Summary Background Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of ...year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. Methods In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17–25 weeks vs 26–34 weeks). Women were eligible if they were married, 15–40 years of age, 17–34 weeks' gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0–180 days postpartum, the incidence of low birthweight (<2500 g), and the incidence of laboratory-confirmed infant influenza disease from 0 to 180 days. This trial is registered with ClinicalTrials.gov , number NCT01034254. Findings From April 25, 2011, to Sept 9, 2013, we enrolled 3693 women in two cohorts of 2090 (1041 assigned to placebo and 1049 to vaccine) and 1603 (805 assigned to placebo and 798 to vaccine), with 3646 liveborn infants (cohort 1, 999 in placebo group and 1010 in vaccine group; cohort 2, 805 in placebo group and 798 in vaccine group). Immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1 to 34) in the combined cohorts; 9% efficacy (−16 to 29) in the first cohort, and 36% efficacy (9 to 55) in the second cohort. For laboratory-confirmed influenza infections in infants aged 0–6 months, immunisation had an overall efficacy for the combined cohorts of 30% (95% CI 5 to 48); in the first cohort, the efficacy was 16% (−19 to 41), and in the second cohort it was 60% (26 to 88). Maternal immunisation reduced the rates of low birthweight by 15% (95% CI 3–25) in both cohorts combined. The rate of small for gestational age infants was not modified by immunisation. The number of adverse events was similar regardless of immunisation status. Miscarriage occurred in three (0·2%) participants in the placebo group versus five (0·3%) in the vaccine group, stillbirth occurred in 31 (1·7%) versus 33 (1·8%), and congenital defects occurred in 18 (1·0%) versus 20 (1·1%). Five women died in the placebo group and three died in the vaccine group. The number of infant deaths at age 0–6 months was similar in each group (50 in the placebo group and 61 in the vaccine group). No serious adverse events were associated with receipt of immunisation. Interpretation Year-round maternal influenza immunisation significantly reduced maternal influenza-like illness, influenza in infants, and low birthweight over the entire course of the study, indicating the strategy could be useful in subtropical regions. Funding Bill & Melinda Gates Foundation.
Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology ...and clinical presentation of RSV in pregnant and postpartum women is not well-described.
Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction.
RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011-2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants.
RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.
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.
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.
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.
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.
•Aflatoxin B1-lysine albumin biomarkers were measured in rural South Asian women during pregnancy and across the first 1000 days of life.
Aflatoxin B1 is a potent carcinogen, occurring from mold ...growth that contaminates staple grains in hot, humid environments. In this investigation, aflatoxin B1-lysine albumin biomarkers were measured by mass spectrometry in rural South Asian women, during the first and third trimester of pregnancy, and their children at birth and at two years of age. These subjects participated in randomized community trials of antenatal micronutrient supplementation in Sarlahi District, southern Nepal and Gaibandha District in northwestern Bangladesh. Findings from the Nepal samples demonstrated exposure to aflatoxin, with 94% detectable samples ranging from 0.45 to 2939.30 pg aflatoxin B1-lysine/mg albumin during pregnancy. In the Bangladesh samples the range was 1.56 to 63.22 pg aflatoxin B1-lysine/mg albumin in the first trimester, 3.37 to 72.8 pg aflatoxin B1-lysine/mg albumin in the third trimester, 4.62 to 76.69 pg aflatoxin B1-lysine/mg albumin at birth and 3.88 to 81.44 pg aflatoxin B1-lysine/mg albumin at age two years. Aflatoxin B1-lysine adducts in cord blood samples demonstrated that the fetus had the capacity to convert aflatoxin into toxicologically active compounds and the detection in the same 2-year-old children illustrates exposure over the first 1000 days of life.
Objectives
To assess the association between maternal characteristics, adverse birth outcomes (small-for-gestational-age (SGA) and/or preterm) and neonatal mortality in rural Nepal.
Design
This is a ...secondary observational analysis to identify risk factors for neonatal mortality, using data from a randomised trial to assess the impact of newborn massage with different oils on neonatal mortality in Sarlahi district, Nepal.
Setting
Rural Sarlahi district, Nepal.
Participants
40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017.
Main outcome
The outcome variable is neonatal death. Cox regression was used to estimate adjusted Hazard Ratios (aHRs) to assess the association between adverse birth outcomes and neonatal mortality.
Results
There were 32 004 live births and 998 neonatal deaths. SGA and/or preterm birth was strongly associated with increased neonatal mortality: SGA and preterm (aHR: 7.09, 95% CI: (4.44 to 11.31)), SGA and term/post-term (aHR: 2.12, 95% CI: (1.58 to 2.86)), appropriate-for-gestational-age/large-for-gestational-age and preterm (aHR: 3.23, 95% CI: (2.30 to 4.54)). Neonatal mortality was increased with a history of prior child deaths (aHR: 1.53, 95% CI: (1.24 to 1.87)), being a twin or triplet (aHR: 5.64, 95% CI: (4.25 to 7.48)), births at health posts/clinics or in hospital (aHR: 1.34, 95% CI: (1.13 to 1.58)) and on the way to facilities or outdoors (aHR: 2.26, 95% CI: (1.57 to 3.26)). Risk was lower with increasing maternal height from <145 cm to 145–150 cm (aHR: 0.78, 95% CI: (0.65 to 0.94)) to ≥150 cm (aHR: 0.57, 95% CI: (0.47 to 0.68)), four or more antenatal care (ANC) visits (aHR: 0.67, 95% CI: (0.53 to 0.86)) and education >5 years (aHR: 0.75, 95% CI: (0.62 to 0.92)).
Conclusion
SGA and/or preterm birth are strongly associated with increased neonatal mortality. To reduce neonatal mortality, interventions that prevent SGA and preterm births by promoting ANC and facility delivery, and care of high-risk infants after birth should be tested.
Trial registration number
NCT01177111
.
Natural vegetable oils are widely used for newborn massage in many low resource settings. Animal models indicated that sunflower seed oil (SSO) can accelerate skin barrier recovery following damage, ...while other oils, including mustard oil (MO), may cause further skin barrier damage. The objective was to compare the effects of two SSO and MO used for routine massage on skin integrity in premature and full-term neonates.
This community-based cluster randomized controlled trial included 995 neonates assigned to full body massage with sunflower seed oil (SSO, intervention) or mustard seed oil (MO, standard practice) from July 2012-May 2014 in Sarlahi, Nepal. Skin integrity measures were evaluated over 28 days, including skin condition (erythema, rash, dryness), skin surface pH, stratum corneum (SC) cohesion/protein concentration, and transepidermal water loss (TEWL). Overall means and rates of change in these skin measures were compared between oil groups using bivariate random-effects models.
500 and 495 live born neonates received repeated massage with MO and SSO, respectively. Skin pH decreased more quickly for SSO than MO in the first week of life, with a difference in mean daily reductions of 0.02 (95% CI: 0.002-0.040). Erythema, rash and dryness increased (worsened) over days 1-14 then decreased by day 28, with no significant oil group differences. TEWL increased over time, with no significant oil group differences. Gestational age did not modify the effect; the slightly faster decrease in skin pH among SSO infants was similar in magnitude between term and preterm infants.
Oil type may contribute to differences in skin integrity when neonates are massaged regularly. The more rapid acid mantle development observed for SSO may be protective for neonates in lower resource settings.
ClinicalTrials.gov (NCT01177111); registered August 6th, 2010.
ObjectivesThis study aimed to examine the validity of maternal recall of total number of antenatal care (ANC) visits during pregnancy and factors associated with the accuracy of maternal ...recall.DesignThis was a longitudinal cohort study conducted from December 2018 through November 2020.SettingFive government health posts in the Sarlahi district of Southern Nepal.Participants402 pregnant women between ages 15 and 49 who presented for their first ANC visit at the study health posts.Main outcomesThe observed number of ANC visits (gold standard) and the reported number of ANC visits at the postpartum interview (maternal recall).ResultsOn average, women in the study who had a live birth attended 4.7 ANC visits. About 65% of them attended four or more ANC visits during pregnancy as recommended by the Nepal government, and 38.3% of maternal report matched the categorical ANC visits as observed by the gold standard. The individual validity was poor to moderate, with the highest area under the receiver operating characteristic curve (AUC) being 0.69 (95% CI: 0.65 to 0.74) in the 1–3 visits group. Population-level bias (as distinct from individual-level bias) was observed in the 1–3 visits and 4 visits groups, where 1–3 visits were under-reported (inflation factor (IF): 0.69) and 4 ANC visits were highly over-reported (IF: 2.12). The binary indicator ANC4+ (1–3 visits vs 4+ visits) showed better population-level validity (AUC: 0.69; IF: 1.17) compared with the categorical indicators (1–3 visits, 4 visits, 5–6 visits and more than 6 visits). Report accuracy was not associated with maternal characteristics but was related to ANC frequency. Women who attended more ANC visits were less likely to correctly report their total number of visits.ConclusionMaternal report of number of ANC visits during pregnancy may not be a valid indicator for measuring ANC coverage. Improvements are needed to measure the frequency of ANC visits.
Abstract
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
).
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.
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.
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.
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.
Countries without complete civil registration and vital statistics systems rely on retrospective full pregnancy history surveys (FPH) to estimate incidence of pregnancy and mortality outcomes, ...including stillbirth and neonatal death. Yet surveys are subject to biases that impact demographic estimates, and few studies have quantified these effects. We compare data from an FPH vs. prospective records from a population-based cohort to estimate validity for maternal recall of live births, stillbirths, and neonatal deaths in a rural population in Sarlahi District, Nepal.
We used prospective data, collected through frequent visits of women from early pregnancy through the neonatal period, from a population-based randomized trial spanning 2010-2017. We randomly selected 76 trial participants from three pregnancy outcome groups: live birth (n = 26), stillbirth (n = 25), or neonatal death (n = 25). Data collectors administered the Nepal 2016 Demographic and Health Surveys (DHS)-VII pregnancy history survey between October 22, 2021, and November 18, 2021. We compared total pregnancy outcomes and numbers of pregnancy and neonatal outcomes between the two data sources. We matched pregnancy outcomes dates in the two sources within ± 30 days and calculated measures of validity for adverse outcomes.
Among 76 participants, we recorded 122 pregnancy outcomes in the prospective data and 104 outcomes in the FPH within ± 30 days of each woman's total observation period in the trial. Among 226 outcomes, we observed 65 live births that survived to 28 days, 25 stillbirths, and 32 live births followed by neonatal death in the prospective data and participants reported 63 live births that survived to 28 days, 15 stillbirths, and 26 live births followed by neonatal death in the pregnancy history survey. Sixty-two FPH outcomes were matched by date within ± 30 days to an outcome in prospective data. Stillbirth, neonatal death, higher parity, and delivery at a health facility were associated with likelihood of a non-matched pregnancy outcome.
Stillbirth and neonatal deaths were underestimated overall by the FPH, potentially underestimating the burden of mortality in this population. There is a need to develop tools to reduce or adjust for biases and errors in retrospective surveys to improve reporting of pregnancy and mortality outcomes.
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