A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries

Objective: To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths.Methods: A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum.Findings: Between 2010 and 2012, 214,070 of 220,235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100,000 live births, ranging from 69 per 100,000 in Argentina to 316 per 100,000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97-11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26-5.67) and 7-day (RR: 3.94; 95% CI: 2.74-5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54-9.77).Conclusions: Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality

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

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks\u27 gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks\u27 gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (\u3c34 \u3eweeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development

A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study

Background: 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.Methods: 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.Outcomes: 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.Discussion: 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

Stillbirth rates in low-middle income countries 2010 - 2013: a population-based, multi-country study from the Global Network

Abstract Background Stillbirth rates remain nearly ten times higher in low-middle income countries (LMIC) than high income countries. In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented characteristics or care for mothers with stillbirths. Non-macerated stillbirths, those occurring around delivery, are generally considered preventable with appropriate obstetric care. Methods We undertook a prospective, population-based observational study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Results From 2010 through 2013, 269,614 enrolled women had 272,089 births, including 7,865 stillbirths. The overall stillbirth rate was 28.9/1000 births, ranging from 13.6/1000 births in Argentina to 56.5/1000 births in Pakistan. Stillbirth rates were stable or declined in 6 of the 7 sites from 2010-2013, only increasing in Pakistan. Less educated, older and women with less access to antenatal care were at increased risk of stillbirth. Furthermore, women not delivered by a skilled attendant were more likely to have a stillbirth (RR 2.8, 95% CI 2.2, 3.5). Compared to live births, stillbirths were more likely to be preterm (RR 12.4, 95% CI 11.2, 13.6). Infants with major congenital anomalies were at increased risk of stillbirth (RR 9.1, 95% CI 7.3, 11.4), as were multiple gestations (RR 2.8, 95% CI 2.4, 3.2) and breech (RR 3.0, 95% CI 2.6, 3.5). Altogether, 67.4% of the stillbirths were non-macerated. 7.6% of women with stillbirths had cesarean sections, with obstructed labor the primary indication (36.9%). Conclusions Stillbirth rates were high, but with reductions in most sites during the study period. Disadvantaged women, those with less antenatal care and those delivered without a skilled birth attendant were at increased risk of delivering a stillbirth. More than two-thirds of all stillbirths were non-macerated, suggesting potentially preventable stillbirth. Additionally, 8% of women with stillbirths were delivered by cesarean section. The relatively high rate of cesarean section among those with stillbirths suggested that this care was too late or not of quality to prevent the stillbirth; however, further research is needed to evaluate the quality of obstetric care, including cesarean section, on stillbirth in these low resource settings. Study registration Clinicaltrials.gov (ID# NCT01073475

A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries

To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths

A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries

OBJETIVO: Cuantificar la mortalidad materna, fetal y neonatal en países de ingresos bajos y medios a fin de identificar cuándo se producen muertes y las relaciones entre las muertes maternas y la mortalidad prenatal y neonatal. MÉTODOS: Se realizó un estudio prospectivo de los resultados del embarazo en 106 comunidades en siete lugares en Argentina, Guatemala, India, Kenya, Pakistán y Zambia. Se inscribieron mujeres embarazadas, de las que se hizo un seguimiento hasta seis semanas tras el parto. RESULTADOS: Entre 2010 y 2012, 214 070 de las 220 235 mujeres inscritas (97,2%) completaron el seguimiento. La tasa de mortalidad materna fue de 168 por 100 000 nacidos vivos, con una variación que va desde 69 por 100 000 en Argentina a 316 por 100 000 en Pakistán. En general, el 29% (98/336) de las muertes maternas se produjo en torno al momento del parto: la mayoría se atribuyó a hemorragias (86/336), preeclampsia o eclampsia (55/336), o sepsis (39/336). Alrededor del 70% (4349/6213) de las muertes prenatales se produjo probablemente en el parto; el 34% (1804/5230) de los recién nacidos murieron el día del parto y el 14% (755/5230), al día siguiente. Las muertes prenatales fueron más comunes en las mujeres que fallecieron que en aquellas con vida seis semanas después del parto (riesgo relativo, RR: 9,48; intervalo de confianza 95%, IC: 7,97–11,27), al igual que las muertes perinatales (RR: 4,30; IC del 95%: 3,26–5,67) y las muertes de neonatos a 7 días (RR: 3,94; IC del 95%: 2,74–5,65) y a 28 días (RR: 7,36; IC del 95%: 5,54–9,77). CONCLUSIÓN: La mayoría de las muertes maternas, prenatales y neonatales ocurrieron en o en torno al parto y se atribuyeron a causas evitables. La muerte materna aumentó el riesgo de muerte perinatal y neonatal. Mejorar la atención obstétrica y neonatal en el momento del nacimiento ofrece las mayores posibilidades para reducir la mortalidad.OBJECTIVE: To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths. METHODS: A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum. FINDINGS: Between 2010 and 2012, 214,070 of 220,235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100,000 live births, ranging from 69 per 100,000 in Argentina to 316 per 100,000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97-11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26-5.67) and 7-day (RR: 3.94; 95% CI: 2.74-5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54-9.77). CONCLUSION: Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality.OBJECTIF: Quantifier la mortalité maternelle, foetale et néonatale dans les pays à revenus faible et intermédiaire pour identifier à quel moment survient le décès et pour analyser les relations entre les décès maternels et les mortinaissances/décès néonataux. MÉTHODES: Une étude prospective sur des grossesses a été effectuée dans 106 collectivités sur 7 sites: Argentine, Guatemala, Inde, Kenya, Pakistan et Zambie. Les femmes enceintes ont été inscrites et suivies jusqu’à 6 semaines après leur accouchement. RÉSULTATS: Entre 2010 et 2012, 214 070 femmes inscrites sur 220 235 (97,2%) ont participé au suivi. Le taux de mortalité maternelle était de 168 pour 100 000 naissances d’enfants vivants, allant de 69 pour 100 000 en Argentine à 316 pour 100 000 au Pakistan. Dans l’ensemble, 29% (98/336) des décès maternels ont eu lieu au moment de la naissance: la plupart des décès ont été dus à une hémorragie (86/336), une prééclampsie ou une éclampsie (55/336), ou encore une septicémie (39/336). Environ 70% (4349/6213) des enfants sont mortnés intrapartum; 34% (1804/5230) des nouveau-nés sont morts le jour de leur naissance et 14% (755/5230) le lendemain. Les mortinaissances étaient plus fréquentes chez les femmes qui ont aussi perdu la vie que chez celles qui ont survécu 6 semaines après l’accouchement (risque relatif, RR: 9,48; intervalle de confiance à 95%, IC: 7,97–11,27), pour les décès périnatals (RR: 4,30; IC à 95%: 3,26–5,67), à 7 jours (RR: 3,94; IC à 95%: 2,74–5,65), et à 28 jours (RR: 7,36; IC à 95%: 5,54–9,77). CONCLUSION: La plupart des cas de mortalité maternelle, foetale et néonatale se sont produits pendant ou peu avant ou après la naissance et ont été attribués à des causes évitables. La mortalité maternelle a augmenté le risque de mort périnatale et néonatale. L’amélioration des soins obstétricaux et néonatals au moment de la naissance offre les meilleures chances de réduire cette mortalité.Fil: Saleem, Sarah. Aga Khan University; PakistánFil: McClure, Elizabeth M.. RTI International. Social, Statistical and Environmental Sciences; Estados UnidosFil: Goudar, Shivaprasad S.. KLE University. Jawaharlal Nehru Medical College; BélgicaFil: Patel, Archana. Lata Medical Research Foundation; IndiaFil: Esamai, Fabián. Moi University. Department of Pediatrics; KeniaFil: Garces, Ana. Universidad Francisco Marroquin; GuatemalaFil: Chomba, Elwyn. University of Zambia. Department of Pediatrics; ZambiaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Moore, Janet. RTI International. Social, Statistical and Environmental Sciences; Estados UnidosFil: Kodkany, Bhalachandra. KLE University. Jawaharlal Nehru Medical College; BélgicaFil: Pasha, Omrana. Aga Khan University; PakistánFil: Belizan, Jose. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mayansyan, Albert. University of North Carolina; Estados UnidosFil: Derman, Richard J.. Christiana Health Care. Department of Obstetrics and Gynecology; Estados UnidosFil: Hibberd, Patricia L.. Massachusetts General Hospital for Children. Department of Pediatrics; Estados UnidosFil: Liechty, Edward A.. Indiana University; Estados UnidosFil: Krebs, Nancy F.. University of Colorado Health Sciences Center. Department of Pediatrics; Estados UnidosFil: Hambidge, K. Michael. University of Colorado Health Sciences Center. Department of Pediatrics; Estados UnidosFil: Buekens, Pierre. University of Tulane; Estados UnidosFil: Carlo, Waldemar A.. University of North Carolina; Estados UnidosFil: Wright, Linda L.. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Jobe, Alan H.. Cincinnati Children’s Hospital. Department of Pediatrics; Estados UnidosFil: Goldenberg, Robert L.. Columbia University; Estados Unido

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry

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