The global network maternal newborn health registry: A multi-country, community-based registry of pregnancy outcomes

Background: The Global Network for Women\u27s and Children\u27s Health Research (Global Network) conducts clinical trials in resource-limited countries through partnerships among U.S. investigators, international investigators based in in low and middle-income countries (LMICs) and a central data coordinating center. The Global Network\u27s objectives include evaluating low-cost, sustainable interventions to improve women\u27s and children\u27s health in LMICs. Accurate reporting of births, stillbirths, neonatal deaths, maternal mortality, and measures of obstetric and neonatal care is critical to determine strategies for improving pregnancy outcomes. In response to this need, the Global Network developed the Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnant women, fetuses and neonates receiving care in defined catchment areas at the Global Network sites. This publication describes the MNHR, including participating sites, data management and quality and changes over time.Methods: Pregnant women who reside in or receive healthcare in select communities are enrolled in the MNHR of the Global Network. For each woman and her offspring, sociodemographic, health care, and the major outcomes through 42-days post-delivery are recorded. Study visits occur at enrollment during pregnancy, at delivery and at 42 days postpartum.Results: From 2010 through 2018, the Global Network MNHR sites were located in Guatemala, Belagavi and Nagpur, India, Pakistan, Democratic Republic of Congo, Kenya, and Zambia. During this period at these sites, 579,140 pregnant women were consented and enrolled in the MNHR, nearly 99% of all eligible women. Delivery data were collected for 99% of enrolled women and 42-day follow-up data for 99% of those delivered. In this supplement, the trends over time and assessment of differences across geographic regions are analyzed in a series of 18 manuscripts utilizing the MNHR data.Conclusions: Improving maternal, fetal and newborn health in countries with poor outcomes requires an understanding of the characteristics of the population, quality of health care and outcomes. Because the worst pregnancy outcomes typically occur in countries with limited health registration systems and vital records, alternative registration systems may prove to be highly valuable in providing data. The MNHR, an international, multicenter, population-based registry, assesses pregnancy outcomes over time in support of efforts to develop improved perinatal healthcare in resource-limited areas. Trial Registration The Maternal Newborn Health Registry is registered at Clinicaltrials.gov (ID# NCT01073475). Registered February 23, 2019. https://clinicaltrials.gov/ct2/show/NCT01073475

Routine antenatal ultrasound in low- And Middle-income Countries: First look - A cluster randomised trial

Objective: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centers in resource-limited countries.Design: Cluster randomized trial.Settings: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia).Methods: Clusters were randomized to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds.Main Outcome Measures: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality.Results: During the 24-month trial, 28 intervention and 28 control clusters had 24,263 and 23,160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa and abnormal lie were within expected ranges. 9% were referred for an ultrasound-diagnosed condition and 71% attended the referral. The ANC (RR 1·0 95% CI 1·00, 1·01) and hospital delivery rates for complicated pregnancies (RR 1·03 95% CI 0·89, 1·20) did not differ between intervention and control clusters nor did the composite outcome (RR 1·09 95% CI 0·97, 1·23) or its individual components.Conclusions: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome as well as the individual components were not reduced. This article is protected by copyright. All rights reserved

Neonatal deaths in infants born weighing ≥ 2500 g in low and middle-income countries

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\u27s 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

Oligohydramnios: a prospective study of fetal, neonatal and maternal outcomes in low-middle income countries

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 \u3c 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

Association of parity with birthweight and neonatal death in five sites: The global network\u27s maternal newborn health registry study

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 \u3c 28-day neonatal mortality rate (27.7 per 1,000 live births) than parous women (17.2 and 20.7 for parity of 1-3 and ≥ 4 respectively). Risk of preterm birth was higher among women with ≥ 4 previous pregnancies (15.5%) compared to 11.3% for the nulliparous group and 11.8% for women with one to three previous pregnancies (p = 0.0072).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

Development of the global network for women\u27s and children\u27s health research\u27s socioeconomic status index for use in the network\u27s sites in low and lower middle-income countries

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\u27s and Children\u27s 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 \u3c 0.001). African sites had lower mean SES scores than the Asian and Central American sites. The SES index demonstrated good internal consistency reliability (Cronbach\u27s alpha = 0.81). Higher SES scores were significantly associated with formal education, more education, having received antenatal care, and facility delivery (p \u3c 0.001).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 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\u27s 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

An approach to identify a minimum and rational proportion of caesarean sections in resource-poor settings: A global network study

Background: Caesarean section prevalence is increasing in Asia and Latin America while remaining low in most African regions. Caesarean section delivery is effective for saving maternal and infant lives when they are provided for medically-indicated reasons. On the basis of ecological studies, caesarean delivery prevalence between 9% and 19% has been associated with better maternal and perinatal outcomes, such as reduced maternal land fetal mortality. However, the specific prevalence of obstetric and medical complications that require caesarean section have not been established, especially in low-income and middle-income countries (LMICs). We sought to provide information to inform the approach to the provision of caesarean section in low-resource settings.Methods: We did a literature review to establish the prevalence of obstetric and medical conditions for six potentially life-saving indications for which caesarean section could reduce mortality in LMICs. We then analysed a large, prospective population-based dataset from six LMICs (Argentina, Guatemala, Kenya, India, Pakistan, and Zambia) to determine the prevalence of caesarean section by indication for each site. We considered that an acceptable number of events would be between the 25th and 75th percentile of those found in the literature.Findings: Between Jan 1, 2010, and Dec 31, 2013, we enrolled a total of 271 855 deliveries in six LMICs (seven research sites). Caesarean section prevalence ranged from 35% (3467 of 9813 deliveries in Argentina) to 1% (303 of 16 764 deliveries in Zambia). Argentina\u27s and Guatemala\u27s sites all met the minimum 25th percentile for five of six indications, whereas sites in Zambia and Kenya did not reach the minimum prevalence for caesarean section for any of the indications. Across all sites, a minimum overall caesarean section of 9% was needed to meet the prevalence of the six indications in the population studied.Interpretation: In the site with high caesarean section prevalence, more than half of the procedures were not done for life-saving conditions, whereas the sites with low proportions of caesarean section (below 9%) had an insufficient number of caesarean procedures to cover those life-threatening causes. Attempts to establish a minimum caesarean prevalence should go together with focusing on the life-threatening causes for the mother and child. Simple methods should be developed to allow timely detection of life-threatening conditions, to explore actions that can remedy those conditions, and the timely transfer of women with those conditions to health centres that could provide adequate care for those conditions

Looking beyond the numbers: Quality assurance procedures in the global network for women\u27s and children\u27s health research maternal newborn health registry

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\u27s and Children\u27s 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

A combined community and facility-based approach to improve pregnancy outcomes in low-resource settings: A global network cluster randomized trial

Background: Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries. These differences have been related to poor access to and poor quality of obstetric and neonatal care.Methods: This trial tested the hypothesis that teams of health care providers, administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations. In seven geographic areas in five low-income and one middle-income country, most with high perinatal mortality rates and substantial numbers of home deliveries, we performed a cluster randomized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport, community birth attendant training in problem recognition, and facility staff training in the management of obstetric and neonatal emergencies. The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g.Results: Despite extensive effort in all sites in each of the three intervention areas, no differences emerged in the primary or any secondary outcome between the intervention and control clusters. In both groups, the mean perinatal mortality was 40.1/1,000 births (P = 0.9996). Neither were there differences between the two groups in outcomes in the last six months of the project, in the year following intervention cessation, nor in the clusters that best implemented the intervention.Conclusions: This cluster randomized comprehensive, large-scale, multi-sector intervention did not result in detectable impact on the proposed outcomes. While this does not negate the importance of these interventions, we expect that achieving improvement in pregnancy outcomes in these settings will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial, and without them provider training and community mobilization will not be sufficient. Our results highlight the critical importance of evaluating outcomes in randomized trials, as interventions that should be effective may not be.Trial Registration: ClinicalTrials.gov NCT01073488

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network´s (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health.Fil: Goudar, Shivaprasad S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Stolka, Kristen B.. Research Triangle Institute International; Estados UnidosFil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Honnungar, Narayan V.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Mastiholi, Shivanand C.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Ramadurg, Umesh Y.. S. Nijalingappa Medical College; IndiaFil: Dhaded, Sangappa M.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Pasha, Omrana. Aga Khan University; PakistánFil: Patel, Archana. Indira Gandhi Government Medical College and Lata Medical Research Foundation; IndiaFil: Esamai, Fabian. University School of Medicine; KeniaFil: Chomba, Elwyn. University of Zambia; ZambiaFil: Garces, Ana. Universidad de San Carlos; GuatemalaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Carlo, Waldemar A.. University of Alabama at Birmingahm; Estados UnidosFil: Goldenberg, Robert L.. Columbia University; Estados UnidosFil: Hibberd, Patricia L.. Massachusetts General Hospital for Children; Estados UnidosFil: Liechty, Edward A.. Indiana University; Estados UnidosFil: Krebs, Nancy F.. University of Colorado School of Medicine; Estados UnidosFil: Hambidge, Michael K.. University of Colorado School of Medicine; Estados UnidosFil: Moore, Janet L.. Research Triangle Institute International; Estados UnidosFil: Wallace, Dennis D.. Research Triangle Institute International; Estados UnidosFil: Derman, Richard J. Christiana Care Health Services; Estados UnidosFil: Bhalachandra, Kodkany S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Bose, Carl L.. University of North Carolina; Estados Unido