Marion Koso-Thomas

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial

BACKGROUND Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The Maternal and Newborn Health Registry Study of the Global Network for Women's and Children's Health Research

To implement a vital statistics registry system to register pregnant women and document birth outcomes in the Global Network for Womens and Childrens Health Research sites in Asia, Africa, and Latin America.

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). 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.

Epidemiology of stillbirth in low-middle income countries: A Global Network Study

Objective. To determine population‐based stillbirth rates and to determine whether the timing and maturity of the stillbirths suggest a high proportion of potentially preventable deaths. Design. Prospective observational study. Setting. Communities in six low‐income countries (Democratic Republic of Congo, Kenya, Zambia, Guatemala, India, and Pakistan) and one site in a mid‐income country (Argentina). Population. Pregnant women residing in the study communities. Methods. Over a five‐year period, in selected catchment areas, using multiple methodologies, trained study staff obtained pregnancy outcomes on each delivery in their area. Main outcome measures. Pregnancy outcome, stillbirth characteristics. Results. Outcomes of 195 400 deliveries were included. Stillbirth rates ranged from 32 per 1 000 in Pakistan to 8 per 1 000 births in Argentina. Three‐fourths (76%) of stillbirth offspring were not macerated, 63% were ≥37 weeks and 48% weighed 2 500g or more. Across all sites, women with no education, of high and low parity, of older age, and without access to antenatal care were at significantly greater risk for stillbirth (p<0.001). Compared to those delivered by a physician, women delivered by nurses and traditional birth attendants had a lower risk of stillbirth. Conclusions. In these low‐middle income countries, most stillbirth offspring were not macerated, were reported as ≥37 weeks’ gestation, and almost half weighed at least 2 500g. With access to better medical care, especially in the intrapartum period, many of these stillbirths could likely be prevented.

Communities, birth attendants and health facilities: a continuum of emergency maternal and newborn care (the global network's EmONC trial)

BackgroundMaternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven. Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes.Methods/DesignWe have developed a cluster-randomized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization, birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities. This trial will take place in 106 clusters (300-500 deliveries per year each) across 7 sites of the Global Network for Womens and Childrens Health Research in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. The trial intervention has three key elements, community mobilization, home-based life saving skills for communities and birth attendants, and training of providers at obstetric facilities to improve quality of care. The primary outcome of the trial is perinatal mortality. Secondary outcomes include rates of stillbirth, 7-day neonatal mortality, maternal death or severe morbidity (including obstetric fistula, eclampsia and obstetrical sepsis) and 28-day neonatal mortality.DiscussionIn this trial, we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes. If successful, the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries.Trial RegistrationClinicalTrials.gov NCT01073488

Adverse maternal and perinatal outcomes in adolescent pregnancies: The Global Network’s Maternal Newborn Health Registry study

BackgroundAdolescent girls between 15 and 19 years give birth to around 16 million babies each year, around 11% of births worldwide. We sought to determine whether adolescent mothers are at higher risk of maternal and perinatal adverse outcomes compared with mothers aged 20–24 years in a prospective, population-based observational study of newborn outcomes in low resource settings.MethodsWe undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in six low-middle income countries (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). The study population for this analysis was restricted to women aged 24 years or less, who gave birth to infants of at least 20 weeks’ gestation and 500g or more. We compared adverse pregnancy maternal and perinatal outcomes among pregnant adolescents 15-19 years, <15 years, and adults 20-24 years.ResultsA total of 269,273 women were enrolled from January 2010 to December 2013. Of all pregnancies 11.9% (32,097/269,273) were in adolescents 15-19 years, while 0.14% (370/269,273) occurred among girls <15 years. Pregnancy among adolescents 15-19 years ranged from 2% in Pakistan to 26% in Argentina, and adolescent pregnancies <15 year were only observed in sub-Saharan Africa and Latin America. Compared to adults, adolescents did not show increased risk of maternal adverse outcomes. Risks of preterm birth and LBW were significantly higher among both early and older adolescents, with the highest risks observed in the <15 years group. Neonatal and perinatal mortality followed a similar trend in sub-Saharan Africa and Latin America, with the highest risk in early adolescents, although the differences in this age group were not significant. However, in South Asia the risks of neonatal and perinatal death were not different among adolescents 15-19 years compared to adults.ConclusionsThis study suggests that pregnancy among adolescents is not associated with worse maternal outcomes, but is associated with worse perinatal outcomes, particularly in younger adolescents. However, this may not be the case in regions like South Asia where there are decreasing rates of adolescent pregnancies, concentrated among older adolescents. The increased risks observed among adolescents seems more likely to be associated with biological immaturity, than with socio-economic factors, inadequate antenatal or delivery care.Trial registration numberNCT01073475

Home birth attendants in low income countries: who are they and what do they do?

BackgroundNearly half the world’s babies are born at home. We sought to evaluate the training, knowledge, skills, and access to medical equipment and testing for home birth attendants across 7 international sites.MethodsFace-to-face interviews were done by trained interviewers to assess level of training, knowledge and practices regarding care during the antenatal, intrapartum and postpartum periods. The survey was administered to a sample of birth attendants conducting home or out-of-facility deliveries in 7 sites in 6 countries (India, Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia).ResultsA total of 1226 home birth attendants were surveyed. Less than half the birth attendants were literate. Eighty percent had one month or less of formal training. Most home birth attendants did not have basic equipment (e.g., blood pressure apparatus, stethoscope, infant bag and mask manual resuscitator). Reporting of births and maternal and neonatal deaths to government agencies was low. Indian auxilliary nurse midwives, who perform some home but mainly clinic births, were far better trained and differed in many characteristics from the birth attendants who only performed deliveries at home.ConclusionsHome birth attendants in low-income countries were often illiterate, could not read numbers and had little formal training. Most had few of the skills or access to tests, medications and equipment that are necessary to reduce maternal, fetal or neonatal mortality.

Postpartum contraceptive use and unmet need for family planning in five low-income countries

BackgroundDuring the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period.MethodsUsing the NICHD Global Network for Women’s and Children’s Health Research’s multi-site, prospective, ongoing, active surveillance system to track pregnancies and births in 100 rural geographic clusters in 5 countries (India, Pakistan, Zambia, Kenya and Guatemala), we assessed fertility intention and contraceptive usage at day 42 post-partum.ResultsWe gathered data on 36,687 women in the post-partum period. Less than 5% of these women wished to have another pregnancy within the year. Despite this, rates of modern contraceptive usage varied widely and unmet need ranged from 25% to 96%. Even amongst users of modern contraceptives, the uptake of the most effective long-acting reversible contraceptives (intrauterine devices) was low. Women of age less than 20 years, parity of two or less, limited education and those who deliver at home were at highest risk for having unmet need.ConclusionsSix weeks postpartum, almost all women wish to delay or prevent a future pregnancy. Even in sites where early contraceptive adoption is common, there is substantial unmet need for family planning. This is consistently highest amongst women below the age of 20 years. Interventions aimed at increasing the adoption of effective contraceptive methods are urgently needed in the majority of sites in order to reduce unmet need and to improve both maternal and infant outcomes, especially amongst young women.Study registrationClinicaltrials.gov (ID# NCT01073475)

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

BackgroundStillbirth 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.MethodsWe 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.ResultsFrom 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%).ConclusionsStillbirth 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 registrationClinicaltrials.gov (ID# NCT01073475)

First look: a cluster-randomized trial of ultrasound to improve pregnancy outcomes in low income country settings

BackgroundIn high-resource settings, obstetric ultrasound is a standard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care. Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-resource settings is unknown.Methods/DesignThis multi-country cluster randomized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss, stillbirth and neonatal mortality in low-resource community settings. The trial will utilize an existing research infrastructure, the Global Network for Women’s and Children’s Health Research with sites in Pakistan, Kenya, Zambia, Democratic Republic of Congo and Guatemala. A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population-based rates of maternal mortality and morbidity, stillbirth, neonatal mortality and morbidity, and health care utilization for study clusters. A total of 58 study clusters each with a health center and about 500 births per year will be randomized (29 intervention and 29 control). The intervention includes training of health workers (e.g., nurses, midwives, clinical officers) to perform ultrasound examinations during antenatal care, generally at 18–22 and at 32–36 weeks for each subject. Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care. Finally, the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities.DiscussionIn summary, our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural, low-resource settings. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately.Trial registrationClinicaltrials.gov (NCT # 01990625)