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The objective of this study was to determine the rates and trends in the reporting of preferred language, socioeconomic factors, sexual orientation, and gender identity in published pediatric clinical trials.A cross-sectional study of pediatric clinical trials conducted in the U.S. published from January 1, 2011 through December 31, 2020 in 5 general pediatric and 5 general medical journals with the highest impact factor in their respective fields was performed. Outcomes were reporting of preferred language, socioeconomic factors, sexual orientation, and gender identity. In late 2021, descriptive statistics and logistic regression to understand how reporting of preferred language and socioeconomic factors changed over time were performed.Of 612 trials, 29.6% (n=181) reported preferred language. Among these, 64.6% (n=117 of 181) exclusively enrolled participants whose preferred language was English. From 2011 to 2020, there was a relative increase in the reporting of preferred language (8.6% per year, 95% CI=1.8, 16.0). Socioeconomic factors were reported in 47.9% (n=293) of trials. There was no significant change in the reporting of socioeconomic factors (8.2% per year, 95% CI= -1.9, 15.1). Only 5.1% (9 of 179) of published trial results among adolescent participants reported any measure of sexual orientation, and 1.1% (2 of 179) reported gender identity.Preferred language, socioeconomic factors, sexual orientation, and gender identity were infrequently reported in pediatric clinical trial results despite these characteristics being increasingly recognized as social determinants of health. To achieve more inclusiveness and to reduce unmeasured disparities, these characteristics should be incorporated into routine trial registration, design, funding decisions, and reporting.

Background Combination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal human immunodeficiency virus (HIV) transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens. Methods We analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy. Results Among women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation compared with after 20 weeks had increased risk of preterm birth (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.03–1.67) but decreased risk of small-for-gestational age birth (RR, 0.71; 95% CI, .55–.93). Conclusions With increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes.

Purpose of Review Aquatic foods are increasingly being recognized as a diverse, bioavailable source of nutrients, highlighting the importance of fisheries and aquaculture for human nutrition. However, studies focusing on the nutrient supply of aquatic foods often differ in the nutrients they examine, potentially biasing their contribution to nutrition security and leading to ineffective policies or management decisions. Recent Findings We create a decision framework to effectively select nutrients in aquatic food research based on three key domains: human physiological importance, nutritional needs of the target population (demand), and nutrient availability in aquatic foods compared to other accessible dietary sources (supply). We highlight 41 nutrients that are physiologically important, exemplify the importance of aquatic foods relative to other food groups in the food system in terms of concentration per 100 g and apparent consumption, and provide future research pathways that we consider of high importance for aquatic food nutrition. Summary Overall, our study provides a framework to select focal nutrients in aquatic food research and ensures a methodical approach to quantifying the importance of aquatic foods for nutrition security and public health.

Objective:To assess the cost-effectiveness of prophylactic Zn supplementation for preventing diarrhoea in young children in Tanzania.Design:Cost-effectiveness analysis using decision-analytic modelling. Cost-effectiveness ratios were calculated as the incremental cost (2019 USD) per disability-adjusted life year (DALY) averted, from a societal perspective, and with a 3 % discount rate applied to future outcomes. Sensitivity analyses were performed to test the robustness of results to alternative assumptions.Setting:Tanzania.Participants:A hypothetical cohort of 10 000 children aged 6 weeks to 18 months.Results:The intervention costs of Zn supplementation were estimated as $109 800 (95 % uncertainty interval: 61 716, 171 507). Zn supplementation was estimated to avert 2200 (776, 3737) diarrhoeal episodes, 14 080 (4692, 25 839) sick days, 1584 (522, 2927) outpatient visits, 561 (160–1189) inpatient bed days, 0·51 (0·15, 1·03) deaths and 19·3 (6·1, 37·5) DALY (discounted at 3 % per year). Zn supplementation reduced diarrhoea care costs by $12, 887 (4089, 25 058). The incremental cost per DALY averted was $4950 (1678, 17 933). Incremental cost-effectiveness ratios (ICER) estimated from a health system perspective were similar to the results from the societal perspective. ICER were substantially lower (more favourable) when future outcomes were not discounted, but all ICER were above contemporary thresholds for cost-effectiveness in this setting.Conclusion:Prophylactic Zn reduced diarrhoea incidence and associated healthcare utilisation; however, it did not appear to be cost-effective for prevention of childhood diarrhoea in the scenario examined in this study. Reducing intervention costs, or identifying high risk groups for intervention targeting, may be needed to improve cost-effectiveness in this setting.

Background Anaemia is common among HIV-infected children and iron supplementation is prescribed routinely for the prevention and management of anaemia among children. Limited evidence suggests iron supplementation may have adverse effects among HIV-infected populations. We aimed to estimate the effect of iron supplement use on mortality, disease progression and haematological outcomes among HIV-infected children in Dar es Salaam, Tanzania. Methods A prospective cohort study was conducted among HIV-infected children (aged 0–14 years) receiving antiretroviral treatment or supportive care between October 2004 and September 2014. Clinical data were recorded on morbidity and vital status, haematological status and prescriptions at each clinical visit. Cox proportional hazards models adjusted for time-varying covariates were used to estimate the association of time-varying iron supplementation on the hazard rate of mortality, HIV disease stage progression, tuberculosis incidence and anaemia and microcytosis persistence. Results In all, 4229 children were observed during 149 260 clinic visits for a mean follow-up of 2.9 years. After adjustment for time-varying clinical covariates, time-varying iron supplementation was associated with a 2.87 times higher hazard rate of mortality (95% CI: 1.70, 4.87) and a 1.48 times higher hazard rate of HIV disease stage progression (95% CI: 1.10, 1.98). Iron supplementation was also associated with a lower rate of anaemia persistence (HR = 0.47; 95% CI: 0.37, 0.61). No differences in the association between iron supplementation and clinical outcomes were observed by antiretroviral therapy or anaemia status. Conclusions Iron supplementation may increase the risk of HIV disease stage progression and mortality among HIV-infected children, while reducing the risk of anaemia.

Equitable representation of participants who are members of racial and ethnic minority groups in clinical trials enhances inclusivity in the scientific process and generalizability of results.To assess participant race and ethnicity in pediatric clinical trials published from 2011 to 2020.This cross-sectional study examined articles reporting pediatric clinical trials conducted in the US published in 5 leading general pediatric and 5 leading general medical journals from January 1, 2011, to December 31, 2020.Reporting of participant race and ethnicity and comparison of enrolled participants vs US census populations of pediatric racial and ethnic groups in published clinical trials.The study included 612 articles reporting pediatric clinical trials during the study period, with 565 618 total participants (median per trial, 200 participants [IQR, 90-571 participants]). Of the 612 articles, 486 (79.4%) reported participant race and 338 (55.2%) reported participant ethnicity. From 2011 to 2020, relative rates of reporting of participant race increased by 7.9% per year (95% CI, 0.2%-16.3% per year) and reporting of ethnicity increased by 11.4% per year (95% CI, 4.8%-18.4% per year). Among articles reporting race and ethnicity, the method of assignment was not reported in 261 of 511 articles (51.1%) and 207 of 359 articles (57.7%), respectively. Black/African American children were enrolled proportionally more than the US population of Black/African American children (odds ratio [OR], 1.88; 95% CI, 1.87-1.89). Hispanic/Latino children were enrolled commensurately with the US population of Hispanic/Latino children (OR, 1.02; 95% CI, 1.01-1.03). American Indian/Alaska Native (OR, 0.82; 95% CI, 0.79-0.85), Asian (OR, 0.56; 95% CI, 0.55-0.57), and Native Hawaiian/Pacific Islander (OR, 0.66; 95% CI, 0.61-0.72) children were enrolled significantly less compared with the respective US populations of these groups. White children were enrolled less than expected (OR, 0.84; 95% CI, 0.84-0.85) but represented 188 156 (46.0%) of participants in trials reporting race or ethnicity.This cross-sectional study revealed that the proportion of published pediatric clinical trials that reported participant race and ethnicity increased from 2011 to 2020, but participant race and ethnicity were still underreported. Disparities existed in pediatric clinical trial enrollment of American Indian/Alaska Native, Asian, and Native Hawaiian/Pacific Islander children. The greater representation of Black/African American children compared with the US population suggests inclusive research practices that could be extended to other historically disenfranchised racial and ethnic groups.

To evaluate symptoms, enteral tolerance, growth, and antibiotic regimens in pediatric intestinal failure (IF) patients after treated with antibiotic therapy for small bowel bacterial overgrowth (SBBO).Single-center retrospective review of children 0-18 years with IF with endoscopic cultures demonstrating10 5 CFU/mL from 2010 to 2017. Symptoms, enteral tolerance, growth, and antibiotic regimens were evaluated at the time of endoscopy and 6 months later.Of 505 patients followed in our intestinal rehabilitation program, 104 underwent upper gastrointestinal endoscopy and 78 had positive duodenal cultures. Clinical data pre- and post-endoscopy were available for 56 patients. Compared to baseline, in the 6 months following targeted antibiotic treatment, children showed significant improvement in emesis or feeding intolerance (58.9% vs 23.2%, P0.001), abdominal pain (16.1% vs 7.1%, P = 0.02), high stool output (42.9% vs 19.6%, P = 0.002), and gross GI bleeding (19.6% vs 3.6%, P = 0.003). Mean BMI-for-age z scores increased significantly (-0.03 ± 0.94 vs 0.27 ± 0.82, P = 0.03); however, height-for-age z scores, weight-for-age z scores, and percent of calories from enteral intake were not significantly different after therapy. Antibiotic regimens remained highly variable.Children with IF and culture-positive SBBO showed significant improvement in symptoms and BMI-for-age z scores after duodenal culture with subsequent targeted antibiotic therapy. Longer follow-up may be needed to detect improvements in linear growth and percent of calories from enteral feeds. Antibiotic regimens remain highly variable. Long-term consequences of chronic antimicrobial therapy, including antimicrobial resistance, remain unknown. Prospective studies focused on standardizing duodenal sampling technique, correlating culture and pathology data, and evaluating antibiotic resistance patterns are needed.

An acute shortage of infant formulas in the United States occurred in early 2022, exacerbating a longer-standing, less severe shortage that has occurred over the last several years. The shortage has been particularly problematic for specialized formulas such as those needed for infants and children with food allergies, intestinal failure, kidney disease, and metabolic disorders. Although undoubtedly the magnitude of the current shortage will abate over time, it has affected many children and caused tremendous distress for thousands of families. We propose a series of interventions to be undertaken as soon as feasible to help ensure that the conditions that led to this problem do not recur and families regain confidence in the safety and supply reliability of formulas for infants and young children regardless of their medical needs.

BACKGROUND: Animal models have demonstrated that maternal nutrition can alter fetal vulnerability to prenatal alcohol exposure (PAE). Few human studies have examined the role of nutrition in fetal alcohol spectrum disorders (FASD). OBJECTIVES: Our objectives were to examine whether fetal vulnerability to PAE-related growth restriction is modified by: 1) rate of gestational weight gain; or prenatal dietary intakes of 2) energy, 3) iron, or 4) choline. METHODS: In a prospective longitudinal birth cohort in Cape Town, South Africa, 118 heavy-drinking and 71 abstaining/light-drinking pregnant women were weighed and interviewed regarding demographics, alcohol, cigarette/other drug use, and diet at prenatal visits. Infant length, weight, and head circumference were measured at 2 wk and 12 mo postpartum. RESULTS: Heavy-drinking mothers reported a binge pattern of drinking [Mean = 129 mL (∼7.2 drinks)/occasion on 1.3 d/wk). Rate of gestational weight gain and average daily dietary energy, iron, and choline intakes were similar between heavy-drinking women and controls. In regression models adjusting for maternal age, socioeconomic status, cigarette use, and weeks gestation at delivery, PAE [ounces (30 mL) absolute alcohol per day] was related to smaller 2-wk length and head circumference and 12-mo length, weight, and head circumference z-scores (β = −0.43 to −0.67; all P values

IntroductionOver half of the 5 million annual deaths among children aged 0–59 months occur in sub-Saharan Africa. The period immediately after hospitalisation is a vulnerable time in the life of a child in sub-Saharan Africa as postdischarge mortality rates are as high as 1%–18%. Identification of neonates and children who are at highest risk for postdischarge mortality may allow for the direction of interventions to target patients at highest risk.Methods and analysisThe Predicting Post-Discharge Mortality study is a prospective, observational study being conducted at Muhimbili National Hospital (Dar es Salaam, Tanzania) and John F. Kennedy Medical Center (Monrovia, Liberia). The aim is to derive and validate two, age population specific, clinical prediction rules for the identification of neonates (n=2000) and children aged 1–59 months (n=2000) at risk for all-cause mortality within 60 days of discharge from the neonatal intensive care unit or paediatric ward. Caregivers of participants will receive phone calls 7, 14, 30, 45 and 60 days after discharge to assess vital status. Candidate predictor variables will include demographic, anthropometric and clinical factors. Elastic net regression will be used to derive the clinical prediction rules. Bootstrapped selection with repetitions will be used for internal validation. Planned secondary analyses include the external validation of existing clinical prediction models, determination of clinicians’ ability to identify neonates and children at risk of postdischarge mortality at discharge, analysis of factors associated with hospital readmission and unplanned clinic visits and description of health-seeking behaviours in the postdischarge period.Ethics and disseminationThis study received ethical clearance from the Tanzania National Institute of Medical Research, Muhimbili University of Health and Allied Sciences, the John F. Kennedy Medical Center Institutional Review Board, and the Boston Children’s Hospital Institutional Review Board. Findings will be disseminated at scientific conferences and as peer-reviewed publications.

OBJECTIVES To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.

Background Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants. Methods and findings We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12–27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (z-score < −2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent. Conclusions The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania. Trial registration ClinicalTrials.gov Identifier: NCT02305927.

OBJECTIVE: To identify demographic, clinical, and hospital factors associated with mortality on readmission within 180 days following an inpatient hospitalization. STUDY DESIGN: We conducted a retrospective cohort study including 33 US children’s hospitals in the Pediatric Health Information System from January 2010-June 2020. Our primary outcome was death during readmission ≤180 days of an index hospitalization among children aged 0-18 years. Illness severity during the index hospitalization was defined according to the All Patient-Refined Diagnosis-Related Group categorized illness severity (i.e., minor, moderate, and major/extreme). We performed multivariable logistic regression analysis to identify factors during the index hospitalization associated with mortality during readmission. RESULTS: Among 2,677,111 children discharged, 12.6% (n=337,385) were readmitted within 180 days of the index hospitalization and 2,913 (0.8%) died during readmission. 26.2% of deaths among children who were readmitted and died occurred within 10 days after discharge from index hospitalizations. Factors independently associated with mortality during readmission included: multiple complex chronic conditions, index admissions lasting >7 days, moderate or severe/extreme illness during the index hospitalization, and public insurance. Children whose race was reported as Black had greater odds of mortality during readmission than children of other races. CONCLUSIONS: Among hospitalized children, several demographic and clinical factors present during index hospitalizations were associated with mortality during readmission. Greater odds of mortality during readmission among children whose race was reported as Black likely reflects disparities in social determinants of health and clinical care. Interventions to reduce mortality during readmission may target high-risk populations in the period immediately following discharge.

Low and middle income countries report a higher prevalence of antenatal depression. The association between antenatal depressive symptoms and behavioral outcomes in children at 78 months in motherchild dyads who participated in a randomized control trial of maternal B12 supplementation during pregnancy was examined in this study.Children of 140 women, out of 366 who had participated in the placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy and 6 weeks post-partum, on whom serial assessments of depressive symptoms in each of the trimesters were done using the Kessler's 10 Psychological Distress Scale (K10), were assessed using the Strength and Difficulties Questionnaire (SDQ) at 78 months.Thirty seven women (26.4%) reported depressive symptoms at one trimester (intermittent group) and 28 women (20%) had depressive symptoms in at least 2 trimesters (persistent group). On adjusted bivariate regression analysis, children of women with intermittent antenatal depressive symptoms scored lower on the prosocial behavior subscale of SDQ compared to children of mothers with no depressive symptoms ( B=;-0.91, 95% CI: -1.65,-0.18; p=0.016).The use of a screening measure to assess maternal depression, the assessment of the children's behavior based only on the mothers' reports and the small number of women with persistent depressive symptoms in our sample is important limitations.The possible association between antenatal depressive symptoms and prosocial behavior in children point to the need for routine assessment and intervention for emotional disorders during pregnancy.

The association between geographic diversity of medical journal editorial staff and publications reporting research conducted in low- and middle-income countries (LMICs) is unclear.To examine the association between having editorial staff members affiliated with LMICs and publishing research articles from LMICs in leading biomedical journals.This cross-sectional study included biomedical journals in fields representing the largest disease burden globally from January 1 to December 31, 2020. Websites of the 5 leading journals in general medicine, pediatrics, surgery, obstetrics and gynecology, cancer, cardiovascular diseases, infectious diseases, psychiatry, and nutrition were reviewed to obtain the country affiliations of editorial staff members. To determine article study countries, original research articles in each journal were reviewed through MEDLINE. Editorial staff country affiliations and study country locations were classified according to World Bank income brackets and regions.Editorial staff country affiliation.Descriptive statistics of the proportion of editorial staff affiliated with each income bracket and region and Spearman rank correlation coefficients were used to assess the association between the proportion of editorial staff affiliated with LMICs and the proportion of published articles reporting work conducted in these countries.There were 3819 editorial staff members in the 45 included journals: 3637 (95.2%) were affiliated with high-income countries, 140 (3.7%) with upper-middle-income countries, 37 (1.0%) with lower-middle-income countries, and 5 (0.1%) with low-income countries. All 48 editors-in-chief were affiliated with a high-income country. Editorial staff members were mostly affiliated with North American countries (n = 2120 [55.5%]) and European or Central Asian countries (n = 1256 [32.9%]). Of the 10 096 original research articles included in our analysis, 7857 (77.8%) reported research conducted in high-income countries, 1562 (15.5%) reported research conducted in upper-middle-income countries, 507 (5.0%) reported research conducted in lower-middle-income countries, and 170 (1.7%) reported research conducted in low-income countries. Greater editorial staff representation correlated moderately with more published articles reporting research conducted in LMICs (Spearman ρ = 0.51; 95% CI, 0.25-0.70; P .001).In this cross-sectional study, editorial staff in leading biomedical journals were largely composed of individuals affiliated with high-income countries in North America and Europe. A correlation was found between greater editorial staff representation and publication of research focused on LMICs, suggesting that the inclusion of editorial staff affiliated with LMICs may promote the publication of research conducted in those countries.