Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

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.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

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

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

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.

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.

Validation of maternal report of nutrition-related interventions and counselling during antenatal care in southern Nepal.

The delivery of nutrition-related interventions and counselling during antenatal care is critical for a healthy pregnancy for both mother and child. However, the accuracy of maternal reports of many of these services during household surveys has not yet been examined. Our objectives were to assess the validity of the maternal reports of 10 antenatal nutrition interventions, including counselling, and examine associates between maternal characteristics and accuracy. Maternal report of services received collected during a post-partum survey was compared to the gold standard, the direct observation of all women's antenatal care visits. Individual-level validity was assessed by calculating indicator sensitivity, specificity and area under the operating curve (AUC). The inflation factor (IF) measured population-level bias. For five indicators, the high true coverage limited our ability to assess the validity of the maternal reports. There were no indicators that had both high individual-level validity (AUC > 0.70) and low population bias (0.75 < IF < 1.25). Indicators with greater true coverage estimates had higher sensitivity and lower specificity estimates compared to those indicators with lower true coverage. There were no maternal characteristics associated with the accuracy of the report. Maternal report of antenatal nutrition-related interventions and counselling during household surveys was found to have variable validity across indicators. Additional research in settings with varying coverage levels should be considered to best inform antenatal care coverage measurement in household surveys.

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.

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.

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 ).

Assessment of facility and health worker readiness to provide quality antenatal, intrapartum and postpartum care in rural Southern Nepal.

BACKGROUND: Increased coverage of antenatal care and facility births might not improve maternal and newborn health outcomes if quality of care is sub-optimal. Our study aimed to assess the facility readiness and health worker knowledge required to provide quality maternal and newborn care. METHODS: Using an audit tool and interviews, respectively, facility readiness and health providers' knowledge of maternal and immediate newborn care were assessed at all 23 birthing centers (BCs) and the District hospital in the rural southern Nepal district of Sarlahi. Facility readiness to perform specific functions was assessed through descriptive analysis and comparisons by facility type (health post (HP), primary health care center (PHCC), private and District hospital). Knowledge was compared by facility type and by additional skilled birth attendant (SBA) training. RESULTS: Infection prevention items were lacking in more than one quarter of facilities, and widespread shortages of iron/folic acid tablets, injectable ampicillin/gentamicin, and magnesium sulfate were a major barrier to facility readiness. While parenteral oxytocin was commonly provided, only the District hospital was prepared to perform all seven basic emergency obstetric and newborn care signal functions. The required number of medical doctors, nurses and midwives were present in only 1 of 5 PHCCs. Private sector SBAs had significantly lower knowledge of active management of third stage of labor and correct diagnosis of severe pre-eclampsia. While half of the health workers had received the mandated additional two-month SBA training, comparison with the non-trained group showed no significant difference in knowledge indicators. CONCLUSIONS: Facility readiness to provide quality maternal and newborn care is low in this rural area of Nepal. Addressing the gaps by facility type through regular monitoring, improving staffing and supply chains, supervision and refresher trainings is important to improve quality.

Feasibility of training community health workers to conduct periodontal examinations: a validation study in rural Nepal.

BACKGROUND: In many low- and middle-income countries, insufficient human resources limit access to oral health services. Shifting clinical tasks to less specialized health professionals, such as community health workers, has been used as a strategy to expand the health workforce, especially in remote or underserved locations. The objective of this study was to evaluate the validity of periodontal examinations conducted by auxiliary nurse midwives in a rural home setting in Nepal. METHODS: Twenty-one pregnant women < 26 weeks gestation from Sarlahi District, Nepal, underwent full mouth periodontal examinations measuring probing depth (PD) and bleeding on probing (BOP) on 6 sites per tooth by one of five auxiliary nurse midwives, who were trained for this study but had no previous training in dentistry. After a 15-min break, each participant was examined again by an experienced dentist. Measures of validity for PD and BOP were calculated comparing the pooled and individual auxiliary nurse midwives to the dentist. A multivariable GEE model estimated the effect of periodontal characteristics on agreement between the auxiliary nurse midwives and the dentist. RESULTS: Participant mean age was 22 years (SD: ±3 years), mean PD was 1.4 mm (SD: 03 mm), and 86% of women had BOP (according to the dentist). Percent agreement, weighted kappa scores, and intraclass correlation coefficients for PD, with an allowance of ±1 mm, exceeded 99%, 0.7, and 0.9, respectively, indicating an acceptable level of agreement. Auxiliary nurse midwives tended to report higher PD scores relative to the dentist, although this over-estimation was small and unlikely to impact population-based estimates of important indicators of oral health status. GEE regression modeling indicated similar agreement for mandible vs. maxilla, left vs. right side, and PD (≤2 mm, > 2 mm), and lower agreement for posterior teeth and lingual and proximal sites. CONCLUSION: Auxiliary nurse midwives were able to accurately conduct periodontal examinations in a rural home setting, suggesting the potential to shift tasks away from highly trained dentists and periodontal examiners in low-resource communities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01177111 (Nepal Oil Massage Study); registered on August 6th, 2010.

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.

Inflammation throughout pregnancy and fetal growth restriction in rural Nepal.

Maternal systemic inflammation during pregnancy may restrict embryo-fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal-newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53-0.76) and 0.40 (0.33-0.50) g/l, and 0.56 (0.25-1.54) and 1.07 (0.43-2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10-6), and 0.45 (P = 3.1 × 10-5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10-7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.