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).

Comparison of pregnancy and neonatal outcomes in a retrospective full pregnancy history survey versus population-based prospective records: a validation study in rural Sarlahi District, Nepal.

INTRODUCTION: Countries without complete civil registration and vital statistics systems rely on retrospective full pregnancy history surveys (FPH) to estimate incidence of pregnancy and mortality outcomes, including stillbirth and neonatal death. Yet surveys are subject to biases that impact demographic estimates, and few studies have quantified these effects. We compare data from an FPH vs. prospective records from a population-based cohort to estimate validity for maternal recall of live births, stillbirths, and neonatal deaths in a rural population in Sarlahi District, Nepal. METHODS: We used prospective data, collected through frequent visits of women from early pregnancy through the neonatal period, from a population-based randomized trial spanning 2010-2017. We randomly selected 76 trial participants from three pregnancy outcome groups: live birth (n = 26), stillbirth (n = 25), or neonatal death (n = 25). Data collectors administered the Nepal 2016 Demographic and Health Surveys (DHS)-VII pregnancy history survey between October 22, 2021, and November 18, 2021. We compared total pregnancy outcomes and numbers of pregnancy and neonatal outcomes between the two data sources. We matched pregnancy outcomes dates in the two sources within ± 30 days and calculated measures of validity for adverse outcomes. RESULTS: Among 76 participants, we recorded 122 pregnancy outcomes in the prospective data and 104 outcomes in the FPH within ± 30 days of each woman's total observation period in the trial. Among 226 outcomes, we observed 65 live births that survived to 28 days, 25 stillbirths, and 32 live births followed by neonatal death in the prospective data and participants reported 63 live births that survived to 28 days, 15 stillbirths, and 26 live births followed by neonatal death in the pregnancy history survey. Sixty-two FPH outcomes were matched by date within ± 30 days to an outcome in prospective data. Stillbirth, neonatal death, higher parity, and delivery at a health facility were associated with likelihood of a non-matched pregnancy outcome. CONCLUSIONS: Stillbirth and neonatal deaths were underestimated overall by the FPH, potentially underestimating the burden of mortality in this population. There is a need to develop tools to reduce or adjust for biases and errors in retrospective surveys to improve reporting of pregnancy and mortality outcomes.

Validation of maternal recall of number of antenatal care visits attended in rural Southern Nepal: a longitudinal cohort study.

OBJECTIVES: This study aimed to examine the validity of maternal recall of total number of antenatal care (ANC) visits during pregnancy and factors associated with the accuracy of maternal recall. DESIGN: This was a longitudinal cohort study conducted from December 2018 through November 2020. SETTING: Five government health posts in the Sarlahi district of Southern Nepal. PARTICIPANTS: 402 pregnant women between ages 15 and 49 who presented for their first ANC visit at the study health posts. MAIN OUTCOMES: The observed number of ANC visits (gold standard) and the reported number of ANC visits at the postpartum interview (maternal recall). RESULTS: On average, women in the study who had a live birth attended 4.7 ANC visits. About 65% of them attended four or more ANC visits during pregnancy as recommended by the Nepal government, and 38.3% of maternal report matched the categorical ANC visits as observed by the gold standard. The individual validity was poor to moderate, with the highest area under the receiver operating characteristic curve (AUC) being 0.69 (95% CI: 0.65 to 0.74) in the 1-3 visits group. Population-level bias (as distinct from individual-level bias) was observed in the 1-3 visits and 4 visits groups, where 1-3 visits were under-reported (inflation factor (IF): 0.69) and 4 ANC visits were highly over-reported (IF: 2.12). The binary indicator ANC4+ (1-3 visits vs 4+ visits) showed better population-level validity (AUC: 0.69; IF: 1.17) compared with the categorical indicators (1-3 visits, 4 visits, 5-6 visits and more than 6 visits). Report accuracy was not associated with maternal characteristics but was related to ANC frequency. Women who attended more ANC visits were less likely to correctly report their total number of visits. CONCLUSION: Maternal report of number of ANC visits during pregnancy may not be a valid indicator for measuring ANC coverage. Improvements are needed to measure the frequency of ANC visits.

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.

Risk factors for neonatal mortality: an observational cohort study in Sarlahi district of rural southern Nepal.

OBJECTIVES: To assess the association between maternal characteristics, adverse birth outcomes (small-for-gestational-age (SGA) and/or preterm) and neonatal mortality in rural Nepal. DESIGN: This is a secondary observational analysis to identify risk factors for neonatal mortality, using data from a randomised trial to assess the impact of newborn massage with different oils on neonatal mortality in Sarlahi district, Nepal. SETTING: Rural Sarlahi district, Nepal. PARTICIPANTS: 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017. MAIN OUTCOME: The outcome variable is neonatal death. Cox regression was used to estimate adjusted Hazard Ratios (aHRs) to assess the association between adverse birth outcomes and neonatal mortality. RESULTS: There were 32 004 live births and 998 neonatal deaths. SGA and/or preterm birth was strongly associated with increased neonatal mortality: SGA and preterm (aHR: 7.09, 95% CI: (4.44 to 11.31)), SGA and term/post-term (aHR: 2.12, 95% CI: (1.58 to 2.86)), appropriate-for-gestational-age/large-for-gestational-age and preterm (aHR: 3.23, 95% CI: (2.30 to 4.54)). Neonatal mortality was increased with a history of prior child deaths (aHR: 1.53, 95% CI: (1.24 to 1.87)), being a twin or triplet (aHR: 5.64, 95% CI: (4.25 to 7.48)), births at health posts/clinics or in hospital (aHR: 1.34, 95% CI: (1.13 to 1.58)) and on the way to facilities or outdoors (aHR: 2.26, 95% CI: (1.57 to 3.26)). Risk was lower with increasing maternal height from <145 cm to 145-150 cm (aHR: 0.78, 95% CI: (0.65 to 0.94)) to ≥150 cm (aHR: 0.57, 95% CI: (0.47 to 0.68)), four or more antenatal care (ANC) visits (aHR: 0.67, 95% CI: (0.53 to 0.86)) and education >5 years (aHR: 0.75, 95% CI: (0.62 to 0.92)). CONCLUSION: SGA and/or preterm birth are strongly associated with increased neonatal mortality. To reduce neonatal mortality, interventions that prevent SGA and preterm births by promoting ANC and facility delivery, and care of high-risk infants after birth should be tested. TRIAL REGISTRATION NUMBER: NCT01177111.

How does social desirability bias influence survey-based estimates of the use of antenatal care in rural Nepal? A validation study.

OBJECTIVES: Social desirability bias is often speculated to influence survey responses but seldom studied in healthcare. The objective was to explore whether social desirability scores (SDS) or the presence of interview observers is associated with inaccurate recall and overestimation of antenatal care (ANC) services. DESIGN: Longitudinal validation study comparing recalled receipt of ANC services and nutrition components of ANC against direct observations of care. An adapted short form Marlowe-Crowne questionnaire was used to generate an SDS, and the presence of interview observers was treated as a separate exposure. We assessed accuracy and overestimation of recalled receipt of ANC services against observed receipt using log-binomial regression, adjusting for age, education, first-pregnancy and socioeconomic status. SETTING: Rural Southern Nepal with recruitment from five government health posts. PARTICIPANTS: 401 pregnant women. RESULTS: Social desirability scores did not significantly predict accuracy or overestimation of most types of ANC care except counselling on nausea. Higher SDS was associated with more accurate recall (adjusted RR, aRR 1.08 (95% CI 1.03, 1.12)) and less overestimation (aRR 0.85 (0.80, 0.91)). The presence of mothers-in-law or husbands during interviews was associated with greater overestimation of the number of ANC visits received by more than three visits (aRR 2.07 (1.11, 3.84)) and (aRR 4.19 (2.17, 8.10)), respectively. Those interviewed with friends present tended to overestimate the receipt of counselling on nausea, avoiding alcohol and not smoking. CONCLUSION: The presence of observers can lead to overestimation of the receipt of ANC care and support the conduct of interviews in private settings despite challenges of doing so in village contexts. Findings that the SDS did not predict the accuracy of most types of ANC care might reflect a reality that such questions may not be sensitive from a social-norms perspective. Additional local adaptation of SDS is recommended.

Prevalence and predictors of spontaneous preterm births in Nepal: findings from a prospective, population-based pregnancy cohort in rural Nepal-a secondary data analysis.

OBJECTIVE: Preterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal. DESIGN: This is a secondary observational analysis of trial data (registration number NCT01177111). SETTING: Rural Sarlahi district, Nepal. PARTICIPANTS: 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017. OUTCOME MEASURES: The outcome variable is spontaneous preterm birth. Generalized Estimating Equations Poisson regression with robust variance was fitted to present effect estimates as risk ratios. RESULT: The prevalence of spontaneous preterm birth was 14.5% (0.5% non-spontaneous). Characteristics not varying in pregnancy associated with increased risk of preterm birth were maternal age less than 18 years (adjusted risk ratio=1.13, 95% CI: 1.02 to 1.26); being Muslim (1.53, 1.16 to 2.01); first pregnancy (1.15, 1.04 to 1.28); multiple births (4.91, 4.20 to 5.75) and male child (1.10, 1.02 to 1.17). Those associated with decreased risk were maternal education >5 years (0.81, 0.73 to 0.90); maternal height ≥150 cm (0.89, 0.81 to 0.98) and being from wealthier families (0.83, 0.74 to 0.93). Pregnancy-related morbidities associated with increased risk of preterm birth were vaginal bleeding (1.53, 1.08 to 2.18); swelling (1.37, 1.17 to 1.60); high systolic blood pressure (BP) (1.47, 1.08 to 2.01) and high diastolic BP (1.41, 1.17 to 1.70) in the third trimester. Those associated with decreased risk were respiratory problem in the third trimester (0.86, 0.79 to 0.94); having poor appetite, nausea and vomiting in the second trimester (0.86, 0.80 to 0.92) and third trimester (0.86, 0.79 to 0.94); and higher weight gain from second to third trimester (0.89, 0.87 to 0.90). CONCLUSION: The prevalence of preterm birth is high in rural Nepal. Interventions that increase maternal education may play a role. Monitoring morbidities during antenatal care to intervene to reduce them through an effective health system may help reduce preterm birth.

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.

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.

Does higher early neonatal mortality in boys reverse over the neonatal period? A pooled analysis from three trials of Nepal.

OBJECTIVES: Neonatal mortality is generally 20% higher in boys than girls due to biological phenomena. Only a few studies have examined more finely categorised age patterns of neonatal mortality by sex, especially in the first few days of life. The objective of this study is to examine sex differentials in neonatal mortality by detailed ages in a low-income setting. DESIGN: This is a secondary observational analysis of data. SETTING: Rural Sarlahi district, Nepal. PARTICIPANTS: Neonates born between 1999 and 2017 in three randomised controlled trials. OUTCOME MEASURES: We calculated study-specific and pooled mortality rates for boys and girls by ages (0-1, 1-3, 3-7, 7-14, 14-21 and 21-28 days) and estimated HR using Cox proportional hazards models for male versus female mortality for treatment and control groups together (n=59 729). RESULTS: Neonatal mortality was higher in boys than girls in individual studies: 44.2 vs 39.7 in boys and girls in 1999-2000; 30.0 vs 29.6 in 2002-2006; 33.4 vs 29.4 in 2010-2017; and 33.0 vs 30.2 in the pooled data analysis. Pooled data found that early neonatal mortality (HR=1.17; 95% CI: 1.06 to 1.30) was significantly higher in boys than girls. All individual datasets showed a reversal in mortality by sex after the third week of life. In the fourth week, a reversal was observed, with mortality in girls 2.43 times higher than boys (HR=0.41; 95% CI: 0.31 to 0.79). CONCLUSIONS: Boys had higher mortality in the first week followed by no sex difference in weeks 2 and 3 and a reversal in risk in week 4, with girls dying at more than twice the rate of boys. This may be a result of gender discrimination and social norms in this setting. Interventions to reduce gender discrimination at the household level may reduce female neonatal mortality. TRIAL REGISTRATION NUMBER: NCT00115271, NCT00109616, NCT01177111.

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.

Dissecting Fc signatures of protection in neonates following maternal influenza vaccination in a placebo-controlled trial.

Influenza is an important cause of illness and morbidity for infants. Seasonal influenza vaccination during pregnancy aims to provide protection to mothers, but it can also provide immunity to infants. The precise influence of maternal vaccination on immunity in infants and how vaccine-elicited antibodies provide protection in some but not all infants is incompletely understood. We comprehensively profiled the transfer of functional antibodies and defined humoral factors contributing to immunity against influenza in a clinical trial of maternal influenza vaccination. Influenza-specific antibody subclass levels, Fc ɣ receptor (FCGR) binding levels, and antibody-dependent innate immune functions were all profiled in the mothers during pregnancy and at birth, as well as in cord blood. Vaccination increased influenza-specific antibody levels, antibody binding to FCGR, and specific antibody-dependent innate immune functions in both maternal and cord blood, with FCGR binding most enhanced via vaccination. Influenza-specific FCGR binding levels were lower in cord blood of infants who subsequently developed influenza infection. Collectively these data suggest that in addition to increased antibody amounts, the selective transfer of FCGR-binding antibodies contributes to the protective immune response in infants against influenza.

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 MINORMIX Approach for Estimation of Low Birthweight Prevalence Using a Rural Nepal Dataset.

BACKGROUND: The Global Nutrition Target of reducing low birthweight (LBW) by ≥30% between 2012 and 2025 has led to renewed interest in producing accurate, population-based, national LBW estimates. Low- and middle-income countries rely on household surveys for birthweight data. These data are frequently incomplete and exhibit strong "heaping." Standard survey adjustment methods produce estimates with residual bias. The global database used to report against the LBW Global Nutrition Target adjusts survey data using a new MINORMIX (multiple imputation followed by normal mixture) approach: 1) multiple imputation to address missing birthweights, followed by 2) use of a 2-component normal mixture model to account for heaping of birthweights. OBJECTIVES: To evaluate the performance of the MINORMIX birthweight adjustment approach and alternative methods against gold-standard measured birthweights in rural Nepal. METHODS: As part of a community-randomized trial in rural Nepal, we measured "gold-standard" birthweights at birth and returned 1-24 mo later to collect maternally reported birthweights using standard survey methods. We compared estimates of LBW from maternally reported data derived using: 1) the new MINORMAX approach; 2) the previously used Blanc-Wardlaw adjustment; or 3) no adjustment for missingness or heaping against our gold standard. We also assessed the independent contribution of multiple imputation and curve fitting to LBW adjustment. RESULTS: Our gold standard found 27.7% of newborns were LBW. The unadjusted LBW estimate based on maternal report with simulated missing birthweights was 14.5% (95% CI: 11.6, 18.0%). Application of the Blanc-Wardlaw adjustment increased the LBW estimate to 20.6%. The MINORMIX approach produced an estimate of 26.4% (95% CI: 23.5, 29.3%) LBW, closest to and with bounds encompassing the measured point estimate. CONCLUSIONS: In a rural Nepal validation dataset, the MINORMIX method generated a more accurate LBW estimate than the previously applied adjustment method. This supports the use of the MINORMIX method to produce estimates for tracking the LBW Global Nutrition Target.

Causes of neonatal mortality using verbal autopsies in rural Southern Nepal, 2010-2017.

The burden of neonatal mortality remains high worldwide, particularly in South Asia. Verbal Autopsy is a method used to identify cause of death (COD) where vital registration capabilities are lacking. This study examines the causes of neonatal mortality in a large study population in rural Southern Nepal. The data used is from a larger cluster-randomized community-based trial. The study includes 984 neonatal deaths with complete verbal autopsy information which occurred between 2010 and 2017. The InterVA-5 software was used to identify COD. COD included severe infection (sepsis, pneumonia, meningitis/encephalitis), intrapartum related events (identified as birth asphyxia), congenital malformations, and other. The neonatal mortality rate was 31.2 neonatal deaths per 1000 live births. The causes of neonatal mortality were identified as prematurity (40%), intrapartum related events (35%), severe infection (19%), congenital abnormalities (4%), and other (2%). A high proportion, 42.5% of neonatal deaths occurred in the first 24 hours after birth. Over half (56.4%) of deaths occurred at home. This large prospective study identifies population level neonatal causes of death in rural Southern Nepal, which can contribute to national and regional COD estimates. Interventions to decrease neonatal mortality should focus on preventative measures and ensuring the delivery of high risk infants at a healthcare facility in the presence of a skilled birth attendant.

Antenatal care processes in rural Southern Nepal: gaps in and quality of service provision-a cohort study.

OBJECTIVES: This study aimed to compare a standard quality of care definition to one that reflected focused antenatal care (FANC) guidelines and examine associations with receipt of good quality of care. DESIGN: This study was a longitudinal cohort study. SETTINGS: Five government health posts in the Sarlahi district of Southern Nepal PARTICIPANTS: Pregnant women between the ages of 15 and 49 who presented for their first antenatal care (ANC) visit at the study health posts. MAIN OUTCOMES: There were two quality of care definitions: (1) provision of seven services at least once during pregnancy (QOC1) and (2) provision of services to reflect the FANC guidelines by incorporating a frequency of care dimension for certain services (QOC4+). RESULTS: There was variation in service provision both in terms of frequency of provision and by gestational age at the visit. There were 213 women (49.1%) that received good quality care by the first definition, but when the frequency of service provision was included for the second definition the percentage dropped to 6.2%. There were significant differences in provision of quality care by health post for both definitions. The number of visits (QOC1 adjusted risk ratio (aRR) 1.18, 95% CI 1.13 to 1.23; QOC4+ aRR 1.46, 95% CI 1.11 to 2.80) and care during the first trimester (QOC1 aRR 1.22, 95% CI 1.01 to 1.49) and maternal age (QOC1 aRR 1.27, 95% CI 1.03 to 1.58) were associated with greater likelihood of good quality ANC. CONCLUSION: This analysis demonstrated that measuring quality of care by receipt of services at least once during pregnancy may overestimate the true coverage of quality of ANC. Future efforts should improve feasibility of including frequency of care in quality of care definitions.

Birthweight and Environmental Conditions Impact Skin Barrier Adaptation in Neonates Receiving Natural Oil Massage.

INTRODUCTION: Skin interventions have been implemented to reduce neonatal mortality, demonstrating the skin's role in neonatal innate immunity. We examined the impact of birthweight and environmental conditions on skin integrity in infants receiving oil massage in rural Nepal. METHODS: In a community-based cluster randomized controlled trial, 991 premature and full-term infants were grouped by birthweight as: (1) 920-1,560 g, (2) 1,570-2,450 g, (3) 2,460-2,990 g, and (4) 3,000-4,050 g and by high or low heat index (HI). Skin integrity was measured as erythema, rash, dryness, pH, protein concentration, and transepidermal water loss (TEWL). RESULTS: Skin pH was higher for the smallest (group 1) than the largest infants (group 4) and higher for group 2 than 3 and 4. Arm and leg rash differed for all 4 groups, with the least amount of rash for the smallest babies. Erythema was lower for group 1 than all others. The lower day 1 values for pH, TEWL and protein at high versus low HI remained lower over 28 days. The pH reduction was faster at high HI. Erythema (arm, leg) was more severe at high HI. Rash severity was greater at high HI for arms and legs every day. CONCLUSIONS: Birthweight influenced the skin response to oil massage. The smallest infants had the lowermost skin irritation, suggesting diminished ability to mount an inflammatory response. High HI may be protective for premature infants in low resource settings.

Reliability of maternal recall of delivery and immediate newborn care indicators in Sarlahi, Nepal.

BACKGROUND: The intrapartum period is a time of high mortality risk for newborns and mothers. Numerous interventions exist to minimize risk during this period. Data on intervention coverage are needed for health system improvement. Maternal report of intrapartum interventions through surveys is the primary source of coverage data, but they may be invalid or unreliable. METHODS: We assessed the reliability of maternal report of delivery and immediate newborn care for a sample of home and health facility births in Sarlahi, Nepal. Mothers were visited as soon as possible following delivery (< 72 h) and asked to report circumstances of labor and delivery. A subset was revisited 1-24 months after delivery and asked to recall interventions received using standard household survey questions. We assessed the reliability of each indicator by comparing what mothers reported immediately after delivery against what they reported at the follow-up survey. We assessed potential variation in reliability of maternal report by characteristics of the mother, birth event, or intervention prevalence. RESULTS: One thousand five hundred two mother/child pairs were included in the reliability study, with approximately half of births occurring at home. A higher proportion of women who delivered in facilities reported "don't know" when asked to recall specific interventions both initially and at follow-up. Most indicators had high observed percent agreement, but kappa values were below 0.4, indicating agreement was primarily due to chance. Only "received any injection during delivery" demonstrated high reliability among all births (kappa: 0.737). The reliability of maternal report was typically lower among women who delivered at a facility. There was no difference in reliability based on time since birth of the follow-up interview. We observed over-reporting of interventions at follow-up that were more common in the population and under-reporting of less common interventions. CONCLUSIONS: This study reinforces previous findings that mothers are unable to report reliably on many interventions within the peripartum period. Household surveys which rely on maternal report, therefore, may not be an appropriate method for collecting data on coverage of many interventions during the peripartum period. This is particularly true among facility births, where many interventions may occur without the mother's full knowledge.

Human Metapneumovirus Infection and Genotyping of Infants in Rural Nepal.

BACKGROUND: Acute respiratory tract infections are a serious clinical burden in infants; human metapneumovirus (HMPV) is an important etiological agent. We investigated genotypic variation and molecular epidemiological patterns among infants infected with HMPV in Sarlahi, Nepal, to better characterize infection in a rural, low-resource setting. METHODS: Between May 2011 and April 2014, mid-nasal swabs were collected from 3528 infants who developed respiratory symptoms during a longitudinal maternal influenza vaccine study. Sequencing glycoprotein genes permitted genotyping and analyses among subtypes. RESULTS: HMPV was detected by reverse-transcriptase polymerase chain reaction (RT-PCR) in 187 (5%) infants, with seasonality observed during fall and winter months. Phylogenetic investigation of complete and partial coding sequences for the F and G genes, respectively, revealed that 3 genotypes were circulating: A2, B1, and B2. HMPV-B was most frequently detected with a single type predominating each season. Both HMPV genotypes exhibited comparable median viral loads. Clinically significant differences between genotypes were limited to increased cough duration and general respiratory symptoms for type B. CONCLUSIONS: In rural Nepal, multiple HMPV genotypes circulate simultaneously with an alternating predominance of a single genotype and definitive seasonality. No difference in viral load was detected by genotype and symptom severity was not correlated with RT-PCR cycle threshold or genotype.

Adherence to and acceptability of three alcohol-free, antiseptic oral rinses: A community-based pilot randomized controlled trial among pregnant women in rural Nepal.

OBJECTIVES: Antiseptic oral rinses have been evaluated as interventions to reduce the risk of adverse pregnancy outcomes associated with periodontal disease in pregnant women. Oral rinse use is not common in Nepal or other countries in South Asia, where the prevalence of adverse pregnancy outcomes is high. Understanding whether pregnant women in rural communities in this region would incorporate rinse use into their daily teeth cleaning routine is an important prerequisite to future research on this topic in South Asia. METHODS: We conducted a community-based pilot randomized controlled trial of three alcohol-free, antiseptic oral rinses among pregnant women <22 weeks pregnant in rural Nepal with the aim of assessing rinse acceptability, adherence, and effect on clinical periodontal measures. At baseline, participants underwent a clinical periodontal examination, and then were classified as healthy or having at least mild gingivitis (≥1 site with probing depth (PD) 3 mm and bleeding on probing (BOP) or ≥4 mm (PD)). Participants were stratified by periodontal status and randomized within each exposure category to chlorhexidine (CHX) (0.12%), cetylpyridinium chloride (CPC) (0.05%), salt and water (NaCl), or control (no rinse). Rinse participants were followed weekly for 12 weeks, and all participants underwent a second periodontal examination and answered a questionnaire. RESULTS: Pregnant women in the rural Terai region of Nepal showed high adherence to (mean weekly rinse use: 185 mL (standard deviation: 66 mL)) a recommended 210 mL and acceptability of all three rinses. Participants reported greater frequency of tooth brushing with toothpaste and improvements in other recommended oral hygiene behaviours. CHX significantly reduced rates of gingivitis (defined as a participant with BOP ≥ 10% of sites) and the extent of BOP (gingivitis at the end of follow-up for CHX vs control: RR 0.37, 95% CI: 0.16, 0.84). CPC and NaCl rinse groups had rates of gingivitis and extent of BOP similar to the control group (gingivitis at the end of follow-up for CPC: RR 0.81, 95% CI: 0.47, 1.38; NaCl: RR 0.92, 95% CI: 0.55, 1.56). CONCLUSIONS: Adherence to and acceptability of three alcohol-free, antiseptic oral rinses were high among pregnant women in rural Nepal. Among participants with mild gingivitis at baseline, CHX rinse was most effective at reducing signs of disease compared to the control group. Oral rinse should be considered as a supplement to current oral self-care routines for pregnant women in settings where rinse use is uncommon and access to oral health services is limited.