A comparison of MITS counseling and informed consent processes in Pakistan, India, Bangladesh, Kenya, and Ethiopia

Globally, more than 5 million stillbirths and neonatal deaths occur annually. For many, the cause of death (CoD) is unknown. Minimally invasive tissue sampling (MITS) has been increasingly used in postmortem examinations for ascertaining the CoD in stillbirths and neonates. Our study compared the counseling and consent methods used in MITS projects in five countries in Africa and south Asia. Key informant interviews were conducted with researchers to describe the characteristics and backgrounds of counselors, the environment and timing of consent and perceived facilitators and barriers encountered during the consent process. Counselors at all sites had backgrounds in social science, psychology and counseling or clinical expertise in obstetrics/gynecology or pediatrics. All counsellors received training about techniques for building rapport and offering emotional support to families; training duration and methods differed across sites. Counselling environments varied significantly; some sites allocated a separate room, others counselled families at the bedside or nursing stations. All counsellors had a central role in explaining the MITS procedure to families in their local languages. Most sites did not use visual aids during the process, relying solely on verbal descriptions. In most sites, parents were approached within one hour of death. The time needed for decision making by families varied from a few minutes to 24 h. In most sites, extended family took part in the decision making. Because many parents wanted burial as soon as possible, counsellors ensured that MITS would be conducted promptly after receiving consent. Barriers to consent included decreased comprehension of information due to the emotional and psychological impact of grief. Moreover, having more family members engaged in decision-making increased the complexity of counselling and achieving consensus to consent for the procedure. While each site adapted their approach to fit the context, consistencies and similarities across sites were observed

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 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

Safety of daily low-dose aspirin use during pregnancy in low-income and middle-income countries

Background: The daily use of low-dose aspirin may be a safe, widely available, and inexpensive intervention for reducing the risk of preterm birth. Data on the potential side effects of low-dose aspirin use during pregnancy in low- and middle-income countries are needed.Objective: This study aimed to assess differences in unexpected emergency medical visits and potential maternal side effects from a randomized, double-blind, multicountry, placebo-controlled trial of low-dose aspirin use (81 mg daily, from 6 to 36 weeks\u27 gestation).Study design: This study was a secondary analysis of data from the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial, a trial of the Global Network for Women\u27s and Children\u27s Health conducted in India (2 sites), Pakistan, Guatemala, Democratic Republic of the Congo, Kenya, and Zambia. The outcomes for this analysis were unexpected emergency medical visits and the occurrence of the following potential side effects-overall and separately-nausea, vomiting, rash or hives, diarrhea, gastritis, vaginal bleeding, allergic reaction, and any other potential side effects. Analyses were performed overall and by geographic region.Results: Between the aspirin (n=5943) and placebo (n=5936) study groups, there was no statistically significant difference in the risk of unexpected emergency medical visits or the risk of any potential side effect (overall). Of the 8 potential side effects assessed, only 1 (rash or hives) presented a different risk by treatment group (4.2% in the aspirin group vs 3.5% in the placebo group; relative risk, 1.20; 95% confidence interval, 1.01-1.43; P=.042).Conclusion: The daily use of low-dose aspirin seems to be a safe intervention for reducing the risk of preterm birth and well tolerated by nulliparous pregnant women between 6 and 36 weeks\u27 gestation in low- and middle-income countries

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

The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe): a protocol of a prospective, cohort study of causes of mortality among preterm births and stillbirths

Background: In South Asia, where most stillbirths and neonatal deaths occur, much remains unknown about the causes of these deaths. About one-third of neonatal deaths are attributed to prematurity, yet the specific conditions which cause these deaths are often unclear as is the etiology of stillbirths. In low-resource settings, most women are not routinely tested for infections and autopsy is rare.Methods: This prospective, cohort study will be conducted in hospitals in Davengere, India and Karachi, Pakistan. All women who deliver either a stillbirth or a preterm birth at one of the hospitals will be eligible for enrollment. With consent, the participant and, when applicable, her offspring, will be followed to 28-days post-delivery. A series of research tests will be conducted to determine infection and presence of other conditions which may contribute to the death. In addition, all routine clinical investigations will be documented. For both stillbirths and preterm neonates who die ≤ 28 days, with consent, a standard autopsy as well as minimally invasive tissue sampling will be conducted. Finally, an expert panel will review all available data for stillbirths and neonatal deaths to determine the primary and contributing causes of death using pre-specified guidance.Conclusion: This will be among the first studies to prospectively obtain detailed information on causes of stillbirth and preterm neonatal death in low-resource settings in Asia. Determining the primary causes of death will be important to inform strategies most likely to reduce the high mortality rates in South Asia

Evaluating the effect of care around labor and delivery practices on early neonatal mortality in the global network\u27s maternal and newborn health registry

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\u27s (UN\u27s) 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\u27s 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\u27s Global Network\u27s (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 \u3c 0.0001]. Despite an overall association between CAD and early neonatal mortality (RR \u3c 1.0 for all early mortality): delivery by skilled birth attendant; presence of fetal heart and delayed bathing were associated with increased early neonatal mortality.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

Anthropometric indices for non-pregnant women of childbearing age differ widely among four low-middle income populations

Background: Maternal stature and body mass indices (BMI) of non-pregnant women (NPW) of child bearing age are relevant to maternal and offspring health. The objective was to compare anthropometric indices of NPW in four rural communities in low- to low-middle income countries (LMIC).Methods: Anthropometry and maternal characteristics/household wealth questionnaires were obtained for NPW enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass index (BMI, kg/m2) was calculated. Z-scores were determined using WHO reference data.Results: A total of 7268 NPW participated in Equateur, DRC (n = 1741); Chimaltenango, Guatemala (n = 1695); North Karnataka, India (n = 1823); and Thatta, Sindh, Pakistan (n = 2009). Mean age was 23 y and mean parity 1.5. Median (P25-P75) height (cm) ranged from 145.5 (142.2-148.9) in Guatemala to 156.0 (152.0-160.0) in DRC. Median weight (kg) ranged from 44.7 (39.9-50.3) in India to 52.7 (46.9-59.8) in Guatemala. Median BMI ranged from 19.4 (17.6-21.9) in India to 24.9 (22.3-28.0) in Guatemala. Percent stunted (\u3c-2SD height for age z-score) ranged from 13.9% in DRC to 80.5% in Guatemala; % underweight (BMI \u3c18.5) ranged from 1.2% in Guatemala to 37.1% in India; % overweight/obese (OW, BMI ≥25.0) ranged from 5.7% in DRC to 49.3% in Guatemala. For all sites, indicators for higher SES and higher age were associated with BMI. Lower SES women were underweight more frequently and higher SES women were OW more frequently at all sites. Younger women tended to be underweight, while older women tended to be OW.Conclusions: Anthropometric data for NPW varied widely among low-income rural populations in four countries located on three different continents. Global comparisons of anthropometric measurements across sites using standard reference data serve to highlight major differences among populations of low-income rural NPW and assist in evaluating the rationale for and the design of optimal intervention trials

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