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

ObjectivesEarly detection is of crucial importance for prevention of type 2 diabetes and pre-diabetes. Diagnosis of these conditions relies on the oral glucose tolerance test and haemoglobin A1c estimation which are invasive and challenging for large-scale screening. We aimed to combine the non-invasive nature of ECG with the power of machine learning to detect diabetes and pre-diabetes.MethodsData for this study come from Diabetes in Sindhi Families in Nagpur study of ethnically endogenous Sindhi population from central India. Final dataset included clinical data from 1262 individuals and 10 461 time-aligned heartbeats recorded digitally. The dataset was split into a training set, a validation set and independent test set (8892, 523 and 1046 beats, respectively). The ECG recordings were processed with median filtering, band-pass filtering and standard scaling. Minority oversampling was undertaken to balance the training dataset before initiation of training. Extreme gradient boosting (XGBoost) was used to train the classifier that used the signal-processed ECG as input and predicted the membership to ‘no diabetes’, pre-diabetes or type 2 diabetes classes (defined according to American Diabetes Association criteria).ResultsPrevalence of type 2 diabetes and pre-diabetes was ~30% and ~14%, respectively. Training was smooth and quick (convergence achieved within 40 epochs). In the independent test set, the DiaBeats algorithm predicted the classes with 97.1% precision, 96.2% recall, 96.8% accuracy and 96.6% F1 score. The calibrated model had a low calibration error (0.06). The feature importance maps indicated that leads III, augmented Vector Left (aVL), V4, V5 and V6 were most contributory to the classification performance. The predictions matched the clinical expectations based on the biological mechanisms of cardiac involvement in diabetes.ConclusionsMachine-learning-based DiaBeats algorithm using ECG signal data accurately predicted diabetes-related classes. This algorithm can help in early detection of diabetes and pre-diabetes after robust validation in external datasets.

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 While the relationship between hemoglobin (Hb) concentrations and pregnancy outcomes has been studied often, most reports have focused on a specific Hb cutoff used to define anemia. Fewer studies have evaluated pregnancy outcomes across the entire range of Hb values. Moreover, to date, most studies of the relationship of Hb concentrations to pregnancy outcomes have been done in high-income countries. Thus, we have sought to determine the relationship between the range of maternal Hb concentrations and adverse birth outcomes among South Asian pregnant women. Methods For this study, we used data collected from two South Asian countries (Pakistan – Sindh Province and two sites in India - Belagavi and Nagpur) in a prospective maternal and newborn health registry study. To assess the association between Hb concentrations and various maternal and fetal outcomes, we classified the Hb concentrations into seven categories. Regression analyses adjusting for multiple potential confounders were performed to assess adverse pregnancy outcomes across the range of Hb concentrations. Findings Between January 2012 and December 2018, 130,888 pregnant women were enrolled in the South Asian sites had a Hb measurement available, delivered and were included in the analyses. Overall, the mean Hb concentration of pregnant women from the sites was 9.9 g/dL, 10.0 g/dL in the Indian sites and 9.5 g/dL in the Pakistan site. Hb concentrations 35 years of age, women with ≥4 children and those who enrolled in the third trimester were more likely to have Hb concentrations of Interpretation This study documented the relationship between maternal Hb concentrations and adverse pregnancy outcomes in women from the Pakistani and Indian sites across the range of Hb values. Both low and high Hb concentrations were associated with risk of at least some adverse outcomes. Hence, both low and high values of Hb should be considered risk factors for the mother and fetus.

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 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 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 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 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.

BackgroundTo determine the gender differences in neonatal mortality, stillbirths, and perinatal mortality in south Asia using the Global Network data from the Maternal Newborn Health Registry.MethodsThis study is a secondary analysis of prospectively collected data from the three south Asian sites of the Global Network. The maternal and neonatal demographic, clinical characteristics, rates of stillbirths, early neonatal mortality (1–7 days), late neonatal mortality (8–28 days), mortality between 29–42 days and the number of infants hospitalized after birth were compared between the male and female infants.ResultsBetween 2010 and 2018, 297,509 births [154,790 males (52.03%) and 142,719 females (47.97%)] from two Indian sites and one Pakistani site were included in the analysis [288,859 live births (97.1%) and 8,648 stillbirths (2.9%)]. The neonatal mortality rate was significantly higher in male infants (33.2/1,000 live births) compared to their female counterparts (27.4/1,000, p ConclusionThe risks of stillbirths, and early neonatal mortality were higher among male infants than their female counterparts. However, there was no gender difference in mortality after 7 days of age. Our results highlight the importance of stratifying neonatal mortality into early and late neonatal period to better understand the impact of gender on neonatal mortality. The information from this study will help in developing strategies and identifying measures that can reduce differences in sex-specific mortality.

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.

Background: Assessment of gestational age (GA) based on the last date of menstrual period is often inaccurate. Scores to predict GA of newborns are difficult to use particularly by health workers. An accurate, easy to use the method of assessing GA, particularly in low birth weight (LBW) babies, is needed to detect and link premature newborns to the appropriate level of care. Objectives: The objectives were (1) to develop a “simplified GA score” (SGAS) by selecting items from 3 standard GA scores that significantly predict the GA as measured by the best obstetric estimate (BOE), (2) to validate the accuracy of SGAS against the BOE, (3) to compare the accuracy of SGAS to assess the GA as compared to the accuracy of GA assessment by the New Ballard Score (NBS), and (4) to assess inter rater agreement of SGAS as compared to that of NBS. Materials and Methods: Both the development and validation studies were cross-sectional studies. In the development study, two neonatology residents trained in the use of the 3 scores assessed LBW (

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.

Background Over the last decade, infant and young child feeding (IYCF) indicators in India have improved. However, poor IYCF practices are still apparent, associated with pervasive high rates of child under-nutrition. Interventions to improve IYCF need augmentation by appropriate policy support to consolidate gains. The aim of this study was to identify opportunities to strengthen and support IYCF policies through a policy content and stakeholder network analysis. Methods IYCF policies and guidelines were systematically mapped and coded using predetermined themes. Six ‘net-map’ group interviews were conducted for stakeholder analysis with data analyzed using ORA (organizational risk analyzer, copyright Carley, Carnegie Mellon University) software. The study was carried out at a national level and in the states of Maharashtra and unified Andhra Pradesh. Results Thirty relevant policy documents were identified. Support for IYCF was clearly apparent and was actioned within sectoral policies and strategic plans. We identified support for provision of information to mothers and caregivers in both sectoral and high-level/strategic policy documents. At a sectoral level, there was support for training health care workers and for enabling mothers to access IYCF. Opportunities to strengthen policy included expanding coverage and translating policy goals into implementation level documents. At the national level, Ministry of Women and Child Development [MoWCD], Ministry of Health and Family Welfare [MoHFW] and the Prime Minister’s Nutrition Council [PMNC] were the most influential actors in providing technical support while MoHFW, MoWCD, and Bill Melinda Gates Foundation were the most influential actors in providing funding and were therefore influential stakeholders in shaping IYCF policies and programs. Conclusion We identified a wide range of strengths in the IYCF policy environment in India and also opportunities for improvement. One key strength is the integration of IYCF policies into a range of agendas and guidelines related to health and child development service delivery at the national and state level. However, the lack of a specific national policy on IYCF means that there is no formal mechanism for review and monitoring implementation across sectors and jurisdictions. Another opportunity identified is the development of IYCF policy guidelines in emergencies and for tribal populations. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4339-z) contains supplementary material, which is available to authorized users.

Background South Asian countries experience some of the highest levels of child undernutrition in the world, strongly linked to poor infant and young child feeding (IYCF) practices. Strong and responsive policy support is essential for effective interventions to improve IYCF. This study aimed to identify opportunities for strengthening the policy environment in the region to better support appropriate infant and young child feeding. Methods We mapped policies relevant to infant and young child feeding in India, Pakistan, Bangladesh, Sri Lanka and Nepal, based on a common matrix. The matrix described potentially relevant policies ranging from high-level strategic policy documents to implementation-level guidelines. We analyzed the data based on themes focused on caregiver interactions with IYCF interventions: provision of correct information to mothers, training of frontline workers, enabling mothers to engage with service providers and strategic support for IYCF. Results Policy support for IYCF was present in relation to each of the themes assessed. In all countries, there was support for nutrition in National Development Plans, and all countries had some level of maternity protection and restrictions on marketing of breast milk substitutes. Sectoral and implementation-level policy documents contained provisions for system strengthening for IYCF and for training of frontline workers. Conclusions The key opportunities for strengthening IYCF policy support were in relation to translating strategic directives into implementation level documents; improving multi-sectoral support and coordination; and increased clarity regarding roles and responsibilities of frontline workers interacting with mothers. These findings can support efforts to strengthen IYCF policy at the national and regional level.

Background In 2008, the Indian government introduced financial assistance to encourage health facility deliveries. Facility births have increased, but maternal and neonatal morbidity and mortality have not decreased raising questions about the quality of care provided in facilities and access to a quality referral system. We evaluated the potential role of inter-institutional transfers of women admitted for labor and delivery on adverse maternal and neonatal outcomes in an ongoing prospective, population-based Maternal and Newborn Health Registry in Central India. Methods Pregnant women from 20 rural Primary Health Centers near Nagpur, Maharashtra were followed throughout pregnancy and to day 42 post-partum. Inter- institutional referral was defined as transfer of a woman from a first or second level facility where she was admitted for labor and delivery to facility providing higher level of care, after admission to the day of delivery. Maternal mortality, stillbirth, early and late neonatal mortality were compared in mothers who were and were not referred. Factors associated with inter-institutional referral were analyzed using multivariable models with generalized estimating equations, adjusted for clustering at the level of the Primary Health Center. Results Between June 2009 and June 2013, 3236 (9.4%) of 34,319 women had inter-institutional referral. Factors associated with referrals were maternal age (adjusted Relative Risk or aRR 1.1; 1.0–1.2); moderate or severe anemia (aRR 1.2; 1.2–1.4), gestational age

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

Refereed/Peer-reviewed Reduction of childhood stunting is difficult to achieve by interventions that focus only on improving nutrition during infancy. Comprehensive interventions that extend through the continuum of care from pregnancy to infancy are needed. Mobile phones are now successfully being used for behaviour change communication to improve health. We present the methodology of an mHealth intervention "Mobile Solutions Aiding Knowledge for Health Improvement" (M-SAKHI) to be delivered by rural community health workers or Accredited Social Health Activists (ASHAs) for rural women, below or up to 20 weeks of pregnancy through delivery until their infant is 12 months of age. This protocol paper describes the cluster randomized controlled trial to evaluate the effectiveness of M-SAKHI. The primary objective of the trial is to reduce the prevalence of stunting (height-for-age z-score) in children at 18 months of age by 8% in the intervention as compared with control. The secondary objectives include evaluating the impact on maternal dietary diversity, birth weight, infant and young child feeding practices, infant development, and child morbidity, along with a range of intermediate outcomes for maternal, neonatal, and infant health. A total of 297 ASHAs, five trained counsellors, and 2,501 participants from 244 villages are participating in this study. The outcome data are being collected by 51 field research officers. This study will provide evidence regarding the efficacy of M-SAKHI to reduce stunting in young children in rural India, and if effective, the cost-effectiveness of M-SAKHI.

Background: In India, biomass fuel is burned in many homes under inefficient conditions, leading to a complex milieu of particulate matter and environmental toxins known as household air pollution (HAP). Pregnant women are particularly vulnerable as they and their fetus may suffer from adverse consequences of HAP. Fractional exhaled nitric oxide (FeNO) is a noninvasive, underutilized tool that can serve as a surrogate for airway inflammation. We evaluated the prevalence of respiratory illness, using pulmonary questionnaires and FeNO measurements, among pregnant women in rural India who utilize biomass fuel as a source of energy within their home. Methods: We prospectively studied 60 pregnant women in their 1st and 2nd trimester residing in villages near Nagpur, Central India. We measured FeNO levels in parts per billion (ppb), St. George&rsquo, s Respiratory Questionnaire (SGRQ-C) scores, and the Modified Medical Research Council (mMRC) Dyspnea Scale. We evaluated the difference in the outcome distributions between women using biomass fuels and those using liquefied petroleum gas (LPG) using two-tailed t-tests. Results: Sixty-five subjects (32 in Biomass households, 28 in LPG households, 5 unable to complete) were enrolled in the study. Age, education level, and second-hand smoke exposure were comparable between both groups. FeNO levels were higher in the Biomass vs. LPG group (25.4 ppb vs. 8.6 ppb, p-value = 0.001). There was a difference in mean composite SGRQ-C score (27.1 Biomass vs. 10.8 LPG, p-value &lt, 0.001) including three subtotal scores for Symptoms (47.0 Biomass vs. 20.2 LPG, p-value&lt, 0.001), Activity (36.4 Biomass vs. 16.5 LPG, 0.001) and Impact (15.9 Biomass vs. 5.2 LPG, 0.001). The mMRC Dyspnea Scale was higher in the Biomass vs. LPG group as well (2.9 vs. 0.5, p &lt, 0.001). Conclusion: Increased FeNO levels and higher dyspnea scores in biomass-fuel-exposed subjects confirm the adverse respiratory effects of this exposure during pregnancy. More so, FeNO may be a useful, noninvasive biomarker of inflammation that can help better understand the physiologic effects of biomass smoke on pregnant women. In the future, larger studies are needed to characterize the utility of FeNO in a population exposed to HAP.

BackgroundIn low resource settings recall of the date of the mother's last menstrual period may be unreliable and due to limited availability of prenatal ultrasound, gestational age of newborns may not be assessed reliably. Preterm babies are at high risk of morbidity and mortality so an alternative strategy is to identify them soon after birth is needed for early referral and management.ObjectiveThe objective of this study was to assess the accuracy in assessing prematurity of newborn, over and above birthweight, using a pictorial Simplified Gestational Age Score adapted for use as a Tablet App.MethodsTwo trained nurse midwives, blinded to each other's assessment and the actual gestational age of the baby used the app to assess gestational age at birth in 3 hospitals based on the following 4 parameters-newborn's posture, skin texture, breast and genital development. Inter-observer variation was evaluated and the optimal scoring cut-off to detect preterm birth was determined. Sensitivity and specificity of gestational age score using the tablet was estimated using combinations of last menstrual period and ultrasound as reference standards to assess preterm birth. The predictive accuracy of the score using the area under a receiver operating characteristic curve was also determined. To account for potential reference standard bias, we also evaluated the score using latent class models.ResultsA total of 8,591 live singleton births whose gestational age by last menstrual period and ultrasound was within 1 weeks of each other were enrolled. There was strong agreement between assessors (concordance correlation coefficient 0.77 (95% CI 0.76-0.78) and Fleiss' kappa was 0.76 (95% CI 0.76-0.78). The optimal cut-off for the score to predict preterm was 13. Irrespective of the reference standard, the specificity of the score was 90% and sensitivity varied from 40-50% and the predictive accuracy between 74%-79% for the reference standards. The likelihood ratio of a positive score varied between 3.75-4.88 while the same for a negative likelihood ratio consistently varied between 0.57-0.72. Latent class models showed similar results indicating no reference standard bias.ConclusionGestational age scores had strong inter-observer agreement, robust prediction of preterm births simplicity of use by nurse midwives and can be a useful tool in resource-limited scenarios.Trial registrationThe Tablet App for the Simplified Gestational Age Score (T-SGAS) study was registered at ClinicalTrials.gov NCT02408783.

BACKGROUND Although rates of preterm birth continue to increase globally, identification of preterm from low birth weight infants remains a challenge. The burden of low birth weight vs preterm is greatest in resource-limited settings, where gestational age (GA) prior to delivery is frequently not known because ultrasound in early pregnancy is not available and estimates of the date of the mother’s last menstrual period (LMP) may not be reliable. An alternative option is to assess GA at birth to optimize referral and care of preterm newborns. We previously developed and pilot-tested a system to measure the simplified gestational age score (SGAS) based on 4 easily observable neonatal characteristics. OBJECTIVE The objective of this study is to adapt the scoring system as a tablet app (potentially scalable approach) to assess feasibility of use and to validate whether the scoring system accurately predicts prematurity by itself, over and above birth weight in a large sample of newborns. METHODS The study is based in Nagpur, India, at the Research Unit of the National Institute of Child Health and Human Development’s Global Network for Women’s and Children’s Health Research. The Android tablet app for the SGAS (T-SGAS) displays de-identified photographs of skin, breasts, and genitalia across a range of GAs and line drawings of infant posture. Each item is associated with a score. The user is trained to choose the photograph or line drawing that most closely matches the newborn being evaluated, and the app determines the neonate’s GA category (preterm or term) from the cumulative score. The validation study will be conducted in 3 second level care facilities (most deliveries in India occur in hospitals, and women known to be at risk of preterm birth are referred to second level care facilities). Within 24 hours of delivery, women and their babies who are stable will be enrolled in the study. Two auxiliary nurse midwives (ANMs) blinded to prior GA assessments will use the T-SGAS to estimate the GA status of the newborn. An independent data collector will abstract the GA from the ultrasound recorded in the hospital chart and record the date of the mother’s LMP. Eligibility for analysis is determined by the ultrasound and LMP data being collected within 1 week of each other to have a rigorous assessment of true GA. RESULTS Publication of the results of the study is anticipated in 2019. CONCLUSIONS Until GA dating by ultrasound is universally available and easy to use in resource-limited settings, and where there are restrictions on ultrasound use due to their use for sex determination and abortion of female fetuses, this study will determine whether the T-SGAS app can accurately assess GA in risk categories at birth. CLINICALTRIAL ClinicalTrials.gov NCT02408783; https://clinicaltrials.gov/ct2/show/NCT02408783 (Archived by Webcite at http://www.webcitation.org/75S2kmr3T) INTERNATIONAL REGISTERED REPORT DERR1-10.2196/11913

Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB. Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) confirmed by ultrasound prior to enrollment, no more than two previous first trimester pregnancy losses, and no contraindications to aspirin. Intervention: Daily administration of low dose (81 mg) aspirin, initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo. Compliance and outcomes will be assessed biweekly. Primary outcome: Incidence of PTB (birth prior to 37 0/7 weeks GA). Secondary outcomes Incidence of preeclampsia/eclampsia, small for gestational age and perinatal mortality. This study is unique as it will examine the impact of LDA early in pregnancy in low-middle income countries with preterm birth as a primary outcome. The importance of developing low-cost, high impact interventions in low-middle income countries is magnified as they are often unable to bear the financial costs of treating illness. ClinicalTrials.gov identifier: NCT02409680 Date: March 30, 2015