Changes in Global Nutrition Practices in Critically Ill Children and the Influence of Emerging Evidence: A Secondary Analysis of the Pediatric International Nutrition Studies, 2009-2018.

BACKGROUND: The timeline of the 3 Pediatric International Nutrition Studies (PINS) coincided with the publication of 2 major guidelines for the timing of parenteral nutrition (PN) and recommended energy and protein delivery dose. OBJECTIVE: The study's main objective was to describe changes in the nutrition delivery practice recorded in PINS1 and PINS2 (PINS1-2) (conducted in 2009 and 2011, preexposure epoch) vs PINS3 (conducted in 2018, postexposure epoch), in relation to the published practice guidelines. DESIGN: This study is a secondary analysis of data from a multicenter prospective cohort study. PARTICIPANTS/SETTING: Data from 3650 participants, aged 1 month to 18 years, admitted to 100 unique hospitals that participated in 3 PINS was used for this study. MAIN OUTCOME MEASURES: The time in days from pediatric intensive care unit admission to the initiation of PN and enteral nutrition delivery were the primary outcomes. Prescribed energy and protein goals were the secondary outcomes. STATISTICAL ANALYSES PERFORMED: A frailty model with a random intercept per hospital with stratified baseline hazard function by region for the primary outcomes and a mixed-effects negative binomial regression with random intercept per hospital for the secondary outcomes. RESULTS: The proportion of patients receiving enteral nutrition (88.3% vs 80.6%; P < .001) was higher, and those receiving PN (20.6% vs 28.8%; P < .001) was lower in the PINS3 cohort compared with PINS1-2. In the PINS3 cohort, the odds of initiating PN during the first 10 days of pediatric intensive care unit admission were lower, compared with the PINS1-2 cohort (hazard ratio 0.8, 95% CI 0.67 to 0.95; P = .013); and prescribed energy goal was lower compared with the PINS1-2 cohort (incident rate ratio 0.918, 95% CI 0.874 to 0.965; P = .001). CONCLUSIONS: The likelihood of initiation of PN delivery significantly decreased during the first 10 days after admission in the PINS3 cohort compared with PINS1-2. Energy goal prescription in children receiving mechanical ventilation significantly decreased in the postguidelines epoch compared with the preguidelines epoch.

Phase angle as a prognostic indicator in critically ill children: A systematic review.

Phase angle (PhA) may reflect the integrity of cellular membranes, hydration status, and total body cell mass. Studies have shown that PhA can be used as a good predictor for evaluation of disease severity in critically ill adults. However, there is a lack of studies assessing the association between PhA and clinical outcomes in critically ill children. This systematic review described the association between PhA at pediatric intensive care unit (PICU) admission with clinical outcomes in critically ill children. The search was conducted using PubMed/Medline, Scopus, Web of Science, EMBASE and LILACS until July 22, 2022. Studies that evaluate the association between PhA at PICU admission in critically ill children and clinical outcomes were eligible. Data regarding population, study design, setting, bioelectrical impedance analysis (BIA) protocol used, PhA classification, and outcome analysis were extracted. Risk of bias was assessed by Newcastle-Ottawa Scale. Among the 4669 articles screened, five prospective studies were included. The studies have shown association between lower values of PhA at PICU admission with longer PICU and hospital length of stay, duration of mechanical ventilation, septic shock, and higher mortality risk. Small sample size, different clinical conditions, and methodological differences of the studies regarding BIA equipment and cutoffs of PhA were observed. Although the studies have limitations, the PhA has a potential role in predicting clinical outcomes in critically ill children. Larger studies with standardized PhA protocols and other relevant clinical outcomes are necessary.

Anthropometric indicators as discriminators of high body fat in children and adolescents with HIV: comparison with reference methods.

BACKGROUND: Body fat assessment is needed in individuals with HIV. The objective was to identify the discriminatory capacity of the abdominal skinfold (ASF) tricipital skinfold (TSF), subscapular fold (SSF), calf skinfold (CSF), body adiposity index (BAI), body mass index, conicity index (IC), mid-upper arm circumference (MUAC), waist circumference (WC), perimeter of neck (PN) and waist-to-height ratio (WHtR) for high body fat in children and adolescents with HIV, compared Dual energy X-ray absorptiometry (DXA) and air displacement plethysmography (ADP). METHODS: Descriptive study, cross - sectional study, with 65 children and adolescents with HIV by vertical transmission. Body fat was measured by DXA and ADP. Measures were measured by international standardization. The diagnostic properties for high body fat were assessed by area under the ROC curve (AUC). RESULTS: For boys, having DXA as a reference for fat, ASF (AUC: 0.920), TSF (AUC: 0.792), SSF (AUC: 0.766), CSF (AUC: 0.866), BAI satisfactory discriminatory capacity. With ADP as the reference method, ASF (AUC: 0.920), TSF (AUC: 0.921), SSF (AUC: 0.766), CSF (AUC: 0.901), BAI (AUC: 0.756) and BMI (AUC: 0.699) presented satisfactory results. For girls, having DXA as a reference for fat, ASF (AUC: 0.838), TSF (AUC: 0.842), SSF (AUC: 0.840), CSF (AUC: 0.887), BAI (AUC: 0.846), and BMI (AUC: 0.859) presented satisfactory discriminatory capacity. Assuming ADP as a reference for fat, ASF (AUC [AUC: 0.799], TSF [AUC: 0.825], SSF [AUC: 0.767], CSF [AUC: 0.897], BAI 0.788), were satisfactory. CONCLUSIONS: The ASF, TSF, SSF, CSF, BAI and BMI anthropometric indicators may be suggested as the most suitable for the detection of high body fat in children and adolescents with HIV.

Muscle Strength Assessed by Handgrip Strength Moderates the Relationship Between Overweight and Obesity With Cardiometabolic Risk Markers Among Adults and Older Adults.

Background and aims: Few population-based studies have studied whether muscle strength (MS) levels influence the relationship between cardiometabolic markers with excess body weight. We investigate the possible moderator role of MS in the relationship between overweight and obesity with cardiometabolic markers. Methods: Cross-sectional analysis using data from two studies in Florianópolis, Brazil (EpiFloripa Adult Cohort Study, n = 862, 39.3 ± 11.4 years; EpiFloripa Aging Cohort Study, n = 1,197, 69.7 ± 7.1 years). MS was assessed by handgrip strength. Body mass index (BMI) was classified as overweight or obesity (BMI 25.0-29.9 or ≥30.0 kg/m2, respectively). Cardiometabolic markers included systolic (SBP) and diastolic blood pressure (DBP), C-reactive protein (CRP), lipids, glucose markers, and carotid intima-media thickness (CIMT). Linear regression models stratified by age groups (adults: <60 years; older adults: ≥60 years) and adjusted for confounders were used. Results: Compared to those with a normal BMI, overweight and obesity were related to higher SBP, DBP, lnCRP, ln triglycerides, fasting glucose (FG), and glicated hemoglobin (HbA1c), and inversely associated with HDL-C among adults and older adults (p value < .05 for all). Additionally, BMI was positively associated with LDL-C and CIMT only among adults (p value < .05). Among adults and older adults, elevated MS attenuated the adverse relationship between excess body weight with FG and HbA1c. Conclusion: Higher MS might help adults and older adults with overweight or obesity reduce their cardiovascular risk by keeping their FG and HbA1c at the same levels of those with a normal BMI.

Clusters of lifestyle behaviors associated with atherosclerosis risk factors in children and adolescents with congenital heart disease: Floripa CHild Study.

Secondary cardiovascular disease is the main cause of mortality in congenital heart disease (CHD) patients. The cardiovascular risk could be widely prevented with adherence to a healthy lifestyle; however, clusters of lifestyle behaviors related to atherosclerosis risk factors in children and adolescents with CHD remain unclear. We aimed to describe the clusters of lifestyle behaviors of children and adolescents with CHD and to evaluate their association with atherosclerosis risk factors. We conducted a cross-sectional study on 227 children and adolescents with CHD (median age:10.02 [IQR:7.08-13.02] years). Dietary intake, physical activity (PA), and sedentary behavior (SB) were evaluated. Clusters of lifestyle behaviors were determined using a two-step cluster analysis. Atherosclerosis risk factors evaluated include body fat mass, central obesity, blood pressure, lipid parameters, glucose, C-reactive protein, and carotid intima-media thickness (cIMT). Multiple logistic regressions were used. The "unhealthy: high SB + low PA" cluster was associated with elevated body fat mass, central obesity, and elevated cIMT. Furthermore, the "unhealthy: low PA + unhealthy eating habits" cluster was associated with elevated body fat mass, central obesity, and elevated glucose. The unhealthier lifestyle behavior clusters were associated with atherosclerosis risk factors in children and adolescents with CHD. Multidisciplinary strategies to promote healthy behaviors are needed to prevent cardiovascular disease in later life.

Bone Density and Bone Geometry in University Athletes From Sports With Different Levels of Impact: Simultaneous Association With Multiple Factors.

ABSTRACT: Moraes, MS, Fernandes, RA, Moreno, YMF, Pelegrini, A, and Silva, DAS. Bone density and bone geometry in university athletes from sports with different levels of impact: simultaneous association with multiple factors. J Strength Cond Res 36(11): 3113-3121, 2022-The aim of this study was to use the bone loading unit (BLU) classification to compare bone density and bone geometry of sports with different levels of impact, simultaneously controlling the multiple factors that interfere with bone metabolism in athletes. Overall, 167 university athletes (92 men) participated in the study. Bone mineral density (BMD), strength index, cross-sectional area (CSA) at the moment of inertia, section modulus (Z), CSA, neck-shaft angle (NSA), and hip axis length (HAL) were measured. Sports were categorized by level of impact, high BLU (higher impact) and moderate/low BLU (lower impact). Covariates were fat mass, lean tissue mass, training volume, time of practice, dietary supplementation, use of oral contraceptives and menstrual status. Multiple linear regression with 5% significance level ( p < 0.05) was used. In men, HAL was higher in sports with high BLU compared with those with moderate/low BLU (ß: -0.21; R2 : 0.30; p = 0.03). In women, NSA was higher in sports with moderate/low BLU compared with those with high BLU (ß: 0.31; R2 : 0.11; p = 0.02). There was no difference between BLU groups for BMD. These results persisted when the simultaneous interference of covariates was controlled. Thus, this study recommends BLU to classify sports and reinforces the importance of monitoring HAL and NSA in athletes in addition to the control of multiple factors that interfere with bone metabolism, because they influence physical performance and bone health during and after athletic life.

Nutritional screening tool for critically ill children: a systematic review.

CONTEXT: Nutritional screening tools (NSTs) are used to identify patients who are at risk of nutritional status (NS) deterioration and associated clinical outcomes. Several NSTs have been developed for hospitalized children; however, none of these were specifically developed for Pediatric Intensive Care Unit (PICU) patients. OBJECTIVE: A systematic review of studies describing the development, application, and validation of NSTs in hospitalized children was conducted to critically appraise their role in PICU patients. DATA SOURCES: PubMed, Embase, Web of Science, Scopus, SciELO, LILACS, and Google Scholar were searched from inception to December 11, 2020. DATA EXTRACTION: The review included 103 studies that applied NSTs at hospital admission. The NST characteristics collected included the aims, clinical setting, variables, and outcomes. The suitability of the NSTs in PICU patients was assessed based on a list of variables deemed relevant for this population. DATA ANALYSIS: From 19 NSTs identified, 13 aimed to predict NS deterioration. Five NSTs were applied in PICU patients, but none was validated for this population. NSTs did not include clinical, NS, laboratory, or dietary variables that were deemed relevant for the PICU population. CONCLUSION: None of the available NSTs were found to be suitable for critically ill children, so a new NST should be developed for this population. AQ6. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020167898.

Subclinical atherosclerosis in children and adolescents with congenital heart disease.

BACKGROUND: Subclinical atherosclerosis in childhood can be evaluated by carotid intima-media thickness, which is considered a surrogate marker for atherosclerotic disease in adulthood. The aims of this study were to evaluate carotid intima-media thickness and, to investigate associated factors. METHODS: Cross-sectional study with children and adolescents with congenital heart disease (CHD). Socio-demographic and clinical characteristics were assessed. Subclinical atherosclerosis was evaluated by carotid intima-media thickness. Cardiovascular risk factors, such as physical activity, screen time, passive smoke, systolic and diastolic blood pressure, waist circumference, dietary intake, lipid parameters, glycaemia, and C-reactive protein, were also assessed. Factors associated with carotid intima-media thickness were analysed using multiple logistic regression. RESULTS: The mean carotid intima-media thickness was 0.518 mm and 46.7% had subclinical atherosclerosis (carotid intima-media thickness ≥ 97th percentile). After adjusting for confounding factors, cyanotic CHD (odds ratio: 0.40; 95% confidence interval: 0.20; 0.78), cardiac surgery (odds ratio: 3.17; 95% confidence interval: 1.35; 7.48), and be hospitalised to treat infections (odds ratio: 1.92; 95% confidence interval: 1.04; 3.54) were associated with subclinical atherosclerosis. CONCLUSION: Clinical characteristics related to CHD were associated with subclinical atherosclerosis. This finding suggests that the presence of CHD itself is a risk factor for subclinical atherosclerosis. Therefore, the screen and control of modifiable cardiovascular risk factors should be made early and intensively to prevent atherosclerosis.

Assessing body composition in rugby players: agreement between different methods and association with physical performance.

BACKGROUND: This study investigated the comparability between air displacement plethysmography (ADP), dual-energy X-ray absorptiometry (DXA), and bioelectrical impedance analysis (BIA) methods for body composition assessment and their correlations with physical performance in rugby players. METHODS: Nineteen male elite players participated in the study. ADP, DXA, and BIA were used to assess fat-mass and fat-free mass. Physical performance was assessed by means of Carminatti's test of peak velocity (PVTCAR), countermovement jump (CMJ), sprint speed (10 and 30-m), and match performance analyses (sprinting, distance covered, and high-intensity running). RESULTS: BIA overestimated fat-mass (13±41%; r2=0.60) and underestimated fat-free mass (-1±7%; r2=0.66) compared to ADP (P=0.001). BIA underestimated fat-mass (-28±3%; r2=0.92) and overestimated fat-free mass (10±5%; r2=0.87) compared to DXA (P<0.001). ADP underestimated fat-mass (-36±37%; r2=0.69) and overestimated fat-free mass (11±8%; r2=0.52) compared to DXA (P<0.001). Fat-mass measured by ADP, DXA, and BIA negatively correlated with PVTCAR (r2≥0.49), height and peak power from CMJ (r2≥0.30), sprinting ability (r2≥0.65), and match performance variables (r2≥0.30). CONCLUSIONS: As long as one considers that ADP and BIA underestimated fat-mass and overestimated fat-free mass compared to DXA, the methods can be used to estimate body composition, particularly to track body fat-mass changes, which negatively influence several physical capacities determinant to rugby performance. The limitations of the methods should be borne in mind when assessing the body composition of rugby athletes.

Enteral Protein Supplementation in Critically Ill Children: A Randomized Controlled Pilot and Feasibility Study.

BACKGROUND: Loss of muscle mass in critically ill children can negatively impact outcomes. The aims of this study were to conduct a pilot randomized control trial (RCT) to examine the difference in protein delivery and nitrogen balance in critically ill children with enteral protein supplementation vs controls. We also aimed to assess the feasibility, safety, and tolerance of the pilot trial. METHODS: This is a 3-arm RCT in critically ill children eligible for enteral nutrition (EN) therapy. Patients were randomized to 1 of the 3 groups: (1) control (routine EN), (2) polymeric protein module added to EN to reach protein goal by day 4, or (3) oligomeric protein supplementation. Demographics, clinical characteristics, nutrition status, and daily nutrition intake variables were recorded. Protein delivery, nitrogen balance, feasibility variables, and rate of adverse events were the outcomes. RESULTS: After screening 286 consecutive patients admitted to the pediatric intensive care unit over 11 months, we enrolled and randomized 25 patients. Twenty-two patients (88% of the enrolled) completed the study procedures. Significantly higher protein prescription and actual protein intake within the first 5 days was achieved in the intervention groups, compared with the control group. Nitrogen balance was obtained in 15 patients. There was no significant difference between the groups for the rate of adverse effects and clinical outcomes. CONCLUSION: In our pilot trial, protein supplementation was safe and well tolerated. Our preliminary results suggest that a larger RCT is potentially feasible, with some modifications of the entry criteria. Trial enrollment was low, likely due to restrictive entry criteria.

Priorities for Nutrition Research in Pediatric Critical Care.

BACKGROUND: Widespread variation exists in pediatric critical care nutrition practices, largely because of the scarcity of evidence to guide best practice recommendations. OBJECTIVE: The objective of this paper was to develop a list of topics to be prioritized for nutrition research in pediatric critical care in the next 10 years. METHODS: A modified 3-round Delphi process was undertaken by a newly established multidisciplinary group comprising 11 international researchers in the field of pediatric critical care nutrition. Items were ranked on a 5-point Likert scale. RESULTS: Forty-five research topics (with a mean priority score >3(0-5) were identified within the following 10 domains: the pathophysiology and impact of malnutrition in critical illness; nutrition assessment: nutrition risk assessment and biomarkers; accurate assessment of energy requirements in all phases of critical illness; the role of protein intake; the role of pharmaco-nutrition; effective and safe delivery of enteral nutrition; enteral feeding intolerance: assessment and management; the role of parenteral nutrition; the impact of nutrition status and nutrition therapies on long-term patient outcomes; and nutrition therapies for specific populations. Ten top research topics (that received a mean score >4(0-5) were identified as the highest priority for research. CONCLUSIONS: This paper has identified important consensus-derived priorities for clinical research in pediatric critical care nutrition. Future studies should determine topics that are a priority for patients and parents. Research funding should target these priority areas and promote an international collaborative approach to research in this field, with a focus on improving relevant patient outcomes.

Feasibility of Enteral Protein Supplementation in Critically Ill Children.

BACKGROUND: We describe the protein type and concentration in standard enteral nutrition (EN) formulas and the effect of protein supplementation on the osmolality of standard formulas. We also aimed to examine factors associated with optimal protein delivery in critically ill children. METHODS: Protein content and other characteristics of pediatric EN formulas used worldwide were recorded. Factors associated with achievement of recommended protein delivery and tolerance of protein-supplemented formulas were recorded prospectively in a cohort of critically ill children. A range of protein supplement doses was added to 2 standard formulas and water, and the osmolality was recorded by cryoscopy in a bench experiment. RESULTS: We reviewed 125 formulas used in a multicenter study including sites from >13 countries. A majority of the EN formulas (73.6%) were polymeric, with a nonprotein calorie/nitrogen ratio of 182 ± 66 and protein content of 3.53 ± 2.00 g/100 mL. In the cohort of critically ill children, 28.5% achieved protein intake goal within 4 days, with no intolerance. In addition to optimal protein prescription (P < 0.001), protein supplementation (P = 0.018) and early EN initiation (P = 0.006) were associated with significantly higher odds of achieving goal protein intake. Formulas supplemented with up to 8 g/100 mL polymeric protein had osmolality <450 mOsm/kg. CONCLUSIONS: The protein content of current pediatric formulas may be inadequate to meet the needs of critically ill children. Protein supplementation of formulas allows early achievement of goal and is likely to be safe.).

Impact of the structure and dose of protein intake on clinical and metabolic outcomes in critically ill children: A systematic review.

OBJECTIVE: The aim of this study was to describe the effects of structure/type and total amount of protein intake on protein balance and clinical outcomes in critically ill children. METHODS: We conducted a systematic review of relevant literature on Embase, PubMed/Medline, Web of Science, Scopus, and Latin American and Caribbean Health Sciences. A partial gray literature search was undertaken and the reference lists of the selected articles were searched manually. Observational and clinical trials that evaluated the total protein intake, structure of the protein source, or both, in critically ill children were included. Nitrogen balance and clinical outcomes (mortality, length of stay, and duration of mechanical ventilation) were the main outcomes of interest. RESULTS: We found 18 eligible studies, of which 17 assessed the quantity and one described protein structure in relation to the outcomes. In all, 2118 pediatric critically ill patients <18 y of age were included. The total daily protein intake ranged from 0.67 to 4.7 g/kg. Average daily total protein intake >1.1 g/kg, especially >1.5 g/kg, was associated with positive protein balance and lower mortality. CONCLUSION: In critically ill children, total daily protein intake >1.1 g/kg was associated with positive effects on clinical outcomes and protein balance. The existing data are not sufficient for determining the optimal structure of protein delivered by enteral route in critically ill children.

Nutritional status as a predictor of duration of mechanical ventilation in critically ill children.

OBJECTIVES: Critically ill children admitted to the pediatric intensive care unit (PICU) often are malnourished. The aim of this study was to determine the role of nutritional status on admission as a predictor of the duration of mechanical ventilation in critically ill children. METHODS: This was a single-center, prospective cohort study, including consecutive children (ages 1 mo to 15 y) admitted to a PICU. Demographic characteristics, clinical characteristics, and nutritional status were recorded and patients were followed up until hospital discharge. Nutritional status was evaluated by anthropometric parameters and malnutrition was considered if the Z-scores for the parameters were ≤-2. Adjusted Cox's regression analysis was used to determine the association between nutritional status and duration of mechanical ventilation. RESULTS: In all, 72 patients were included. The prevalence of malnutrition was 41.2%, according to height-for-age Z-score, 18.6% according to weight-for-height Z-score, and 22.1% according body mass index-for-age Z-score. Anthropometrical parameters that predicted the duration of mechanical ventilation were weight-for-age (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.44-5.18); height-for-age (HR, 2.49; 95% CI, 1.44-4.28); and upper arm muscle area-for-age (HR, 5.22; 95% CI, 1.19-22.76). CONCLUSION: Malnutrition, based on a variety of anthropometric variables, was associated with the duration of mechanical ventilation in this cohort of critically ill children. Assessment of nutritional status by anthropometry should be performed on admission to the PICU to allow targeted nutritional rehabilitation for the subset of children with existing malnutrition.

Problems With Optimal Energy and Protein Delivery in the Pediatric Intensive Care Unit.

BACKGROUND: Optimal nutrition therapy (NT) delivery is associated with improved outcomes in critically ill children. However, avoidable barriers impede delivery of optimal energy and protein in the pediatric intensive care unit (PICU). This study aims to describe the gap between energy and protein prescription and actual intake. METHODS: Single-center prospective cohort study, including consecutive children (age: 1 month to 15 years) admitted to the PICU in southern Brazil. Demographics, clinical characteristics, and NT details were recorded. RESULTS: We enrolled 130 patients: 37% female; median (interquartile range) age, 29.43 months (4.03, 100.63); PICU length of stay, 6 days (4, 13). Median predicted energy expenditure by Schofield equation and prescribed and actual energy intake were 47.13 kcal/kg/d (38.60, 55.38), 31.94 kcal/kg/d (13.99, 51.90), and 25.06 kcal/kg/d (10.21, 46.92), respectively. On average, actual energy intake was 47% of the predicted energy expenditure, and 68% of patients were underfed. Actual protein intake was 49% of the estimated requirement. NT was interrupted in 64% of patients. CONCLUSIONS: There were significant gaps among the predicted requirement, prescription, and actual delivery of energy and protein in the PICU. Suboptimal prescription and multiple feeding interruptions resulted in underfeeding.

Impaired Bacillus Calmette-Guérin cellular immune response in HIV-exposed, uninfected infants.

OBJECTIVE: To evaluate cell-mediated immune response to Bacillus Calmette-Guérin (BCG) vaccination in uninfected, HIV-1-exposed infants, comparing it with unexposed children. DESIGN: It is designed as a cross-sectional study. METHODS: BCG-specific lymphoproliferation and T-cell subsets (CD4(+), CD8(+) and TCR γδ(+)) by flow cytometry and interleukin-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) concentration by ELISA were analyzed in HIV-exposed and unexposed infants. Whole blood lymphocyte immunophenotyping and blood counts were performed in exposed children. Nonparametric tests were used (P < 0.05). RESULTS: Given the ontogeny of the immune system, exposed infants were separated into three groups according to age: exposed 1 (E1, aged 6.1-8.8 months), E2 (aged 9.1-17.1 months) and E3 (aged 18.1-26.3 months). Unexposed infants (UE group) and E1 were matched for age. Cell proliferation was not different among the three exposed groups, neither for BCG nor for phytohemagglutinin (PHA)-stimulated cultures. Furthermore, BCG-stimulated lymphoproliferation was reduced in the E1 group in comparison with the UE group. T-lymphocyte subpopulations also showed differences, with the youngest HIV-exposed groups (E1 and E2) showing a predominant proliferation of CD4(+) T cells in cultures with BCG, whereas E3 and UE groups had a robust γδ(+) T-cell expansion. There was lower IFN-γ concentration in the samples from E1 group in comparison with all of the other groups. The unexposed infants showed higher TNF-α concentration in cultures with BCG and PHA in comparison with E1 group. CONCLUSION: BCG-specific T-cell proliferation was reduced in HIV-exposed uninfected infants and IFN-γ concentration was lower in younger exposed infants, showing a delay in immune system maturation of HIV-exposed infants.