Search

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.

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.

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone&ndash, insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores &lt, &minus, 2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72, p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93, p for trend = 0.019), a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12, p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.

(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by I2 and τ2 statistic, stratified analyses, and meta-regression, and publication bias by Egger’s and Begg’s tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: −0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52–1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09–0.38), weight (WMD = 0.14 kg, 95%CI: 0.07–0.21), and weight-for-age Z-score (WMD = 0.04, 95%CI: 0.001–0.087), but not height-for-age Z-score (WMD = 0.02, 95%CI: −0.01–0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: −0.03–0.06). Child age at zinc supplementation appeared to modify the effects on height (P-interaction = 0.002) and HAZ (P-interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50–2.25; WMD for HAZ = 0.12, 95%CI: 0.05–0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children.

Objective To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. Study design Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. Results One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. Conclusions Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction. Trial registration ClinicalTrials.gov: NCT00197730 and NCT00421668.

Impaired childhood development has lifelong consequences for educational attainment and wage-earning potential. Micronutrient supplements have the potential to improve development. The objective of this study was to determine the effect of daily zinc and/or multivitamin (vitamins C, E and B-complex) supplements on development among Tanzanian infants. In this randomized, 2 × 2 factorial, double-blind trial, 2400 infants were randomized to zinc (Zn), multivitamins (MV), zinc and multivitamins (Zn + MV) or placebo at 6 weeks of age. At approximately 15 months, a sub-sample of 247 children underwent developmental assessment using the cognitive, language (receptive and expressive) and motor (fine and gross) scales of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Mean BSID-III scores were compared using univariate and multivariate linear regression models adjusted for child's sex, post-conceptual age and test administrator. Logistic regressions were used to assess odds of low developmental scores. We did not detect a significant difference in mean BSID-III scores in any of the five domains in univariate or multivariate models comparing each of the four treatment groups. We also did not detect a significant difference in mean BSID-III scores when comparing children who received zinc supplements versus those who did not, or in comparisons of children who received multivitamin supplements versus those who did not. There was no significant difference in odds of a low BSID-III score in any of the five domains in treatment arms either. Because neither daily zinc nor multivitamin (vitamins B-complex, C and E) supplementation led to improvements in any of the developmental domains assessed using the BSID-III, we recommend pursuing alternative interventions to promote early childhood development in vulnerable populations. © 2016 John WileySons Ltd.

To describe the design of a clinical trial testing the hypothesis that children randomized to tight glycemic control with intensive insulin therapy after cardiac surgery will have improved clinical outcomes compared to children randomized to conventional blood glucose management.Two-center, randomized controlled trial.Cardiac ICUs at two large academic pediatric centers.Children from birth to those aged 36 months recovering in the cardiac ICU after surgery with cardiopulmonary bypass.Subjects in the tight glycemic control (intervention) group receive an intravenous insulin infusion titrated to achieve normoglycemia (target blood glucose range of 80-110 mg/dL; 4.4-6.1 mmol/L). The intervention begins at admission to the cardiac ICU from the operating room and terminates when the patient is ready for discharge from the ICU. Continuous glucose monitoring is performed during insulin infusion to minimize the risks of hypoglycemia. The standard care group has no target blood glucose range.The primary outcome is the development of any nosocomial infection (bloodstream, urinary tract, and surgical site infection or nosocomial pneumonia). Secondary outcomes include mortality, measures of cardiorespiratory function and recovery, laboratory indices of nutritional balance, immunologic, endocrinologic, and neurologic function, cardiac ICU and hospital length of stay, and neurodevelopmental outcome at 1 and 3 yrs of age. A total of 980 subjects will be enrolled (490 in each treatment arm) for sufficient power to show a 50% reduction in the prevalence of the primary outcome.Pediatric cardiac surgery patients may recognize great benefit from tight glycemic control in the postoperative period, particularly with regard to reduction of nosocomial infections. The Safe Pediatric Euglycemia after Cardiac Surgery trial is designed to provide an unbiased answer to the question of whether this therapy is indeed beneficial and to define the associated risks of therapy.