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

Maternal mortality in six low and lower-middle income countries from 2010 to 2018: risk factors and trends

Background Maternal mortality is a public health problem that disproportionately affects low and lower-middle income countries (LMICs). Appropriate data sources are lacking to effectively track maternal mortality and monitor changes in this health indicator over time. Methods We analyzed data from women enrolled in the NICHD Global Network for Women’s and Children’s Health Research Maternal Newborn Health Registry (MNHR) from 2010 through 2018. Women delivering within research sites in the Democratic Republic of Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia are included. We evaluated maternal and delivery characteristics using log-binomial models and multivariable models to obtain relative risk estimates for mortality. We used running averages to track maternal mortality ratio (MMR, maternal deaths per 100,000 live births) over time. Results We evaluated 571,321 pregnancies and 842 maternal deaths. We observed an MMR of 157 / 100,000 live births (95% CI 147, 167) across all sites, with a range of MMRs from 97 (76, 118) in the Guatemala site to 327 (293, 361) in the Pakistan site. When adjusted for maternal risk factors, risks of maternal mortality were higher with maternal age > 35 (RR 1.43 (1.06, 1.92)), no maternal education (RR 3.40 (2.08, 5.55)), lower education (RR 2.46 (1.54, 3.94)), nulliparity (RR 1.24 (1.01, 1.52)) and parity > 2 (RR 1.48 (1.15, 1.89)). Increased risk of maternal mortality was also associated with occurrence of obstructed labor (RR 1.58 (1.14, 2.19)), severe antepartum hemorrhage (RR 2.59 (1.83, 3.66)) and hypertensive disorders (RR 6.87 (5.05, 9.34)). Before and after adjusting for other characteristics, physician attendance at delivery, delivery in hospital and Caesarean delivery were associated with increased risk. We observed variable changes over time in the MMR within sites. Conclusions The MNHR is a useful tool for tracking MMRs in these LMICs. We identified maternal and delivery characteristics associated with increased risk of death, some might be confounded by indication. Despite declines in MMR in some sites, all sites had an MMR higher than the Sustainable Development Goals target of below 70 per 100,000 live births by 2030. Trial registration The MNHR is registered at NCT01073475

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\u27s 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

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\u27s and Children\u27s 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 mil

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\u27s and children\u27s 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\u27s and Children\u27s Health\u27s 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 positivit

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\u27s and Children\u27s Health\u27s 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