Human Milk Micronutrients and Child Growth and Body Composition in the First 2 years: A Systematic Review.

Human milk (HM) provides a plethora of nutritional and non-nutritional compounds that support infant development. For many compounds, concentrations vary substantially among mothers and across lactation, and their impact on infant growth is poorly understood. We systematically searched MEDLINE, Embase, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. Outcomes included weight-for-length, length-for-age, weight-for-age, body mass index (in kg/m2)-for-age, and growth velocity. From 9992 abstracts screened, 144 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Micronutrients (vitamins and minerals) are reported here, based on 28 articles involving 2526 mother-infant dyads. Studies varied markedly in their designs, sampling times, geographic and socioeconomic settings, reporting practices, and the HM analytes and infant anthropometrics measured. Meta-analysis was not possible because data were sparse for most micronutrients. The most-studied minerals were zinc (15 articles, 1423 dyads) and calcium (7 articles, 714 dyads). HM iodine, manganese, calcium, and zinc concentrations were positively associated with several outcomes (each in ≥2 studies), whereas magnesium (in a single study) was negatively associated with linear growth during early lactation. However, few studies measured HM intake, adjusted for confounders, provided adequate information about complementary and formula feeding, or adequately described HM collection protocols. Only 4 studies (17%) had high overall quality scores. The biological functions of individual HM micronutrients are likely influenced by other HM components; yet, only 1 study analyzed data from multiple micronutrients simultaneously, and few addressed other HM components. Thus, available evidence on this topic is largely inconclusive and fails to address the complex composition of HM. High-quality research employing chronobiology and systems biology approaches is required to understand how HM components work independently and together to influence infant growth and to identify new avenues for future maternal, newborn, or infant nutritional interventions.

Process evaluation of paediatric fellowship training programs at a University Hospital in Pakistan.

BACKGROUND: Fellowship programs offer training in a subspecialty focusing on distinct and advanced clinical/academic skills. This advanced postgraduate training allows physicians, who desire a more specialized practice, to further develop clinical, academic, research, and leadership/administrative skills. The Aga Khan University (AKU) is one of the few institutes offering paediatric sub-specialty training in Pakistan. We aimed to evaluate the current Paediatric fellowship programs at AKU. METHODS: Process evaluation of six paediatric fellowship programs (cardiology, neurology, endocrinology, critical care medicine, neonatology, and infectious disease) was conducted from September 2020 to April 2021 by senior clinicians and medical educationists. Evidence was collected through document review (using existing postgraduate medical education program information form), observation of teaching and learning support, and focused group discussions/interviews with program faculty and fellows were conducted. A review of the evaluation report was done as part of this study. This study received an exemption from the ethical review committee. The quantitative data were analyzed using SPSS (22.0) while the reports of discussion with fellows and friends underwent content analysis. RESULTS: All fellowship programs met the criteria for having a robust competency-based fellowship curriculum as per the institutional and national guidelines. Formative assessment in the form of continuous evaluation was found to be integrated into all the fellowship programs, however, most of the programs were found to lack a summative assessment plan. Fellows in training and program faculty were satisfied with the opportunities for mentorship, teaching, and learning. Thematic analysis of the discussion reports with faculty and fellows revealed three key themes including, program aspects translating into strengthening the training, gaps in the training program in delivering the expectations, and making ways to reach par excellence. CONCLUSIONS: The process evaluation of paediatric fellowship programs provided an opportunity to holistically review the current strengths and quality of the training in individual programs along with the unmet needs of the trainees. This will help the program stakeholders to prioritize, align and allocate the resources to further enhance the quality of training and outcome of individual fellowship programs to ensure wider impacts at a regional, national, and international health system level.

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.

World Health Organization and knowledge translation in maternal, newborn, child and adolescent health and nutrition.

The World Health Organization (WHO) has a mandate to promote maternal and child health and welfare through support to governments in the form of technical assistance, standards, epidemiological and statistical services, promoting teaching and training of healthcare professionals and providing direct aid in emergencies. The Strategic and Technical Advisory Group of Experts (STAGE) for maternal, newborn, child and adolescent health and nutrition (MNCAHN) was established in 2020 to advise the Director-General of WHO on issues relating to MNCAHN. STAGE comprises individuals from multiple low-income and middle-income and high-income countries, has representatives from many professional disciplines and with diverse experience and interests.Progress in MNCAHN requires improvements in quality of services, equity of access and the evolution of services as technical guidance, community needs and epidemiology changes. Knowledge translation of WHO guidance and other guidelines is an important part of this. Countries need effective and responsive structures for adaptation and implementation of evidence-based interventions, strategies to improve guideline uptake, education and training and mechanisms to monitor quality and safety. This paper summarises STAGE's recommendations on how to improve knowledge translation in MNCAHN. They include support for national and regional technical advisory groups and subnational committees that coordinate maternal and child health; support for national plans for MNCAHN and their implementation and monitoring; the production of a small number of consolidated MNCAHN guidelines to promote integrated and holistic care; education and quality improvement strategies to support guidelines uptake; monitoring of gaps in knowledge translation and operational research in MNCAHN.

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.

Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial.

BACKGROUND: Infection in young infants is a major cause of morbidity and mortality in low-middle income countries, with high neonatal mortality rates. Timely case management is lifesaving, but the current standard of hospitalization for parenteral antibiotic therapy is not always feasible. Alternative, simpler antibiotic regimens that could be used in outpatient settings have the potential to save thousands of lives. METHODS: This trial aims to determine whether 2 simplified antibiotic regimens are equivalent to the reference therapy with 7 days of once-daily (OD) intramuscular (IM) procaine penicillin and gentamicin for outpatient management of young infants with clinically presumed systemic bacterial infection treated in primary health-care clinics in 5 communities in Karachi, Pakistan. The reference regimen is close to the current recommendation of the hospital-based intravenous ampicillin and gentamicin therapy for neonatal sepsis. The 2 comparison arms are (1) IM gentamicin OD and oral amoxicillin twice daily for 7 days; and (2) IM penicillin and gentamicin OD for 2 days, followed by oral amoxicillin twice daily for 5 days; 2250 "evaluable" infants will be enrolled. The primary outcome of this trial is treatment failure (death, deterioration or lack of improvement) within 7 days of enrollment. Results are expected by early 2014. DISCUSSION: This trial will determine whether simplified antibiotic regimens with fewer injections in combination with high-dose amoxicillin are equivalent to 7 days of IM procaine penicillin and gentamicin in young infants with clinical severe infection. Results will have program and policy implications in countries with limited access to hospital care and high burden of neonatal deaths.