Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.

BACKGROUND: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. METHODS: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. RESULTS: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. CONCLUSIONS: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).

The Global Network COVID-19 studies: a review.

With the paucity of data available regarding COVID-19 in pregnancy in low- and middle-income countries (LMICs), near the start of the pandemic, the Global Network for Women's and Children's Health Research, funded by the National Institute of Child Health and Human Development (NICHD), initiated four separate studies to better understand the impact of the COVID-19 pandemic in eight LMIC sites. These sites included: four in Asia, in Bangladesh, India (two sites) and Pakistan; three in Africa, in the Democratic Republic of the Congo (DRC), Kenya and Zambia; and one in Central America, in Guatemala. The first study evaluated changes in health service utilisation; the second study evaluated knowledge, attitudes and practices of pregnant women in relationship to COVID-19 in pregnancy; the third study evaluated knowledge, attitude and practices related to COVID-19 vaccination in pregnancy; and the fourth study, using antibody status at delivery, evaluated changes in antibody status over time in each of the sites and the relationship of antibody positivity with various pregnancy outcomes. Across the Global Network, in the first year of the study there was little reduction in health care utilisation and no apparent change in pregnancy outcomes. Knowledge related to COVID-19 was highly variable across the sites but was generally poor. Vaccination rates among pregnant women in the Global Network were very low, and were considerably lower than the vaccination rates reported for the countries as a whole. Knowledge regarding vaccines was generally poor and varied widely. Most women did not believe the vaccines were safe or effective, but slightly more than half would accept the vaccine if offered. Based on antibody positivity, the rates of COVID-19 infection increased substantially in each of the sites over the course of the pandemic. Most pregnancy outcomes were not worse in women who were infected with COVID-19 during their pregnancies. We interpret the absence of an increase in adverse outcomes in women infected with COVID-19 to the fact that in the populations studied, most COVID-19 infections were either asymptomatic or were relatively mild.

COVID-19 symptoms and antibody positivity among unvaccinated pregnant women: An observational study in seven countries from the Global Network.

OBJECTIVE: To determine the relation of COVID-19 symptoms to COVID-19 antibody positivity among unvaccinated pregnant women in low- and middle-income countries (LMIC). DESIGN: COVID-19 infection status measured by antibody positivity at delivery was compared with the symptoms of COVID-19 in the current pregnancy in a prospective, observational cohort study in seven LMICs. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR), a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Bangladesh, Pakistan, India (Belagavi and Nagpur sites) and Guatemala. POPULATION: Pregnant women enrolled in the ongoing pregnancy registry at study sites. METHODS: Data on COVID-19 symptoms during the current pregnancy were collected by trained staff between October 2020 and June 2022. COVID-19 antibody testing was performed on samples collected at delivery. The relation between COVID-19 antibody positivity and symptoms was assessed using generalised linear models with a binomial distribution adjusting for site and symptoms. MAIN OUTCOME MEASURES: COVID-19 antibody status and symptoms of COVID-19 among pregnant women. RESULTS: Among 19 218 non-vaccinated pregnant women who were evaluated, 14.1% of antibody-positive women had one or more symptoms compared with 13.4% in antibody-negative women. Overall, 85.3% of antibody-positive women reported no COVID-19 symptoms during the present pregnancy. Reported fever was significantly associated with antibody status (relative risk [RR] 1.10, 95% CI 1.03-11.18; P = 0.008). A multiple variable model adjusting for site and all eight symptoms during pregnancy showed similar results (RR 1.13, 95% CI 1.04-1.23; P = 0.012). None of the other symptoms was significantly related to antibody positivity. CONCLUSIONS: In a population-based cohort in LMICs, unvaccinated pregnant women who were antibody-positive had slightly more symptoms during their pregnancy and a small but significantly greater increase in fever. However, for prevalence studies, evaluating COVID-19-related symptoms does not appear to be useful in differentiating pregnant women who have had a COVID-19 infection.

Aspirin delays the onset of hypertensive disorders of pregnancy among nulliparous pregnant women: A secondary analysis of the ASPIRIN trial.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. DESIGN: Non-prespecified secondary analysis of a randomised masked trial of LDA. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites-Belagavi and Nagpur) and Guatemala. POPULATION: Nulliparous singleton pregnancies between 6+0 weeks and 13+6 weeks in six low-middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial. METHODS: We compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat). MAIN OUTCOME MEASURES: Our primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality. RESULTS: Among the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02-1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17-0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49-0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94-1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67-0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64-1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33-0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022). CONCLUSIONS: In this secondary analysis of a study of low-risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP.

Trends over time in the knowledge, attitude and practices of pregnant women related to COVID-19: A cross-sectional survey from seven low- and middle-income countries.

OBJECTIVE: To understand trends in the knowledge, attitudes and practices (KAP) of pregnant women related to COVID-19 in seven low- and middle-income countries. DESIGN: Multi-country population-based prospective observational study. SETTING: Study sites in Bangladesh, the Demographic Republic of Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: Pregnant women in the Global Network's Maternal and Neonatal Health Registry (MNHR). METHODS: Pregnant women enrolled in the MNHR were interviewed to assess their KAP related to COVID-19 from September 2020 through July 2022 across all study sites. MAIN OUTCOME MEASURES: Trends of COVID-19 KAP were assessed using the Cochran-Armitage test for trend. RESULTS: A total of 52 297 women participated in this study. There were wide inter-country differences in COVID-19-related knowledge. The level of knowledge of women in the DRC was much lower than that of women in the other sites. The ability to name COVID-19 symptoms increased over time in the African sites, whereas no such change was observed in Bangladesh, Belagavi and Guatemala. All sites observed decreasing trends over time in women avoiding antenatal care visits. CONCLUSIONS: The knowledge and attitudes of pregnant women related to COVID-19 varied substantially among the Global Network sites over a period of 2 years; however, there was very little change in knowledge related to COVID-19 over time across these sites. The major change observed was that fewer women reported avoiding medical care because of COVID-19 across all sites over time.

Birth weight and gestational age distributions in a rural Kenyan population.

BACKGROUND: With the increased availability of access to prenatal ultrasound in low/middle-income countries, there is opportunity to better characterize the association between fetal growth and birth weight across global settings. This is important, as fetal growth curves and birthweight charts are often used as proxy health indicators. As part of a randomized control trial, in which ultrasonography was utilized to establish accurate gestational age of pregnancies, we explored the association between gestational age and birthweight among a cohort in Western Kenya, then compared our results to data reported by the INTERGROWTH-21st study. METHODS: This study was conducted in 8 geographical clusters across 3 counties in Western Kenya. Eligible subjects were nulliparous women carrying singleton pregnancies. An early ultrasound was performed between 6 + 0/7 and 13 + 6/7 weeks gestational age. At birth, infants were weighed on platform scales provided either by the study team (community births), or the Government of Kenya (public health facilities). The 10th, 25th, median, 75th, and 90th BW percentiles for 36 to 42 weeks gestation were determined; resulting percentile points were plotted, and curves determined using a cubic spline technique. A signed rank test was used to quantify the comparison of the percentiles generated in the rural Kenyan sample with those of the INTERGROWTH-21st study. RESULTS: A total of 1291 infants (of 1408 pregnant women randomized) were included. Ninety-three infants did not have a measured birth weight. The majority of these were due to miscarriage (n = 49) or stillbirth (n = 27). No significant differences were found between subjects who were lost to follow-up. Signed rank comparisons of the observed median of the Western Kenya data at 10th, 50th, and 90th birthweight percentiles, as compared to medians reported in the INTERGROWTH-21st distributions, revealed close alignment between the two datasets, with significant differences at 36 and 37 weeks. Limitations of the current study include small sample size, and detection of potential digit preference bias. CONCLUSIONS: A comparison of birthweight percentiles by gestational age estimation, among a sample of infants from rural Kenya, revealed slight differences as compared to those from the global population (INTERGROWTH-21st). TRIAL REGISTRATION: This is a single site sub-study of data collected in conjunction with the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN) Trial, which is listed at  ClinicalTrials.gov ,  NCT02409680 (07/04/2015).

Predictors of Plasmodium falciparum Infection in the First Trimester Among Nulliparous Women From Kenya, Zambia, and the Democratic Republic of the Congo.

BACKGROUND: Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-trimester malaria. METHODS: We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics. RESULTS: First-trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%-8.8%] in the Zambian site, 37.8% (95% CI, 34.2%-41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%-67.2%) in the DRC site. First-trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified. CONCLUSIONS: First-trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-trimester malaria in high-prevalence settings.

Regional trends in birth weight in low- and middle-income countries 2013-2018.

BACKGROUND: Birth weight (BW) is a strong predictor of neonatal outcomes. The purpose of this study was to compare BWs between global regions (south Asia, sub-Saharan Africa, Central America) prospectively and to determine if trends exist in BW over time using the population-based maternal and newborn registry (MNHR) of the Global Network for Women'sand Children's Health Research (Global Network). METHODS: The MNHR is a prospective observational population-based registryof six research sites participating in the Global Network (2013-2018), within five low- and middle-income countries (Kenya, Zambia, India, Pakistan, and Guatemala) in threeglobal regions (sub-Saharan Af rica, south Asia, Central America). The birth weights were obtained for all infants born during the study period. This was done either by abstracting from the infants' health facility records or from direct measurement by the registry staff for infants born at home. After controlling for demographic characteristics, mixed-effect regression models were utilized to examine regional differences in birth weights over time. RESULTS: The overall BW meanswere higher for the African sites (Zambia and Kenya), 3186 g (SD 463 g) in 2013 and 3149 g (SD 449 g) in 2018, ascompared to Asian sites (Belagavi and Nagpur, India and Pakistan), 2717 g (SD450 g) in 2013 and 2713 g (SD 452 g) in 2018. The Central American site (Guatemala) had a mean BW intermediate between the African and south Asian sites, 2928 g (SD 452) in 2013, and 2874 g (SD 448) in 2018. The low birth weight (LBW) incidence was highest in the south Asian sites (India and Pakistan) and lowest in the African sites (Kenya and Zambia). The size of regional differences varied somewhat over time with slight decreases in the gap in birth weights between the African and Asian sites and slight increases in the gap between the African and Central American sites. CONCLUSIONS: Overall, BWmeans by global region did not change significantly over the 5-year study period. From 2013 to 2018, infants enrolled at the African sites demonstrated the highest BW means overall across the entire study period, particularly as compared to Asian sites. The incidence of LBW was highest in the Asian sites (India and Pakistan) compared to the African and Central American sites. Trial registration The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475.

Stillbirth 2010-2018: a prospective, population-based, multi-country study from the Global Network.

BACKGROUND: Stillbirth rates are high and represent a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented cause of stillbirths or the trends in rate of stillbirth over time. METHODS: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Cause of stillbirth was assigned by algorithm. RESULTS: From 2010 through 2018, 573,148 women were enrolled with delivery data obtained. Of the 552,547 births that reached 500 g or 20 weeks gestation, 15,604 were stillbirths; a rate of 28.2 stillbirths per 1000 births. The stillbirth rates were 19.3 in the Guatemala site, 23.8 in the African sites, and 33.3 in the Asian sites. Specifically, stillbirth rates were highest in the Pakistan site, which also documented a substantial decrease in stillbirth rates over the study period, from 56.0 per 1000 (95% CI 51.0, 61.0) in 2010 to 44.4 per 1000 (95% CI 39.1, 49.7) in 2018. The Nagpur, India site also documented a substantial decrease in stillbirths from 32.5 (95% CI 29.0, 36.1) to 16.9 (95% CI 13.9, 19.9) per 1000 in 2018; however, other sites had only small declines in stillbirth over the same period. Women who were less educated and older as well as those with less access to antenatal care and with vaginal assisted delivery were at increased risk of stillbirth. The major fetal causes of stillbirth were birth asphyxia (44.0% of stillbirths) and infectious causes (22.2%). The maternal conditions that were observed among those with stillbirth were obstructed or prolonged labor, antepartum hemorrhage and maternal infections. CONCLUSIONS: Over the study period, stillbirth rates have remained relatively high across all sites. With the exceptions of the Pakistan and Nagpur sites, Global Network sites did not observe substantial changes in their stillbirth rates. Women who were less educated and had less access to antenatal and obstetric care remained at the highest burden of stillbirth. STUDY REGISTRATION: Clinicaltrials.gov (ID# NCT01073475).

Evaluating the effect of care around labor and delivery practices on early neonatal mortality in the Global Network's Maternal and Newborn Health Registry.

BACKGROUND: Neonatal deaths in first 28-days of life represent 47% of all deaths under the age of five years globally and are a focus of the United Nation's (UN's) Sustainable Development Goals. Pregnant women are delivering in facilities but that does not indicate quality of care during delivery and the postpartum period. The World Health Organization's Essential Newborn Care (ENC) package reduces neonatal mortality, but lacks a simple and valid composite index that measures its effectiveness. METHODS: Data on 5 intra-partum and 3 post-partum practices (indicators) recommended as part of ENC, routinely collected in NICHD's Global Network's (GN) Maternal Newborn Health Registry (MNHR) between 2010 and 2013, were included. We evaluated if all 8 practices (Care around Delivery - CAD), combined as an index was associated with reduced early neonatal mortality rates (days 0-6 of life). RESULTS: A total of 150,848 live births were included in the analysis. The individual indicators varied across sites. All components were present in 19.9% births (range 0.4 to 31% across sites). Present indicators (8 components) were associated with reduced early neonatal mortality [adjusted RR (95% CI):0.81 (0.77, 0.85); p < 0.0001]. Despite an overall association between CAD and early neonatal mortality (RR < 1.0 for all early mortality): delivery by skilled birth attendant; presence of fetal heart and delayed bathing were associated with increased early neonatal mortality. CONCLUSIONS: Present indicators (8 practices) of CAD were associated with a 19% reduction in the risk of neonatal death in the diverse health facilities where delivery occurred within the GN MNHR. These indicators could be monitored to identify facilities that need to improve compliance with ENC practices to reduce preventable neonatal deaths. Three of the 8 indicators were associated with increased neonatal mortality, due to baby being sick at birth. Although promising, this composite index needs refinement before use to monitor facility-based quality of care in association with early neonatal mortality. Trial registration The identifier of the Maternal Newborn Health Registry at ClinicalTrials.gov is NCT01073475.

Trends and determinants of stillbirth in developing countries: results from the Global Network's Population-Based Birth Registry.

BACKGROUND: Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten-fold higher than in high-income countries. The United Nations' Every Newborn Action Plan has set a goal of 12 stillbirths per 1000 births by 2030 for all countries. METHODS: From a population-based pregnancy outcome registry, including data from 2010 to 2016 from two sites each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of annual decline as well as risk factors for 427,111 births of which 12,181 were stillbirths. RESULTS: The mean stillbirth rates for the sites were 21.3 per 1000 births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per 1000 births for an average annual decline of 3.0%. Risk factors for stillbirth were similar across the sites and included maternal age < 20 years and age > 35 years. Compared to parity 1-2, zero parity and parity > 3 were both associated with increased stillbirth risk and compared to women with any prenatal care, women with no prenatal care had significantly increased risk of stillbirth in all sites. CONCLUSIONS: At the current rates of decline, stillbirth rates in these sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by 2030. More attention to the risk factors and treating the causes of stillbirths will be required to reach the Every Newborn Action Plan goal of stillbirth reduction. TRIAL REGISTRATION: NCT01073475 .

The Global Network Neonatal Cause of Death algorithm for low-resource settings.

AIM: This study estimated the causes of neonatal death using an algorithm for low-resource areas, where 98% of the world's neonatal deaths occur. METHODS: We enrolled women in India, Pakistan, Guatemala, the Democratic Republic of Congo, Kenya and Zambia from 2014 to 2016 and tracked their delivery and newborn outcomes for up to 28 days. Antenatal care and delivery symptoms were collected using a structured questionnaire, clinical observation and/or a physical examination. The Global Network Cause of Death algorithm was used to assign the cause of neonatal death, analysed by country and day of death. RESULTS: One-third (33.1%) of the 3068 neonatal deaths were due to suspected infection, 30.8% to prematurity, 21.2% to asphyxia, 9.5% to congenital anomalies and 5.4% did not have a cause of death assigned. Prematurity and asphyxia-related deaths were more common on the first day of life (46.7% and 52.9%, respectively), while most deaths due to infection occurred after the first day of life (86.9%). The distribution of causes was similar to global data reported by other major studies. CONCLUSION: The Global Network algorithm provided a reliable cause of neonatal death in low-resource settings and can be used to inform public health strategies to reduce mortality.

Self-reported practices among traditional birth attendants surveyed in western Kenya: a descriptive study.

BACKGROUND: The high rate of home deliveries conducted by unskilled birth attendants in resource-limited settings is an important global health issue because it is believed to be a significant contributing factor to maternal and newborn mortality. Given the large number of deliveries that are managed by unskilled or traditional birth attendants outside of health facilities, and the fact that there is on-going discussion regarding the role of traditional birth attendants in the maternal newborn health (MNH) service continuum, we sought to ascertain the practices of traditional birth attendants in our catchment area. The findings of this descriptive study might help inform conversations regarding the roles that traditional birth attendants can play in maternal-newborn health care. METHODS: A structured questionnaire was used in a survey that included one hundred unskilled birth attendants in western Kenya. Descriptive statistics were employed. RESULTS: Inappropriate or outdated practices were reported in relation to some obstetric complications and newborn care. Encouraging results were reported with regard to positive relationships that traditional birth attendants have with their local health facilities. Furthermore, high rates of referral to health facilities was reported for many common obstetric emergencies and similar rates for reporting of pregnancy outcomes to village elders and chiefs. CONCLUSIONS: Potentially harmful or outdated practices with regard to maternal and newborn care among traditional birth attendants in western Kenya were revealed by this study. There were high rates of traditional birth attendant referrals of pregnant mothers with obstetric complications to health facilities. Policy makers may consider re-educating and re-defining the roles and responsibilities of traditional birth attendants in maternal and neonatal health care based on the findings of this survey.

A pre-post study of a multi-country scale up of resuscitation training of facility birth attendants: does Helping Babies Breathe training save lives?

BACKGROUND: Whether facility-based implementation of Helping Babies Breathe (HBB) reduces neonatal mortality at a population level in low and middle income countries (LMIC) has not been studied. Therefore, we evaluated HBB implementation in this context where our study team has ongoing prospective outcome data on all pregnancies regardless of place of delivery. METHODS: We compared outcomes of birth cohorts in three sites in India and Kenya pre-post implementation of a facility-based intervention, using a prospective, population-based registry in 52 geographic clusters. Our hypothesis was that HBB implementation would result in a 20 % decrease in the perinatal mortality rate (PMR) among births ≥1500 g. RESULTS: We enrolled 70,704 births during two 12-month study periods. Births within each site did not differ pre-post intervention, except for an increased proportion of <2500 g newborns and deliveries by caesarean section in the post period. There were no significant differences in PMR among all registry births; however, a post-hoc analysis stratified by birthweight documented improvement in <2500 g mortality in Belgaum in both registry and in HBB-trained facility births. No improvement in <2500 g mortality measures was noted in Nagpur or Kenya and there was no improvement in normal birth weight survival. CONCLUSIONS: Rapid scale up of HBB training of facility birth attendants in three diverse sites in India and Kenya was not associated with consistent improvements in mortality among all neonates ≥1500 g; however, differential improvements in <2500 g survival in Belgaum suggest the need for careful implementation of HBB training with attention to the target population, data collection, and ongoing quality monitoring activities. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov: NCT01681017 .

Helping Babies Breathe (HBB) training: What happens to knowledge and skills over time?

BACKGROUND: The first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities. METHODS: We conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post- initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training. RESULTS: One hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training). CONCLUSIONS: HBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01681017 ; 04 September 2012, retrospectively registered.

Evaluation of an educational program for essential newborn care in resource-limited settings: Essential Care for Every Baby.

BACKGROUND: Essential Care for Every Baby (ECEB) is an evidence-based educational program designed to increase cognitive knowledge and develop skills of health care professionals in essential newborn care in low-resource areas. The course focuses on the immediate care of the newborn after birth and during the first day or until discharge from the health facility. This study assessed the overall design of the course; the ability of facilitators to teach the course; and the knowledge and skills acquired by the learners. METHODS: Testing occurred at 2 global sites. Data from a facilitator evaluation survey, a learner satisfaction survey, a multiple choice question (MCQ) examination, performance on two objective structured clinical evaluations (OSCE), and pre- and post-course confidence assessments were analyzed using descriptive statistics. Pre-post course differences were examined. Comments on the evaluation form and post-course group discussions were analyzed to identify potential program improvements. RESULTS: Using ECEB course material, master trainers taught 12 facilitators in India and 11 in Kenya who subsequently taught 62 providers of newborn care in India and 64 in Kenya. Facilitators and learners were satisfied with their ability to teach and learn from the program. Confidence (3.5 to 5) and MCQ scores (India: pre 19.4, post 24.8; Kenya: pre 20.8, post 25.0) improved (p < 0.001). Most participants demonstrated satisfactory skills on the OSCEs. Qualitative data suggested the course was effective, but also identified areas for course improvement. These included additional time for hands-on practice, including practice in a clinical setting, the addition of video learning aids and the adaptation of content to conform to locally recommended practices. CONCLUSION: ECEB program was highly acceptable, demonstrated improved confidence, improved knowledge and developed skills. ECEB may improve newborn care in low resource settings if it is part of an overall implementation plan that addresses local needs and serves to further strengthen health systems.

Lost to follow-up among pregnant women in a multi-site community based maternal and newborn health registry: a prospective study.

BACKGROUND: It is important when conducting epidemiologic studies to closely monitor lost to follow up (LTFU) rates. A high LTFU rate may lead to incomplete study results which in turn can introduce bias to the trial or study, threatening the validity of the findings. There is scarce information on LTFU in prospective community-based perinatal epidemiological studies. This paper reports the rates of LTFU, describes socio-demographic characteristics, and pregnancy/delivery outcomes of mothers LTFU in a large community-based pregnancy registry study. METHODS: Data were from a prospective, population-based observational study of the Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR). This is a multi-centre, international study in which pregnant women were enrolled in mid-pregnancy, followed through parturition and 42 days post-delivery. Risk for LTFU was calculated within a 95%CI. RESULTS: A total of 282,626 subjects were enrolled in this study, of which 4,893 were lost to follow-up. Overall, there was a 1.7% LTFU to follow up rate. Factors associated with a higher LTFU included mothers who did not know their last menstrual period (RR 2.2, 95% CI 1.1, 4.4), maternal age of < 20 years (RR 1.2, 95% CI 1.1, 1.3), women with no formal education (RR 1.2, 95% CI 1.1, 1.4), and attending a government clinic for antenatal care (RR 2.0, 95% CI 1.4, 2.8). Post-natal factors associated with a higher LTFU rate included a newborn with feeding problems (RR 1.6, 94% CI 1.2, 2.2). CONCLUSIONS: The LTFU rate in this community-based registry was low (1.7%). Maternal age, maternal level of education, pregnancy status at enrollment and using a government facility for ANC are factors associated with being LTFU. Strategies to ensure representation and high retention in community studies are important to informing progress toward public health goals. TRIAL REGISTRATION: Registration at the Clinicaltrials.gov (ID# NCT01073475).

Rates and determinants of early initiation of breastfeeding and exclusive breast feeding at 42 days postnatal in six low and middle-income countries: A prospective cohort study.

BACKGROUND: Early initiation of breastfeeding after birth and exclusive breastfeeding through six months of age confers many health benefits for infants; both are crucial high impact, low-cost interventions. However, determining accurate global rates of these crucial activities has been challenging. We use population-based data to describe: (1) rates of early initiation of breastfeeding (defined as within 1 hour of birth) and of exclusive breastfeeding at 42 days post-partum; and (2) factors associated with failure to initiate early breastfeeding and exclusive breastfeeding at 42 days post-partum. METHODS: Prospectively collected data from women and their live-born infants enrolled in the Global Network's Maternal and Newborn Health Registry between January 1, 2010-December 31, 2013 included women-infant dyads in 106 geographic areas (clusters) at 7 research sites in 6 countries (Kenya, Zambia, India [2 sites], Pakistan, Argentina and Guatemala). Rates and risk factors for failure to initiate early breastfeeding were investigated for the entire cohort and rates and risk factors for failure to maintain exclusive breastfeeding was assessed in a sub-sample studied at 42 days post-partum. RESULT: A total of 255,495 live-born women-infant dyads were included in the study. Rates and determinants for the exclusive breastfeeding sub-study at 42 days post-partum were assessed from among a sub-sample of 105,563 subjects. Although there was heterogeneity by site, and early initiation of breastfeeding after delivery was high, the Pakistan site had the lowest rates of early initiation of breastfeeding. The Pakistan site also had the highest rate of lack of exclusive breastfeeding at 42 days post-partum. Across all regions, factors associated with failure to initiate early breastfeeding included nulliparity, caesarean section, low birth weight, resuscitation with bag and mask, and failure to place baby on the mother's chest after delivery. Factors associated with failure to achieve exclusive breastfeeding at 42 days varied across the sites. The only factor significant in all sites was multiple gestation. CONCLUSIONS: In this large, prospective, population-based, observational study, rates of both early initiation of breastfeeding and exclusive breastfeeding at 42 days post-partum were high, except in Pakistan. Factors associated with these key breastfeeding indicators should assist with more effective strategies to scale-up these crucial public health interventions. TRIAL REGISTRATION: Registration at the Clinicaltrials.gov website (ID# NCT01073475).

A prospective observational description of frequency and timing of antenatal care attendance and coverage of selected interventions from sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia.

BACKGROUND: The Global Network for Women's and Children's Health Research is one of the largest international networks for testing and generating evidence-based recommendations for improvement of maternal-child health in resource-limited settings. Since 2009, Global Network sites in six low and middle-income countries have collected information on antenatal care practices, which are important as indicators of care and have implications for programs to improve maternal and child health. We sought to: (1) describe the quantity of antenatal care attendance over a four-year period; and (2) explore the quality of coverage for selected preventative, screening, and birth preparedness components. METHODS: The Maternal Newborn Health Registry (MNHR) is a prospective, population-based birth and pregnancy outcomes registry in Global Network sites, including: Argentina, Guatemala, India (Belgaum and Nagpur), Kenya, Pakistan, and Zambia. MNHR data from these sites were prospectively collected from January 1, 2010 - December 31, 2013 and analyzed for indicators related to quantity and patterns of ANC and coverage of key elements of recommended focused antenatal care. Descriptive statistics were generated overall by global region (Africa, Asia, and Latin America), and for each individual site. RESULTS: Overall, 96% of women reported at least one antenatal care visit. Indian sites demonstrated the highest percentage of women who initiated antenatal care during the first trimester. Women from the Latin American and Indian sites reported the highest number of at least 4 visits. Overall, 88% of women received tetanus toxoid. Only about half of all women reported having been screened for syphilis (49%) or anemia (50%). Rates of HIV testing were above 95% in the Argentina, African, and Indian sites. The Pakistan site demonstrated relatively high rates for birth preparation, but for most other preventative and screening interventions, posted lower coverage rates as compared to other Global Network sites. CONCLUSIONS: Results from our large, prospective, population-based observational study contribute important insight into regional and site-specific patterns for antenatal care access and coverage. Our findings indicate a quality and coverage gap in antenatal care services, particularly in regards to syphilis and hemoglobin screening. We have identified site-specific gaps in access to, and delivery of, antenatal care services that can be targeted for improvement in future research and implementation efforts. TRIAL REGISTRATION: Registration at Clinicaltrials.gov (ID# NCT01073475).

Feasibility and acceptability of a novel biomedical device to prevent neonatal hypothermia and augment Kangaroo Mother Care in Kenya: Qualitative analysis of focus group discussions and key Informant Interviews.

Hypothermia is a leading newborn complication, especially among premature and/or low birth weight infants. Within low/middle-income countries where incubators and radiant warmers are often in short supply, leading to gaps in the thermal care chain, neonatal hypothermia underlies high rates of newborn morbidity and mortality. Kangaroo Mother Care/Skin-to-skin care is an effective method for prevention of hypothermia in premature and low birthweight babies but can be very burdensome for families and healthcare providers. Our international multidisciplinary team has developed a prototype for a wearable biomedical device ("NeoWarm") to provide continuous thermal care and augment kangaroo mother care practices in low-resource settings. The objective of this study was to assess the feasibility and acceptability of NeoWarm and to obtain user design feedback for an early prototype from among adult end-users in Western Kenya. We performed key informant interviews (n = 17) among healthcare providers and 5 focus group discussions (FGDs) among 3 groups of adult stakeholders of premature babies, including: (1) parents/family members of premature babies aged 6 weeks or less (3 FGDs); (2) healthcare providers of newborns (e.g., nurses; physicians; 1 FGD); (3) community opinion leaders and stakeholders (e.g., traditional birth attendants; pastors; village elders; 1 FGD). Content and thematic analyses of transcripts indicate that NeoWarm is acceptable and feasible in promoting facility-based kangaroo mother care in the Kenyan setting. Novel findings derived from respondents include (1) the ability of the device to potentially overcome several barriers to traditional kangaroo mother care methods and (2) user-driven encouragement to expand the use case of the device to potentially include community-based kangaroo mother care and neonatal transport. User design feedback obtained during the interviews informed several key design iterations for subsequent prototypes of the device.