RESULTS: We focused on 46 of 559 deaths (8.2%) that were determined to be injury-related. Of the 46, 28% were identified as intentionally self-inflicted, and 11% as intentionally inflicted by another. Inconsistencies were noted between verbal autopsy reports of causes of deaths and physician assessments. Conflicts within the family figured prominently in the narratives. Women with unstable family situations and suffering from mental illness were often described as having experienced violent deaths. CONCLUSIONS: Findings highlight that intervention efforts might be necessary especially in situations where there are poor family dynamics or mental health issues in order to prevent potential intrafamily violence and possible death. Results also point to the need for further documentation of violent deaths in rural Nepal.

Risk factors and neonatal/infant mortality risk of small-for-gestational-age and preterm birth in rural Nepal.

OBJECTIVE: Our study seeks to elucidate risk factors for and mortality consequences of small-for-gestational-age (SGA) and preterm birth in rural Nepal. In contrast with previous literature, we distinguish the epidemiology of SGA and preterm birth from each other. METHODS: We analyzed data from a maternal micronutrient supplementation trial in rural Nepal (n = 4130). We estimated adjusted risk ratios (aRR) for risk factors of SGA and preterm birth, and aRRs for the associations between SGA/preterm birth and neonatal/infant mortality. We used mutually exclusive categories of term-appropriate-for-gestational-age (AGA), term-SGA, preterm-AGA, and preterm-SGA (with term-AGA as reference) in our analyses. RESULTS: Stunted (<145 cm) and wasted (<18.5 kg/m(2)) women both had increased risk of having term-SGA (aRR 1.36, 95% CI: 1.14-1.61, aRR 1.22, 95% CI: 1.09-1.36 respectively) and preterm-SGA (aRR 2.48, 95% CI: 1.29-4.74, aRR 1.99, 95% CI: 1.33-2.97 respectively), but not preterm-AGA births. Similar results were found for low maternal weight gain per gestational week. Those born preterm-SGA generally experienced the highest neonatal and infant mortality risk, although term-SGA and preterm-AGA newborns also had statistically significantly high mortality risks compared to term-AGA babies. CONCLUSIONS: SGA and preterm birth have distinct risk factors and mortality patterns. Maternal chronic and acute malnutrition appear to be associated with SGA outcomes. Because of high SGA prevalence in South Asia and the increased neonatal and infant mortality risk associated with SGA, there is an urgent need to intervene with effective interventions.

Incidence of and risk factors for neonatal jaundice among newborns in southern Nepal.

OBJECTIVE: To quantify the incidence of and risk factors for neonatal jaundice among infants referred for care from a rural, low-resource, population-based cohort in southern Nepal. METHODS: Study participants were 18,985 newborn infants born in Sarlahi District in southern Nepal from May 2003 through January 2006 who participated in a cluster-randomised, placebo-controlled, community-based trial to evaluate the effect of newborn chlorhexidine cleansing on neonatal mortality and morbidity. Jaundice was assessed based on visual assessment of the infant by a study worker and referral for care. Adjusted relative risks (RR) were estimated to identify risk factors for referral for neonatal jaundice using Poisson regression. RESULTS: The incidence of referral for neonatal jaundice was 29.3 per 1000 live births (95% confidence interval: 26.9, 31.7). Male sex, high birth weight, breastfeeding patterns, warm air temperature, primiparity, skilled birth attendance, place of delivery, prolonged labour, oil massage, paternal education and ethnicity were significant risk factors (P-values < 0.01). After multivariable adjustment, sex, birth weight, difficulty feeding, prolonged labour, primiparity, oil massage, ambient air temperature and ethnicity remained important factors. Among infants with difficulty feeding, exclusive breastfeeding was a risk factor for neonatal jaundice, whereas exclusive breastfeeding was protective among infants with no report of difficulty feeding. CONCLUSIONS: Several known risk factors for neonatal jaundice in a low-resource setting were confirmed in this study. Unique observed associations of jaundice with ambient air temperature and oil massage may be explained by the opportunity for phototherapy based on the cultural practices of this study population. Future research should investigate the role of an infant's difficulty in feeding as a potential modifier in the association between exclusive breastfeeding and jaundice.

Effects of zinc and iron supplementation fail to improve motor and language milestone scores of infants and toddlers.

OBJECTIVE: To assess the effects of zinc and iron-folic acid supplementation on motor and language milestones in Nepali children. METHODS: Five hundred forty-four children 4 to 17 mo old residing in Ishwarpur, Nepal were randomized to receive placebo, iron-folic acid, zinc, or zinc plus iron-folic acid daily. Data were collected at baseline and at 3-mo intervals for 1 y. The main effects of zinc and iron folic-acid supplementation were estimated for motor and language milestones. Crude and adjusted mean cumulative changes in scores from visits 1 to 5 and adjusted rates of change were modeled. RESULTS: Adjusted differences in motor milestone scores from visits 1 to 5 and rates of change were not significantly different for the zinc and non-zinc groups (adjusted ß = -0.7, 95% confidence interval [CI] -1.4 to 0.01; adjusted ß = -0.1, 95% CI -0.5 to 0.3, respectively). Motor milestones in children receiving and not receiving iron supplements were not significantly different (adjusted ß = 0.1, 95% CI -0.7 to 0.8, from visits 1 to 5; adjusted ß = 0.1, 95% CI -0.3 to 0.5, for rate of change). Children receiving zinc had a 0.8 lower mean crude change in language score from visits 1 to 5 compared with children not receiving zinc (95% CI -1.3 to -0.3), but the significance was lost after adjustment (adjusted ß = -0.2, 95% CI -0.6 to 0.2, for visits 1 to 5; ß = -0.1, 95% CI -0.3 to 0.2, for rate of change). No significant difference in motor or language milestone scores from iron supplementation was observed. CONCLUSION: After 1 y, neither zinc nor iron-folic acid supplementation in Nepali children improved the attainment of motor or language milestones.

Effects of vitamin A and ß-carotene supplementation on birth size and length of gestation in rural Bangladesh: a cluster-randomized trial.

BACKGROUND: Micronutrient deficiencies may be related to poor fetal growth and short gestation. Few studies have investigated the contribution of maternal vitamin A deficiency to these outcomes. OBJECTIVE: In rural northwestern Bangladesh, we examined the effects of weekly antenatal vitamin A and ß-carotene supplementation on birth weight, length, circumferential body measures, and length of gestation. DESIGN: With the use of a cluster-randomized, placebo-controlled trial design, pregnant women were enrolled in the first trimester and began receiving their allocated supplements (vitamin A, ß-carotene, or placebo) weekly until 3 mo postpartum. Birth anthropometric measures were made at home. RESULTS: Of 13,709 newborns whose birth weight was measured within 72 h of birth, mean (±SD) weight was 2.44 ± 0.42 kg, the prevalence of low birth weight (LBW) was 54.4%, and that of small-for-gestational age (SGA) was 70.5%. Birth weight, length, and chest, head, and arm circumferences did not differ between supplementation and placebo groups nor did rates of LBW and SGA. Mean gestational age at birth was 38.3 ± 2.9 wk, and 25.6% of births occurred before 37 wk. Neither gestational age nor preterm birth rate differed with vitamin A or ß-carotene supplementation. CONCLUSIONS: In this rural South Asian population with a high burden of LBW and preterm birth but modest levels of maternal vitamin A deficiency, antenatal vitamin A or ß-carotene supplementation did not benefit these birth outcomes. Other nutritional and nonnutritional interventions should be examined to reduce risks of these adverse outcomes in rural South Asia. This trial was registered at clinicaltrials.gov as NCT00198822.

Preschool micronutrient supplementation effects on intellectual and motor function in school-aged Nepalese children.

OBJECTIVE: To examine intellectual and motor functioning of children who received micronutrient supplementation from 12 to 35 months of age. DESIGN: Cohort follow-up of children 7 to 9 years of age who participated in a 2 × 2 factorial, placebo-controlled, randomized trial from October 2001 through January 2006. SETTING: Rural Nepal. PARTICIPANTS: A total of 734 children 12 to 35 months of age at supplementation and 7 to 9 years of age at testing. INTERVENTIONS: Children received iron plus folic acid (12.5 mg of iron and 50 µg of folic acid); zinc (10 mg); iron plus folic acid and zinc; or placebo. MAIN OUTCOME MEASURES: Intellectual, motor, and executive function. RESULTS: In both the unadjusted and adjusted analyses, iron plus folic acid supplementation had no effect overall or on any individual outcome measures being tested. In the unadjusted analysis, zinc supplementation had an overall effect, although none of the individual test score differences were significant. In the adjusted analysis, the overall difference was not significant. CONCLUSION: In rural Nepal, we found that iron plus folic acid or zinc supplementation during the preschool years had no effect on aspects of intellectual, executive, and motor function at 7 to 9 years of age, suggesting no long-term developmental benefit of iron or zinc supplementation during 12 to 35 months of age.

Pneumococcal carriage at age 2 months is associated with growth deficits at age 6 months among infants in South India.

Nasopharyngeal colonization is the first step in the pathway to Streptococcus pneumoniae (Spn) infection, a leading cause of childhood morbidity and mortality. We investigated the effect of Spn colonization at ages 2 and 4 mo on growth at age 6 mo among 389 infants living in rural South India by using data from an Spn carriage study nested within a randomized, double-blind, placebo-controlled community trial designed to evaluate the impact of newborn vitamin A supplementation on Spn carriage in the first 6 mo of life. Primary outcomes were weight, length, and anthropometric indices of nutritional status. Growth data at age 6 mo were available for 84% (389 of 464) of infants in the Spn carriage study. Carriage at age 2 mo was associated with increased odds of stunting [OR: 3.07 (95% CI: 1.29, 7.36) P = 0.012] and lower weight [ß: -266 g (95% CI: -527, -5) P = 0.045], length [ß: -1.31 cm (95% CI: -2.32, -0.31) P = 0.010], and length-for-age Z scores [ß: -0.59; (95% CI: -1.05, -0.13) P = 0.012] at age 6 mo. Spn carriage at age 4 mo did not affect growth. Carriage of invasive serotypes at age 2 mo was associated with decreases in mean weight [ß: -289 g; (95% CI: -491, -106) P = 0.002] and length [ß:-0.38 cm (95% CI: -1.49, -0.01) P = 0.047] at age 6 mo. Newborn vitamin A supplementation did not modify the association between Spn carriage and growth. Results suggest that pneumococcal carriage at age 2 mo is an independent risk factor for poor growth in young infants. Future studies need to clarify the role of Spn carriage on growth retardation in low-income countries.

Vitamin A supplementation in preschool children and risk of hearing loss as adolescents and young adults in rural Nepal: randomised trial cohort follow-up study.

OBJECTIVE: To determine whether vitamin A supplementation administered in the preschool years can lower the risk of hearing loss in adolescence and adulthood. DESIGN: Follow-up study of adolescents and young adults who, as preschool aged children in 1989, were enrolled into a cluster randomised, double blinded, placebo controlled trial of vitamin A supplementation. SETTING: South central, rural Nepal. PARTICIPANTS: 2378 adolescents and young adults aged 14 to 23, representing 51% of those who finished the original trial and 71% of those living in the study area in 2006. INTERVENTIONS: Every four months for 16 months preschool children were visited at home, given an oral 200,000 IU dose of vitamin A (half dose at age 1-11 months, quarter dose at <1 month) or placebo and the parents were queried about any childhood illnesses in the previous week, including purulent discharge from the ears. MAIN OUTCOME MEASURES: Prevalence of mild or worse hearing loss (≥ 30 dB) in the most affected ear and tympanometric measures of middle ear function (peak height, ear canal volume, and gradient). RESULTS: During the original trial, the prevalence of middle ear infection during the preschool years did not differ between the supplement groups. By adolescence and early adulthood, a non-significant 17% reduction in hearing loss occurred among those who had periodically received vitamin A compared with placebo as preschool aged children (odds ratio 0.83, 95% confidence interval 0.62 to 1.12). Among participants with any ear discharge in early childhood, vitamin A supplementation was associated with a reduced risk of hearing loss, by 42% (0.58, 0.37 to 0.92) compared with controls, after adjusting the confidence interval for the design effect of the original trial. Abnormal tympanometric peak height of the middle ear system was less likely among participants supplemented with vitamin A in childhood. CONCLUSION: In undernourished settings, periodic, high dose vitamin A supplementation may reduce the risk of hearing loss associated with purulent ear infections in early childhood.