Risk and burden of adverse intrapartum-related outcomes associated with non-cephalic and multiple birth in rural Nepal: a prospective cohort study

Objectives Intrapartum-related complications are the second leading cause of neonatal death worldwide. We estimate the community-level risk and burden of intrapartum-related fetal/neonatal mortality and morbidity associated with non-cephalic and multiple birth in rural Sarlahi District, Nepal. Design Community-based prospective cohort study. Setting Rural Sarlahi District, Nepal. Participants Pregnant women residing in the study area. Methods We collected data on maternal background characteristics, conditions during labour and delivery, fetal presentation and multiple birth during home visits. We ran log-binomial regression models to estimate the associations between non-cephalic/multiple births and fresh stillbirth, early neonatal mortality and signs of neonatal encephalopathy, respectively, and calculated the per cent attributable fraction. To better understand the context under which these adverse birth outcomes are occurring, we also collected data on maternal awareness of non-cephalic presentation and multiple gestation prior to delivery. Primary outcome measures Risk of experiencing fresh stillbirth, early neonatal encephalopathy and early neonatal mortality associated with non-cephalic and multiple birth, respectively. Results Non-cephalic presentation had a particularly high risk of fresh stillbirth (aRR 12.52 (95% CI 7.86 to 19.95), reference: cephalic presentation). 20.2% of all fresh stillbirths were associated with non-cephalic presentation. For multiple births, there was a fourfold increase in early neonatal mortality (aRR: 4.57 (95% CI 1.44 to 14.50), reference: singleton births). 3.4% of early neonatal mortality was associated with multiple gestation. Conclusions Globally and in Nepal, a large percentage of stillbirths and neonatal mortality is associated with intrapartum-related complications. Despite the low incidence of non-cephalic and multiple birth, a notable proportion of adverse intrapartum-related outcomes is associated with these conditions. As the proportion of neonatal deaths attributable to intrapartum-related complications continues to rise, there is a need to investigate how best to advance diagnostic capacity and management of these conditions. Trial registration number NCT01177111; pre-results

Maternal vitamin A supplementation increases natural antibody concentrations of preadolescent offspring in rural Nepal

AbstractObjectiveB1a lymphocytes—which constitutively produce most natural antibodies (NAb)—arise from an early wave of progenitors unique to fetal life. Vitamin A regulates early lymphopoiesis. In animals, deficiency during this critical period compromises B1 cell populations. The aim of this study was to investigate the effect of maternal supplementation with vitamin A or β-carotene from preconception through lactation on NAb concentrations of offspring.MethodsParticipants (N = 290) were born to participants of a cluster-randomized, placebo-controlled trial of weekly maternal vitamin A or β-carotene supplementation (7000 μg retinol equivalents) conducted in Sarlahi, Nepal (1994–1997) and assessed at ages 9 to 13 y (2006–2008). Serum retinol was measured by reversed-phase high-performance liquid chromatography at mid-pregnancy and 3 mo of age. Enzyme-linked immunosorbent assay (ELISA) was used to measure children's plasma NAb concentrations at 9 to 13 y.ResultsUnadjusted geometric mean concentrations were 20.08 U/mL (95% confidence interval [CI], 17.82–22.64) in the vitamin A group compared with 17.64 U/mL (95% CI, 15.70–19.81) and 15.96 U/mL (95% CI, 13.43–18.96) in the β-carotene and placebo groups (P = 0.07), respectively. After adjustment, maternal vitamin A supplementation was associated with a 0.39 SD increase in NAb concentrations (P = 0.02). The effect was mediated by infant serum retinol in our statistical models. Although girls had 1.4-fold higher NAb concentrations (P < 0.001), sex did not modify the vitamin A effect.ConclusionsIn an undernourished population, maternal vitamin A supplementation enhanced NAb concentrations of preadolescent children. We posit that this was due to a greater allotment of B1a precursors during fetal life and a sustained higher count of NAb-secreting B1a cells

Risk and Burden of Adverse Intrapartum-Related Outcomes Associated with Non-Cephalic and Multiple Birth in Rural Nepal: a Prospective Cohort Study.

OBJECTIVES: Intrapartum-related complications are the second leading cause of neonatal death worldwide. We estimate the community-level risk and burden of intrapartum-related fetal/neonatal mortality and morbidity associated with non-cephalic and multiple birth in rural Sarlahi District, Nepal. DESIGN: Community-based prospective cohort study. SETTING: Rural Sarlahi District, Nepal. PARTICIPANTS: Pregnant women residing in the study area. METHODS: We collected data on maternal background characteristics, conditions during labour and delivery, fetal presentation and multiple birth during home visits. We ran log-binomial regression models to estimate the associations between non-cephalic/multiple births and fresh stillbirth, early neonatal mortality and signs of neonatal encephalopathy, respectively, and calculated the per cent attributable fraction. To better understand the context under which these adverse birth outcomes are occurring, we also collected data on maternal awareness of non-cephalic presentation and multiple gestation prior to delivery. PRIMARY OUTCOME MEASURES: Risk of experiencing fresh stillbirth, early neonatal encephalopathy and early neonatal mortality associated with non-cephalic and multiple birth, respectively. RESULTS: Non-cephalic presentation had a particularly high risk of fresh stillbirth (aRR 12.52 (95% CI 7.86 to 19.95), reference: cephalic presentation). 20.2% of all fresh stillbirths were associated with non-cephalic presentation. For multiple births, there was a fourfold increase in early neonatal mortality (aRR: 4.57 (95% CI 1.44 to 14.50), reference: singleton births). 3.4% of early neonatal mortality was associated with multiple gestation. CONCLUSIONS: Globally and in Nepal, a large percentage of stillbirths and neonatal mortality is associated with intrapartum-related complications. Despite the low incidence of non-cephalic and multiple birth, a notable proportion of adverse intrapartum-related outcomes is associated with these conditions. As the proportion of neonatal deaths attributable to intrapartum-related complications continues to rise, there is a need to investigate how best to advance diagnostic capacity and management of these conditions. TRIAL REGISTRATION NUMBER: NCT01177111; pre-results

Validity of home-based sonographic diagnosis of obstetric risk factors by auxiliary nurse midwives in rural Nepal

Background Approximately 2·3 million fetal, neonatal, or maternal deaths occur annually during the intrapartum period or on the day of birth. Several risk factors for intrapartum-related complications require ultrasonography for accurate diagnosis, but sonographic services are scarce in low-resource settings. In this study, we aimed to assess the feasibility of community-based ultrasonography conducted by auxiliary nurse midwives to identify basic obstetric risk factors, in rural Sarlahi District, Nepal. We aimed to assess the validity at which these health workers can detect noncephalic position, multiple gestation, and placenta previa and to explore whether sonographic diagnosis could improve outcomes for women with these high-risk conditions. Methods Three auxiliary nurse midwives (ANM) received two 1-week ultrasound trainings at Tribhuvan University Teaching Hospital in Kath mandu, Nepal. Women at 32 weeks’ or more gestation were enrolled in the study, and received ultrasonography from the ANMs during home visits. ANMs used ultrasonography to identify non-cephalic position, multiple gestation, and placenta previa. Images were saved and later reassessed by gold standard ultrasonographers to determine the validity of the ANM assessment. We also compared adverse outcomes in noncephalic or multiple gestation births from the study group with those in a comparison group of women who did not receive ultrasonography from our study, but the study was not powered to detect a difference. Findings We collected data from 815 women. The kappa statistics for diagnosis of non-cephalic position were 0·92, 0·98, and 0·94, respectively, for the three ANMs against the gold standard. Sensitivity, specificity, positive predictive value, and negative predictive value were between 90% and 100% for all ANMs. For multiple gestation pregnancies (n=6), the ANMs were in perfect agreement with both the gold standard reading and maternal postpartum self-report. Two cases of placenta previa were detected, and the gold standard was in agreement with both. There were 4 adverse outcomes out of 19 women (21%) with non-cephalic or multiple gestation pregnancies in the study group compared with 10 out of 36 (28%) in the comparison group. This difference was not significant (p=0·586). Interpretation Our findings suggest that it is feasible for ANMs to conduct ultrasonography to identify basic obstetric risk factors in low-income settings. The difference in birth outcomes in non-cephalic and multiple births, comparing those antenatally diagnosed by ultrasound and those who were not, was not significant; the sample size was too small to detect a diff erence. Further investigation is warranted to determine whether sonographic diagnosis of selected obstetric factors could contribute to improved care-seeking and health outcomes in low-income settings. Funding Cappsci Data for Life Award, SonoSite Soundcaring Program, National Institutes of Health/National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation

Sex differences in morbidity and care-seeking during the neonatal period in rural southern Nepal

Background South Asian studies, including those from Nepal, have documented increased risk of neonatal mortality among girls, despite their early biologic survival advantage. We examined sex differences in neonatal morbidity and care-seeking behavior to determine whether such differences could help explain previously observed excess late neonatal mortality among girls in Nepal. Methods A secondary analysis of data from a trial of chlorhexidine use among neonates in rural Nepal was conducted. The objective was to examine sex differences in neonatal morbidity and care-seeking behavior for ill newborns. Girls were used as the reference group. Results Referral for care was higher during the early neonatal period (ENP: 0–7 days old) (50.7 %) than the late neonatal period (LNP: 8–28 days old) (31.3 %), but was comparable by sex. There were some significant differences in reasons for referral by sex. Boys were significantly more often referred for convulsions/stiffness, having yellow body/eyes, severe skin infection, and having at least two of the following: difficulty breathing, difficulty feeding, fever, or vomiting during the ENP. Girls were more often referred for hypothermia. During the LNP, boys were significantly more often referred for having yellow body/eyes, persistent watery stool, and severe skin infection. There were no referral types in the LNP for which girls were more often referred. Less than half of those referred at any point were taken for care (47.0 %) and referred boys were more often taken than girls (Neonatal Period OR: 1.77, 95 % CI: 1.64 - 1.91). Family composition differentially impacted the relationship between care-seeking and sex. The greatest differences were in families with only prior living girls (Pahadi - ENP OR: 1.78, 95 % CI: 1.29 - 2.45 and LNP OR: 1.51, 95 % CI: 1.03 - 2.21; Madeshi - ENP OR: 2.86, 95 % CI: 2.28 – 3.59 and LNP OR: 2.45, 95 % CI: 1.84 – 3.26). Conclusions Care-seeking was inadequate for both sexes, but ill boys were consistently more often taken for care than girls, despite comparable referral. Behavioral interventions to improve care-seeking, especially in the early neonatal period, are needed to improve neonatal survival. Addressing gender bias in care-seeking, explicitly and within interventions, is essential to reducing neonatal mortality differentials between boys and girls

Effect of an improved biomass stove on acute lower respiratory infections in young children in rural Nepal: a cluster-randomised, step-wedge trial

Background Acute lower respiratory infections (ALRI) are an important cause of death in young children in low income countries. High concentrations of fine particulate matter (PM2.5) indoors caused by open burning of biomass are associated with risk of ALRI. However, improved biomass stoves reduce emissions and might reduce the incidence of lower respiratory illness. A cluster-randomised, step-wedge, community-based trial was conducted to estimate the eff ect that a change from open burning of biomass to improved biomass stoves could have on rates of ALRI in children younger than 36 months in a rural area of southern Nepal. Methods Households were enrolled in Sarlahi district that had at least one child aged younger than 36 months or a married woman aged 15–30 years. Respiratory morbidity data were collected for 6 months prior to the introduction of improved biomass stoves between March, 2010, and December, 2010. Mothers were asked about respiratory signs and symptoms (cough, difficult or rapid breathing, wheeze, ear discharge, fever) in their participating children in the past 7 days during weekly visits from local study staff. A 12-month stepped-wedge introduction of an improved biomass stove with chimney to participating households followed the 6-month run-in period (Envirofit Corp. Colorado Springs, CO, USA). Weekly morbidity assessments continued during the step-wedge period (from January, 2011, to February, 2012) and for 6 months after stove introduction (from March, 2012, to December, 2012). Children were discharged at age 36 months. The primary outcome was ALRI, defined as a maternal report of 2 or more consecutive days of fast or difficult breathing accompanied by fever. Episodes were separated by a minimum of 7 symptom-free days. An environmental assessment was done in households once before and once after the improved stove was installed. The trial is registered at clinicaltrials.gov (NCT00786877). Findings 5254 children from 3376 households were enrolled either at baseline or during the trial period. Mean 20-h kitchen concentration of PM2.5 was reduced from 1386 μg/m3 to 930 μg/m3 There was a strong secular decline in the incidence of ALRI over the period of the study. The intervention was associated with a 13% decline in the incidence of ALRI but the strength of evidence was weak (0·87, 95% CI 0·67–1·13). There were statistically significant reductions in persistent cough (0·91, 0·85–0·97), wheeze (0·87, 0·78–0·97) and burn injury (0·68, 0·48–0·95) but not for fever, severe ALRI, or ear discharge. Interpretation There was weak evidence for a modest decline in the incidence of ALRI. Post-installation PM2.5 concentrations remained well above current indoor air standards of 25 μg/m3 . Better performing biomass stoves or cleaner fuels such as liquid petroleum gas or ethanol are needed to reduce concentrations enough to estimate the impact on ALRI incidence

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

Inconsistent Effects of Iron-Folic Acid and/or Zinc Supplementation on the Cognitive Development of Infants

Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 µg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (≥85% correct; A-not-B), deteriorated performance (<75% correct and >1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio=0.67; 95% confidence interval 0.46-0.97; p<0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p>0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors

Seasonality of birth outcomes in rural Sarlahi District, Nepal: a population-based prospective cohort

Background While seasonality of birth outcomes has been documented in a variety of settings, data from rural South Asia are lacking. We report a descriptive study of the seasonality of prematurity, low birth weight, small for gestational age, neonatal deaths, and stillbirths in the plains of Nepal. Methods Using data collected prospectively during a randomized controlled trial of neonatal skin and umbilical cord cleansing with chlorhexidine, we analyzed a cohort of 23,662 babies born between September 2002 and January 2006. Project workers collected data on birth outcomes at the infant’s household. Supplemental data from other studies conducted at the same field site are presented to provide context. 95% confidence intervals were constructed around monthly estimates to examine statistical significance of findings. Results Month of birth was associated with higher risk for adverse outcomes (neonatal mortality, low birthweight, preterm, and small for gestational age), even when controlling for maternal characteristics. Infants had 87% (95% CI: 27 – 176%) increased risk of neonatal mortality when born in August, the high point, versus March, the low point. Conclusion Seasonality of neonatal deaths, stillbirths, birth weight, gestational age, and small for gestational age were found in Nepal. Maternal factors, meteorological conditions, infectious diseases, and nutritional status may be associated with these adverse birth outcomes. Further research is needed to understand the causal mechanisms that explain the seasonality of adverse birth outcomes

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