Change In WAZ Research Articles

Association of Circulating Biomarkers with Growth and Cognitive Development in Rural Tanzania: A Secondary Analysis of the Early Life Interventions in Childhood Growth and Development In Tanzania (ELICIT) Study

BackgroundChildren in low-resource areas experience nutritional and infection challenges delaying growth and cognitive development. ObjectivesOur goal was to assess for associations of circulating biomarkers related to nutrition and inflammation, with growth and developmental outcomes among children in a birth cohort in a resource-poor area in rural Tanzania. MethodsWe assessed data from 1,120 children participating in the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) study. At age 12 and 18 mo, participants had blood tests performed for hemoglobin, collagen-X, insulin-like growth factor-1 (IGF-1), fibroblast growth factor-21 (FGF21), thyroglobulin, ferritin, soluble transferrin receptor (sTFR), retinol binding protein-4 (RBP4), C-reactive protein (CRP), α1-acid glycoprotein (AGP), and CD14. At 18 mo, participants had anthropometry measured and converted to z-scores for length-for-age (LAZ), weight-for-age (WAZ) and head-circumference-for-age (HCZ) and had the Malawi Developmental Assessment Tool (MDAT) performed to evaluate cognitive development. We performed linear regression assessing biomarkers (predictor variable) on anthropometry and MDAT scores (dependent variables), adjusted for sex, socioeconomic status, and baseline values. ResultsThere was a high degree of intrafactor correlation between 12 and 18 mo and interfactor correlation between biomarkers. IGF-1 and sTFR were positively and FGF21 and ferritin negatively associated with LAZ at 18 mo, whereas collagen-X and CD14 were additionally associated with recent linear growth. Only markers predominantly related to nutrition were consistently linked with WAZ at 18 mo, while RBP4 and AGP were additionally associated with recent change in WAZ. IGF-1 was positively and thyroglobulin, RBP4, and CD14 negatively linked to MDAT scores. IGF-1 was the only factor linked to both 18-mo LAZ and MDAT. ConclusionsIndividual biomarkers were consistently linked to growth and cognitive outcomes, providing support for relationships between nutrition and inflammation in early child development. Further research is needed to assess overlaps in how biomarker-related processes interact with both growth and learning. Registered at clinicaltrials.govNCT03268902.

Respiratory and diarrhoeal pathogens in Malawian children hospitalised with diarrhoea and association with short-term growth: A prospective cohort study

Background: Pneumonia and diarrhoea are the leading causes of childhood mortality and morbidity worldwide. The gut-lung axis is associated with disease, and these common infections, especially the parasite Cryptosporidium, are associated with malnutrition. We sought to evaluate the association of respiratory and gastrointestinal (GI) pathogens with short-term growth among children hospitalised with diarrhoeal disease. Methods: In this sub-study, we followed 27 children (two-24 months) who tested positive for Cryptosporidium spp. for eight weeks with two weekly sampling of the respiratory and GI tract. Respiratory and stool pathogens were detected using quantitative molecular methods. Nutritional outcomes were assessed as length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z-scores. Changes over the study period were compared using repeated analysis of variance and mixed effects model analysis. Results: In this period,104 sputum and stool samples were collected. All stool samples had at least one pathogen detected, with an average of 5.1 (SD 2.1) stool pathogens, compared to 84% of the sputum samples with an average 3.5 (SD 1.8). Diarrhoeagenic E. coli were the most common stool pathogens (89%), followed by Cryptosporidium (57.6%) and Adenovirus pan (41%). In sputum, Streptococcus pneumoniae was the most prevalent pathogen (84%), followed by hinovirus (56%) and Moraxella catarrhalis (50%). There was a significant change in WAZ over the follow-up period. Children who had ≥3 GI pathogens had significantly a lower LAZ mean score at enrolment (-1.8 [SD 1.4]) and across the follow-up period. No relationship between respiratory pathogens and short-term growth was observed. Out of 49 sputum samples that had ≥3 pathogens, 42 (85%) concurrent stool samples had ≥3 GI pathogens. Conclusions: Among young children hospitalised with diarrhoea, multiple GI and respiratory pathogens were prevalent over an eight-week follow-up period. The presence of more GI, but not respiratory, pathogens was significantly associated with reduced short-term growth.

Maternal and child FUT2 and FUT3 status demonstrate relationship with gut health, body composition and growth of children in Bangladesh

Fucosyltransferase 2 (FUT2) and 3 (FUT3) may influence host biological functions. We aim to assess the relationship between maternal and child FUT2 (Secretor) and FUT3 (Lewis) status with growth, body composition, gut health and histologic features in Bangladeshi children. We conducted a case–control study where secretor and Lewis status were ascertained from saliva samples of 408 mother–child dyads. Upper-arm fat area estimate (UFE) and total upper arm area (TUA) were found higher among children of Lewis negative mothers (p = 0.01 and p = 0.07, respectively). Changes in UFE after nutrition intervention were significantly greater among Lewis positive children than those of negative for Lewis (p = 0.05). Significant differences were observed for child UFE based on secretor and Lewis status of the mothers (p = 0.04). Lewis positive children had greater changes in WAZ (p = 0.07) and WLZ (p = 0.02) than Lewis negative children at the end of nutrition intervention. Fecal Reg1B was elevated in secretor positive children compared to their counterparts (p = 0.03). Lewis negative children had higher concentrations of MPO compared to Lewis positive children (p = 0.08). We also observed a higher frequency of subtotal villous atrophy among secretor negative and Lewis positive children (p = 0.09 and p = 0.01, respectively) than those of their counterparts. The findings provide insights for further studies to elucidate causal influences.

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

Comparing Attained Weight and Weight Velocity during the First 6 Months in Predicting Child Undernutrition and Mortality

BackgroundThe first 6 mo of life are critical for subsequent risk of undernutrition and mortality. The predictive abilities of attained weight at the end of each month and monthly weight velocity for undernutrition and mortality need to be compared. ObjectivesThis study aimed to examine the predictive abilities of different weight metrics during the first 6 mo of life in predicting undernutrition and mortality. MethodsThis study used a cohort of infants in Tanzania. Weight and length were measured monthly from birth to 18 mo of age. Three weight metrics during the first 6 mo of life were considered as predictors, including attained weight-for-age z score (WAZ) at the end of each month, monthly change in WAZ, and monthly weight velocity z score (WVZ). Logistic models were used with undernutrition (at 6 or 12 mo) and mortality (over the first 18 mo) as outcomes. AUC values were compared across metrics. ResultsFor predicting wasting at 6 mo, WVZ (AUC: 0.80) had a greater predictive ability than attained WAZ (AUC: 0.76) and change in WAZ (AUC: 0.71) during the second month of life. After 2 mo, attained WAZ (AUC: 0.81–0.89) had greater predictive abilities than WVZ (AUC: 0.71–0.77) and change in WAZ (AUC: 0.65–0.67). For predicting stunting at 6 mo, attained WAZ (AUC: 0.75–0.79) had consistently greater predictive abilities than WVZ (AUC: 0.56–0.66) and change in WAZ (AUC: 0.50–0.57). The weight metrics had similar abilities in predicting mortality, with the AUC rarely reaching >0.65. ConclusionsAttained weight at the end of each month had greater abilities than monthly weight velocity in the same month in predicting undernutrition. Attained weight remains a useful indicator for identifying infants at greater risk of undernutrition.

Nutrition delivery and growth outcomes in infants with long-gap esophageal atresia who undergo the Foker process

BackgroundPredictors of growth outcomes in patients with long-gap esophageal atresia (LGEA) are not known. We examined nutrition and growth in-hospital and post-discharge in LGEA patients who underwent the Foker Process (FP). MethodsSingle-center, retrospective cohort study of infants with LGEA undergoing primary (non-rescue) FP from 2014 to 2020. Weight-for-age z scores (WAZ, 0 = average), macronutrient prescription, anthropometry, and clinical variables were collected. Longitudinal median regression evaluated differences in WAZ over time. Multivariable median regression examined variables associated with change in WAZ at 1 year. Results45 patients met criteria, with median (IQR) age at repair of 4 (2, 5.8) months and WAZ of -0.96 (-1.55, -0.40). On admission, 11% were moderately (WAZ < -2) and 9% were severely (WAZ < -3) malnourished. Lower admission WAZ was significantly associated with improvement in WAZ at 1-year follow-up (p = 0.002); EA type (59% type A), esophageal leak (16%), median days paralyzed (13), ventilated (21), on parenteral nutrition (35), or to full enteral nutrition (35) were not associated with change in WAZ. Median WAZ remained stable while in-hospital, and patients maintained their growth curves through 3-year follow-up. ConclusionThroughout infancy, most primary FP LGEA patients have weight for age that is below average. Using targeted nutritional intervention, those who present with malnutrition can still achieve adequate growth despite prolonged and complicated hospital courses.

Influences on catch-up growth using relative versus absolute metrics: evidence from the MAL-ED cohort study

BackgroundPoor growth in early childhood has been considered irreversible after 2–3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child’s environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics.MethodsAcross six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression.ResultsAt 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0–24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD.ConclusionsThe study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD).

Standardized Feeding Approach Mitigates Weight Loss in Infants with Congenital Heart Disease

To evaluate the effect of a standardized feeding approach using a clinical nutrition pathway on weight-for-age Z score (WAZ) over hospital length of stay (HLOS) for infants with congenital heart disease (CHD). A 10-year retrospective cohort study examined eligible infants who underwent neonatal cardiac surgery between July 2009 and December 2018 (n=987). Eligibility criteria included infants born at least 37weeks of gestation and a minimum birth weight of 2kg who underwent cardiac surgery for CHD within the first 30days of life. Using the best linear unbiased predictions from a linear mixed effects model, WAZ change over HLOS was estimated before and after January 2013, when the standardized feeding approach was initiated. The best linear unbiased predictions model included adjustment for patient characteristics including sex, race, HLOS, and class of cardiac defect. The change in WAZ over HLOS was significantly higher from 2013 to 2018 than from 2009 to 2012 (β=0.16; SE=0.02; P<.001), after controlling for sex, race, HLOS, and CHD category, indicating that infants experienced a decreased WAZ loss over HLOS after the standardized feeding approach was initiated. Additionally, differences were found in WAZ loss over HLOS between infants with single ventricle CHD (β=0.26; SE=0.04; P<.001) and 2 ventricle CHD (β=0.04; SE=0.02; P=.04). These data suggest that an organized, focused approach for nutrition therapy using a standardized pathway improves weight change outcomes before hospital discharge for infants with single and 2 ventricle CHD who require neonatal cardiac surgery.

Identifying Influences on Catch-up Growth Using Relative versus Absolute Metrics: Evidence from the MAL-ED Study (P10-014-19)

ObjectivesTo identify factors associated with improvement (‘catch-up’) in height and weight from 24–60 mo of age, and to determine whether associated factors differ depending on the metric used (absolute or relative difference from WHO growth standards). MethodsAt seven MAL-ED sites, 942 children had anthropometry data at 24 and 60 mo, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9–24 mo, and micronutrient status. Anthropometric changes were categorized in terms of positive changes in Height- or Weight for-Age Z-score (HAZ, WAZ) or their differences (HAD, WAD) and recovery from stunting/underweight, and then modeled using multivariate linear regression. Results42% of the children were stunted at 24 or 60 mo, and 24% of the children were underweight at 24 or 60 mo. 44% of the children who were stunted at 24 mo were not at 60 mo, and 34% of those underweight at 24 mo were no longer at 60 mo. Among the sites, 49–92% of children had positive changes in their HAZ, whereas 25–60% had positive changes in HAD. Linear regression models indicate that female sex (-0.21 HAZ (95% CI -0.27, -0.15); -0.75 HAD (95% CI -1.07, -0.43)) and mean LMZ (-0.10 HAZ (95% CI -0.16, -0.04); -0.47 HAD (95% CI -0.73, -0.21)) were negatively associated with change in both HAZ and HAD, whereas maternal height was positively associated with change in both HAZ and HAD (0.09 HAZ (95% CI 0.03, 0.15); 0.45 HAD (95% CI 0.15, 0.75)). Similar relationships were identified for change in WAZ and WAD. Dietary protein density was negatively associated with change in WAZ and WAD (-0.05 WAZ (95% CI -0.09, -0.01); -0.11 WAD (95% CI -0.21, -0.01)), and plasma transferrin receptor concentration was positively associated with change in WAZ and WAD (0.02 WAZ (95% CI 0.0, 0.04); 0.04 WAD (95% CI 0.0, 0.08)). ConclusionsChildren in the MAL-ED study demonstrated recovery from stunting and underweight from 24 to 60 mo of age. Given the similarities in the factors associated with changes in HAZ and HAD (and WAZ and WAD), both be used as complementary approaches to characterize and explain catch-up growth during early childhood. Funding SourcesThe MAL-ED study was supported by the Bill & Melinda Gates Foundation, with grants to the Foundation for the NIH and NIH/FIC.

Association between enteropathogens and malnutrition in children aged 6–23 mo in Bangladesh: a case-control study1–3

Background: Early exposure to enteropathogens has been associated with malnutrition in children in low-resource settings. However, the contribution of individual enteropathogens remains poorly defined. Molecular diagnostics offer an increase in sensitivity for detecting enteropathogens but have not been comprehensively applied to studies of malnutrition.Objective: We sought to identify enteropathogens associated with malnutrition in Bangladesh.Design: Malnourished children [weight-for-age z score (WAZ) <−2] aged 6–23 mo in Dhaka, Bangladesh, and identified by active community surveillance were enrolled as cases, and normal-weight children (WAZ >−1) of the same age and from the same community were enrolled as controls. Stools were collected at enrollment and, for cases, after a 5-mo nutritional intervention. Enrollment and follow-up stools were tested by quantitative polymerase chain reaction for 32 enteropathogens with the use of a custom-developed TaqMan Array Card.Results: Enteropathogen testing was performed on 486 cases and 442 controls upon enrollment and 365 cases at follow-up. At enrollment, the detection of enteroaggregative Escherichia coli (OR: 1.39; 95% CI: 1.05, 1.83), Campylobacter spp. (OR: 1.46; 95% CI: 1.11, 1.91), heat-labile enterotoxin-producing E. coli (OR: 1.55; 95% CI: 1.04, 2.33), Shigella/enteroinvasive E. coli (OR: 1.65; 95% CI: 1.10, 2.46), norovirus genogroup I (OR: 1.66; 95% CI: 1.23, 2.25), and Giardia (OR: 1.73; 95% CI: 1.20, 2.49) were associated with malnourished cases, and the total burden of these pathogens remained associated with malnutrition after adjusting for sociodemographic factors. The number of these pathogens at follow-up was negatively associated with the change in WAZ during the intervention (−0.10 change in WAZ per pathogen detected; 95% CI: −0.14, −0.06), whereas the number at enrollment was positively associated with the change in WAZ (0.05 change in WAZ per pathogen detected; 95% CI: 0.00, 0.10).Conclusions: A subset of enteropathogens was associated with malnutrition in this setting. Broad interventions designed to reduce the burden of infection with these pathogens are needed. This trial was registered at clinicaltrials.gov as NCT02441426.

A Randomized Controlled Trial of Two Ready-to-Use Supplementary Foods Demonstrates Benefit of the Higher Dairy Supplement for Reduced Wasting in Mothers, and Differential Impact in Infants and Children Associated With Maternal Supplement Response

There is no consensus over best approaches to reliably prevent malnutrition in rural communities in low-income countries. We compared the effectiveness of 2 lipid-based ready-to-use supplementary foods (RUSFs) differing in dairy protein content to improve the nutritional status of mothers and at-risk infants and young children in rural Guinea-Bissau. A 3-month cluster-randomized controlled pilot trial of 2 RUSFs was conducted with 692 mothers and 580 mildly or moderately malnourished infants (6-23 months) and children (24-59 months) from 13 villages. The RUSFs contained either 478 (mothers, children) or 239 kcal/d (infants) with 15% or 33% of protein from dairy and were distributed at community health centers 5 d/wk. Controls were wait-listed to receive RUSF. Primary outcomes were mid-upper arm circumference (MUAC) in mothers, and weight-for-age and height-for-age z-scores (WAZ and HAZ) in infants and children. There was a significant effect of the RUSF-33% on MUAC in mothers ( P = .03). The WAZ and HAZ increased substantially, by ≈1 z-score, in infants and children ( P < .01) independent of group randomization. In children, but not infants, baseline WAZ and change in maternal MUAC were associated with change in WAZ (β = .07, P = .02). Ready-to-use supplementary foods with higher dairy protein content had a significant benefit in village mothers, supporting a comparable recent finding in preschool children. In addition, supplementation of children <2 years resulted in improved growth independent of family nutritional status, whereas success in older children was associated with change in maternal nutrition, suggesting the need for community-level education about preventing malnutrition in older, as well as younger, children.

Infant nutritional status and markers of environmental enteric dysfunction are associated with mid‐childhood anthropometry and blood pressure in Tanzania

BackgroundIn industrialized countries, risk factors for chronic diseases are linked with infant nutritional status; however, limited data exist from resource‐poor settings, where rates of undernutrition, infectious disease, environmental enteric dysfunction (EED), and impaired child growth in infancy and childhood are high.ObjectiveTo assess the extent to which growth and biomarkers of EED in infancy are related to health outcomes in mid‐childhood in Dar es Salaam, Tanzania.MethodsChildren who participated in one of two randomized controlled trials of micronutrient supplements in infancy were followed‐up in mid‐childhood (4.6–9.8 years). Anthropometry was measured at age 6 and 52 weeks in both trials, while blood samples were available from all children at 6 weeks and 6 months from one of the two trials. Linear regression models were used to assess whether length‐for‐age, weight‐for‐age and weight‐for‐length z‐scores (LAZ, WAZ and WLZ) at age 6 weeks, and change from 6 to 52 weeks, as well as flagellin IgG and IgA and LPS IgG and IgG predicted height‐for‐age, body‐mass‐index and weight for age z‐scores (HAZ, BMIZ and WAZ) as well as systolic and diastolic blood pressure in mid‐childhood.Results113 children were re‐enrolled in the follow‐up study in mid‐childhood. LAZ at 6 weeks and change in LAZ from 6 to 52 weeks were independent, positive predictors of HAZ in mid‐childhood in multivariate models (p&lt;0.001 for both), while change in WAZ and WLZ from 6 to 52 weeks were also positively correlated with mid‐childhood HAZ in multivariate models. 6‐week WLZ and change in WLZ from 6 to 52 weeks were independently, positively associated with BMIZ in mid‐childhood in multivariate models as were WAZ at 6 weeks and change in WAZ during infancy. BMIZ in mid‐childhood was in turn positively associated with systolic blood pressure at follow‐up. Among the 66 children from the second trial who had blood samples analyzed for EED biomarkers, serum anti‐flagellin IgA concentration at 6 weeks was significantly associated with systolic and diastolic blood pressure in mid‐childhood in multivariate models (p=0.001 for both).ConclusionsLength at 6 weeks and gains in length in the first year of life are independently, positively associated with attained height in childhood, while weight at 6 weeks and weight gain throughout infancy are independently associated with an increased BMIZ in mid‐childhood. EED in infancy may also have long‐term consequences for cardio‐metabolic risk. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and EED risk.Support or Funding InformationNational Institutes of Health (R01 HD043688‐01, R01 HD048969‐01, K24HD058795 and K24 DK104676), Bill and Melinda Gates Foundation (OPP1066203) and the Feed the Future Food Innovation Lab for Nutrition which is funded by the United States Agency for International Development (USAID).

Growth Recovery Among HIV-infected Children Randomized to Lopinavir/Ritonavir or NNRTI-based Antiretroviral Therapy.

Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy (ART). We examined growth recovery in a rural Ugandan cohort of HIV-infected children randomized to lopinavir/ritonavir (LPV/r) or non nucleoside reverse transcription inhibitor-based ART. HIV-infected children 2 months to 6 years of age were randomized to LPV/r- or non nucleoside reverse transcription inhibitor-based ART. Changes in weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height Z-scores for 24 months were evaluated using generalized linear repeated measures models. Recovery from being underweight (WAZ<-2), stunted (HAZ<-2) and wasted (weight-for-height <-2) to Z-scores greater than -2 was also compared by arm using Kaplan-Meier survival and Cox proportional hazard modeling. A total of 129 children with median age of 3 years initiated therapy; 64 received LPV/r-based and 65 non nucleoside reverse transcription inhibitor-based ART (nevirapine: 36 and efavirenz: 29). The median (interquartile range) difference in growth measures between baseline and 24 months for LPV/r (n = 45) versus non nucleoside reverse transcription inhibitor-based therapy (n = 40) were as follows: WAZ, 0.47 (0.10, 1.62) versus 0.53 (0.03, 1.14) (P = 0.59) and HAZ, median 1.55 (0.78, 1.86) versus 1.19 (0.62, 1.65) (P = 0.23), respectively. ART regimen was not predictive of change in WAZ (β: -0.02, 95% confidence interval: -0.25, 0.20) or HAZ (β: 0.05, 95% confidence interval: -0.10, 0.19). The presence of confirmed virologic failure was not associated with growth. Most ART-naive children experienced recovery of both WAZ and HAZ over the 24 months after ART initiation, with no significant difference between those receiving LPV/r versus non nucleoside reverse transcriptase inhibitor-based ART. However, the persistence of median Z-scores below 0 underscores the need for additional strategies to improve growth outcomes in HIV+ African children.

Growth reconstitution following antiretroviral therapy and nutritional supplementation: systematic review and meta-analysis.

As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following ART in resource-limited (RLS) and developed settings. Systematic review and meta-analysis. We searched publications reporting growth [weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z scores] in HIV-infected children following ART through August 2014. Inclusion criteria were as follows: younger than 18 years; ART; at least 20 patients; growth at ART; and post-ART growth. Standardized and overall weighted mean differences were calculated using random-effects models. A total of 67 articles were eligible (RLS = 54; developed settings = 13). Mean age was 5.8 years, and comparable between settings (P = 0.90). Baseline growth was substantially lower in RLS vs. developed settings (WAZ -2.1 vs. -0.5; HAZ -2.2 vs. -0.9; both P < 0.01). Rate of weight but not height reconstitution during 12 and 24 months was higher in RLS (12-month WAZ change 0.84 vs. 0.17, P < 0.01). Growth deficits persisted in RLS after 2 years ART (P = 0.04). Younger cohort age was associated with greater growth reconstitution. Protease inhibitor and nonnucleoside reverse-transcriptase inhibitor regimens yielded comparable growth. Adjusting for age and setting, cohorts with nutritional supplements had greater growth gains (24-month rate difference: WAZ 0.55, P = 0.03; HAZ 0.60, P = 0.007). Supplement benefits were attenuated after adjusting for baseline cohort growth. RLS children had substantial growth deficits compared with developed settings counterparts at ART; growth shortfalls in RLS persisted despite reconstitution. Earlier age and nutritional supplementation at ART may improve growth outcomes. Scant data on supplementation limit evaluation of impact and underscores need for systematic data collection regarding supplementation in pediatric ART programmes/cohorts.

The Effectiveness of Two Ready to Use Supplementary Foods (RUSFs) Differing in Dairy Protein Content on Growth and Nutritional Status of Young Children: A Pilot Study in Preschools in Guinea‐Bissau

A USDA‐funded cluster‐randomized controlled trial compared two RUSF containing 500 calories and either 15% or 33% of dietary protein from dairy for 3 months versus a wait‐listed control. Each RUSF was provided 5 days per week. Intention‐to‐treat analyses were conducted with changes in weight‐for‐age and height‐for‐age Z‐scores (WAZ, HAZ) as primary outcomes. Additional outcomes included mid‐upper arm circumference (MUAC), hemoglobin and retinol binding protein levels and disease incidence.Z‐scores increased significantly in all groups over baseline (P=&gt;0.01) but there was no significant effect of the RUSFs on changes in WAZ or HAZ. There was a significant effect of supplementation on the association between baseline WAZ and WAZ gain (P&lt;0.002). There was a significant positive effect of randomization to the 33% RUSF on change in MUAC (P&lt;0.05). There was a significant decrease in reported rates of malaria in children randomized to either supplement.This study provides the first evidence that RUSF with 33% versus the more typical 15% of protein provided by dairy may have particular benefit for prevention of wasting. It also indicates that RUSFs demonstrate growth benefits across the range of baseline anthropometric measures. It further shows that preschools can be an effective platform for implementation of intensive programs for prevention of malnutrition in young children living in low‐income countries.

Association between infant nutrition and anthropometry, and pre-pubertal body composition in urban South African children.

Early life nutrition and growth are related to subsequent obesity risk in high-income countries. We investigated the association between nutrition and growth during infancy, and body composition at 10 years of age in 140 children selected from the Bone Health sub-study of the Birth-to-Twenty cohort from Soweto, Johannesburg, South Africa. Infant feeding and dietary data were collected during the first 12 months, and weight and height were measured at 1 and 2 years of age. At 10 years, anthropometry and dual-energy X-ray absorptiometry (DXA)-derived body composition were measured. Regression models were used to determine associations between independent and dependent variables at the 1% level of significance. A one z-score increase in birth weight was associated with a 1051 g increase in lean mass and a 0.22 increase in body mass index (BMI) z-score at the age of 10 years. After adjusting for confounders, stunting at age 1 year was associated with lower fat mass only at 10 years of age while at age 2 years, it was associated with lower lean mass only. Being underweight at one year of age was significantly associated with lower lean mass only. Weight-for-age (WAZ) change in the second year of infancy was a predictor of fat mass and BMI only. Body fatness at 10 years of age was positively associated with infant WAZ change rather than height-for-age change. There were no significant associations between infant dietary patterns, wasting and being underweight at age 2 years and pre-pubertal body composition. Further studies are needed to assess whether these associations continue during adolescence as pubertal development may be an important modifier of these associations.

Gestational weight gain and predicted changes in offspring anthropometrics between early infancy and 3 years

To determine how gestational weight gain (GWG), categorized using the 2009 Institute of Medicine recommendations, relates to changes in offspring weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length z-scores (WLZ) between early infancy and 3 years. Women with singleton infants were recruited from the third cohort of the Pregnancy, Infection, and Nutrition Study (2001-2005). Term infants with at least one weight or length measurement during the study period were included (n = 476). Multivariable linear mixed effects regression models estimated longitudinal changes in WAZ, LAZ and WLZ associated with GWG. In early infancy, compared with infants of women with adequate weight gain, those of women with excessive weight gains had higher WAZ, LAZ and WLZ. Excessive GWG ≥ 200% of the recommended amount was associated with faster rates of change in WAZ and LAZ and noticeably higher predicted mean WAZ and WLZ that persisted across the study period. GWG is associated with significant differences in offspring anthropometrics in early infancy that persisted to 3 years of age. More longitudinal studies that utilize maternal and paediatric body composition measures are necessary to understand the nature of this association.

Nutrition supplementation of HIV‐infected women during lactation does not consistently influence infant growth from 0–24 weeks

This study evaluated the effect of daily consumption of lipid-based nutrient supplements (LNS) by 2112 lactating HIV-infected mothers on the growth of their exclusively breastfed HIV-uninfected infants from 0–24 wks. Malawian mothers participating in the Breastfeeding, Antiretroviral, and Nutrition (BAN) study were randomized to receive either no LNS or 140g/d of LNS, to meet lactation energy and protein needs. Within these groups, there was further randomization to maternal antiretroviral drugs, daily infant nevirapine, or no postnatal antiretroviral regimen. Outcomes included infant weight-for-age (WAZ), length-for-age (LAZ), and body-mass index (BMIZ) z-scores estimated in longitudinal random effects models, and the likelihood of growth faltering (change in WAZ or LAZ>−0.67) estimated using logistic regression. Maternal supplementation was associated with a higher WAZ (p<0.01) and BMIZ (p<0.01) only in boys receiving the infant drug. Supplement did not reduce the odds of faltering in weight or length from 0–24 wks in any group. These results agree with other studies showing minimal or delayed effects of maternal supplementation during lactation on infant growth. Generalizability may be limited because BAN mothers were healthy (CD4≥200, Hb≥7 and BMI≥17) and infants were full term and weighed≥2 kg at birth. Supported by CDC (U48-DP000059-01) and Bill & Melinda Gates Foundation (OPP53107).