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.

Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan-a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial).

BACKGROUND: Maternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. METHODS: The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and < 19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of nicotinamide and choline (intervention arm 3). TRIAL REGISTRATION: ClinicalTrials.gov NCT04012177 . Registered on July 9, 2019.

Implementation of the ANISA Study in Karachi, Pakistan: Challenges and Solutions.

BACKGROUND: Aetiology of Neonatal Infection in South Asia (ANISA) is a multicenter study in Bangladesh, India and Pakistan exploring the incidence and etiology of neonatal infections. A periurban site in Karachi was selected for its representativeness of the general population in neonatal health indicators. An established demographic surveillance system and other infrastructure needed for conducting the study already existed at this site. ANISA presents a unique challenge because of the need to capture every birth outcome in the community within a few hours of delivery to reliably estimate the incidence and etiology of early-onset sepsis in a setting where home births and deaths are common. CONTEXTUAL CHALLENGES: Major challenges at the Karachi site are related to early birth reporting and newborn assessment for births outside the catchment areas, parental refusal to participate, diverse ethnicity of the population, collection of biological specimens from healthy controls, political instability and crime, power outages and blood culture contamination. Some of the remedial actions taken include prolonging working hours; developing counseling skills of field workers; hiring staff with different linguistic abilities from within the study community; liaising with health facilities, key community informants, Lady Health Workers and traditional birth attendants; hiring community mobilizers; enhancing community sensitization; developing contingency plans for field work interruptions and procuring backup generators. The specimen contamination rate has decreased through training, supervision and video monitoring of blood collection procedures with individualized counseling of phlebotomists. CONCLUSION: ANISA offers lessons for successful implementation of complex study protocols in areas of high child mortality and challenging social environments.