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.

Assessment of indirect protection from maternal influenza immunization among non-vaccinated household family members in a randomized controlled trial in Sarlahi, Nepal.

Influenza is a significant cause of morbidity and mortality worldwide, and the World Health Organization highly recommends maternal vaccination during pregnancy. The indirect effect of maternal vaccination on other close contacts other than newborns is unknown. To evaluate this, we conducted a nested substudy between 2011 and 2012 of influenza and acute respiratory illness (ARI) among household members of pregnant women enrolled in a randomized placebo-controlled trial of antenatal influenza vaccination in the rural district of Sarlahi, Nepal. Women were assigned to receive influenza vaccination or placebo during pregnancy and then they and their household members were followed up to 6 months postpartum with weekly symptom surveillance and nasal swab collection. Swabs were tested by RT-PCR for influenza. Rates of laboratory-confirmed influenza and of ARI were compared between vaccine and placebo groups using generalized estimating equations with a Poisson link function. Overall, 1752 individuals in 520 households were eligible for inclusion. There were 82 laboratory-confirmed influenza illness episodes, for a rate of 7.0 per 100 person-years overall. Of the influenza strains able to be typed, 29 were influenza A, 40 were influenza B, and 6 were coinfections with influenza A and B. The rate did not differ significantly whether the household was in the vaccine or placebo group (rate ratio (RR) 1.37, 95% confidence interval (CI) 0.83-2.26). The rate of ARI was 28.5 per 100 person-years overall and did not differ by household group (RR 0.99, 95% CI 0.72-1.36). Influenza vaccination of pregnant women did not provide indirect protection of unvaccinated household members.

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.

Respiratory syncytial virus infection in infants in rural Nepal.

OBJECTIVES: Respiratory syncytial virus (RSV) pneumonia is a leading cause of infant mortality worldwide. The risk of RSV infection associated with preterm birth is not well-characterized in resource-limited settings. We aimed to obtain precise estimates of risk factors and disease burden of RSV in infants in rural southern Nepal. METHODS: Pregnant women were enrolled, and along with their infants, followed to six months after birth with active weekly home-based surveillance for acute respiratory illness (ARI). Mid-nasal swabs were obtained and tested for RSV by PCR for all illness episodes. Birth outcomes were assessed at a postpartum home visit. RESULTS: 311 (9%) of 3509 infants had an RSV ARI. RSV ARI incidence decreased from 551/1000 person-years in infants born between 28 and 31 weeks to 195/1000 person-years in infants born full-term (p = 0.017). Of 220 infants (71%) evaluated in the health system, 41 (19%) visited a hospital or physician. Of 287 infants with an assessment performed, 203 (71%) had a lower respiratory tract infection. CONCLUSIONS: In a rural south Asian setting with intensive home-based surveillance, RSV caused a significant burden of respiratory illness. Preterm infants had the highest incidence of RSV ARI, and should be considered a priority group for RSV preventive interventions in resource-limited settings.

Community survey on awareness and use of obstetric ultrasonography in rural Sarlahi District, Nepal.

OBJECTIVE: To assess levels of awareness and use of obstetric ultrasonography in rural Nepal. METHODS: Between March 2014 and March 2015, a cross-sectional survey was conducted among married women aged 15-40years residing in rural Sarlahi District, Nepal, regarding their knowledge and use of obstetric ultrasonography during their most recent pregnancy. Regression analyses were conducted to identify reproductive health, socioeconomic, and other characteristics that increased the likelihood of undergoing an obstetric ultrasonographic examination. RESULTS: Among 6182 women, 1630 (26.4%) had undergone obstetric ultrasonography during their most recent pregnancy, of whom 1011 (62.0%) received only one examination. Odds of receiving an ultrasonographic examination were higher among women with post-secondary education than among those with none (≥11years' education: adjusted odds ratio [aOR] 10.28, 95% confidence interval [CI] 5.55-19.04), and among women whose husbands had post-secondary education than among those with husbands with none (≥11years' education: aOR 1.99, 95% CI 1.47-2.69). Odds were lower among women younger than 18years than among those aged 18-34years (aOR 0.72, 95% confidence interval 0.59-0.90). CONCLUSION: Utilization of obstetric ultrasonography in rural Nepal was very limited. Further research is necessary to assess the potential health impact of obstetric ultrasonography in low-resource settings, while addressing limitations such as cost and misuse.

Evaluation of a Novel Single-administration Food Frequency Questionnaire for Assessing Seasonally Varied Dietary Patterns among Women in Rural Nepal.

Novel dietary assessment methods are needed to study chronic disease risk in agrarian cultures where food availability is highly seasonal. In 16,320 rural Nepalese women, we tested a novel food frequency questionnaire, administered once, to assess past 7-day intake and usual frequency of intake throughout the year for year-round foods and when in season for seasonal foods. Spearman rank correlations between usual and past 7-day intakes were 0.12-0.85 and weighted kappa statistics, representing chance-corrected agreement, were 0.10-0.80, with better agreement for frequently consumed foods. The questionnaire performed well, but may require refinement for settings of extremely low dietary diversity.

Seasonal dietary intakes and socioeconomic status among women in the Terai of Nepal.

Despite widespread nutritional deficiencies, investigations of usual diet in rural South Asia remain sparse. The present study characterizes year-round and seasonal dietary patterns of women in the Terai of Nepal by sociodemographic status, using a novel, weekly single-visit and usual food frequency questionnaire that links recall to the agricultural season. The study was conducted across seasons in 2006-2008 among 15,899 women of reproductive age in Sarlahi district. Intakes were tabulated for all foods, overall and by socioeconomic status (SES), and in and out of season, as appropriate. Foods consumed regularly [median (interquartile range) weekly frequency] were rice [13 (7-13)], potatoes [10 (5-13)], legumes [6 (2-9)], and vegetable oil [13 (13-13)]. Animal products were infrequently consumed [1 (0-2) time per week] as were fruits and vegetables, most with a median weekly intake frequency of 0. Higher SES was associated with more frequent consumption of most food-groups, including in-season fruits and vegetables. Diets of women in the Terai of Nepal lack diversity and, likely, nutrient adequacy, which may pose health risks.

Household wealth and neurocognitive development disparities among school-aged children in Nepal.

BACKGROUND: Wealth disparities in child developmental outcomes are well documented in developed countries. We sought to (1) describe the extent of wealth-based neurocognitive development disparities and (2) examine potential mediating factors of disparities among a population-based cohort of children in rural Nepal. METHODS: We investigated household wealth-based differences in intellectual, executive and motor function of n = 1692 children aged between 7 and 9 years in Nepal. Using linear mixed models, wealth-based differences were estimated before and after controlling for child and household demographic characteristics. We further examined wealth-based differences adjusted for three sets of mediators: child nutritional status, home environment, and schooling pattern. RESULTS: We observed a positive gradient in child neurocognitive performance by household wealth. After adjusting for child and household control factors, disparities between children in the highest and lowest wealth quintiles persisted in intellectual and motor function, but not executive function. No statistically significant wealth-based differentials in outcomes remained after accounting for nutritional status, home environment, and schooling patterns. The largest differences in neurocognitive development were associated with schooling pattern. CONCLUSIONS: Household wealth patterns child neurocognitive development in rural Nepal, likely through its influence on nutritional status, the home environment, and schooling. In the current context, improving early and regular schooling in this setting is critical to addressing wealth-based disparities in outcomes.

Sex differences in neonatal mortality in Sarlahi, Nepal: the role of biology and environment.

BACKGROUND: Studies in South Asia have documented increased risk of neonatal mortality among girls, despite evidence of a biological survival advantage. Associations between gender preference and mortality are cited as reasons for excess mortality among girls. This has not, however, been tested in statistical models. METHODS: A secondary analysis of data from a population-based randomised controlled trial of newborn infection prevention conducted in rural southern Nepal was used to estimate sex differences in early and late neonatal mortality, with girls as the reference group. The analysis investigated which underlying biological factors (immutable factors specific to the newborn or his/her mother) and environmental factors (mutable external factors) might explain observed sex differences in mortality. RESULTS: Neonatal mortality was comparable by sex (Ref=girls; OR 1.06, 95% CI 0.92 to 1.22). When stratified by neonatal period, boys were at 20% (OR 1.20, 95% CI 1.02% to 1.42%) greater risk of early and girls at 43% (OR 0.70, 95% CI 0.51% to 0.94%) greater risk of late neonatal mortality. Biological factors, primarily respiratory depression and unconsciousness at birth, explained excess early neonatal mortality among boys. Increased late neonatal mortality among girls was explained by a three-way environmental interaction between ethnicity, sex and prior sibling composition (categorised as primiparous newborns, infants born to families with prior living boys or boys and girls, and infants born to families with only prior living girls). CONCLUSIONS: Risk of neonatal mortality inverted between the early and late neonatal periods. Excess risk of early neonatal death among boys was consistent with biological expectations. Excess risk for late neonatal death among girls was not explained by overarching gender preference or preferential care-seeking for boys as hypothesised, but was driven by increased risk among Madeshi girls born to families with only prior girls.

A cross-sectional study of the prevalence and risk factors for hypertension in rural Nepali women.

BACKGROUND: The prevalence of hypertension is increasing in much of the South Asian region, including Nepal. This paper reports the prevalence and risk factors of hypertension and pre-hypertension among adult women in a rural community of Nepal. METHODS: Cross-sectional data on socioeconomic status (SES), lifestyle factors and blood pressure (BP) were collected from a cohort of 15,934 women in rural Nepal in 2006-08. Among a subsample (n = 1679), anthropometry and biomarkers of cardiovascular risk were measured. RESULTS: The mean age of women was 34.2 years (range 16.4-71.2 years). More than three percent (3.3%) had hypertension and 14.4% had pre-hypertension. In an adjusted analysis, lower SES, especially lower household farm assets and storage of food for long term consumption, was associated with increased odds of hypertension (OR = 1.14 for mid-level SES and OR = 1.40 for low SES; p for trend < 0.01). Smoking, alcohol use and not working outside the home were also associated with higher risk. In a subsample, both systolic BP (SBP) and diastolic BP (DBP) were positively associated with high triglycerides (SBP ß = 4.1 mm Hg; DBP ß =3.6 mm Hg), high HbA1c (SBP ß = 14.0; DBP ß = 9.2), raised fasting glucose (SBP ß = 10.0; DBP ß = 6.9), high BMI (SBP ß = 6.7; DBP ß = 5.1) and high waist circumference (SBP ß = 6.2; DBP ß = 5.3) after adjusting for potential confounders (p for all <0.01). CONCLUSIONS: Although the prevalence of hypertension was low in this cohort, it was more prevalent among the poorer women and was strongly associated with other cardiovascular risks. These associations at a relatively young age may confer greater risk for cardiovascular disease among women in later life, indicating the need for interventions to reduce the progression from pre-hypertension to hypertension.

Determinants of compliance to antenatal micronutrient supplementation and women's perceptions of supplement use in rural Nepal.

OBJECTIVE: We examined factors affecting compliance to antenatal micronutrient supplementation and women's perceptions of supplement use. DESIGN: Randomized controlled supplementation trial of four alternative combinations of micronutrients given during pregnancy through to 3 months postpartum. Women were visited twice weekly to monitor compliance and to replenish tablets by female study workers. At 6 weeks postpartum women with live births (n 4096) were interviewed regarding their perceptions of the supplement. Median compliance calculated as percentage of total eligible doses received by women was high (84 %). SETTING: Rural southern Nepal. SUBJECTS: Pregnant women. RESULTS: Women with high compliance (above the median of 84 %) were likely to be older, less educated, poorer, undernourished, belong to lower caste and of Pahadi (hill) ethnicity compared with women with low compliance (at or below the median of 84 %). Smoking and drinking alcohol in the past week during pregnancy were strongly associated with low compliance. The major reason for irregular intake was forgetting to take supplements. A higher proportion of the high compliers liked taking the supplements but only half of them were willing to purchase them in the future. A large proportion of women (91 %) perceived a benefit from taking the supplement such as improved strength and health, whereas only about 10 % perceived any side-effects which were not a major barrier to compliance. CONCLUSIONS: The present analysis highlights that poor, undernourished, uneducated women can have high compliance to antenatal supplementation if they are supplied with the tablets and reminded to take them regularly, and counselled about side-effects.

Antenatal and postnatal iron supplementation and childhood mortality in rural Nepal: a prospective follow-up in a randomized, controlled community trial.

The long-term benefits of antenatal iron supplementation in child survival are not known. In 1999-2001, 4,926 pregnant women in rural Nepal participated in a cluster-randomized, double-masked, controlled trial involving 4 alternative combinations of micronutrient supplements, each containing vitamin A. The authors examined the impact on birth weight and early infant mortality in comparison with controls, who received vitamin A only. They followed the surviving offspring of these women at approximately age 7 years to study effects of in utero supplementation on survival. Of 4,130 livebirths, 209 infants died in the first 3 months and 8 were lost to follow-up. Of those remaining, 3,761 were followed, 150 died between ages 3 months and 7 years, and 152 were lost to follow-up. Mortality rates per 1,000 child-years from birth to age 7 years differed by maternal supplementation group, as follows: folic acid, 13.4; folic acid-iron, 10.3; folic acid-iron-zinc, 12.0; multiple micronutrients; 14.0; and controls, 15.2. Hazard ratios were 0.90 (95% confidence interval (CI): 0.65, 1.22), 0.69 (95% CI: 0.49, 0.99), 0.80 (95% CI: 0.58, 1.11), and 0.93 (95% CI: 0.66, 1.31), respectively, in the 4 supplementation groups. Maternal iron-folic acid supplementation reduced mortality among these children by 31% between birth and age 7 years. These results provide additional motivation for strengthening antenatal iron-folic acid programs.

Young maternal age and the risk of neonatal mortality in rural Nepal.

OBJECTIVES: To investigate the relationship between adolescent pregnancy and neonatal mortality in a nutritionally deprived population in rural Nepal, and to determine mechanisms through which low maternal age may affect neonatal mortality. DESIGN: Nested cohort study using data from a population-based, cluster-randomized, placebo-controlled trial of newborn skin and umbilical cord cleansing with chlorhexidine. SETTING: Sarlahi District of Nepal. PARTICIPANTS: Live-born singleton infants of mothers younger than 25 years who were either parity 0 or 1 (n = 10,745). MAIN EXPOSURE: Maternal age at birth of offspring. OUTCOME MEASURE: Crude and adjusted odds ratios of neonatal mortality by maternal age category. RESULTS: Infants born to mothers aged 12 to 15 years were at a higher risk of neonatal mortality than those born to women aged 20 to 24 years (odds ratio, 2.24; 95% confidence interval, 1.40-3.59). After adjustment for confounders, there was a 53% excess risk of neonatal mortality among infants born to mothers in the youngest vs oldest age category (1.53; 0.90-2.60). This association was attenuated on further adjustment for low birth weight, preterm birth, or small-for-gestational-age births. CONCLUSIONS: The higher risk of neonatal mortality among younger mothers in this setting is partially explained by differences in socioeconomic factors in younger vs older mothers; risk is mediated primarily through preterm delivery, low birth weight, newborns being small for gestational age, and/or some interaction of these variables. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00109616.

Risk factors for pregnancy-related mortality: a prospective study in rural Nepal.

OBJECTIVES: This study examined the risk factors of mortality related to pregnancy for the first year post partum in a cohort of 25,580 pregnancies. STUDY DESIGN: Longitudinal cohort follow-up. METHODS: Details of socio-economic status, mid-upper arm circumference (MUAC), diet, illness, work, substance use and previous pregnancy history were collected during early to mid-gestation, and these women were followed for 1 year post partum. All-cause mortality rates per 100,000 pregnancies were calculated for deaths during pregnancy or up to 42 days post partum (early period) and 43-364 days post partum (late period). Odds ratios (OR) of mortality were estimated using five groups of risk factors: biological; morbidity; dietary; lifestyle; and socio-economic. Significant factors within each group were included in a single risk model for each time period. RESULTS: Early and late pregnancy-related mortality rates were 469 [95% confidence interval (CI) 385-553] and 254 (95% CI 192-316), respectively. Maternal age > or = 35 years was associated with a three- to four-fold increase in mortality, whereas increasing parity conferred increasing protection. In the final model, a larger MUAC and consumption of dark green leaves were associated with decreased risk of death in the early period (OR 0.76, 95% CI 0.67-0.87 and 0.64, 95% CI 0.41-0.99, respectively). A larger MUAC was also associated with a lower risk of death in the late period. Diarrhoea/dysentery and pre-eclampsia were associated with increased risk of death in the early period (OR 2.78, 95% CI 1.40-5.51 and 2.95, 95% CI 1.48-5.90, respectively). Factors weakly associated (P<0.1) with mortality in both periods included night blindness, strenuous work activity and cigarette smoking. No socio-economic factors were significant in the models. CONCLUSIONS: Maternal age, parity, MUAC, diet and illness in early to mid-gestation were associated with risk of death during pregnancy and the first year post partum in rural Nepal.