Search

Background Adequate gestational weight gain (GWG) is essential for healthy fetal growth. However, in low- and middle-income countries, where malnutrition is prevalent, little information is available about GWG and how it might be modified by nutritional status and interventions. Objective We describe GWG and its associations with fetal growth and birth outcomes. We also examined the extent to which prepregnancy BMI, and preconception and early weight gain modify GWG, and its effects on fetal growth. Methods This was a secondary analysis of the Women First Trial, including 2331 women within the Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan, evaluating weight gain from enrollment to ∼12 weeks of gestation and GWG velocity (kg/wk) between ∼12 and 32 weeks of gestation. Adequacy of GWG velocity was compared with 2009 Institute of Medicine recommendations, according to maternal BMI. Early weight gain (EWG), GWG velocity, and adequacy of GWG were related to birth outcomes using linear and Poisson models. Results GWG velocity (mean ± SD) varied by site: 0.22 ± 0.15 kg/wk in DRC, 0.30 ± 0.23 in Pakistan, 0.31 ± 0.14 in Guatemala, and 0.39 ± 0.13 in India, (P

Background Preconceptional maternal small-quantity lipid-based nutrient supplementation (SQLNS) improved intrauterine linear growth in low-resource countries as demonstrated by the Women First Preconception Maternal Nutrition Trial (WF). Fetal growth is dependent on nutrient availability and regulated by insulin-like growth factor 1 (IGF-1) through changes in placental transfer capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway. Objectives Our objective was to evaluate the role of placental mTOR and IGF-1 signaling on fetal growth in women from 2 low-resource countries with high rates of stunting after they received preconceptional SQLNS. Methods We studied 48 women from preconception through delivery who were from Guatemala and Pakistan and received SQLNS or not, as part of the WF study. Placental samples were obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA expression of eukaryotic translation initiation factor binding protein-1 (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase α (AMPKA), IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were determined. Maternal serum IGF-1, insulin-like growth factor binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured. Results Mean ± SEM maternal prepregnancy BMI differed between participants in Guatemala (26.5 ± 1.3) and Pakistan (19.8 ± 0.7) (P

Background Few studies have shown how the move toward institutional delivery in low and middle-income countries (LMIC) impacts stillbirth and newborn mortality. Objectives The study evaluated trends in institutional delivery in research sites in Belagavi and Nagpur India, Guatemala, Kenya, Pakistan, and Zambia from 2010 to 2018 and compared them to changes in the rates of neonatal mortality and stillbirth. Methods We analyzed data from a nine-year interval captured in the Global Network (GN) Maternal Newborn Health Registry (MNHR). Mortality rates were estimated from generalized estimating equations controlling for within-cluster correlation. Cluster-level analyses were performed to assess the association between institutional delivery and mortality rates. Results From 2010 to 2018, a total of 413,377 deliveries in 80 clusters across 6 sites in 5 countries were included in these analyses. An increase in the proportion of institutional deliveries occurred in all sites, with a range in 2018 from 57.7 to 99.8%. In 2010, the stillbirth rates ranged from 19.3 per 1000 births in the Kenyan site to 46.2 per 1000 births in the Pakistani site and by 2018, ranged from 9.7 per 1000 births in the Belagavi, India site to 40.8 per 1000 births in the Pakistani site. The 2010 neonatal mortality rates ranged from 19.0 per 1000 live births in the Kenyan site to 51.3 per 1000 live births in the Pakistani site with the 2018 neonatal mortality rates ranging from 9.2 per 1000 live births in the Zambian site to 50.2 per 1000 live births in the Pakistani site. In multivariate modeling, in some but not all sites, the reductions in stillbirth and neonatal death were significantly associated with an increase in the institutional deliveries. Conclusions There was an increase in institutional delivery rates in all sites and a reduction in stillbirth and neonatal mortality rates in some of the GN sites over the past decade. The relationship between institutional delivery and a decrease in mortality was significant in some but not all sites. However, the stillbirth and neonatal mortality rates remain at high levels. Understanding the relationship between institutional delivery and stillbirth and neonatal deaths in resource-limited environments will enable development of targeted interventions for reducing the mortality burden. Trial registration The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475.

Background Preterm birth continues to be a major public health problem contributing to 75% of the neonatal mortality worldwide. Low birth weight (LBW) is an important but imperfect surrogate for prematurity when accurate assessment of gestational age is not possible. While there is overlap between preterm birth and LBW newborns, those that are both premature and LBW are at the highest risk of adverse neonatal outcomes. Understanding the epidemiology of preterm birth and LBW is important for prevention and improved care for at risk newborns, but in many countries, data are sparse and incomplete. Methods We conducted data analyses using the Global Network’s (GN) population-based registry of pregnant women and their babies in rural communities in six low- and middle-income countries (Democratic Republic of Congo, Kenya, Zambia, Guatemala, India and Pakistan). We analyzed data from January 2014 to December 2018. Trained study staff enrolled all pregnant women in the study catchment area as early as possible during pregnancy and conducted follow-up visits shortly after delivery and at 42 days after delivery. We analyzed the rates of preterm birth, LBW and the combination of preterm birth and LBW and studied risk factors associated with these outcomes across the GN sites. Results A total of 272,192 live births were included in the analysis. The overall preterm birth rate was 12.6% (ranging from 8.6% in Belagavi, India to 21.8% in the Pakistani site). The overall LBW rate was 13.6% (ranging from 2.7% in the Kenyan site to 21.4% in the Pakistani site). The overall rate of both preterm birth and LBW was 5.5% (ranging from 1.2% in the Kenyan site to 11.0% in the Pakistani site). Risk factors associated with preterm birth, LBW and the combination were similar across sites and included nulliparity [RR − 1.27 (95% CI 1.21–1.33)], maternal age under 20 [RR 1.41 (95% CI 1.32–1.49)] years, severe antenatal hemorrhage [RR 5.18 95% CI 4.44–6.04)], hypertensive disorders [RR 2.74 (95% CI − 1.21–1.33], and 1–3 antenatal visits versus four or more [RR 1.68 (95% CI 1.55–1.83)]. Conclusions Preterm birth, LBW and their combination continue to be common public health problems at some of the GN sites, particularly among young, nulliparous women who have received limited antenatal care services. Trial registration The identifier of the Maternal and Newborn Health Registry at ClinicalTrials.gov is NCT01073475.Trial registration: The identifier of the Maternal and Newborn Health Registry at ClinicalTrials.gov is NCT01073475.

Background Pakistan has among the poorest pregnancy outcomes worldwide, significantly worse than many other low-resource countries. The reasons for these differences are not clear. In this study, we compared pregnancy outcomes in Pakistan to other low-resource countries and explored factors that might help explain these differences. Methods The Global Network (GN) Maternal Newborn Health Registry (MNHR) is a prospective, population-based observational study that includes all pregnant women and their pregnancy outcomes in defined geographic communities in six low-middle income countries (India, Pakistan, Democratic Republic of Congo, Guatemala, Kenya, Zambia). Study staff enroll women in early pregnancy and follow-up soon after delivery and at 42 days to ascertain delivery, neonatal, and maternal outcomes. We analyzed the maternal mortality ratios (MMR), neonatal mortality rates (NMR), stillbirth rates, and potential explanatory factors from 2010 to 2018 across the GN sites. Results From 2010 to 2018, there were 91,076 births in Pakistan and 456,276 births in the other GN sites combined. The MMR in Pakistan was 319 per 100,000 live births compared to an average of 124 in the other sites, while the Pakistan NMR was 49.4 per 1,000 live births compared to 20.4 in the other sites. The stillbirth rate in Pakistan was 53.5 per 1000 births compared to 23.2 for the other sites. Preterm birth and low birthweight rates were also substantially higher than the other sites combined. Within weight ranges, the Pakistani site generally had significantly higher rates of stillbirth and neonatal mortality than the other sites combined, with differences increasing as birthweights increased. By nearly every measure, medical care for pregnant women and their newborns in the Pakistan sites was worse than at the other sites combined. Conclusion The Pakistani pregnancy outcomes are much worse than those in the other GN sites. Reasons for these poorer outcomes likely include that the Pakistani sites' reproductive-aged women are largely poorly educated, undernourished, anemic, and deliver a high percentage of preterm and low-birthweight babies in settings of often inadequate maternal and newborn care. By addressing the issues highlighted in this paper there appears to be substantial room for improvements in Pakistan’s pregnancy outcomes.

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).

Background While trends in caesarean birth by maternal request in low- and middle-income countries are unclear, age, education, multiple gestation and hypertensive disease appear associated with the indication when compared with caesarean birth performed for medical indications. Methods We performed a secondary analysis of a prospectively collected population-based study of home and facility births using descriptive statistics, bivariate comparisons and multilevel mixed-effects logistic regression. Results Of 28 751 patients who underwent caesarean birth and had a documented primary indication for the surgery, 655 (2%) were attributed to caesarean birth by maternal request. The remaining 98% were attributed to maternal and foetal indications and prior caesarean birth. In a multilevel mixed effects logistic regression adjusted for site and cluster of birth, when compared with caesareans performed for medical indications, caesarean birth performed for maternal request had a higher odds of being performed among women ≥35 y of age, with a university or higher level of education, with multiple gestations and with pregnancies complicated by hypertension (P < 0.01). Caesarean birth by maternal request was associated with a two-times increased odds of breastfeeding within 1 h of delivery, but no adverse outcomes (when compared with women who underwent caesarean birth for medical indications; P < 0.01). Conclusion Caesarean performed by maternal request is more common in older and more educated women and those with multifoetal gestation or hypertensive disease. It is also associated with higher rates of breastfeeding within 1 h of delivery.

Background The World Health Organization (WHO-2007) and the International Obesity Task Force (IOTF-Cole) systems assess child weight status. However, derived estimations often differ. We aimed to a) compare the prevalence of overweight and obesity, b) analyze individual and contextual factors associated with child weight using multilevel analysis and c) explore the spatial distribution of overweight and obesity using both classification systems. Methods We used data from the 2015/2016 National School Height and Weight Census in El Salvador. Information on 111,991 children aged 6.0–9.9 years attending the first grade was analyzed. Body mass index Z-score (BMIZ), overweight and obesity were defined with both classification systems. Weighted kappa was used to measure agreement. Child, school and municipal potential determinants of BMIZ were examined by multilevel analysis. Municipal spatial clustering of overweight and obesity was tested using Moran’s Index and Getis-ord Gi* statistics. Results The combined prevalence of overweight and obesity was higher according to the WHO system than the IOTF (30.4% vs 23.1%). The weighted kappa was 0.83. Boys, children attending urban schools, children attending private schools, and children residing in municipalities with high human development index had higher BMIZ than their counterparts. The Moran’s indexes were positives and significant. Clusters of high prevalence (above the national prevalence) of overweight and obesity were found in 29 municipalities using the WHO and IOTF systems. For obesity, 28 and 23 municipalities in clusters of high prevalence were detected using the WHO and IOTF criteria, respectively. Conclusions Overweight and obesity is high among school-age children in El Salvador. The prevalence of overweight and obesity was higher when using the WHO system, as compared to the IOTF system. Irrespective of the classification system, the multilevel and spatial analysis derived similar interpretations. These results support the need for national preventive interventions with targeting strategies to reduce overweight and obesity in school-age children.

To assess, on a population basis, the medical care for pregnant women in specific geographic regions of six countries before and during the first year of the coronavirus disease 2019 (COVID-19) pandemic in relationship to pregnancy outcomes.Prospective, population-based study.Communities in Kenya, Zambia, the Democratic Republic of the Congo, Pakistan, India and Guatemala.Pregnant women enrolled in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry.Pregnancy/delivery care services and pregnancy outcomes in the pre-COVID-19 time-period (March 2019-February 2020) were compared with the COVID-19 time-period (March 2020-February 2021).Stillbirth, neonatal mortality, preterm birth, low birthweight and maternal mortality.Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID-19 and COVID-19 periods (18.9% versus 20.3%, adjusted relative risk [aRR] 1.12, 95% CI 1.05-1.19). A small but significant decrease in the mean number of antenatal care visits (from 4.1 to 4.0, p = 0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight infants in the COVID-19 period occurred (15.7% versus 14.6%, aRR 0.94, 95% CI 0.89-0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites.Small but significant increases in home births and decreases in the antenatal care services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birthweight, or preterm birth rates during the COVID-19 period compared with the previous year. Further research should help to elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period.

Background The objective of this analysis was to observe whether maternal and perinatal/neonatal outcomes of birth vary by timing of repeat cesarean among women with a history of one prior cesarean birth in a Guatemalan cohort. Methods This secondary analysis was conducted using data from a prospective study conducted in communities in Chimaltenango, Guatemala through the Global Network for Women’s and Children’s Health Research. Results Between January 2017 and April 2020, 26,465 women delivered; 3,143 (11.9%) of those women had a singleton gestation and a history of prior cesarean delivery. 2,210 (79.9%) women with a history of prior cesarean birth had data available on mode of delivery and gave birth by repeat cesarean; 1312 (59.4%) were pre-labor cesareans while 896 (40.5%) were intrapartum cesarean births. Risk factors associated with an increased risk of intrapartum cesarean birth included hospital delivery as compared to “other” location (ARR 1.6 [1.2,2.1]) and dysfunctional labor (ARR 1.6 [1.4,1.9]). Variables associated with a reduced risk of intrapartum cesarean birth were hypertensive disease (ARR 0.7 [0.6,0.9]), schooling (ARR 0.9 [0.8,0.9]), and increasing age, which was associated with a very slight reduction in the outcome (ARR 0.99 [0.98,0.99]). Maternal and neonatal outcomes did not vary by type of cesarean birth. Conclusion Outcomes of cesarean birth do not seem to vary by timing of repeat cesarean birth, with hypertensive disease increasing the likelihood of pre-labor cesarean. This information might be useful in counseling women that outcomes after failed trial of labor do not appear worse than those after pre-labor cesarean birth.

Recent World Health Organization (WHO) antenatal care recommendations include an ultrasound scan as a part of routine antenatal care. The First Look Study, referenced in the WHO recommendation, subsequently shows that the routine use of ultrasound during antenatal care in rural, low-income settings did not improve maternal, fetal or neonatal mortality, nor did it increase women's use of antenatal care or the rate of hospital births. This article reviews the First Look Study, reconsidering the assumptions upon which it was built in light of these results, a supplemental descriptive study of interviews with patients and sonographers that participated in the First Look study intervention, and a review of the literature. Two themes surface from this review. The first is that focused emphasis on building the pregnancy risk screening skills of rural primary health care personnel may not lead to adaptations in referral hospital processes that could benefit the patient accordingly. The second is that agency to improve the quality of patient reception at referral hospitals may need to be manufactured for obstetric ultrasound screening, or remote pregnancy risk screening more generally, to have the desired impact. Stemming from the literature, this article goes on to examine the potential for complementarity between obstetric ultrasound screening and another approach encouraged by the WHO, the maternity waiting home. Each approach may address existing shortcomings in how the other is currently understood. This paper concludes by proposing a path toward developing and testing such a hybrid approach.

Background Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. Methods We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. Results Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25–65 USD). Conclusions Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). Trial registration Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov).

Objectives Our objectives were to analyze how pregnancy outcomes varied by cesarean birth as compared to vaginal birth across varying interpregnancy intervals (IPI) and determine if IPI modified mode of birth. Methods This secondary analysis used data from a prospective registry of home and hospital births in Chimaltenango, Guatemala from January 2017 through April 2020, through the Global Network for Women’s and Children’s Health Research. Bivariate comparisons and multivariable logistic regression were used to answer our study question, and the data was analyzed with STATA software v.15.1. Results Of 26,465 Guatemalan women enrolled in the registry, 2794 (10.6%) had a history of prior cesarean. 560 (20.1%) women delivered by vaginal birth after cesarean with the remaining 2,233 (79.9%) delivered by repeat cesarean. Repeat cesarean reduced the risk of needing a dilation and curettage compared to vaginal birth after cesarean, but this association did not vary by IPI, all p-values > p = 0.05. Repeat cesarean delivery, as compared to vaginal birth after cesarean, significantly reduced the likelihood a woman breastfeeding within one hour of birth (AOR ranged from 0.009 to 0.10), but IPI was not associated with the outcome. Regarding stillbirth, repeat cesarean birth reduced the likelihood of stillbirth as compared to vaginal birth (AOR 0.2), but again IPI was not associated with the outcome. Conclusion Outcomes by mode of delivery among a Guatemalan cohort of women with a history of prior cesarean birth do not vary by IPI., Plain English Summary During a qualitative study where providers at one public hospital in Guatemala were interviewed about their beliefs, attitudes, and general practices regarding mode of delivery among women with a history of prior cesarean birth, providers reported that women with a short interval pregnancy (less than 18 or 24 months depending on provider interviewed) were not candidates for trial of labor after cesarean in their facility due to risk of adverse outcomes. We wished to test the hypothesis that adverse pregnancy outcomes are no more likely with an interval of shorter than 18 or 24 months compared to a longer interval, regardless of whether a woman delivers by vaginal or cesarean birth. This analysis suggests that outcomes can be worse for infants with vaginal birth after cesarean as compared to elective repeat cesarean birth, but these outcomes do not vary by interpregnancy interval. Therefore, our hypothesis was correct, and we look forward to disseminating this information to providers in the region in effort to improve evidence-based obstetric care.

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.

Background Socioeconomic status (SES) is an important determinant of health globally and an important explanatory variable to assess causality in epidemiological research. The 10th Sustainable Development Goal is to reduce disparities in SES that impact health outcomes globally. It is easier to study SES in high-income countries because household income is representative of the SES. However, it is well recognized that income is poorly reported in low- and middle- income countries (LMIC) and is an unreliable indicator of SES. Therefore, there is a need for a robust index that will help to discriminate the SES of rural households in a pooled dataset from LMIC. Methods The study was nested in the population-based Maternal and Neonatal Health Registry of the Global Network for Women’s and Children’s Health Research which has 7 rural sites in 6 Asian, sub-Saharan African and Central American countries. Pregnant women enrolling in the Registry were asked questions about items such as housing conditions and household assets. The characteristics of the candidate items were evaluated using confirmatory factor analyses and item response theory analyses. Based on the results of these analyses, a final set of items were selected for the SES index. Results Using data from 49,536 households of pregnant women, we reduced the data collected to a 10-item index. The 10 items were feasible to administer, covered the SES continuum and had good internal reliability and validity. We developed a sum score-based Item Response Theory scoring algorithm which is easy to compute and is highly correlated with scores based on response patterns (r = 0.97), suggesting minimal loss of information with the simplified approach. Scores varied significantly by site (p Conclusions While measuring SES in LMIC is challenging, we have developed a Global Network Socioeconomic Status Index which may be useful for comparisons of SES within and between locations. Next steps include understanding how the index is associated with maternal, perinatal and neonatal mortality. Trial Registration NCT01073475 Plain English summary Socioeconomic status (SES) is an important determinant of health globally, and improving SES is important to reduce disparities in health outcomes. It is easier to study SES in high-income countries because it can be measured by income and what income is spent on, but this concept does not translate easily to low and middle income countries. We developed a questionnaire that includes 10 items to determine SES in low-resource settings that was added to an ongoing Maternal and Neonatal Health Registry that is funded by the National Institutes of Child Health and Human Development’s Global Network. The Registry includes sites that collect outcomes of pregnancies in women and their babies in rural areas in 6 countries in South Asia, sub-Saharan Africa and Central America. The Registry is population based and tracks women from early in pregnancy to day 42 post-partum. The questionnaire is easy to administer and has good reliability and validity. Next steps include understanding how the index is associated with maternal, fetal and neonatal mortality.

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.

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 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.

Background Quality assurance (QA) is a process that should be an integral part of research to protect the rights and safety of study participants and to reduce the likelihood that the results are affected by bias in data collection. Most QA plans include processes related to study preparation and regulatory compliance, data collection, data analysis and publication of study results. However, little detailed information is available on the specific procedures associated with QA processes to ensure high-quality data in multi-site studies. Methods The Global Network for Women’s and Children’s Health Maternal Newborn Health Registy (MNHR) is a prospective population-based registry of pregnancies and deliveries that is carried out in 8 international sites. Since its inception, QA procedures have been utilized to ensure the quality of the data. More recently, a training and certification process was developed to ensure that standardized, scientifically accurate clinical definitions are used consistently across sites. Staff complete a web-based training module that reviews the MNHR study protocol, study forms and clinical definitions developed by MNHR investigators and are certified through a multiple choice examination prior to initiating study activities and every six months thereafter. A standardized procedure for supervision and evaluation of field staff is carried out to ensure that research activites are conducted according to the protocol across all the MNHR sites. Conclusions We developed standardized QA processes for training, certification and supervision of the MNHR, a multisite research registry. It is expected that these activities, together with ongoing QA processes, will help to further optimize data quality for this protocol.

Background Babies born weighing ≥ 2500 g account for more than 80% of the births in most resource-limited locations and for nearly 50% of the 28-day neonatal deaths. In contrast, in high-resource settings, 28-day neonatal mortality among this group represents only a small fraction of the neonatal deaths. Yet mortality risks for birth weight of ≥ 2500 g is limited. Knowledge regarding the factors associated with mortality in these babies will help in identifying interventions that can reduce mortality. Methods The Global Network’s Maternal Newborn Health Registry (MNHR) is a prospective, population-based observational study that includes all pregnant women and their pregnancy outcomes in defined geographic communities that has been conducted in research sites in six low-middle income countries (India, Pakistan, Democratic Republic of Congo, Guatemala, Kenya and Zambia). Study staff enroll all pregnant women as early as possible during pregnancy and conduct follow-up visits to ascertain delivery and 28-day neonatal outcomes. We analyzed the neonatal mortality rates (NMR) and risk factors for deaths by 28 days among all live-born babies with a birthweight ≥ 2500 g from 2010 to 2018 across the Global Network sites. Results Babies born in the Global Network sites from 2010 to 2018 with a birthweight ≥ 2500 g accounted for 84.8% of the births and 45.4% of the 28-day neonatal deaths. Among this group, the overall NMR was 13.1/1000 live births. The overall 28-day NMR for ongoing clusters was highest in Pakistan (29.7/1000 live births) and lowest in the Zambian/Kenyan sites (9.3/1000) for ≥ 2500 g infants. ≥ 2500 g NMRs declined for Zambia/Kenya and India. For Pakistan and Guatemala, the NMR remained almost unchanged over the period. The ≥ 2500 g risks related to maternal, delivery and newborn characteristics varied by site. Maternal factors that increased risk and were common for all sites included nulliparity, hypertensive disease, previous stillbirth, maternal death, obstructed labor, severe postpartum hemorrhage, and abnormal fetal presentation. Neonatal characteristics including resuscitation, hospitalization, congenital anomalies and male sex, as well as lower gestational ages and birthweights were also associated with increased mortality. Conclusions Nearly half of neonatal deaths in the Global Network sites occurred in infants born weighing ≥ 2500 g. The NMR for those infants was 13.1 per 1000 live births, much higher than rates usually seen in high-income countries. The changes in NMR over time varied across the sites. Even among babies born ≥ 2500 g, lower gestational age and birthweight were largely associated with increased risk of mortality. Since many of these deaths should be preventable, attention to preventing mortality in these infants should have an important impact on overall NMR. Trial registration: https://ClinicalTrials.gov Identifier: NCT01073475

Background Due to high fertility rates in some low and lower-middle income countries, the interval between pregnancies can be short, which may lead to adverse maternal and neonatal outcomes. Methods We analyzed data from women enrolled in the NICHD Global Network Maternal Newborn Health Registry (MNHR) from 2013 through 2018. We report maternal characteristics and outcomes in relationship to the inter-delivery interval (IDI, time from previous delivery [live or stillborn] to the delivery of the index birth), by category of 6–17 months (short), 18–36 months (reference), 37–60 months, and 61–180 months (long). We used non-parametric tests for maternal characteristics, and multivariable logistic regression models for outcomes, controlling for differences in baseline characteristics. Results We evaluated 181,782 women from sites in the Democratic Republic of Congo, Zambia, Kenya, Guatemala, India, and Pakistan. Women with short IDI varied by site, from 3% in the Zambia site to 20% in the Pakistan site. Relative to a 18–36 month IDI, women with short IDI had increased risk of neonatal death (RR = 1.89 [1.74, 2.05]), stillbirth (RR = 1.70 [1.56, 1.86]), low birth weight (RR = 1.38 [1.32, 1.44]), and very low birth weight (RR = 2.35 [2.10, 2.62]). Relative to a 18–36 month IDI, women with IDI of 37–60 months had an increased risk of maternal death (RR 1.40 [1.05, 1.88]), stillbirth (RR 1.14 [1.08, 1.22]), and very low birth weight (RR 1.10 [1.01, 1.21]). Relative to a 18–36 month IDI, women with long IDI had increased risk of maternal death (RR 1.54 [1.10, 2.16]), neonatal death (RR = 1.25 [1.14, 1.38]), stillbirth (RR = 1.50 [1.38, 1.62]), low birth weight (RR = 1.22 [1.17, 1.27]), and very low birth weight (RR = 1.47 [1.32,1.64]). Short and long IDIs were also associated with increased risk of obstructed labor, hemorrhage, hypertensive disorders, fetal malposition, infection, hospitalization, preterm delivery, and neonatal hospitalization. Conclusions IDI varies by site. When compared to 18–36 month IDI, women with both short IDI and long IDI had increased risk of adverse maternal and neonatal outcomes. Trial registration The MNHR is registered at NCT01073475.

Design: Our objectives were to analyze how interpregnancy interval (IPI) was associated with delivery mode and how outcomes varied by these characteristics.Methods: This secondary analysis used data from a prospective study conducted in Chimaltenango, Guatemala from January 2017 through April 2020.Results: Of 26,465 Guatemalan women, 3,170 (12.0%) had a history of prior cesarean. 560 (20.1%) women delivered by vaginal birth after cesarean with the remaining 2,233 (79.9%) delivered by repeat cesarean delivery. Repeat cesarean reduced the risk of needing a dilation and curettage compared to vaginal birth after cesarean, but this association did not vary by IPI (AOR 0.01 – 0.03, p < 0.001). Repeat cesarean delivery, as compared to vaginal birth after cesarean, significantly reduced the likelihood a woman breastfeeding within one hour of birth (AOR 0.009 – 0.10, p < 0.001), but IPI was not associated with the outcome. Regarding stillbirth, repeat cesarean birth reduced the likelihood of stillbirth as compared to vaginal birth (AOR 0.2, p = 0.001 – 0.002), but again IPI was not associated with the outcome.Conclusion: Outcomes by mode of delivery among a Guatemalan cohort of women with a history of prior cesarean birth do not vary by IPI.

Background Oligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios. Methods We included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster. Results Of 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths Conclusions Oligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings. Trial registration NCT01990625.

Background The objectives of this analysis were to document trends in and risk factors associated with the cesarean birth rate in low- and middle-income country sites participating in the Global Network for Women’s and Children’s Health Research (Global Network). Methods This is a secondary analysis of a prospective, population-based study of home and facility births conducted in the Global Network sites. Results Cesarean birth rates increased uniformly across all sites between 2010 and 2018. Across all sites in multivariable analyses, women younger than age twenty had a reduced risk of cesarean birth (RR 0.9 [0.9, 0.9]) and women over 35 had an increased risk of cesarean birth (RR 1.1 [1.1, 1.1]) compared to women aged 20 to 35. Compared to women with a parity of three or more, less parous women had an increased risk of cesarean (RR 1.2 or greater [1.2, 1.4]). Four or more antenatal visits (RR 1.2 [1.2, 1.3]), multiple pregnancy (RR 1.3 [1.3, 1.4]), abnormal progress in labor (RR 1.1 [1.0, 1.1]), antepartum hemorrhage (RR 2.3 [2.0, 2.7]), and hypertensive disease (RR 1.6 [1.5, 1.7]) were all associated with an increased risk of cesarean birth, p Conclusion Cesarean birth rates continue to rise within the Global Network. The proportions of cesarean birth are higher among women with no history of cesarean birth in the African sites and among women with primary elective cesarean, primary cesarean after induction, and repeat cesarean in the non-African sites.

Background Nulliparity has been associated with lower birth weight (BW) and other adverse pregnancy outcomes, with most of the data coming from high-income countries. In this study, we examined birth weight for gestational age z-scores and neonatal (28-day) mortality in a large prospective cohort of women dated by first trimester ultrasound from multiple sites in low and middle-income countries. Methods Pregnant women were recruited during the first trimester of pregnancy and followed through 6 weeks postpartum from Maternal Newborn Health Registry (MNHR) sites in the Democratic Republic of Congo (DRC), Guatemala, Belagavi and Nagpur, India, and Pakistan from 2017 and 2018. Data related to the pregnancy and its outcomes were collected prospectively. First trimester ultrasound was used for determination of gestational age; (BW) was obtained in grams within 48 h of delivery and later transformed to weight for age z-scores (WAZ) adjusted for gestational age using the INTERGROWTH-21st standards. Results 15,121 women were eligible and included. Infants of nulliparous women had lower mean BWs (males: 2676 gr, females: 2587 gr, total: 2634 gr) and gestational age adjusted weight for age z-scores (males: − 0.73, females: − 0.77, total: − 0.75,) than women with one or more previous pregnancies. The largest differences were between zero and one previous pregnancies among female infants. The associations of parity with BW and z-scores remained even after adjustment for maternal age, maternal height, maternal education, antenatal care visits, hypertensive disorders, and socioeconomic status. Nulliparous women also had a significantly higher Conclusions In this large sample from diverse settings, nulliparity was independently associated with both lower BW and WAZ scores as well as higher neonatal mortality compared to multiparity.

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 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.

Objective To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. Design A population-based, prospective observational study. Setting Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. Population All deaths among pregnant women resident in the study sites from 2014 to December 2016. Methods For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. Main outcome measures Assigned causes of maternal mortality. Results Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. Conclusions The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. Tweetable abstract An algorithmic system for determining maternal cause of death in low-resource settings is described.

Objective The objective of this study was to describe the relationship between early pregnancy body mass index (BMI) and maternal, perinatal, and neonatal outcomes in rural India and Pakistan. Study Design In a prospective, population-based pregnancy registry implemented in communities in Thatta, Pakistan and Nagpur and Belagavi, India, we obtained women's BMI prior to 12 weeks' gestation (categorized as underweight, normal, overweight, and obese following World Health Organization criteria). Outcomes were assessed 42 days postpartum. Results The proportion of women with an adverse maternal outcome increased with increasing maternal BMI. Less than one-third of nonoverweight/nonobese women, 47.2% of overweight women, and 56.0% of obese women experienced an adverse maternal outcome. After controlling for site, maternal age and parity, risks of hypertensive disease/severe preeclampsia/eclampsia, cesarean/assisted delivery, and antibiotic use were higher among women with higher BMIs. Overweight women also had significantly higher risk of perinatal and early neonatal mortality compared with underweight/normal BMI women. Overweight women had a significantly higher perinatal mortality rate. Conclusion High BMI in early pregnancy was associated with increased risk of adverse maternal, perinatal, and neonatal outcomes in rural India and Pakistan. These findings present an opportunity to inform efforts for women to optimize weight prior to conception to improve pregnancy outcomes.

Objective To describe the Global Network Near-Miss Maternal Mortality System and its application in seven sites. Methods In a population-based study, pregnant women eligible for enrollment in the Maternal and Newborn Health Registry at seven sites (Democratic Republic of the Congo; Guatemala; Belagavi and Nagpur, India; Kenya; Pakistan; and Zambia) between January 2014 and April 2016 were screened to identify those likely to have a near-miss event. The WHO maternal near-miss criteria were modified for low-resource settings. The ratio of near-miss events to maternal deaths was calculated. Results Among 122 707 women screened, 18 307 (15.0%) had a potential near-miss event, of whom 4866 (26.6%; 4.0% of all women) had a near-miss maternal event. The overall maternal mortality ratio was 155 per 100 000 live births. The ratio of near-miss events to maternal deaths was 26 to 1. The most common factors involved in near-miss cases were the hematologic/coagulation system, infection, and cardiovascular system. Conclusion By using the Global Network Near-Miss Maternal Mortality System, large numbers of women were screened for near-miss events, including those delivering at home or a low-level maternity clinic. The 4.0% incidence of near-miss maternal mortality is similar to previously reported data. The ratio of 26 near-miss cases to 1 maternal death suggests that near miss might evaluate the impact of interventions more efficiently than maternal mortality. This article is protected by copyright. All rights reserved.