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There is an urgent need to better understand the micronutrient demands of pregnancy due to the complex physiological adaptations during the gestational period and the importance of micronutrients in maternal-fetal health. Rigorous studies of micronutrients in pregnancy are significantly lacking due to a number of issues including the exclusion of pregnant people in research, methodological barriers to studying micronutrients, and the multidisciplinary expertise required for such studies. Stable isotopes present a unique methodological opportunity to quantify pregnancy-related changes in the absorption, distribution, metabolism, and excretion of micronutrients. We demonstrate here through a rapid review of the published literature that this approach is dramatically underutilized outside of calcium. In this perspective, we discuss the use of stable isotopes to study micronutrient physiology and our experiences in addressing the need for more studies in this area. Finally, we discuss how we might overcome major barriers to move toward a better understanding of micronutrient physiology in pregnancy.

To describe the epidemiology and referral patterns of gastroschisis patients in northern Ghana. A hospital-based retrospective review was undertaken at Tamale Teaching Hospital (TTH) Neonatal Intensive Care Unit (NICU) between 2014 and 2019. Data from gastroschisis patients were compared to patients with other surgical diagnoses. Descriptive and inferential statistics were performed with SAS. Referral flow maps were made with ArcGIS. From a total of 360 neonates admitted with surgical conditions, 12 (3%) were diagnosed with gastroschisis. Around 91% (n = 10) of gastroschisis patients were referred from other hospitals, traveling 4 h, on average. Referral patterns showed gastroschisis patients were admitted from three regions, whereas patients with other surgical diagnoses were admitted from eight regions. Only 6% (12/201) of expected gastroschisis cases were reported during the 6-year period in all regions. All gastroschisis deaths occurred within the first week of life. Improving access to surgical care and reducing neonatal mortality related to gastroschisis in northern Ghana is critical. This study provides a baseline to inform future gastroschisis interventions at TTH. Priority areas may include special management of low birth weight newborns, better referral systems, empowerment of community health workers, and increasing access to timely, affordable, and safe neonatal transport.

Critical advancement is needed in the study of human milk as a biological system that intersects and interacts with myriad internal (maternal biology) and external (diet, environment, infections) factors and its plethora of influences on the developing infant. Human-milk composition and its resulting biological function is more than the sum of its parts. Our failure to fully understand this biology in a large part contributes to why the duration of exclusive breastfeeding remains an unsettled science (if not policy). Our current understanding of human-milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation. The overly simplistic, but common, approach to analyzing single, mostly nutritive components of human milk is insufficient to understand the contribution of either individual components or the matrix within which they exist to both maternal and child health. There is a need for a shift in the conceptual approach to studying human milk to improve strategies and interventions to support better lactation, breastfeeding, and the full range of infant feeding practices, particularly for women and infants living in undernourished and infectious environments. Recent technological advances have led to a rising movement towards advancing the science of human-milk biology. Herein, we describe the rationale and critical need for unveiling the multifunctionality of the various nutritional, nonnutritional, immune, and biological signaling pathways of the components in human milk that drive system development and maturation, growth, and development in the very early postnatal period of life. We provide a vision and conceptual framework for a research strategy and agenda to change the field of human-milk biology with implications for global policy, innovation, and interventions.

Nucleic acid (DNA and RNA) vaccines are among the most advanced vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. This will facilitate the assessment by key stakeholders of potential safety issues and understanding of overall benefit-risk. The structured assessment provided by the template can also help improve communication and public acceptance of licensed nucleic acid vaccines.

There are complex barriers that increase delays to surgical care in low- and middle-income countries, particularly among the vulnerable population of children. Understanding these barriers to surgical care can result in targeted and strategic intervention efforts to improve care for children. The three-delay model is a widely used framework in global health for evaluating barriers associated with seeking (D1), reaching (D2), and receiving health care (D3). The goal of our study is to evaluate reasons for delays in the surgical care for children in Somaliland using the three-delay framework. Data were collected in a cross-sectional study in Somaliland from 1503 children through a household survey. Among children with a surgical need, we quantified the number of children seeking, reaching, and receiving care along the surgical care continuum, according to the three-delay framework. We evaluated predictors of the three delays through a multivariate logistic regression model, including the child’s age, gender, village type, household income level, region, and household size. Of the 196 children identified with a surgical condition, 50 (27.3%) children had a delay in seeking care (D1), 28 (20.6%) children had a delay in reaching care (D2), and 84 (71.2%) children had a delay in receiving care (D3), including 10 children who also experienced D1 and D2. The main reasons cited for D1 included seeking a traditional healthcare provider, while lack of money and availability of care were main reasons cited for D2. Significant predictors for delays included household size for D1 and D3 and condition type and region for D2. Children in Somaliland experience several barriers to surgical care along the entire continuum of care, allowing for policy guidance tailored to specific local challenges and resources. Since delays in surgical care for children can substantially impact the effectiveness of surgical interventions, viewing delays in surgical care under the lens of the three-delay framework can inform strategic interventions along the pediatric surgical care continuum, thereby reducing delays and improving the quality of surgical care for children.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

BackgroundThe global burden of disease in children is large and disproportionally affects low-income and middle-income countries (LMICs). Geospatial analysis offers powerful tools to quantify and visualise disparities in surgical care in LMICs. Our study aims to analyse the geographical distribution of paediatric surgical conditions and to evaluate the geographical access to surgical care in Somaliland.MethodsUsing the Surgeons OverSeas Assessment of Surgical Need survey and a combined survey from the WHO’s (WHO) Surgical Assessment Tool—Hospital Walkthrough and the Global Initiative for Children’s Surgery Global Assessment in Paediatric Surgery, we collected data on surgical burden and access from 1503 children and 15 hospitals across Somaliland. We used several geospatial tools, including hotspot analysis, service area analysis, Voronoi diagrams, and Inverse Distance Weighted interpolation to estimate the geographical distribution of paediatric surgical conditions and access to care across Somaliland.ResultsOur analysis suggests less than 10% of children have timely access to care across Somaliland. Patients could travel up to 12 hours by public transportation and more than 2 days by foot to reach surgical care. There are wide geographical disparities in the prevalence of paediatric surgical conditions and access to surgical care across regions. Disparities are greater among children travelling by foot and living in rural areas, where the delay to receive surgery often exceeds 3 years. Overall, Sahil and Sool were the regions that combined the highest need and the poorest surgical care coverage.ConclusionOur study demonstrated wide disparities in the distribution of surgical disease and access to surgical care for children across Somaliland. Geospatial analysis offers powerful tools to identify critical areas and strategically allocate resources and interventions to efficiently scale-up surgical care for children in Somaliland.

Expansion of access to surgical care can improve health outcomes, although the impact that scale-up of the surgical workforce will have on child mortality is poorly defined. In this study, we estimate the number of child deaths potentially avertable by increasing the surgical workforce globally to meet targets proposed by the Lancet Commission on Global Surgery. To estimate the number of deaths potentially avertable through increases in the surgical workforce, we used log-linear regression to model the association between surgeon, anesthetist and obstetrician workforce (SAO) density and surgically amenable under-5 mortality rate (U5MR), infant mortality rate (IMR), and neonatal mortality rate (NMR) for 192 countries adjusting for potential confounders of childhood mortality, including the non-surgical workforce (physicians, nurses/midwives, community health workers), gross national income per capita, poverty rate, female literacy rate, health expenditure per capita, percentage of urban population, number of surgical operations, and hospital bed density. Surgically amenable mortality was determined using mortality estimates from the UN Inter-agency Group for Child Mortality Estimation adjusted by the proportion of deaths in each country due to communicable causes unlikely to be amenable to surgical care. Estimates of mortality reduction due to upscaling surgical care to support the Lancet Commission on Global Surgery (LCoGS) minimum target of 20–40 SAO/100,000 were calculated accounting for potential increases in surgical volume associated with surgical workforce expansion. Increasing SAO workforce density was independently associated with lower surgically amenable U5MR as well as NMR (p

Background Congenital anomalies have risen to become the fifth leading cause of under-five mortality globally. The majority of deaths and disability occur in low- and middle-income countries including Ghana. This 3-year retrospective review aimed to define, for the first time, the characteristics and outcomes of neonatal surgical conditions in northern Ghana. Methods A retrospective study was conducted to include all admissions to the Tamale Teaching Hospital (TTH) neonatal intensive care unit (NICU) with surgical conditions between January 2014 and January 2017. Data were collected on demographics, diagnosis and outcomes. Descriptive analysis was performed on all data, and logistic regression was used to predict determinants of neonatal mortality. p Results Three hundred and forty-seven neonates were included. Two hundred and sixty-one (75.2%) were aged 7 days or less at presentation, with males (n = 177, 52%) slightly higher than females (n = 165, 48%). The majority were delivered by spontaneous vaginal delivery (n = 247, 88%); 191 (58%) were born in hospital. Congenital anomalies accounted for 302 (87%) of the neonatal surgical cases and 45 (96%) deaths. The most common anomalies were omphalocele (n = 48, 13.8%), imperforate anus (n = 34, 9.8%), intestinal obstruction (n = 29, 8.4%), spina bifida (n = 26, 7.5%) and hydrocephalus (n = 19, 5.5%). The overall mortality rate was 13.5%. Two-thirds of the deaths (n = 30) from congenital anomalies were conditions involving the digestive system with gastroschisis having the highest mortality of 88%. Omphalocele (n = 11, 23.4%), gastroschisis (n = 7, 14.9%) and imperforate anus (n = 6, 12.8%) contributed to the most deaths. On multivariate analysis, low birthweight was significantly associated with mortality (OR 3.59, CI 1.4–9.5, p = 0.009). Conclusion Congenital anomalies are a major global health problem associated with high neonatal mortality in Ghana. The highest burden in terms of both caseload and mortality is attributed to congenital anomalies involving the digestive system, which should be targeted to improve outcomes.

ObjectiveTo assess whether sustained, scheduled mobile health team (MHT) services increase antenatal care (ANC), postnatal care (PNC) and childhood immunisation in conflict-affected and remote regions of Afghanistan.DesignCross-sectional, population-based study from 2013 to 2017. Proportions were compared using multivariable linear regression adjusted for clustering and socio-demographic variables.Setting54 intervention and 56 control districts in eight Afghanistan provinces.Participants338 796 pregnant women and 1 693 872 children aged under 5 years.Interventions‘Intervention districts’ that received MHT services for 3 years compared with ‘control districts’ in the same province without any MHT services over the same period.Main outcome measuresDistrict-level and clinic-level ANC, PNC, childhood immunisation (pentavalent 3, measles 1), integrated management of childhood immunisation services.ResultsProportion of pregnant women receiving at least one ANC visit was higher in intervention districts (83.6%, 161 750/193 482) than control districts (61.3%, 89 077/145 314) (adjusted mean difference (AMD) 14.8%;95% CI: 1.6% to 28.0%). Proportion of children under 1 year receiving their first dose of measles vaccine was higher in intervention (73.8%, 142 738/193 412) than control districts (57.3%, 83 253/145 293) (AMD 12.8;95% CI: 2.1% to 23.5%). There was no association with PNC (AMD 2.8%;95% CI: −5.1% to 10.7%). MHTs did not increase clinic-level service provision for ANC (AMD 41.32;95% CI: -52.46 to 135.11) or any other outcomes.ConclusionsSustained, scheduled MHT services to conflict-affected and remote regions were associated with improved coverage of important maternal and child health interventions. Outreach is an essential service and not just an ‘optional extra’ for the most deprived mothers and children.

Objectives Suboptimal breastfeeding contributes to morbidity and mortality in children. Studies in high-income countries (HICs) show that exclusive-breastfeeding (EBF) is associated with longer breastfeeding duration. The aim of this study was to determine whether maternal reports of EBF at six months are associated with longer duration of breastfeeding during the first two years of life in a low and middle-income country (LMIC) setting, and to identify determinants of breastfeeding duration. Methods This prospective cohort includes data from an EBF promotion program in Demak District, Central Java Province, Indonesia, with a non-randomized pretest-posttest control group. Mothers and infants were followed through 26 months postnatal age. Data were analyzed using Cox proportional hazard regression with time to cessation of EBF as the outcome. Results A total of 147 families were included in the study. Longer EBF duration was not associated with prolonged duration of breastfeeding. Longer breastfeeding duration was associated with mothers who disagreed with a statement of being ashamed to breastfeed (HR 0.035, 95%CI 0.003,0.44). Risk factors for shorter breastfeeding duration included mothers’ plan to breastfeed for less than 24 months (HR 4.28 95%CI 1.91,9.60), mothers’ belief that breastfeeding less than 24 months was the norm (HR 2.98 95%CI 1.31,6.77) and exposure to EBF promotion (HR:4.09 95%CI 2.14,7.82). Conclusions In a LMIC community where long breastfeeding duration is common, EBF is not associated with breastfeeding duration. However, modifiable behavioral factors were significant predictors of breastfeeding duration. We therefore recommend that prolonged breastfeeding duration can be achieved through programs that improve breastfeeding behavior.

Investing in surgery has been highlighted as integral to strengthening overall health systems and increasing economic prosperity in low-income and middle-income countries (LMICs). The provision of surgical care in LMICs not only affects economies on a macro-level, but also impacts individual families within communities at a microeconomic level. Given that children represent 50% of the population in LMICs and the burden of unmet surgical needs in these areas is high, investing pediatric-specific components of surgical and anesthesia care is needed. Implementation efforts for pediatric surgical care include incorporating surgery-specific priorities into the global child health initiatives, improving global health financing for scale-up activities for children, increasing financial risk protection mechanisms for families of children with surgical needs, and including comprehensive pediatric surgical models of care into country-level plans.

BackgroundBiannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results.MethodsInvestigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data.FindingsOverall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics.NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol 32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15).Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS.ConclusionNVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.

Background: The coronavirus disease (COVID-19) has spread worldwide with an increasing number of patients, including pregnant women and neonates. This study aims to evaluate morbidity and mortality in the COVID-19 era compared to the preceding year in the Neonatal Intensive Care Unit (NICU) at Tamale Teaching Hospital, Ghana.Methods: This is a cross-sectional study carried out on neonates admitted to NICU between March 1st to August 31st, 2019 (pre-COVID-19 era) and March 1st to August 31st, 2020 (COVID-19 era). Multivariate logistic regression was performed to identify predictors of mortality for both periods.Results: From 2,901 neonates, 1,616 (56%) were admitted before, and 1,285 (44%) were admitted during the pandemic. Admissions decreased during the COVID-19 era, reaching their lowest point between June and August 2020. Compared to the previous year, during the COVID-19 era, admissions of patients born at TTH, delivered at home, and with infections decreased from 50 to 39%, 7 to 4%, and 22 to 13%, respectively. Referred status (OR = 3.3) and vaginal delivery (OR = 1.6) were associated with an increased likelihood of mortality. For low- birth weight neonates, admissions of patients born at TTH, with vaginal and home delivery decreased from 62 to 48%, 8 to 2%, and 59 to 52%, respectively. Neonatal infections and congenital anomalies decreased from 8 to 4%, 5 to 3%, respectively. The likelihood of mortality among referred patients increased by 50%.Conclusion: We observed a marked decrease in admissions and change in the diagnosis landscape and related mortality during the pandemic. Underlying challenges, including fear, financing, and health system capacity, might intensify delays and lack of access to newborn care in northern Ghana, leading to higher rates of lifelong disabilities and mortality. Immediate damage control measures, including an improved home-based continuum of care and equipping families to participate in the newborn care with complemented m-health approaches, are needed with urgency.

Summary box The devastating impact of the COVID-19 pandemic can be partly attributed to a lack of evidence to inform effective prevention and treatment. The global scientific community has been racing against time to rapidly generate such evidence. Prospective meta-analysis (PMA) and other innovative approaches for pooling data from multiple studies are increasingly used and have the potential to expedite the pace at which knowledge is produced, especially for observational or surveillance data. However, investigators engaged in these innovative projects must leave behind some traditional practices of academic research.1 For that …

Introduction: Global surgical care is increasingly recognized in the global health agenda and requires multidisciplinary engagement. Despite high interest among medical students, residents and other learners, many surgical faculty and health experts remain uniformed about global surgical care. Methods: We have operated an interdisciplinary graduate-level course in Global Surgical Care based on didactics and interactive group learning. Students completed a pre- and post-course survey regarding their learning experiences and results were analyzed using the Wilcoxon signed-rank test. Results: Fourteen students completed the pre-course survey, and 11 completed the post-course survey. Eleven students (79%) were enrolled in a Master’s degree program in global health, with eight students (57%) planning to attend medical school. The median ranking of surgery on the global health agenda was fifth at the beginning of the course and third at the conclusion (p = 0.11). Non-infectious disease priorities tended to stay the same or increase in rank from pre- to post-course. Infectious disease priorities tended to decrease in rank (HIV/AIDS, p = 0.07; malaria, p = 0.02; neglected infectious disease, p = 0.3). Students reported that their understanding of global health (p = 0.03), global surgery (p = 0.001) and challenges faced by the underserved (p = 0.03) improved during the course. When asked if surgery was an indispensable part of healthcare, before the course 64% of students strongly agreed, while after the course 91% of students strongly agreed (p = 0.3). Students reported that the interactive nature of the course strengthened their skills in collaborative problem-solving. Conclusions: We describe an interdisciplinary global surgery course that integrates didactics with team-based projects. Students appeared to learn core topics and held a different view of global surgery after the course. Similar courses in global surgery can educate clinicians and other stakeholders about strategies for building healthy surgical systems worldwide.

Background Symptoms of mild COVID‐19 illness are non‐specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID‐19 are not well understood. Methods Adults aged ≥18 years with laboratory‐confirmed COVID‐19 and matched control patients who tested negative for SARS‐CoV‐2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health‐related quality of life. Duration of symptoms, health‐related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank‐sum tests. Symptoms associated with COVID‐19 case status were evaluated by multivariable logistic regression. Results Among 320 participants included, 157 were COVID‐19 cases and 163 were SARS‐CoV‐2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID‐19 in logistic regression models (adjusted odds ratio [aOR] = 32.4; 95% confidence interval [CI], 12.6‐83.1). COVID‐19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14 days after symptom onset (50% vs 32%, P

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health’s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. The Modified Vaccinia Ankara (MVA) vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features specifically of the MVA-BN vector system, followed by a template with details on the safety and characteristics of an MVA-BN based vaccine against Zaire ebolavirus and other filovirus strains. The MVA-BN-Filo vaccine is based on a live, highly attenuated poxviral vector incapable of replicating in human cells and encodes glycoproteins of Ebola virus Zaire, Sudan virus and Marburg virus and the nucleoprotein of the Thai Forest virus. This vaccine has been approved in the European Union in July 2020 as part of a heterologous Ebola vaccination regimen. The MVA-BN vector is attenuated following over 500 serial passages in eggs, showing restricted host tropism and incompetence to replicate in human cells. MVA has six major deletions and other mutations of genes outside these deletions, which all contribute to the replication deficiency in human and other mammalian cells. Attenuation of MVA-BN was demonstrated by safe administration in immunocompromised mice and non-human primates. In multiple clinical trials with the MVA-BN backbone, more than 7800 participants have been vaccinated, demonstrating a safety profile consistent with other licensed, modern vaccines. MVA-BN has been approved as smallpox vaccine in Europe and Canada in 2013, and as smallpox and monkeypox vaccine in the US in 2019. No signal for inflammatory cardiac disorders was identified throughout the MVA-BN development program. This is in sharp contrast to the older, replicating vaccinia smallpox vaccines, which have a known risk for myocarditis and/or pericarditis in up to 1 in 200 vaccinees. MVA-BN-Filo as part of a heterologous Ebola vaccination regimen (Ad26.ZEBOV/MVA-BN-Filo) has undergone clinical testing including Phase III in West Africa and is currently in use in large scale vaccination studies in Central African countries. This paper provides a comprehensive picture of the MVA-BN vector, which has reached regulatory approvals, both as MVA-BN backbone for smallpox/monkeypox, as well as for the MVA-BN-Filo construct as part of an Ebola vaccination regimen, and therefore aims to provide solutions to prevent disease from high-consequence human pathogens.

Several live-attenuated viral vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of live-attenuated viral vaccines. This will help key stakeholders assess potential safety issues and understand the benefit-risk of such vaccines. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed live-attenuated viral vaccines.

Replication-incompetent adenoviral vectors have been under investigation as a platform to carry a variety of transgenes, and express various antigens as a basis for preventive or therapeutic vaccine development. A replication incompetent adenoviral vector based on human adenovirus type 26 (Ad26) has been evaluated in several clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and features of recombinant viral vector vaccines. This paper reviews the biological features of the Ad26 vectors, including tabulation of safety and risk assessment characteristics of Ad26 vector-based vaccines. Substantial information on immunogenicity, clinical safety, biological characteristics and manufacturing are reported. In the Ad26 vector, deletion of the E1 gene, rendering the vector replication incompetent and providing space for transgene insertion, is combined with additional genetic engineering for vaccine manufacturability and transgene expression optimization. These vaccines are manufactured using the E1-complementing PER.C6® cell line, a continuous, human cell-line that can be cultured in serum-free medium in a suspension to high cell densities, providing an effective and flexible system for high-yield manufacturing. Ad26 vector vaccines have favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the Ad26 vaccine safety database version 4.0, with unblinded data from 23 ongoing and completed clinical studies for a total of 3912 participants in Ebola, HIV, Malaria, RSV and Filovirus Ad26-based vaccine programs. Overall, all Ad26-based vaccines have been well tolerated, with no significant safety issues identified from the available data in the current Ad26 vaccine safety database. Evaluation of Ad26-based vaccines to further characterize the safety profile is continuing, with more than 90,000 participants vaccinated as of 1st July 2020 (cut-off date). Extensive evaluation of immunogenicity in humans shows strong and durable humoral and cellular immune responses. Clinical trials have not shown meaningful impact of pre-existing immunity to Ad26 on vaccine immunogenicity, even in the presence of Ad26 neutralizing antibody titers or Ad26-targeting T cell responses at baseline. The first vaccine, against Ebola virus, that makes use of the Ad26 vector, received marketing authorization from EC on 1st July 2020, as part of the Ad26.ZEBOV, MVA BN Filo vaccine regimen. New developments based on the Ad26 vector are underway, including a COVID-19 vaccine, which is currently in clinical evaluation.

Several protein vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template would also help contribute to improved public acceptance and communication of licensed protein vaccines.

Studies conducted to support registration or approval of veterinary anthelmintics generally follow study design recommendations provided by the VICH (International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products), "Efficacy of Anthelmintics: General Requirements" (VICH GL7). For dose confirmation studies, VICH GL7 provides recommendations for determining that the control animals had an adequate infection "to permit the appropriate standards of efficacy to be met with acceptable statistical and biological certitude/confidence." In the simulation studies described in this report, we investigated the performance of one method, the statistical criterion given in Section 4.5 of VICH GL7, for evaluating the adequacy of infection in anthelmintic studies, in combination with the conventional criterion of a minimum of six adequately infected animals. We conducted numerical simulations, based on parasite data from previously conducted dose confirmation studies in dogs and cattle, to investigate how the statistical criterion impacts adequacy of infection determinations when used with the conventional criterion at various sample sizes. Simulation studies in common nematode species in both dogs and cattle indicated that under certain circumstances the statistical criterion can guard against overinterpreting the evaluation of adequacy of infection as sample size is increased. However, the statistical criterion may be overly restrictive for samples with adequate infection but containing multiple zero parasite counts and adding it to the conventional criterion does not provide any additional benefit when the sample contains no zero counts. It is important for investigators designing efficacy studies to understand the potential impact this criterion may have when establishing adequacy of infection criteria in study protocols.

Background Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States. We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. Methods We enrolled outpatients aged ≥6 months with ARI from 50–60 US clinics during 5 winters (2013–2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases with test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. Results Among 37 487 ARI outpatients, 9659 (26%) were influenza positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top 3 prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95% CI, 32–39%). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95% CI, 3.6–4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. Conclusions Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.

Background Community services and supports are essential for children transitioning home to recover from the hospital after surgery. This study assessed the availability and geographic capacity of rehabilitation, assistive devices, familial support, and school reintegration programs for school-aged children in Uganda with identified surgical need. Methods This study assessed the geographic epidemiology and spatial analysis of resource availability in communities in Uganda. Participants were children with identified surgical need using the Surgeons OverSeas Assessment of Surgical need (SOSAS). Community-based resources available to children and adolescents after surgery in Uganda were identified using publicly available data sources and searching for resources through consultation with in-country collaborators We sought resources available in all geographic regions for a variety of services. Results Of 1082 individuals surveyed aged 5 to 14 yearsr, 6.2% had identified surgical needs. Pediatric surgical conditions were most prevalent in the Northern and Central regions of Uganda. Of the 151 community-based services identified, availability was greatest in the Central region and least in the Northern region, regardless of type. Assuming 30% of children with surgical needs will need services, a maximum of 50.1% of these children would have access to the needed services in the extensive capacity estimates, while only 10.0% would have access in the minimal capacity estimates. The capacity varied dramatically by region with the Northern region having much lower capacity in all scenarios as compared to the Central, Eastern, or Western regions. Conclusions Our study found that beyond the city of Kampala in the Central region, community-based services were severely lacking for school-aged children in Uganda. Increased pediatric surgical capacity to additional hospitals in Uganda will need to be met with increased availability and access to community-based services to support recovery and community re-integration.

Access to pediatric surgical intervention in low-income countries is expanding, but investments in post-surgical care have received less attention. This study explored the barriers and supports for school-aged children to access post-surgical, community-based follow-up care in Uganda as perceived by community stakeholders.This qualitative exploratory case study used in-depth, semi-structured interviews and in-country site visits among Ugandan organizations providing follow-up care to school-aged children in Uganda after surgery. Data from eight interviews and eight site visits were coded, analyzed, and cross-tabulated with a modified grounded theory approach.Four key barriers to community-based follow-up care were identified: discrimination, financial barriers, geographical barriers (including transportation), and caregiver limitations to support recovery. Three key supports to successful access to and participation in community-based post-surgical recovery were identified: disability awareness, the provision of sustained follow-up care, and caregiver supports for reintegration.Increasing awareness of disability across local Ugandan communities, educating caregivers with accessible and culturally aware approaches, and funding sustainable follow-up care programming provide promising avenues for pediatric post-surgical recovery and community reintegration in contemporary Uganda.Implications for rehabilitationMultiple, intersecting factors prevent or promote access to post-surgical community-based services among school-aged children in Uganda.The most prominent barriers to pediatric community reintegration in Uganda include discrimination, lack of financial resources, geographical factors, and caregiver limitations.Community and interprofessional alliances must address disability awareness and sources of stigma in local contexts to promote optimal recovery and reintegration after surgery.Collaborative efforts are needed to develop sustainable funding for community-based care programs that specifically support pediatric post-surgical recovery and reintegration.Efforts to provide appropriate and empowering caregiver education are critical, particularly in geographical regions where ongoing access to rehabilitation professionals is minimal.

BackgroundExisting data suggest a large burden of surgical conditions in low- and middle-income countries (LMICs). However, surgical care for children in LMICs remains poorly understood. Our goal was to define the hospital infrastructure, workforce, and delivery of surgical care for children across Somaliland and provide policy guidance to improve care.MethodsWe used two established hospital assessment tools to assess infrastructure, workforce, and capacity at all hospitals providing surgical care for children across Somaliland. We collected data on all surgical procedures performed in children in Somaliland between August 2016 and July 2017 using operative logbooks.ResultsData were collected from 15 hospitals, including eight government, five for-profit, and two not-for-profit hospitals. Children represented 15.9% of all admitted patients, and pediatric surgical interventions comprised 8.8% of total operations. There were 0.6 surgical providers and 1.2 anesthesia providers per 100,000 population. A total of 1255 surgical procedures were performed in children in all hospitals in Somaliland over 1 year, at a rate of 62.4 surgical procedures annually per 100,000 children. Care was concentrated at private hospitals within urban areas, with a limited number of procedures for many high-burden pediatric surgical conditions.ConclusionsWe found a profound lack of surgical capacity for children in Somaliland. Hospital-level surgical infrastructure, workforce, and care delivery reflects a severely resource-constrained health system. Targeted policy to improved essential surgical care at local, regional, and national levels is essential to improve the health of children in Somaliland.

Introduction Road traffic injuries (RTI) are a leading cause of morbidity and mortality around the world. The burden is highest in low and middle-income countries (LMICs) and is increasing. We aimed to describe the epidemiology of RTIs in 4 low-income countries using nationally representative survey data. Methods The Surgeons Overseas Assessment of Surgical Needs (SOSAS) survey tool was administered in four countries: Sierra Leone, Rwanda, Nepal and Uganda. We performed nationally representative cross-sectional, cluster randomized surveys in each country. Information regarding demographics, injury characteristics, anatomic location of injury, healthcare seeking behavior, and disability from injury was collected. Data were reported with descriptive statistics and evaluated for differences between the four countries using statistical tests where appropriate. Results A total of 13,765 respondents from 7115 households in the four countries were surveyed. RTIs occurred in 2.2% (2.0–2.5%) of the population and accounted for 12.9% (11.5–14.2%) of all injuries incurred. The mean age was 34 years (standard deviation ±1years); 74% were male. Motorcycle crashes accounted for 44.7% of all RTIs. The body regions most affected included head/face/neck (36.5%) followed by extremity fractures (32.2%). Healthcare was sought by 78% road injured; 14.8% underwent a major procedure (requiring anesthesia). Major disability resulting in limitations of work or daily activity occurred in 38.5% (33.0–43.9%). Conclusion RTIs account for a significant proportion of disability from injury. Younger men are most affected, raising concerns for potential detrimental consequences to local economies. Prevention initiatives are urgently needed to stem this growing burden of disease; additionally, improved access to timely emergency, trauma and surgical care may help alleviate the burden due to RTI in LMICs.

Metrics to measure the burden of surgical conditions, such as disability weights (DWs), are poorly defined, particularly for pediatric conditions. To summarize the literature on DWs of children’s surgical conditions, we performed a systematic review of disability weights of pediatric surgical conditions in low- and middle-income countries (LMICs). For this systematic review, we searched MEDLINE for pediatric surgery cost-effectiveness studies in LMICs, published between January 1, 1996, and April 1, 2017. We also included DWs found in the Global Burden of Disease studies, bibliographies of studies identified in PubMed, or through expert opinion of authors (ES and HR). Out of 1427 publications, 199 were selected for full-text analysis, and 30 met all eligibility criteria. We identified 194 discrete DWs published for 66 different pediatric surgical conditions. The DWs were primarily derived from the Global Burden of Disease studies (72%). Of the 194 conditions with reported DWs, only 12 reflected pre-surgical severity, and 12 included postsurgical severity. The methodological quality of included studies and DWs for specific conditions varied greatly. It is essential to accurately measure the burden, cost-effectiveness, and impact of pediatric surgical disease in order to make informed policy decisions. Our results indicate that the existing DWs are inadequate to accurately quantify the burden of pediatric surgical conditions. A wider set of DWs for pediatric surgical conditions needs to be developed, taking into account factors specific to the range and severity of surgical conditions.

Background Few studies have previously assessed how pre-existing vitamin E status is associated with risk of tuberculosis (TB) disease progression. Objective We evaluated the association between baseline plasma concentrations of 3 vitamin E isomers (α-tocopherol, γ-tocopherol, and δ-tocopherol) and TB disease risk. Methods We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary TB cases in Lima, Peru. We defined cases as HHCs who developed active TB disease ≥15 d after the diagnosis of the index patient, and we matched each case to 4 control cases who did not develop active TB based on age by year and gender. We used univariate and multivariate conditional logistic regression to calculate ORs for incident TB disease by plasma concentrations of α-tocopherol, γ-tocopherol, and δ-tocopherol. Results Among 6751 HIV-negative HHCs who provided baseline blood samples, 180 developed secondary TB during follow-up. After controlling for possible confounders, we found that baseline α-tocopherol deficiency conferred increased risk of incident TB disease (adjusted OR: 1.59; 95% CI: 1.02, 2.50; P = 0.04). Household contacts in the lowest tertile of δ-tocopherol were also at increased risk of progression to TB disease compared to those in the highest tertile (tertile 1 compared with tertile 3, adjusted OR: 2.29; 95% CI: 1.29, 4.09; P-trend = 0.005). We found no association between baseline concentration of γ-tocopherol and incident TB disease. Conclusions Vitamin E deficiency was associated with an increased risk of progression to TB disease among HHCs of index TB cases. Assessment of vitamin E status among individuals at high risk for TB disease may play a role in TB control efforts.

Background: Adolescents, comprised of 10–19 year olds, form the largest generation of young people in our history. There are an estimated 1.8 billion adolescents in the world, with 90% residing in low- and middle-income countries. The burden of disease among adolescents has its origins in infectious and injury-related causes, but nutritional deficiencies, suboptimal linear growth, and undernutrition are major public health problems, even as overweight may be on the rise in many contexts. Summary and Key Messages: Girls are most vulnerable to the influences of cultural and gender norms, which often discriminate against them. Dietary patterns and physical activity, in addition to schooling and countervailing social norms for early marriage, influence health and nutritional well-being of adolescents. Nutrient requirements – ­including those for energy, protein, iron, calcium, and ­others – increase in adolescence to support adequate growth and development. In settings where dietary intakes are suboptimal, anemia and micronutrient deficiencies are high. Endocrine factors are essential for promoting normal adolescent growth and are sensitive to undernutrition. Growth velocity increases during puberty when peak height velocity occurs and catch-up is possible; in girls, about 15–25% of adult height is attained. A premature pregnancy can halt linear growth and increase the risk of adverse birth outcomes. Research is needed to fill the huge data gaps related to nutrition and growth during adolescence, in addition to testing interventions during this second window of opportunity to enhance growth and development, improve human capital, and to end the intergenerational cycle of growth failure.

ObjectiveThis study evaluates the priority given to surgical care for children within national health policies, strategies and plans (NHPSPs).Participants and settingWe reviewed the NHPSPs available in the WHO’s Country Planning Cycle Database. Countries with NHPSPs in languages different from English, Spanish, French or Chinese were excluded. A total of 124 countries met the inclusion criteria.Primary and secondary outcome measuresWe searched for child-specific and surgery-specific terms in the NHPSPs’ missions, goals and strategies using three analytic approaches: (1) count of the total number of mentions, (2) count of the number of policies with no mentions and (3) count of the number of policies with five or more mentions. Outcomes were compared across WHO regional and World Bank income-level classifications.ResultsWe found that the most frequently mentioned terms were ‘child*’, ‘infant*’ and ‘immuniz*’. The most frequently mentioned surgery term was ‘surg*’. Overall, 45% of NHPSPs discussed surgery and 7% discussed children’s surgery. The majority (93%) of countries did not mention selected essential and cost-effective children’s procedures. When stratified by WHO region and World Bank income level, the West Pacific region led the inclusion of ‘pediatric surgery’ in national health plans, with 17% of its countries mentioning this term. Likewise, low-income countries led the inclusion of surg* and ‘pediatric surgery’, with 63% and 11% of countries mentioning these terms, respectively. In both stratifications, paediatric surgery only equated to less than 1% of the total terms.ConclusionThe low prevalence of children’s surgical search terms in NHPSPs indicates that the influence of surgical care for this population remains low in the majority of countries. Increased awareness of children’s surgical needs in national health plans might constitute a critical step to scale up surgical system in these countries.

Background In low- and middle-income countries (LMICs), an estimated 85% of children do not have access to surgical care. The objective of the current study was to determine the geographic distribution of surgical conditions among children throughout Uganda. Methods Using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey, we enumerated 2176 children in 2315 households throughout Uganda. At the district level, we determined the spatial autocorrelation of surgical need with geographic access to surgical centers variable. Findings The highest average distance to a surgical center was found in the northern region at 14.97km (95% CI: 11.29km–16.89km). Younger children less than five years old had a higher prevalence of unmet surgical need in all four regions than their older counterparts. The spatial regression model showed that distance to surgical center and care availability were the main spatial predictors of unmet surgical need. Interpretation We found differences in unmet surgical need by region and age group of the children, which could serve as priority areas for focused interventions to alleviate the burden. Future studies could be conducted in the northern regions to develop targeted interventions aimed at increasing pediatric surgical care in the areas of most need. Level of Evidence Level III.

Background Based on clinical trial results, the World Health Organization recommends infant HIV testing at age 4-6 weeks and immediate antiretroviral therapy (ART) initiation in all HIV-infected infants. Little is known about the outcomes of HIV-infected infants diagnosed with HIV in the first weeks of life in resource-limited settings. We assessed ART initiation and mortality in the first year of life among infants diagnosed with HIV by 12 weeks of age. Methods Cohort of HIV-infected infants in Kinshasa and Blantyre diagnosed before 12 weeks to estimate 12-month cumulative incidences of ART initiation and mortality, accounting for competing risks. Multivariate models were used to estimate associations between infant characteristics and timing of ART initiation. Results One hundred and twenty-one infants were diagnosed at a median age of 7 weeks (interquartile range, 6-8). The cumulative incidence of ART initiation was 46% [95% confidence interval (CI), 36%, 55%] at 6 months and 70% (95% CI 60%, 78%) at 12 months. Only age at HIV diagnosis was associated with ART initiation by age 6 months, with a subdistribution hazard ratio of 0.70 (95% CI 0.52, 0.91) for each week increase in age at DNA polymerase chain reaction test. The 12-month cumulative incidence of mortality was 20% (95% CI 13%, 28%). Conclusions Despite early diagnosis of HIV, ART initiation was slow and mortality remained high, underscoring the complexity in translating clinical trial findings and World Health Organization's guidance into real-life practice. Novel and creative health system interventions will be required to ensure that all HIV-infected infants achieve optimal treatment outcomes under routine care settings.

OBJECTIVE Existing studies have shown a high overall rate of adverse events (AEs) following pediatric neurosurgical procedures. However, little is known regarding the morbidity of specific procedures or the association with risk factors to help guide quality improvement (QI) initiatives. The goal of this study was to describe the 30-day mortality and AE rates for pediatric neurosurgical procedures by using the American College of Surgeons (ACS) National Surgical Quality Improvement Program–Pediatrics (NSQIP-Peds) database platform. METHODS Data on 9996 pediatric neurosurgical patients were acquired from the 2012–2014 NSQIP-Peds participant user file. Neurosurgical cases were analyzed by the NSQIP-Peds targeted procedure categories, including craniotomy/craniectomy, defect repair, laminectomy, shunts, and implants. The primary outcome measure was 30-day mortality, with secondary outcomes including individual AEs, composite morbidity (all AEs excluding mortality and unplanned reoperation), surgical-site infection, and unplanned reoperation. Univariate analysis was performed between individual AEs and patient characteristics using Fischer's exact test. Associations between individual AEs and continuous variables (duration from admission to operation, work relative value unit, and operation time) were examined using the Student t-test. Patient characteristics and continuous variables associated with any AE by univariate analysis were used to develop category-specific multivariable models through backward stepwise logistic regression. RESULTS The authors analyzed 3383 craniotomy/craniectomy, 242 defect repair, 1811 laminectomy, and 4560 shunt and implant cases and found a composite overall morbidity of 30.2%, 38.8%, 10.2%, and 10.7%, respectively. Unplanned reoperation rates were highest for defect repair (29.8%). The mortality rate ranged from 0.1% to 1.2%. Preoperative ventilator dependence was a significant predictor of any AE for all procedure groups, whereas admission from outside hospital transfer was a significant predictor of any AE for all procedure groups except craniotomy/craniectomy. CONCLUSIONS This analysis of NSQIP-Peds, a large risk-adjusted national data set, confirms low perioperative mortality but high morbidity for pediatric neurosurgical procedures. These data provide a baseline understanding of current expected clinical outcomes for pediatric neurosurgical procedures, identify the need for collecting neurosurgery-specific risk factors and complications, and should support targeted QI programs and clinical management interventions to improve care of children.

This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.

Delayed access to surgical care for congenital conditions in low- and middle-income countries is associated with increased risk of death and life-long disabilities, although the actual burden of delayed access to care is unknown. Our goal was to quantify the burden of disease related to delays to surgical care for children with congenital surgical conditions in Somaliland. We collected data from medical records on all children (n = 280) receiving surgery for a proxy set of congenital conditions over a 12-month time period across all 15 surgically equipped hospitals in Somaliland. We defined delay to surgical care for each condition as the difference between the ideal and the actual ages at the time of surgery. Disability-adjusted life years (DALYs) attributable to these delays were calculated and compared by the type of condition, travel distance to care, and demographic characteristics. We found long delays in surgical care for these 280 children with congenital conditions, translating to a total of 2970 attributable delayed DALYs, or 8.4 avertable delayed DALYs per child, with the greatest burden among children with neurosurgical and anorectal conditions. Over half of the families seeking surgical care had to travel over 2 h to a surgically equipped hospital in the capital city of Hargeisa. Children with congenital conditions in Somaliland experience substantial delays to surgical care and travel long distances to obtain care. Estimating the burden of delayed surgical care with avertable delayed DALYs offers a powerful tool for estimating the costs and benefits of interventions to improve the quality of surgical care.

Background Interpreters improve the care of patients with limited English proficiency. They can potentially act as unofficial health educators to help dispel misunderstandings about medical risks in a culturally appropriate manner. Somali parents in Minnesota are less likely to immunize their children for MMR than other parents because they believe the MMR vaccine causes autism. The low MMR vaccination rate contributed to measles outbreaks in the state in 2011 and 2017. Objective To investigate the effects of an educational session on interpreter beliefs and knowledge about childhood vaccines. Methods A large interpreter service in Minneapolis holds quarterly educational sessions for their interpreters. The investigators presented a one-hour interactive session on childhood vaccinations at one of the meetings. The interpreters were surveyed pre- and post-training to assess their (1) beliefs regarding childhood vaccines, (2) knowledge of childhood vaccination indications and safety, and surveyed pre-training about their perceived impact on patient decision-making. Results Fifty-five of the 78 interpreters attending the training session completed both the pre- and post-training surveys. Participants made significant improvements in their knowledge of vaccines after the training. Interpreters were less likely to believe that vaccines causes autism after the presentation (p = 0.02), and were more likely to indicate that the current evidence does not support a vaccine – autism connection (p Nineteen percent of the interpreters were from Somalia. Somali interpreters were significantly more likely to expand on what is said by the physician than their non-Somali colleagues (OR = 16.2, 95% CI = 2.8–92.9). They were also significantly more likely to encounter parental worry over vaccine safety (OR = 16.2, 95% CI = 1.9–140.5), and to believe that children get too many vaccines (OR = 30.1, 95% CI = 3.4–271.5). Conclusions The training was an effective method to improve interpreters’ knowledge and perceptions of vaccine safety. By training Somali interpreters, they can become a part of a team working toward better MMR vaccination rates.

Inadequate micronutrient intakes are relatively common in low‐ and middle‐income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost‐effectiveness of MMS compared with IFA. Recent meta‐analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual‐participant data meta‐analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost‐effective method to reduce the risk of adverse birth outcomes., This review presents the conclusions of a task force that set out to provide guidance to countries considering using multiple micronutrient supplements in pregnant women by assessing the available evidence.

BackgroundHealth systems for surgical care for children in low- and middle-income countries remain poorly understood. Our goal was to characterize the delivery of surgical care for children across Brazil and to identify associations between surgical resources and childhood mortality.MethodsWe performed a cross-sectional, ecological study to analyze surgical care for children in the public health system (Sistema Único de Saúde) across Brazil from 2010 to 2015. We collected data from several national databases, and used geospatial analysis (two-step floating catchment, Getis-Ord-Gi analysis, and geographically weighted regression) to explore relationships between infrastructure, workforce, access, procedure rate, under-5 mortality rate (U5MR), and perioperative mortality rate (POMR).ResultsA total of 246,769 surgical procedures were performed in 6,007 first level/ district hospitals and 491 referral hospitals across Brazil over the study period. The surgical workforce is distributed unevenly across the country, with 0.13-0.26 pediatric surgeons per 100,000 children in the poorer North, Northeast and Midwest regions, and 0.6-0.68 pediatric surgeons per 100,000 children in the wealthier South and Southeast regions. Hospital infrastructure, procedure rate, and access to care is also unequally distributed across the country, with increased resources in the South and Southeast compared to the Northeast, North, and Midwest. The U5MR varies widely across the country, although procedure-specific POMR is consistent across regions. Increased access to care is associated with lower U5MR across Brazil, and access to surgical care differs by geographic region independent of socioeconomic status.ConclusionsThere are wide disparities in surgical care for children across Brazil, with infrastructure, manpower, and resources distributed unevenly across the country. Access to surgical care is associated with improved U5MR independent of socioeconomic status. To address these disparities, policy should direct the allocation of surgical resources commensurate with local population needs.

Importance: Convalescent plasma is a proposed treatment for COVID-19. Objective: To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs). Data Sources: PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021. Study Selection: The RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting. Data Extraction and Synthesis: Two reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance-weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. Main Outcomes and Measures: All-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events. Results: A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was -1.21% (95% CI, -5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was -2.56% [95% CI, -13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences. Conclusions and Relevance: Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

Nutrient reference values are important parameters that guide nutrition and public health work globally. Micronutrient requirements during the peri-conception period are generally increased, which is essential in ensuring maternal, fetal, and neonatal health. Nevertheless, the current dietary reference intakes (DRIs) may be limited in terms of the methods used and the populations included, particularly the DRIs for pregnancy and lactation. In this proposed review, we will examine the methods (rigor of design, utilization of molecular methods, and presence of modern methods) and the population (inclusion of women, and in particular, pregnant and lactating people) in the studies used to inform the current DRIs. We will apply meta-science methods to this review, which involves formally reviewing the current evidence, and identifying opportunities to improve how we fund, perform, evaluate, and incorporate nutrition science into public health programs for better outcomes.

Purpose Little is known about the prevalence of pediatric surgical conditions in low- and middle-income countries. Many children never seek medical care, thus the true prevalence of surgical conditions in children in Uganda is unknown. The objective of this study was to determine the prevalence of surgical conditions in children in Uganda. Methods Using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey, we enumerated 4248 individuals in 2315 households in 105 randomly selected clusters throughout Uganda. Children aged 0–18 were included if randomly selected from the household; for those who could not answer for themselves, parents served as surrogates. Results Of 2176 children surveyed, 160 (7.4 %) reported a currently untreated surgical condition. Lifetime prevalence of surgical conditions was 14.0 % (305/2176). The predominant cause of surgical conditions was trauma (48.4 %), followed by wounds (19.7 %), acquired deformities (16.2 %), and burns (12.5 %). Of 90 pediatric household deaths, 31.1 % were associated with a surgically treatable proximate cause of death (28/90 deaths). Conclusion Although some trauma-related surgical burden among children can be adequately addressed at district hospitals, the need for diagnostics, human resources, and curative services for more severe trauma cases, congenital deformities, and masses outweighs the current capacity of hospitals and trained pediatric surgeons in Uganda.

Summary box The burden of maternal undernutrition is well defined, but global momentum and political will to address it is lacking. Maternal nutrition has long been neglected largely due to gender-based inequities in resource allocation. The first 1000 days, especially the period from conception through birth (approximately the first 280 days), is a critical window for future growth, development and resilience in the face of possible adversity or disease. Despite this biological imperative, the bulk of resources allocated to maternal and child health have been directed towards the child1—with little attention to a woman’s nutritional status prior to or during pregnancy. A recent estimate noted that 20.5 million babies are born ‘low birth weight’ (LBW

Objectives To evaluate the hypothesis that various maternal, socioeconomic, delivery, and infant nutritional characteristics are associated with early childhood development in young Tanzanian children. Study design We performed a prospective cohort study among 206 HIV-exposed, uninfected and 247 HIV-unexposed Tanzanian infants who had been enrolled in 2 separate micronutrient trials (NCT00197730 and NCT00421668). Trained nurses administered culturally modified Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), to evaluate cognitive, motor, and language development at 15 months of age. This analysis explored predictors of BSID-III z-scores using multivariable linear regression. Results Among maternal determinants, we found that low maternal height predicted all BSID-III domains in HIV-unexposed children; low maternal education predicted lower cognitive (standardized mean difference, -0.41; 95% CI, -0.74 to -0.08) and lower gross motor scores (standardized mean difference, -0.32; 95% CI, -0.61 to -0.04) in HIV-exposed children. Among delivery characteristics, facility delivery predicted higher cognitive scores (standardized mean difference, 1.36; 95% CI, 0.26-2.46); and oxytocin administration predicted lower fine motor scores (standardized mean difference, -0.48; 95% CI, -0.87 to -0.09) in HIV-exposed children. Higher length-for-age z-scores at 6 weeks of age predicted better cognitive (standardized mean difference, 0.15; 95% CI, 0.01-0.29) and expressive language scores (standardized mean difference, 0.16; 95% CI, 0.02-0.29) at 15 months in HIV-exposed infants. Conclusions This hypothesis-generating study found significant associations between nutritional status and health of the mother and child, and maternal educational attainment, with direct measures of early childhood development at 15 months of age. In addition, several aspects of delivery (facility birth and oxytocin administration) were associated with early childhood development. Future intervention trials should focus on modifiable maternal, infant, and obstetric factors to strengthen the evidence base concerning early childhood development. Trial registration ClinicalTrials.gov : NCT00197730 and NCT00421668 .

BACKGROUND In low and middle-income countries, approximately 85% of children have a surgically treatable condition before the age of 15. Within these countries, the burden of pediatric surgical conditions falls heaviest on those in rural areas. The objective of the current study was to evaluate the relationship between rurality, surgical condition and treatment status among a cohort of Ugandan children. METHODS We identified 2176 children from 2315 households throughout Uganda using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey. Children were randomly selected and were included in the study if they were 18 years of age or younger and had a surgical condition. Location of residence, surgical condition, and treatment status was compared among children. RESULTS Of the 305 children identified with surgical conditions, 81.9% lived in rural areas. The most prevalent causes of surgical conditions reported among rural and urban children were masses (24.0% and 25.5%, respectively), followed by wounds due to injury (19.6% and 16.4%, respectively). Among children with untreated surgical conditions, 79.1% reside in rural areas while 20.9% reside in urban areas. Among children with untreated surgical conditions, the leading reason for not seeking surgical care among children living in both rural and urban areas was a lack of money (40.6% and 31.4%, respectively), and the leading reason for not receiving care in both rural and urban settings was a lack of money (48.0% and 42.8%, respectively). CONCLUSIONS Our data suggest that over half of the children with a surgical condition surveyed are not receiving surgical care and a large majority of children with surgical needs were living in rural areas. Future interventions aimed at increasing surgical access in rural areas in low-income countries are needed.

Background The effects of community health worker (CHW) home visiting during the antenatal and postnatal periods in fragile- and conflicted-affected countries such as Afghanistan are not known. Methods We conducted a non-randomised population-based intervention study from March 2015 to February 2016. Two intervention and two control districts were selected. All female CHWs in the intervention districts were trained to provide eight home visits and behaviour change communication messages from pregnancy to 28 days postpartum. The primary outcome was the proportion of women who reported delivering in a health facility. Secondary outcomes were the proportion of women who reported attending a health facility for at least one antenatal and one postnatal visit. Outcomes were analysed at 12 months using multivariable difference-in-difference linear regression models adjusted for clustering. Results Overall, 289 female CHWs in the intervention districts performed home visits and 1407 eligible women (less than 12 months postpartum) at baseline and 1320 endline women provided outcome data (94% response rate). Facility delivery increased in intervention villages by 8.2% and decreased in the control villages by 6.3% (adjusted mean difference (AMD) 11.0%, 95% confidence interval (CI) 4.0–18.0%, p = 0.002). Attendance for at least one antenatal care visit (AMD 10.5%, 95% CI 4.2–16.9%, p = 0.001) and postnatal care visit (AMD 7.2%, 95% CI 0.2–14.2%, p = 0.040) increased in the intervention compared to the control districts. Conclusions CHW home visiting during the antenatal and postnatal periods can improve health service use in fragile- and conflict-affected countries. Commitment to scale-up from Ministries and donors is now needed. Trial registration This trial was retrospectively registered at the Australian and New Zealand Clinical Trial Registry (ACTRN12618000609257).

Objectives To evaluate the risk of newborn and infant mortality associated with preterm, small for gestational age (SGA), and low birth weight (LBW) stratified by maternal HIV status and the location of birth. Study design We created a prospective cohort by pooling 5 individually randomized trials. We used Cox proportional hazard models to estimate the risk of mortality for SGA defined using the recently published Intergrowth standard, preterm, LBW, and gestational age and size for gestational age categories (preterm- appropriate for gestational age [AGA], term-SGA, and preterm-SGA). Effect modification by maternal HIV status and place of residence was assessed using the likelihood ratio test. Results Of the 31 988 infants, 15.3% were preterm, 16.6% were SGA, and 7.3% were LBW. The proportion of preterm and SGA births was higher among the HIV-infected cohort than in the uninfected cohort. Compared with term-AGA groups, infants born both preterm and SGA had a greater risk of neonatal mortality (hazard ratio [HR] 5.43, 95% CI 2.01-14.63) than preterm-AGA infants (HR 2.40, 95% CI 1.89-3.05) and term-SGA infants (HR 2.56, 95% CI 1.96-3.34). Maternal HIV infection modified the risk of infant mortality associated with being born preterm or LBW, with a higher relative risk among those born to HIV-uninfected women. Rural residence significantly modified the risk of neonatal mortality associated with being LBW (P for interaction = .005). Conclusions Preterm and SGA newborns had an increased risk of mortality during the first year of life. Interventions targeting these conditions, especially in HIV-exposed and rural populations, should be integrated into existing maternal and child health programs.

BACKGROUND: Despite growing evidence that early life experiences and exposures can impact child development, there is limited research on how prenatal and early life nutrition and early life parenting practices predict specific domains of child development in resource-limited settings. This study examines the association between prenatal factors, birth outcomes, and early life characteristics with motor, cognitive/language, and socioemotional development in Tanzania. METHODS: We assessed motor, cognitive/language, and socioemotional development among a cohort of 198 children aged 20–39 months in Dar es Salaam, Tanzania, whose mothers were previously enrolled in a randomized, placebo-controlled trial of prenatal vitamin A and zinc supplementation. Linear regression models were used to assess standardized mean differences in child development scores for randomized prenatal regimen and pregnancy, delivery, and early childhood factors. RESULTS: Children born to mothers randomized to prenatal vitamin A had significantly lower reported motor scores in minimally adjusted and multivariate analyses, −0.29 SD, 95% CI [−0.54, −0.04], p = 0.03, as compared with children whose mothers did not receive vitamin A. There was no significant effect of randomized prenatal zinc on any development domain. Greater caregiver–child stimulation was associated with 0.38 SD, 95% CI [0.14, 0.63], p < 0.01, better cognitive/language scores, whereas children who experienced both verbal and physical punishment had 0.29 SD, 95% CI [−0.52, −0.05], p = 0.02, lower scores in socioemotional development. Maternal completion of primary school was associated with higher reported motor and cognitive/language development. Further, children of mothers who were

BACKGROUND/OBJECTIVES To identify factors associated with plasma polyunsaturated fatty acid (PUFA) levels among 3-month-old Tanzanian infants. SUBJECTS/METHODS Infants (n = 238) and mothers (n = 193) randomly selected from participants in the neonatal vitamin A supplementation randomized controlled trial. A cross-sectional study of maternal-infant pairs at 3 months postpartum. RESULTS All infant total, n-3, n-6, and individual PUFA levels were correlated with maternal levels. Infant plasma n-3 PUFA levels were higher when maternal n-3 PUFA levels were higher (mean difference in infant % fatty acid per unit increase in maternal levels ± standard error: 0.79 ± 0.08; P