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.

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.

Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America.

INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

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.

Divergent age patterns of under-5 mortality in south Asia and sub-Saharan Africa: a modelling study.

BACKGROUND: Understanding the age pattern of under-5 mortality is essential for identifying the most vulnerable ages and underlying causes of death, and for assessing why the decline in child mortality is slower in some countries and subnational areas than others. The aim of this study is to detect age patterns of under-5 mortality that are specific to low-income and middle-income countries (LMICs). METHODS: In this modelling study, we used data from 277 Demographic and Health Surveys (DHSs), 58 Health and Demographic Surveillance Systems (HDSSs), two cohort studies, and two sample-registration systems. From these sources, we collected child date of birth and date of death (or age at death) from LMICs between 1966 and 2020. We computed 22 deaths rates from each survey with the following age breakdowns: 0, 7, 14, 21, and 28 days; 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, and 21 months; and 2, 3, 4, and 5 years. We assessed how probabilities of dying estimated for the 22 age groups deviated from predictions generated by a vital registration model that reflects the historical mortality of 25 high-income countries. FINDINGS: We calculated mortality rates of 81 LMICs between 1966 and 2020. In contrast with the other regions of the world, we found that under-5 mortality in south Asia and sub-Saharan Africa was characterised by increased mortality at both ends of the age range (ie, younger than 28 days and older than 6 months) at a given level of mortality. Observed mortality in these regions was up to 2 times higher than predicted by the vital registration model for the younger-than-28 days age bracket, and up to 10 times higher than predicted for the older-than-6 months age bracket. This age pattern of under-5 mortality is significant in 17 countries in south Asia and sub-Saharan Africa. Excess mortality in children older than 6 months without excess mortality in children younger than 28 days was found in 38 countries. In south Asia, results were consistent across data sources. In sub-Saharan Africa, excess mortality in children younger than 28 days was found mostly in DHSs; the majority of HDSSs did not show this excess mortality. We have attributed this difference in data sources mainly to omissions of early deaths in HDSSs. INTERPRETATION: In countries with age patterns of under-5 mortality that diverge from predictions, evidence-based public health interventions should focus on the causes of excess of mortality; notably, the effect of fetal growth restriction and infectious diseases. The age pattern of under-5 mortality will be instrumental in assessing progress towards the decline of under-5 mortality and the Sustainable Development Goals. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health.

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.

Development of an imputation model to recalibrate birth weights measured in the early neonatal period to time at delivery and assessment of its impact on size-for-gestational age and low birthweight prevalence estimates: a secondary analysis of a pregnancy cohort in rural Nepal.

OBJECTIVES: In low-income countries, birth weights for home deliveries are often measured at the nadir when babies may lose up of 10% of their birth weight, biasing estimates of small-for-gestational age (SGA) and low birth weight (LBW). We aimed to develop an imputation model that predicts the 'true' birth weight at time of delivery. DESIGN: We developed and applied a model that recalibrates weights measured in the early neonatal period to time=0 at delivery and uses those recalibrated birth weights to impute missing birth weights. SETTING: This is a secondary analysis of pregnancy cohort data from two studies in Sarlahi district, Nepal. PARTICIPANTS: The participants are 457 babies with daily weights measured in the first 10 days of life from a subsample of a larger clinical trial on chlorhexidine (CHX) neonatal skin cleansing and 31 116 babies followed through the neonatal period to test the impact of neonatal massage oil type (Nepal Oil Massage Study (NOMS)). OUTCOME MEASURES: We developed an empirical Bayes model of early neonatal weight change using CHX trial longitudinal data and applied it to the NOMS dataset to recalibrate and then impute birth weight at delivery. The outcomes are size-for-gestational age and LBW. RESULTS: When using the imputed birth weights, the proportion of SGA is reduced from 49% (95% CI: 48% to 49%) to 44% (95% CI: 43% to 44%). Low birth weight is reduced from 30% (95% CI: 30% to 31%) to 27% (95% CI: 26% to 27%). The proportion of babies born large-for-gestational age increased from 4% (95% CI: 4% to 4%) to 5% (95% CI: 5% to 5%). CONCLUSIONS: Using weights measured around the nadir overestimates the prevalence of SGA and LBW. Studies in low-income settings with high levels of home births should consider a similar recalibration and imputation model to generate more accurate population estimates of small and vulnerable newborns.

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.

Factors Associated with Fluid Sequestration in Patients with Acute Pancreatitis: A Prospective Study in Tertiary Centre Hospital in Nepal.

BACKGROUND: Acute pancreatitis (AP) is associated with extensive fluid sequestration. The aim of this study was to determine association of fluid sequestration at 48 hours after hospital admission (FS48) in AP patients with demographics, clinical parameters, and outcomes of AP. METHODS: A prospective observational study was carried out on all adult patients with AP admitted to Tribhuvan University Teaching Hospital, Nepal, from January to September 2017. FS48 was calculated as the difference between fluid input and output in the first 48 hours of admission. The Kruskal-Wallis test with post hoc Dunn's test examined the difference in FS48 between mild AP, moderately severe AP, and severe AP. Linear regression analysis was used to evaluate association between FS48 with patients' characteristics and outcomes of AP. Outcomes of AP assessed included pancreatic necrosis, persistent organ failure, length of stay, and in-hospital mortality. RESULTS: Eighty patients (median age 44 years; 57% male) with a median FS48 of 1610 mL were evaluated. The median FS48 for mild AP, moderately severe AP, and severe AP were 1,180 mL, 2,380 mL, and 3,500 mL, respectively. There was a significant difference in pairwise comparisons between mild AP and moderately severe AP, along with mild AP and severe AP. Younger age, other etiology, and higher creatinine were independently associated with increased FS48. Increased FS48 was significantly associated with pancreatic necrosis, persistent organ failure, and in-hospital mortality. CONCLUSIONS: In our study population, younger age and higher creatinine were predictors of increased FS48. Increased FS48 was associated with poorer outcomes of AP.

Perception of obesity and overweight among adults living in suburban Nepal: a qualitative study.

OBJECTIVE: To explore the perception of obesity and overweight among Nepalese adults living in a suburban community. DESIGN: A qualitative study composed of focus group discussion (FGD) and in-depth interview (IDI). SETTING: Community and healthcare facilities in Dhulikhel, Nepal. PARTICIPANTS: Four FGDs were conducted with community members (n=22) and four IDIs were conducted with healthcare providers (HCPs). RESULTS: Obesity is a rising problem in this suburban community. Participants had inadequate knowledge regarding the consequences of obesity, and they perceived overweight as normal, healthy and attractive. The participants above 40 years of age did not perceive themselves to be overweight or obese. Despite participants' awareness of the importance of diet control and exercise to prevent obesity, these were not translated into practice. CONCLUSIONS: This study provided insight into perceptions of obesity in a suburban Dhulikhel community through both community members' and HCPs' perspective. Misconceptions and inadequate knowledge of obesity among people in this community indicate the need for health education and intervention programme to increase health awareness and preventive practices.