Summary 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.

Highlights As implemented, the CLIP intervention did not improve the primary composite outcome. ASHAs and ANMs were able to undertake all aspects of the mobile health app-guided visits. Women could not be reached in their communities as frequently as planned. Eight or more POM-guided contacts were associated with fewer stillbirths supporting WHO guidance. Community-level interventions are unlikely to improve outcomes without enhanced facility care.

Summary Background To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries. Methods In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014–17. Consenting pregnant women, aged 12–49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564. Findings Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22–30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90–1·51; p=0·24). No intervention-related serious adverse events occurred, and few adver...

Existing vital health statistics registries in India have been unable to provide reliable estimates of maternal and newborn mortality and morbidity, and region-specific health estimates are essential to the planning and monitoring of health interventions. This study was designed to assess baseline rates as the precursor to a community-based cluster randomized control trial (cRCT)–Community Level Interventions for Pre-eclampsia (CLIP) Trial (NCT01911494; CTRI/2014/01/004352). The objective was to describe baseline demographics and health outcomes prior to initiation of the CLIP trial and to improve knowledge of population-level health, in particular of maternal and neonatal outcomes related to hypertensive disorders of pregnancy, in northern districts the state of Karnataka, India. The prospective population-based survey was conducted in eight clusters in Belgaum and Bagalkot districts in Karnataka State from 2013–2014. Data collection was undertaken by adapting the Maternal and Newborn Health registry platform, developed by the Global Network for Women’s and Child Health Studies. Descriptive statistics were completed using SAS and R. During the period of 2013–2014, prospective data was collected on 5,469 pregnant women with an average age of 23.2 (+/-3.3) years. Delivery outcomes were collected from 5,448 completed pregnancies. A majority of the women reported institutional deliveries (96.0%), largely attended by skilled birth attendants. The maternal mortality ratio of 103 (per 100,000 livebirths) was observed during this study, neonatal mortality ratio was 25 per 1,000 livebirths, and perinatal mortality ratio was 50 per 1,000 livebirths. Despite a high number of institutional deliveries, rates of stillbirth were 2.86%. Early enrollment and close follow-up and monitoring procedures established by the Maternal and Newborn Health registry allowed for negligible lost to follow-up. This population-level study provides regional rates of maternal and newborn health in Belgaum and Bagalkot in Karnataka over 2013–14. The mortality ratios and morbidity information can be used in planning interventions and monitoring indicators of effectiveness to inform policy and practice. Comprehensive regional epidemiologic data, such as that provided here, is essential to gauge improvements and challenges in maternal health, as well as track disparities found in rural areas.