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

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

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

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

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

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

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

Designs of two randomized, community-based trials to assess the impact of influenza immunization during pregnancy on respiratory illness among pregnant women and their infants and reproductive outcomes in rural Nepal

Background: Among the most important causes of illness and death in both pregnant women and their newborn infants are respiratory infections including influenza. Pregnant women in North America have a 4 to 5 fold excess rate of hospitalization compared to non-pregnant women. Rates of infant hospitalization associated with influenza are much higher than in their mothers. Fully half of children hospitalized for influenza in the US are in the age group 0–5 months, a group where no vaccine is licensed. Data on influenza are much fewer in low income countries where the risks of serious morbidity and mortality are much higher. A recent trial in Bangladesh suggested that influenza immunization in pregnant women could have important protective effects against influenza in both mothers and their infants. These trials were designed to provide additional evidence about the effect of influenza vaccination in pregnancy in settings where influenza may circulate for up to ten months/year. Methods/Design: We conducted a consecutive pair of community-based, placebo-controlled, randomized trials of influenza vaccination of pregnant women in a rural district in southern Nepal. Two trials were conducted to insure, as much as possible, the match of circulating strains with those included in the vaccine. Eligible women included all who were or became pregnant over a one year period. Each trial included a one year cohort of pregnant women who were individually randomized to the influenza vaccine available at the time of their enrollment or placebo. Exclusions included a history of allergy to vaccine components, prior influenza vaccine receipt, and for the second trial, participation in the first trial. Morbidity was assessed on a weekly basis for women throughout pregnancy and through 180 days post-partum. Infants were followed weekly through 180 days. Primary outcomes included: 1) incidence of influenza like illness in women, 2) incidence of laboratory confirmed influenza illness in infants, and 3) birthweight among newborn infants. Discussion: We have presented the design and methods of two randomized trials of influenza immunization of pregnant women

Infant vaccination timing: Beyond traditional coverage metrics for maximizing impact of vaccine programs, an example from southern Nepal.

Background Immunization programs currently measure coverage by assessing the proportion of children 12–24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited. Objective To estimate the time to Bacillus Calmette–Guérin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants \u3c6 months of age in a district in southern Nepal where traditional coverage metrics are high. Design/methods Infants enrolled in a randomized controlled trial of maternal influenza vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan–Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine. Results The median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months. Conclusion A significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health

Potential Role of Traditional Birth Attendants in Neonatal Healthcare in Rural Southern Nepal

The potential for traditional birth attendants (TBAs) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health. Randomly-selected TBAs (n=93) were interviewed to gain a more thorough understanding of their knowledge, attitudes, and practices regarding maternal and newborn care. Practices, such as using a clean cord-cutting instrument (89%) and hand-washing before delivery (74%), were common. Other beneficial practices, such as thermal care, were low. Trained TBAs were more likely to wash hands with soap before delivery, use a clean delivery-kit, and advise feeding colostrum. Although mustard oil massage was a universal practice, 52% of the TBAs indicated their willingness to consider alternative oils. Low-cost, evidence-based interventions for improving neonatal outcomes might be implemented by TBAs in this setting where most births take place in the home and neonatal mortality risk is high. Continuing efforts to define the role of TBAs may benefit from an emphasis on their potential as active promoters of essential newborn care