Neonatal Respiratory Support Utilization in Low- and Middle-Income Countries: A Registry-Based Observational Study.

BACKGROUND: Newborns with hypoxemia often require life-saving respiratory support. In low-resource settings, it is unknown if respiratory support is delivered more frequently to term infants or preterm infants. We hypothesized that in a registry-based birth cohort in 105 geographic areas in seven low- and middle-income countries, more term newborns received respiratory support than preterm newborns. METHODS: This is a hypothesis-driven observational study based on prospectively collected data from the Maternal and Newborn Health Registry of the NICHD Global Network for Women's and Children's Health Research. Eligible infants enrolled in the registry were live-born between 22 and 44 weeks gestation with a birth weight ≥400 g and born from January 1, 2015, to December 31, 2018. Frequency data were obtained to report the number of term and preterm infants who received treatment with oxygen only, CPAP, or mechanical ventilation. Test for trends over time were conducted using robust Poisson regression. RESULTS: 177,728 (86.3%) infants included in this study were term, and 28,249 (13.7%) were preterm. A larger number of term infants (n = 5,108) received respiratory support compared to preterm infants (n = 3,287). Receipt of each mode of respiratory support was more frequent in term infants. The proportion of preterm infants who received respiratory support (11.6%) was higher than the proportion of term infants receiving respiratory support (2.9%, p < 0.001). The rate of provision of respiratory support varied between sites. CONCLUSIONS: Respiratory support was more frequently used in term infants expected to be at low risk for respiratory disorders compared to preterm infants.

Maternal age extremes and adverse pregnancy outcomes in low-resourced settings.

Introduction: Adolescent (<20 years) and advanced maternal age (>35 years) pregnancies carry adverse risks and warrant a critical review in low- and middle-income countries where the burden of adverse pregnancy outcomes is highest. Objective: To describe the prevalence and adverse pregnancy (maternal, perinatal, and neonatal) outcomes associated with extremes of maternal age across six countries. Patients and methods: We performed a historical cohort analysis on prospectively collected data from a population-based cohort study conducted in the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia between 2010 and 2020. We included pregnant women and their neonates. We describe the prevalence and adverse pregnancy outcomes associated with pregnancies in these maternal age groups (<20, 20-24, 25-29, 30-35, and >35 years). Relative risks and 95% confidence intervals of each adverse pregnancy outcome comparing each maternal age group to the reference group of 20-24 years were obtained by fitting a Poisson model adjusting for site, maternal age, parity, multiple gestations, maternal education, antenatal care, and delivery location. Analysis by region was also performed. Results: We analyzed 602,884 deliveries; 13% (78,584) were adolescents, and 5% (28,677) were advanced maternal age (AMA). The overall maternal mortality ratio (MMR) was 147 deaths per 100,000 live births and increased with advancing maternal age: 83 in the adolescent and 298 in the AMA group. The AMA groups had the highest MMR in all regions. Adolescent pregnancy was associated with an adjusted relative risk (aRR) of 1.07 (1.02-1.11) for perinatal mortality and 1.13 (1.06-1.19) for neonatal mortality. In contrast, AMA was associated with an aRR of 2.55 (1.81 to 3.59) for maternal mortality, 1.58 (1.49-1.67) for perinatal mortality, and 1.30 (1.20-1.41) for neonatal mortality, compared to pregnancy in women 20-24 years. This pattern was overall similar in all regions, even in the <18 and 18-19 age groups. Conclusion: The maternal mortality ratio in the LMICs assessed is high and increased with advancing maternal age groups. While less prevalent, AMA was associated with a higher risk of adverse maternal mortality and, like adolescence, was associated with adverse perinatal mortality with little regional variation.

Maternal and perinatal outcomes of women with vaginal birth after cesarean section compared to repeat cesarean birth in select South Asian and Latin American settings of the global network for women's and children's health research.

OBJECTIVE: Our objective was to analyze a prospective population-based registry including five sites in four low- and middle-income countries to observe characteristics associated with vaginal birth after cesarean versus repeat cesarean birth, as well as maternal and newborn outcomes associated with the mode of birth among women with a history of prior cesarean. HYPOTHESIS: Maternal and perinatal outcomes among vaginal birth after cesarean section will be similar to those among recurrent cesarean birth. METHODS: A prospective population-based study, including home and facility births among women enrolled from 2017 to 2020, was performed in communities in Guatemala, India (Belagavi and Nagpur), Pakistan, and Bangladesh. Women were enrolled during pregnancy, and delivery outcome data were collected within 42 days after birth. RESULTS: We analyzed 8267 women with a history of prior cesarean birth; 1389 (16.8%) experienced vaginal birth after cesarean, and 6878 (83.2%) delivered by a repeat cesarean birth. Having a repeat cesarean birth was negatively associated with a need for curettage (ARR 0.12 [0.06, 0.25]) but was positively associated with having a blood transfusion (ARR 3.74 [2.48, 5.63]). Having a repeat cesarean birth was negatively associated with stillbirth (ARR 0.24 [0.15, 0.49]) and, breast-feeding within an hour of birth (ARR 0.39 [0.30, 0.50]), but positively associated with use of antibiotics (ARR 1.51 [1.20, 1.91]). CONCLUSIONS: In select South Asian and Latin American low- and middle-income sites, women with a history of prior cesarean birth were 5 times more likely to deliver by cesarean birth in the hospital setting. Those who delivered vaginally had less complicated pregnancy and labor courses compared to those who delivered by repeat cesarean birth, but they had an increased risk of stillbirth. More large scale studies are needed in Low Income Country settings to give stronger recommendations. TRIAL REGISTRATION: NCT01073475, Registered February 21, 2010, https://clinicaltrials.gov/ct2/show/record/NCT01073475 .

Can the date of last menstrual period be trusted in the first trimester? Comparisons of gestational age measures from a prospective cohort study in six low-income to middle-income countries.

OBJECTIVES: We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries. DESIGN: Prospective cohort study SETTING AND PARTICIPANTS: This study included data from the Global Network's population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based on GA estimated either by LMP or USG and had a live or stillbirth with an estimated GA of 20-42 weeks. OUTCOME MEASURES: GA was estimated in weeks and days based on LMP and/or USG. Prematurity was defined as GA of 20 weeks+0 days through 36 weeks+6 days, calculated by both USG and LMP. RESULTS: Overall, average GA varied ≤1 week between LMP and USG. Mean GA for live births by LMP was lower than by USG (adjusted mean difference (95% CI) = -0.23 (-0.29 to -0.17) weeks). Among stillbirths, a higher GA was estimated by LMP than USG (adjusted mean difference (95% CI)= 0.42 (0.11 to 0.72) weeks). Preterm birth rates for live births were significantly higher when dated by LMP (adjusted rate difference (95% CI)= 4.20 (3.56 to 4.85)). There was no significant difference in preterm birth rates for stillbirths. CONCLUSION: The small differences in GA for LMP versus USG in the Guatemalan and Indian sites suggest that LMP may be a useful alternative to USG for GA dating during the first trimester until availability of USG improves in those areas. Further research is needed to assess LMP for first-trimester GA dating in other regions with limited access to USG. TRIAL REGISTRATION NUMBER: NCT01073475.

Building a predictive model of low birth weight in low- and middle-income countries: a prospective cohort study.

BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants. METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine. RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) and approximately 20% (in each Asian site). Of the five models tested, the logistic regression model performed best with an area under the curve of 0.72, an accuracy of 61% and a recall of 72%. All of the top performing models identified clinical site, maternal weight, hypertensive disorders, severe antepartum hemorrhage and antenatal care as key variables in predicting LBW. CONCLUSIONS: Predictive modeling can identify women at high risk for delivering a LBW infant with good sensitivity using clinical variables available prior to delivery in LMICs. Such modeling is the first step in the development of a clinical decision support tool to assist providers in decision-making regarding referral of these women prior to delivery. Consistent referral of women at high-risk for delivering a LBW infant could have extensive public health consequences in LMICs by directing limited resources for advanced neonatal care to the infants at highest risk.

The impact of risk factors on aspirin's efficacy for the prevention of preterm birth.

BACKGROUND: The Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial was a landmark study that demonstrated a reduction in preterm birth and hypertensive disorders of pregnancy in nulliparous women who received low-dose aspirin. All women in the study had at least 1 moderate-risk factor for preeclampsia (nulliparity). Unlike current US Preventative Service Task Force guidelines, which recommend low-dose aspirin for ≥2 moderate-risk factors, women in this study were randomized to receive low-dose aspirin regardless of the presence or absence of an additional risk factor. OBJECTIVE: This study aimed to compare how low-dose aspirin differentially benefits nulliparous women with and without additional preeclampsia risk factors for the prevention of preterm birth and hypertensive disorders of pregnancy. STUDY DESIGN: This was a non-prespecified secondary analysis of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial that randomized nulliparous women with singleton pregnancies from 6 low-middle-income countries to receive low-dose aspirin or placebo. Our primary exposure was having an additional preeclampsia risk factor beyond nulliparity. Our primary outcome was preterm birth before 37 weeks of gestation, and our secondary outcomes included preterm birth before 34 weeks of gestation, preterm birth before 28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality. RESULTS: Among 11,558 nulliparous women who met the inclusion criteria, 66.8% had no additional risk factors. Low-dose aspirin similarly reduced the risk of preterm birth at <37 weeks of gestation in women with and without additional risk factors (relative risk: 0.75 vs 0.85; P=.35). Additionally for our secondary outcomes, low-dose aspirin similarly reduced the risk of preterm birth at <28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality in women with and without additional risk factors. The reduction of preterm birth at <34 weeks of gestation with low-dose aspirin was significantly greater in women without additional risk factors than those with an additional risk factor (relative risk: 0.69 vs 1.04; P=.04). CONCLUSION: Low-dose aspirin's ability to prevent preterm birth, hypertensive disorders of pregnancy, and perinatal mortality was similar in nulliparous women with and without additional risk factors. Professional societies should consider recommending low-dose aspirin to all nulliparous women.

Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial.

INTRODUCTION: Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised clinical trial conducted in a single site in The Gambia showed that treatment with an oral dose of 2 g azithromycin versus placebo for all women in labour reduced certain maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. In a large, multinational randomised trial, we will evaluate the impact of azithromycin given in labour to improve maternal and newborn outcomes. METHODS AND ANALYSIS: This randomised, placebo-controlled, multicentre clinical trial includes two primary hypotheses, one maternal and one neonatal. The maternal hypothesis is to test whether a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labour will reduce maternal death or sepsis. The neonatal hypothesis will test whether this intervention will reduce intrapartum/neonatal death or sepsis. The intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, compared with a single intrapartum oral dose of an identical appearing placebo. A total of 34 000 labouring women from 8 research sites in sub-Saharan Africa, South Asia and Latin America will be randomised with a one-to-one ratio to intervention/placebo. In addition, we will assess antimicrobial resistance in a sample of women and their newborns. ETHICS AND DISSEMINATION: The study protocol has been reviewed and ethics approval obtained from all the relevant ethical review boards at each research site. The results will be disseminated via peer-reviewed journals and national and international scientific forums. TRIAL REGISTRATION NUMBER: NCT03871491 (https://clinicaltrials.gov/ct2/show/NCT03871491?term=NCT03871491&draw=2&rank=1).

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.

Associations between ambient temperature and pregnancy outcomes from three south Asian sites of the Global Network Maternal Newborn Health Registry: A retrospective cohort study.

OBJECTIVE: Growing evidence suggests that environmental heat stress negatively influences fetal growth and pregnancy outcomes. However, few studies have examined the impact of heat stress on pregnancy outcomes in low-resource settings. We combined data from a large multi-country maternal-child health registry and meteorological data to assess the impacts of heat stress. DESIGN: Retrospective cohort study. SETTING: Three sites based in south Asia as part of the Global Network for Women's and Children's Health research in India (Belagavi and Nagpur) and Pakistan (Thatta). POPULATION OR SAMPLE: Data from women enrolled between 2014 and 2020 in the Global Network's Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnancies, were used. METHODS: A total of 126 273 pregnant women were included in this analysis. Daily maximal air temperatures (Tmax ) were acquired from local meteorological records. Associations between averages of daily maximal temperatures for each trimester and main outcomes were analysed using a modified Poisson regression approach. MAIN OUTCOMES MEASURES: Incidence of stillbirth, preterm birth, low birthweight (<2500 g) or evidence of pregnancy hypertension or pre-eclampsia. RESULTS: In the overall cohort, risk of preterm birth was positively associated with greater temperature in the second trimester (relative risk [RR] 1.05, 95% CI 1.02-1.07, p = 0.0002). Among individual sites, the risk of preterm birth was greatest in Nagpur (RR 1.07, 95% CI 1.03-1.11, p = 0.0005) and associated with second-trimester temperature. The overall risk of low birthweight was associated with ambient temperature in second trimester (RR 1.02, 95% CI 1.01-1.04, p = 0.01). The risk for LBW was associated with first-trimester heat in Thatta and with second-trimester heat in Nagpur. Finally, the overall risk of gestational hypertensive disease was associated with greater temperature in the third trimester among all sites (RR 1.07, 95% CI 1.02-1.12, p = 0.005) and was particularly significant for Nagpur (RR 1.13, 95% CI 1.05-1.23, p = 0.002). These findings highlight the increased risk of detrimental obstetric and neonatal outcomes with greater temperature. CONCLUSION: In a multi-country, community-based study, greater risk of adverse outcomes was observed with increasing temperature. The study highlights the need for deeper understanding of covarying factors and intervention strategies, especially in regions where high temperatures are common.

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.

The effect of activity and face masks on exhaled particles in children.

Importance: Despite the high burden of respiratory infections among children, the production of exhaled particles during common activities and the efficacy of face masks in children have not been sufficiently studied. Objective: To determine the effect of type of activity and mask usage on exhaled particle production in children. Methods: Healthy children were asked to perform activities that ranged in intensity (breathing quietly, speaking, singing, coughing, and sneezing) while wearing no mask, a cloth mask, or a surgical mask. The concentration and size of exhaled particles were assessed during each activity. Results: Twenty-three children were enrolled in the study. Average exhaled particle concentration increased by intensity of activity, with the lowest particle concentration during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]) and highest particle concentration during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High-intensity activities were associated with an increase primarily in the respirable size (≤ 5 µm) particle fraction. Surgical and cloth masks were associated with lower average particle concentration compared to no mask (P = 0.026 for sneezing). Surgical masks outperformed cloth masks across all activities, especially within the respirable size fraction. In a multivariable linear regression model, we observed significant effect modification of activity by age and by mask type. Interpretation: Similar to adults, children produce exhaled particles that vary in size and concentration across a range of activities. Production of respirable size fraction particles (≤ 5 µm), the dominant mode of transmission of many respiratory viruses, increases significantly with coughing and sneezing and is most effectively reduced by wearing surgical face masks.

In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Cost-effectiveness of low-dose aspirin for the prevention of preterm birth: a prospective study of the Global Network for Women's and Children's Health Research.

BACKGROUND: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. METHODS: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. FINDINGS: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth, $471 per averted perinatal death, and $15·95 per disability-adjusted life year. INTERPRETATION: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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.).

Examining maternal morbidity across a spectrum of delivery locations: An analysis of the Global Network's Maternal and Neonatal Health Registry.

OBJECTIVE: To better understand maternal morbidity, using quality data from low- and middle-income countries (LMICs), including out-of-hospital deliveries. Additionally, to compare to the WHO estimate that maternal morbidity occurs in 15% of pregnancies, which is based largely on hospital-level data. METHODS: The Global Network for Women's and Children's Health Research Maternal Newborn Health Registry collected data on all pregnancies from seven sites in six LMICs between 2015 and 2020. Rates of maternal mortality and morbidity and the differences in morbidity across delivery location and birth attendant type were evaluated. RESULTS: Among the 280 584 deliveries included in the present analysis, the overall maternal mortality ratio was 138 per 100 000, while 11.7% of women experienced at least one morbidity. Rates of morbidity were generally higher for deliveries occurring within hospitals (19.8%) and by physicians (23.6%). The lowest rates of morbidity were noted among women delivering in non-hospital healthcare facilities (5.6%) or with non-physician clinicians (e.g. nurses, midwives [5.4%]). CONCLUSION: The present study shows important differences in reported maternal morbidity across delivery sites, with a trend towards lower morbidity in non-hospital healthcare facilities and among non-physician clinicians.

COVID-19 antibody positivity over time and pregnancy outcomes in seven low-and-middle-income countries: A prospective, observational study of the Global Network for Women's and Children's Health Research.

OBJECTIVES: To determine COVID-19 antibody positivity rates over time and relationships to pregnancy outcomes in low- and middle-income countries (LMICs). DESIGN: With COVID-19 antibody positivity at delivery as the exposure, we performed a prospective, observational cohort study in seven LMICs during the early COVID-19 pandemic. 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 (two sites), and Guatemala. POPULATION: Pregnant women enrolled in an ongoing pregnancy registry at study sites. METHODS: From October 2020 to October 2021, standardised COVID-19 antibody testing was performed at delivery among women enrolled in MNHR. Trained staff masked to COVID-19 status obtained pregnancy outcomes, which were then compared with COVID-19 antibody results. MAIN OUTCOME MEASURES: Antibody status, stillbirth, neonatal mortality, maternal mortality and morbidity. RESULTS: At delivery, 26.0% of women were COVID-19 antibody positive. Positivity increased over the four time periods across all sites: 13.8%, 15.4%, 21.0% and 40.9%. In the final period, positivity rates were: DRC 27.0%, Kenya 33.1%, Pakistan 32.8%, Guatemala 37.0%, Zambia 37.8%, Bangladesh 47.2%, Nagpur, India 57.4% and Belagavi, India 62.4%. Adjusting for site and maternal characteristics, stillbirth, neonatal mortality, low birthweight and preterm birth were not significantly associated with COVID-19. The adjusted relative risk (aRR) for stillbirth was 1.27 (95% CI 0.95-1.69). Postpartum haemorrhage was associated with antibody positivity (aRR 1.44; 95% CI 1.01-2.07). CONCLUSIONS: In pregnant populations in LMICs, COVID-19 antibody positivity has increased. However, most adverse pregnancy outcomes were not significantly associated with antibody positivity.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.