Risk Factors of Pelvic Floor Disorders Among Women in Rural Nepal: A Case-Control Study.

INTRODUCTION AND HYPOTHESIS: Risk factors for pelvic floor disorders (PFDs) are not well understood in lower resource settings. The objective of this study is to determine the risk factors associated with stress urinary incontinence (SUI), urge urinary incontinence (UUI), and pelvic organ prolapse (POP) among women of reproductive age in rural Nepal. METHODS: This is a case-control study nested within a community-based cross-sectional survey of parous women of reproductive age with PFDs in the Sarlahi District of Nepal. The presence of PFDs was confirmed by clinical assessment. Detailed sociodemographic information and histories were captured. RESULTS: We examined 406 women; the mean (SD, range) age was 32.7 (8.5, 16-49) years, mean BMI (SD) was 19.7 (3.3) kg/m2, and median (range) number of pregnancies was 4 (1-11). Two hundred and three women (50.0%) had either SUI or UUI, 85 (17.8%) had both SUI and UUI, and 71 (17.5%) had POP at or beyond the hymen. After controlling for other variables significant on bivariate analysis, age (adjusted odds ratio [aOR] 1.06 [95% CI 1.03-1.09]), illiteracy (aOR 2.24 [95% CI 1.04-4.80]), and presence of upper gastrointestinal issues (aOR 3.30, [95% CI 1.77-6.16]) were independently associated with SUI/UUI. Age (aOR 1.05 [95% CI 1.02-1.09]), bispinous diameter (aOR 2.88 ([95% CI 1.11-7.47]), and subpubic angle (aOR 2.78 [95% CI 1.55-5.03]) were independently associated with POP. CONCLUSION: Risk factors for PFDs in a homogenous community of parous women of reproductive age in rural Nepal are similar to those found in parous women in higher income countries.

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.

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.

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.

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.

Determinants of Urogenital Schistosomiasis Among Pregnant Women and its Association With Pregnancy Outcomes, Neonatal Deaths, and Child Growth.

BACKGROUND: Schistosoma haematobium is a parasitic helminth that causes urogenital pathology. The impact of urogenital schistosomiasis during pregnancy on birth outcomes and child growth is poorly understood. METHODS: Risk factors for urogenital schistosomiasis were characterized among 4437 pregnant women enrolled in a cluster-randomized community-based trial in rural Zimbabwe. Infection was defined via urine microscopy (≥1 S. haematobium egg) and urinalysis (hematuria). Associations between infection and pregnancy outcomes were assessed in case-control analyses using conditional logistic regression. The association of maternal infection with birthweight and length-for-age Z scores (LAZ) at 1 and 18 months of age were assessed using generalized estimating equations. RESULTS: Urogenital schistosomiasis (egg positive and/or hematuria positive) was detected in 26.8% of pregnant women. Risk factors significantly associated with infection were maternal age, education, marital status, and religion; household drinking water source and latrine; study region; and season. Urogenital schistosomiasis was not significantly associated with adverse pregnancy outcomes (miscarriage, stillbirth, preterm, and small-for-gestational age), birthweight, neonatal death, or LAZ. CONCLUSIONS: Including pregnant women in antihelminthic treatment programs would benefit a large number of women in rural Zimbabwe. However, clearance of the low-intensity infections that predominate in this context is unlikely to have additive benefits for pregnancy outcomes or child growth. CLINICAL TRIALS REGISTRATION: NCT01824940.

Prevalence of symptomatic urinary incontinence and pelvic organ prolapse among women in rural Nepal.

INTRODUCTION AND HYPOTHESIS: Although pelvic floor disorders (PFDs) are a significant public health issue in higher income countries, less is known about these disorders and associated risk factors in low income countries. We aimed to determine prevalence and associated risk factors for stress urinary incontinence (SUI), urge urinary incontinence (UUI), and pelvic organ prolapse (POP) in reproductive age women in Sarlahi District in rural Nepal. METHODS: We conducted a community-based cross-sectional survey of parous, reproductive age women in rural Nepal and screened for pelvic floor disorders using validated screening questions for PFDs. Overall frequency of self-reported symptoms for SUI, UUI, and POP was estimated and compared across demographic and pregnancy history information. RESULTS: Of 14,469 women available for analysis, the mean (SD, range) age was 33.5 (8.2, 13-52) years, and median (range) number of pregnancies was 4 (1-15). The prevalence of SUI was 24.1% (95% CI: 23.3-24.8), of UUI was 13.5% (95% CI: 13.0-14.1), and of POP was 8.0% (95% CI: 7.5-8.4). Bivariate analysis identified the risk of PFD increased incrementally with age and number of vaginal deliveries; these covariates were highly correlated. Multivariable logistic regression revealed age, vaginal deliveries, and previous pelvic surgeries were independently associated with PFD. CONCLUSIONS: PFDs are common in a community of parous, reproductive age women in rural Nepal. Risk factors for these conditions are similar to risk factors found in higher income countries.

Coverage of the WHO's four essential elements of newborn care and their association with neonatal survival in southern Nepal.

BACKGROUND: Despite recent improvements in child survival, neonatal mortality continues to decline at a slower rate and now represents 47% of under-five deaths globally. The World Health Organization developed core indicators to better monitor the quality of maternal and newborn health services. One such indicator for newborn health is "the proportion of newborns who received all four elements of essential care". The four elements are immediate and thorough drying, skin to skin contact, delayed cord clamping, and early initiation of breastfeeding. Although there is existing evidence demonstrating an association with decreased neonatal mortality for each element individually, the cumulative impact has not yet been examined. METHODS: This analysis uses data from a randomized trial to examine the impact of sunflower versus mustard seed oil massage on neonatal mortality and morbidity in the Sarlahi district in Southern Nepal from 2010 to 2017. The proportion of newborn infants receiving an intervention was the exposure and neonatal mortality was the outcome in this analysis. Neonatal mortality was defined as a death between three hours and less than 28 days of age. Associations between neonatal mortality and the essential elements were estimated by Cox proportion hazards models. The hazard ratios and corresponding 95% confidence intervals were reported. RESULTS: 28,121 mother-infant pairs and 753 neonatal deaths were included. The percent receiving the individual elements ranged from 19.5% (skin to skin contact) to 68.2% (delayed cord clamping). The majority of infants received one or two of the elements of essential care, with less than 1% receiving all four. Skin to skin contact and early initiation of breastfeeding were associated with lower risk of neonatal mortality (aHR = 0.64 [0.51, 0.81] and aHR = 0.72 [0.60, 0.87], respectively). The risk of mortality declined as the number of elements received increased; receipt of one element compared to zero was associated with a nearly 50% reduction in risk of mortality and receipt of all four elements resulted in a 72% decrease in risk of mortality. CONCLUSIONS: The receipt of one or more of the four essential elements of newborn care was associated with improved neonatal survival. The more elements of care received, the more survival improved.

Nausea, vomiting and poor appetite during pregnancy and adverse birth outcomes in rural Nepal: an observational cohort study.

BACKGROUND: Nausea and vomiting are experienced by a majority of pregnant women worldwide. Previous studies have yielded conflicting results regarding their impact on birth outcomes and few studies have examined this relationship in settings with limited resources. We aimed to determine the effect of nausea, vomiting and poor appetite during pregnancy on birth outcomes in rural Nepal. METHODS: Observational cohort study using data collected in two randomized, community-based trials to assess the effect of influenza immunization during pregnancy on reproductive and respiratory outcomes among pregnant women and their offspring. Pregnant women in Sarlahi District, Nepal were recruited from 2011 to 2013. Exposure was defined as nausea, vomiting or poor appetite at any point during pregnancy and by trimester; symptoms were recorded monthly throughout pregnancy. Adverse outcomes were low birth weight (LBW), preterm birth and small for gestational age (SGA). Adjusted relative risks (aRR) with 95% CIs are reported from Poisson regressions with robust variance. RESULTS: Among 3,623 pregnant women, the cumulative incidence of nausea, vomiting or poor appetite was 49.5% (n = 1793) throughout pregnancy and 60.6% (n = 731) in the first trimester. Significantly higher aRRs of LBW and SGA were observed among women experiencing symptoms during pregnancy as compared to symptom free women (LBW: aRR 1.20; 95% CI 1.05 1.28; SGA: aRR 1.16; 95% CI 1.05 1.28). Symptoms in the first trimester were not significantly associated with any of the outcomes. In the second trimester, we observed significantly higher aRRs for LBW and SGA (LBW: aRR 1.17; 95% CI 1.01 1.36; SGA: aRR 1.16; 95% CI 1.05 1.29) and a significantly lower aRR for preterm birth (aRR 0.75; 95% CI 0.59 0.96). In the third trimester, we observed significantly higher aRRs for LBW and SGA (LBW: aRR 1.20; 95% CI 1.01 1.43; SGA: aRR 1.14; 95% CI 1.01 1.29). CONCLUSIONS: Symptoms of nausea, vomiting or poor appetite during pregnancy are associated with LBW, SGA and preterm birth in a setting with limited resources, especially beyond the first trimester. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov on Dec 17, 2009 ( NCT01034254 ).

Infant Pneumococcal Carriage During Influenza, RSV, and hMPV Respiratory Illness Within a Maternal Influenza Immunization Trial.

In this post-hoc analysis of midnasal pneumococcal carriage in a community-based, randomized prenatal influenza vaccination trial in Nepal with weekly infant respiratory illness surveillance, 457 of 605 (75.5%) infants with influenza, respiratory syncytial virus (RSV), or human metapneumovirus (hMPV) illness had pneumococcus detected. Pneumococcal carriage did not impact rates of lower respiratory tract disease for these 3 viruses. Influenza-positive infants born to mothers given influenza vaccine had lower pneumococcal carriage rates compared to influenza-positive infants born to mothers receiving placebo (58.1% versus 71.6%, P = 0.03). Maternal influenza immunization may impact infant acquisition of pneumococcus during influenza infection. Clinical Trials Registration. NCT01034254.

Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness.

Background: Transplacental respiratory syncytial virus (RSV) antibody transfer has been characterized, but little is known about the protective effect of breast milk RSV-specific antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutralizing activity. We investigate protection of breast milk pre-F antibodies against RSV acute respiratory infection (ARI). Methods: Breast milk at 1, 3, and 6 months postpartum and midnasal swabs during infant illness episodes were collected in mother-infant pairs in Nepal. One hundred seventy-four infants with and without RSV ARI were matched 1:1 by risk factors for RSV ARI. Pre-F immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels were measured in breast milk. Results: The median breast milk pre-F IgG antibody concentration before illness was lower in mothers of infants with RSV ARI (1.4 [interquartile range {IQR}, 1.1-1.6] log10 ng/mL) than without RSV ARI (1.5 [IQR, 1.3-1.8] log10 ng/mL) (P = .001). There was no difference in median maternal pre-F IgA antibody concentrations in cases vs controls (1.7 [IQR, 0.0-2.2] log10 ng/mL vs 1.7 [IQR, 1.2-2.2] log10 ng/mL, respectively; P = .58). Conclusions: Low breast milk pre-F IgG antibodies before RSV ARI support a potential role for pre-F IgG as a correlate of protection against RSV ARI. Induction of breast milk pre-F IgG may be a mechanism of protection for maternal RSV vaccines.

Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal.

PROBLEM: Rhinoviruses (RVs), the most common causes of acute respiratory infections in young children and infants, are highly diverse genetically. OBJECTIVE: To characterize the RV types detected with respiratory illness episodes in infants in Nepal. STUDY METHODS: Infants born to women enrolled in a randomized trial of maternal influenza immunization in rural, southern Nepal were followed with household-based weekly surveillance until 180 days of age. Infants with respiratory symptoms had nasal swabs tested for twelve respiratory viruses. A subset with RV alone was selected for sequencing of the VP4/2 gene to identify RV types. RESULTS: Among 547 RV-only positive illnesses detected from December 2012 to April 2014, 285 samples (52%) were sequenced. RV-A, B, and C species were detected in 193 (68%), 18 (6%), and 74 (26%) specimens, respectively. A total of 94 unique types were identified from the sequenced samples, including 52 RV-A, 11 RV-B, and 31 RV-C. Multiple species and types circulated simultaneously throughout the study period. No seasonality was observed. The median ages at illness onset were 88, 104, and 88 days for RV-A, B, and C, respectively. The median polymerase chain reaction cycle threshold values did not differ between RV species. No differences between RV species were observed for reported respiratory symptoms, including pneumonia, or for medical care-seeking. CONCLUSIONS: Among very young, symptomatic infants in rural Nepal, all three species and many types of RV were identified; RV-A was detected most frequently. There was no association between RV species and disease severity.

Prevalence, Characteristics, and Risk Factors of Moderate or High Hyperopia among Multiethnic Children 6 to 72 Months of Age: A Pooled Analysis of Individual Participant Data.

PURPOSE: To describe the prevalence, ocular characteristics, and associated risk factors of moderate to high hyperopia in early childhood. DESIGN: Pooled analysis of individual participant data from population-based studies. PARTICIPANTS: Six- to 72-month-old multiethnic children who participated in 4 population-based studies of pediatric eye diseases. METHODS: The pooled studies conducted comparable parental interviews and ocular examinations including cycloplegic autorefraction. Presence of hyperopia was defined based on cycloplegic refractive error in the worse eye. Multivariate analyses were performed to evaluate the association of potential risk factors with hyperopia risk. MAIN OUTCOME MEASURES: Prevalence and odds ratios of moderate to high hyperopia (≥4.0 diopters [D]). RESULTS: Cycloplegic refraction was completed in 15 051 children 6 to 72 months of age. Among these children, the overall prevalence of moderate to high hyperopia (≥4.0 D) in the worse eye was 3.2% (95% confidence interval, 2.9%-3.5%), accounting for 15.6% of all hyperopia (≥2.0 D). Among children with moderate to high hyperopia, both eyes were affected in 64.4%, 28.9% showed spherical anisometropia of 1.0 D or more, and 19.5% showed astigmatism of 1.5 D or more. Among 36- to 72-month-old children with moderate to high hyperopia, 17.6% wore glasses. Prevalence of moderate to high hyperopia was slightly less in 12- to 23-month-old children and was relatively stable in children 24 months of age and older. Non-Hispanic and Hispanic white race and ethnicity, family history of strabismus, maternal smoking during pregnancy, and being a participant in the United States studies were associated with a higher risk of moderate to high hyperopia (P < 0.05). CONCLUSIONS: By assembling similarly designed studies, our consortium provided robust estimates of the prevalence of moderate to high hyperopia in the general population and showed that in 6- to 72-month-old children, moderate to high hyperopia is not uncommon and its prevalence does not decrease with age. Risk factors for moderate to high hyperopia differ from those for low to moderate hyperopia (2.0-<4.0 D) in preschool children, with family history of strabismus and maternal smoking during pregnancy more strongly associated with moderate to high hyperopia than low to moderate hyperopia.

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.

Impact of Timing of Influenza Vaccination in Pregnancy on Transplacental Antibody Transfer, Influenza Incidence, and Birth Outcomes: A Randomized Trial in Rural Nepal.

Background: Maternal influenza vaccination protects mothers and their infants in low resource settings, but little is known about whether the protection varies by gestational age at vaccination. Methods: Women of childbearing age in rural southern Nepal were surveilled for pregnancy, consented and randomized to receive maternal influenza vaccination or placebo, with randomization stratified on gestational age (17-25 or 26-34 weeks). Enrollment occurred in 2 annual cohorts, and vaccinations occurred from April 2011 through September 2013. Results: In sum, 3693 women consented and enrolled, resulting in 3646 live births. Although cord blood antibody titers and the rise in maternal titers were generally greater when women were vaccinated later in pregnancy, this was not statistically significant. The incidence risk ratio (IRR) for maternal influenza in pregnancy through 6 months postpartum was 0.62 (95% confidence interval [CI]: 0.35, 1.10) for those vaccinated 17-25 weeks gestation and 0.89 (95% CI: 0.39, 2.00) for those 26-34 weeks. Infant influenza IRRs were 0.73 (95% CI: 0.51, 1.05) for those whose mothers were vaccinated earlier in gestation, and 0.63 (95% CI: 0.37, 1.08) for those later. Relative risks (RR) for low birthweight were 0.83 (95% CI: 0.71, 0.98) and 0.90 (95% CI: 0.72, 1.12) for 17-25 and 26-34 weeks gestation at vaccination, respectively. IRRs did not differ for small-for-gestational age or preterm. No RRs were statistically different by timing of vaccine receipt. Conclusions: Vaccine efficacy did not vary by gestational age at vaccination, making maternal influenza immunization programs easier to implement where women present for care late in pregnancy. Clinical Trials Registration: NCT01034254.

Burden and Risk Factors for Coronavirus Infections in Infants in Rural Nepal.

Background: Knowledge of risk factors for symptomatic human coronavirus (HCoV) infections in children in community settings is limited. We estimated the disease burden and impact of birth-related, maternal, household, and seasonal factors on HCoV infections among children from birth to 6 months old in rural Nepal. Methods: Prospective, active, weekly surveillance for acute respiratory infections (ARIs) was conducted in infants over a period of 3 years during 2 consecutive, population-based randomized trials of maternal influenza immunization. Midnasal swabs were collected for acute respiratory symptoms and tested for HCoV and other viruses by reverse-transcription polymerase chain reaction. Association between HCoV incidence and potential risk factors was modeled using Poisson regression. Results: Overall, 282 of 3505 (8%) infants experienced an HCoV ARI within the first 6 months of life. HCoV incidence overall was 255.6 (95% confidence interval [CI], 227.3-286.5) per 1000 person-years, and was more than twice as high among nonneonates than among neonates (incidence rate ratio [IRR], 2.53; 95% CI, 1.52-4.21). HCoV ARI incidence was also positively associated with the number of children <5 years of age per room in a household (IRR, 1.13; 95% CI, 1.01-1.28). Of the 296 HCoV infections detected, 46% were coinfections with other respiratory viruses. While HCoVs were detected throughout the study period, seasonal variation was also observed, with incidence peaking in 2 winters (December-February) and 1 autumn (September-November). Conclusions: HCoV is associated with a substantial proportion of illnesses among young infants in rural Nepal. There is an increased risk of HCoV infection beyond the first month of life.

Perceptions, careseeking, and experiences pertaining to non-cephalic births in rural Sarlahi District, Nepal: a qualitative study.

BACKGROUND: In low-resource settings, a significant proportion of fetal, neonatal, and maternal deaths can be attributed to intrapartum-related complications. Certain risk factors, such as non-cephalic presentation, have a particularly high risk of complications. This qualitative study describes experiences around non-cephalic births and highlights existing perceptions and care-seeking behavior specific to non-cephalic presentation in rural Sarlahi District, Nepal. METHODS: We conducted in-depth interviews with 34 individuals, including women who recently gave birth to a non-cephalic infant and female decision-makers in their households. We also conducted two focus groups with mothers (have two or more children, with at least one child under age five) and two focus groups with grandmothers in the community. RESULTS: Several women described scenes of obstructed labor and practices like provision of unspecified injections early in labor to assist with the delivery. There were reports of arduous care-seeking processes from primary health centers to tertiary facilities, and mixed quality of care among home birth attendants and facility-based health workers respectively. Very few women were aware of the fetal presentation prior to delivery, and we identified no consistent understanding among participants of the risks of and care strategies for non-cephalic births. Risk perception around non-cephalic presentation varied widely. Some participants were acutely aware of potential dangers, while others had not heard of non-cephalic birth. Many interviewees said that the position in which a pregnant woman sleeps could impact the fetal position. Several participants had either taken or heard of medication intended to rotate the fetus into the correct position. CONCLUSIONS: Our findings suggest the mixed quality of and access to care associated with non-cephalic birth and a lack of consistent understanding of the risk of and care for non-cephalic births in rural Nepal. The high risk of the condition and the recommended tertiary care present a dilemma in low-resource settings; the logistical difficulties and the mixed quality of care make care-seeking and referral decisions complex. While public health stakeholders strive to improve the quality of and access to the formal health system, those players must also be sensitive to the potential negative implications of promoting institutional care-seeking.

Ethnic and age differences in prediction of mortality by mid-upper arm circumference in children below 3 years of age in Nepal.

OBJECTIVE: To assess ethnicity- and age-modified associations between mid-upper arm circumference (MUAC) and mortality in Nepalese children and whether sociodemographic factors explain these associations. DESIGN: Secondary data analysis of children followed until 3 years of age. Estimated mortality hazard ratios (HR) for MUAC<11·5cm (recommended cut-off for identifying severe acute malnutrition among children ≥6 months old) compared with ≥11·5cm in younger (<6 months) and older children (≥6 months) of Pahadi and Madhesi ethnicity, adjusting for sex, socio-economic status (SES) and mother's education using Cox proportional hazard models. SETTING: Sarlahi, Nepal (21 October 2001-2 February 2006). SUBJECTS: Children (n 48 492) enrolled in the Nepal Nutrition Intervention Project, Sarlahi-4. RESULTS: Among children aged ≥6 months, MUAC<11·5 cm was associated with increased risk of mortality in both Pahadis (HR=4·01; 95 % CI 1·42, 11·76) and Madhesis (HR=5·60; 95 % CI 3·87, 8·11) compared with those with MUAC≥11·5 cm, after adjusting for sex, SES and maternal literacy. Among children <6 months old, MUAC<11·5 cm was not associated with mortality in Pahadis with (HR=1·12; 95 % CI 0·72, 1·73) or without adjusting (HR=1·17; 95 % CI 0·75, 1·18) as compared with Madeshis (adjusted HR=1·76; 95 % CI 1·35, 2·28). CONCLUSIONS: Among older children, MUAC<11·5 cm is associated with subsequent mortality in both ethnicities regardless of other characteristics. However, among children aged <6 months, it predicted mortality only among Madhesis, while sociodemographic factors were more strongly associated with mortality than MUAC<11·5cm among Pahadis.

Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal.

Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011-2014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.