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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 .

Globally, socioeconomic status (SES) is an important health determinant across a range of health conditions and diseases. However, measuring SES within low- and middle-income countries (LMICs) can be particularly challenging given the variation and diversity of LMIC populations. The current study investigates whether maternal SES as assessed by the newly developed Global Network-SES Index is associated with pregnancy outcomes (stillbirths, perinatal mortality, and neonatal mortality) in six LMICs: Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia. The analysis included data from 87,923 women enrolled in the Maternal and Newborn Health Registry of the NICHD-funded Global Network for Women's and Children's Health Research. Generalized estimating equations models were computed for each outcome by SES level (high, moderate, or low) and controlling for site, maternal age, parity, years of schooling, body mass index, and facility birth, including sampling cluster as a random effect. Women with low SES had significantly higher risks for stillbirth (p < 0.001), perinatal mortality (p = 0.001), and neonatal mortality (p = 0.005) than women with high SES. In addition, those with moderate SES had significantly higher risks of stillbirth (p = 0.003) and perinatal mortality (p = 0.008) in comparison to those with high SES. The SES categories were associated with pregnancy outcomes, supporting the validity of the index as a non-income-based measure of SES for use in studies of pregnancy outcomes in LMICs.

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 .

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

Background Before Zika virus (ZIKV) infections were observed in the Americas, an association between ZIKV and microcephaly or other congenital malformations was not well documented. Initial reports suggested strong associations between ZIKV and congenital malformations, but plausible estimates of causal effects from prospective studies with adequate sample size and covariate data were few. Methods From 2016–2018, the Zika in Infants and Pregnancy (ZIP) study enrolled pregnant people before 18 weeks gestation or with confirmed symptomatic ZIKV in a prospective cohort across 10 sites in South and Central America, and in Puerto Rico. Pregnancies were followed monthly through delivery and 6 weeks postpartum. Infants were followed quarterly to age 12 months. Prespecified co-primary analyses evaluated the associations between a composite endpoint of adverse fetal, neonatal, and infant outcomes with intrauterine ZIKV exposure overall and with symptomatic intrauterine ZIKV exposure. Secondary analyses separately evaluated the association of intrauterine ZIKV exposure with individual components of the primary endpoint. Results Six thousand one hundred pregnant participants were included in the primary analysis, including 61 with ZIKV infection during pregnancy confirmed by a ZIKV-specific RNA test. For the primary analyses, the relative risk (RR) for the composite endpoint associated with any ZIKV exposure was 1.64 (95% CI: 0.65, 4.13) and with symptomatic ZIKV exposure 1.08 (95% CI: 0.15, 7.64). Sensitivity analyses provided similar results. Secondary analyses showed significant adjusted RRs [95% CI] for stillbirth (4.28 [1.39, 13.21]), infant death within six weeks (6.20 [1.08, 35.60], and fetal loss before 20 weeks (3.72 [1.82, 7.59]). Conclusions The ZIP study identified an elevated but not statistically significant risk of the primary composite outcome with intrauterine ZIKV exposure, and a significantly increased risk of some adverse fetal and infant outcomes with intrauterine ZIKV exposure in secondary analyses. Fewer than expected infections observed during pregnancy, coincident with a waning epidemic, limited study power to evaluate risk. Combining data from multiple cohorts for future meta-analysis may better define the risks of intrauterine ZIKV exposure. Trial Registration NCT02856984. Registered August 5, 2016. Retrospectively registered.

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 < 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, − 35.9) with oligohydramnios. 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 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.

Multiple factors influence infant and child neurodevelopment in low resource settings. In offspring of participants in the preconception maternal nutrition trial, Women First (WF), we examined the impact of providing a preconception (Arm 1) or prenatal (Arm 2) nutrient supplement (compared to controls, Arm 3) on neurodevelopmental outcomes at 24 months; predictors of neurodevelopment scores; and associations of infant anthropometrics with neurodevelopmental scores. Follow‐up visits for anthropometry were conducted at 6‐, 12‐, 18‐ and 24‐month of age. At 24‐months, in a randomized subset, the Bayley Scales of Infant Development, 3rd edition (BSID‐III), including cognitive, motor and social‐emotional subscales, and the Family Care Indicators (FCI) questionnaire, assessing family and home environment, were completed. Multiple covariates (intervention arm, site, maternal sociodemographic characteristics, FCI subscales, birthweight and 6–24 months' change in anthropometry z‐scores, (e.g., ΔLAZ6–24) were evaluated by linear regression to predict BSID‐III outcomes and to assess associations of anthropometric changes with BSID‐III scores. The analysis consisted of 1386 infants (n = 441, 486, 459 for Arms 1, 2 and 3, respectively). None of the domain‐specific BSID‐III subscale scores differed by maternal intervention arm. Four covariates significantly predicted (p ≤ 0.01) all 3 BSID‐III subscales: secondary maternal education, ΔLAZ6–24, birthweight >2500 g, and FCI play materials. Linear growth was associated with all domains of neurodevelopment. The results underscore the multi‐dimensional aspects of child development represented by the nurturing care framework, including prenatal maternal nutrition, post‐natal growth, maternal education for responsive caregiving and opportunities for early learning. Key messages Preconception and prenatal maternal nutrition is important to ensure adequate fetal growth and healthy birthweight. Preconception and prenatal maternal nutritional supplementation was not associated with young child neurodevelopment but has been shown to improve post‐natal growth. Post‐natal linear growth is consistently associated with offspring neurodevelopment at 24 months. Maternal education to foster responsive caregiving, and opportunities for early learning in the home also positively impact offspring neurodevelopmental outcomes. These findings underscore the importance of multi‐dimensional aspects essential for children to reach their full developmental potential. The study examined the effects of maternal nutrition supplementation started before or during pregnancy (stopped at delivery) on offspring development at 24 months of age. The maternal intervention was not significantly associated with neurodevelopment, but maternal education, fetal and post‐natal growth and home environment were all associated with better developmental outcomes.

This research describes the proportion of children in four low‐ and middle‐income countries with adequate dietary practices at 6, 12, 18 and 24 months of age and how these practices changed over time using the World Health Organisation and UNICEF's infant young child feeding (IYCF) indicators. The associations between the IYCF indicators and anthropometric z‐scores from 6 to 24 months, and between the IYCF indicators and the family care indicators (FCIs) at 24 months are described. This was a longitudinal study of offspring from participants in the Women First Preconception Maternal Nutrition Trial conducted in Sud‐Ubangi, Democratic Republic of Congo; Chimaltenango, Guatemala; Belagavi, North Karnataka, India; and Thatta, Sindh Province, Pakistan. The frequency of the minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum adequate diet (MAD) increased between 6 and 24 months, but even at 24 months MAD remained below 50% at all sites. MDD (β = 0.12; 95% CI = 0.04−0.22) and MMF (β = 0.10; 95% CI = 0.03−0.17) were positively associated with length‐for‐age z‐score at 24 months. All IYCF indicators were positively associated with mean total FCI score: MDD (proportion ratio [PR] = 1.04; 95% CI = 1.02−1.07), MMF (PR = 1.02; 95% CI = 1.01−1.04), MAD (PR = 1.05; 95% CI = 1.02−1.08). Although there are multiple barriers to young children having an adequate diet, our results support a positive association between familial interactions and improved IYCF feeding practices. The infant young child feeding (IYCF) indicators increased from 6 to 24 months in young children in rural settings of four low‐ and middle‐income countries: Democratic Republic of the Congo, Guatemala, India and Pakistan, but the percentage of children who met the minimum dietary diversity (MDD) and minimum acceptable diet remained below 50% at 24 months. MDD and minimum meal frequency were positively associated with length‐for‐age z‐scores at 24 months (solid lines), and the total family care indicator score was positively associated with all three IYCF indicators at 24 months (dashed lines). Key messages Minimum dietary diversity (MDD), minimum meal frequency (MMF) and minimum adequate diet (MAD) increased from 6 to 24 months of age, but MAD remained below 50% frequency at all sites at 24 months. MDD and MMF were positively associated with length‐for‐age z‐scores at 24 months. The total family care indicator score was positively associated with all three infant young child feeding indicators at 24 months.

ObjectivesWe 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.DesignProspective cohort studySetting and participantsThis 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 measuresGA 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.ResultsOverall, 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.ConclusionThe 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 numberNCT01073475.