Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study: protocol of a pragmatic clinical effectiveness study to improve birth outcomes in Ethiopia.

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.

A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings.

BACKGROUND: Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality. METHODS: The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations. RESULTS: Bili-ruler scores on the nose were correlated with TcB and TSB levels (r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another (N = 88). CONCLUSIONS: The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy.

Global Burden, Epidemiologic Trends, and Prevention of Intrapartum-Related Deaths in Low-Resource Settings.

Intrapartum-related neonatal deaths include live-born infants who die in the first 28 days of life from neonatal encephalopathy or die before onset of neonatal encephalopathy and have evidence of intrapartum injury. A smaller portion of the population in poorer countries has access to basic obstetric and postnatal care causing neonatal mortality rates to be higher. Presence of a skilled birth attendant and provision of basic emergency obstetric care can reduce intrapartum birth asphyxia by 40%. With the announcement of Sustainable Development Goals and global Every Newborn Action Plan, there is hope that interventions around continuum of care will save lives.

Maternal and child health in yushu, qinghai province, china.

INTRODUCTION: Surmang, Qinghai Province is a rural nomadic Tibetan region in western China recently devastated by the 2010 Yushu earthquake; little information is available on access and coverage of maternal and child health services. METHODS: A cross-sectional household survey was conducted in August 2004. 402 women of reproductive age (15-50) were interviewed regarding their pregnancy history, access to and utilization of health care, and infant and child health care practices. RESULTS: Women's access to education was low at 15% for any formal schooling; adult female literacy was <20%. One third of women received any antenatal care during their last pregnancy. Institutional delivery and skilled birth attendance were <1%, and there were no reported cesarean deliveries. Birth was commonly attended by a female relative, and 8% of women delivered alone. Use of unsterilized instrument to cut the umbilical cord was nearly universal (94%), while coverage for tetanus toxoid immunization was only 14%. Traditional Tibetan healers were frequently sought for problems during pregnancy (70%), the post partum period (87%), and for childhood illnesses (74%). Western medicine (61%) was preferred over Tibetan medicine (9%) for preventive antenatal care. The average time to reach a health facility was 4.3 hours. Postpartum infectious morbidity appeared to be high, but only 3% of women with postpartum problems received western medical care. 64% of recently pregnant women reported that they were very worried about dying in childbirth. The community reported 3 maternal deaths and 103 live births in the 19 months prior to the survey. CONCLUSIONS: While China is on track to achieve national Millennium Development Goal targets for maternal and child health, women and children in Surmang suffer from substantial health inequities in access to antenatal, skilled birth and postpartum care. Institutional delivery, skilled attendance and cesarean delivery are virtually inaccessible, and consequently maternal and infant morbidity and mortality are likely high. Urgent action is needed to improve access to maternal, neonatal and child health care in these marginalized populations. The reconstruction after the recent earthquake provides a unique opportunity to link this population with the health system.