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Background Stunting and pubertal delay are common among children growing up with human immunodeficiency virus (HIV) and are associated with bone and muscle impairments. We investigated factors associated with bone density and muscle function in adolescents living with HIV (ALWH). Methods The VITALITY trial (PACTR202009897660297) investigated whether vitamin D and calcium supplementation improves musculoskeletal health among ALWH. A total of 842 ALWH aged 11–19 years, established on antiretroviral therapy (ART) for ≥6 months, were enrolled from HIV clinics in Zambia and Zimbabwe. Clinical history and examination were undertaken, and serum 25-hydroxyvitamin D3 (25[OH]D3) was measured. Dual-energy X-ray absorptiometry measured total-body-less-head bone mineral density adjusted for height (TBLH-BMDHT), and lumbar spine bone mineral apparent density (LS-BMAD) z scores. The association between a priori–defined covariates and musculoskeletal outcomes were investigated using baseline enrollment data and multivariable logistic regression. Results TBLH-BMDHT z scores were impaired (mean, −1.42 for male and −0.63 female participants), as were LS-BMAD z scores (mean −1.15 for male and −0.47 for female participants). In bivariate analysis, early pubertal stage, less physical activity, and older age at ART initiation were associated with lower TBLH-BMDHT z scores. Younger age, early pubertal stage, and low socioeconomic status were associated with lower LS-BMAD z scores. Grip-strength-for-height and jump-power-for-height z scores were associated with lower TBLH-BMDHT and LS-BMAD z scores. Low dietary vitamin D and calcium were associated with lower adjusted TBLH-BMDHT z scores. Lower 25(OH)D3 was associated with lower adjusted TBLH-BMDHT and LS-BMAD z scores. Conclusions Deficits in bone density are common in ALWH. Vitamin D and calcium supplementation and promotion of exercise may improve musculoskeletal health among perinatally infected ALWH. [ABSTRACT FROM AUTHOR]

Background Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. Methods and findings We performed a randomized, double-blind, 2 x 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) -3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m.sup.2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m.sup.2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m.sup.2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m.sup.2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration. Conclusions Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered. Trial registration ISRCTN13093195, Author(s): Joseph Mbabazi 1,2, Hannah Pesu 1, Rolland Mutumba 1,2, Suzanne Filteau 3, Jack I. Lewis 1, Jonathan C. Wells 4, Mette F. Olsen 1,5, André Briend 1,6, Kim F. [...]

Background Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. Methods and findings A randomized 2 x 2 x 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Conclusions Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. Trial registration ISRCTN Registry ISRCTN42569496., Author(s): Henrik Friis 1,*, Bernardette Cichon 1, Christian Fabiansen 1,2, Ann-Sophie Iuel-Brockdorff 1, Charles W. Yaméogo 1,3, Christian Ritz 1, Ruth Frikke-Schmidt 4,5, André Briend 1,6, Kim F. Michaelsen 1, [...]

Background: Stress during pregnancy is detrimental to maternal health, pregnancy and birth outcomes and various preventive relaxation interventions have been developed. This systematic review and meta-analysis aimed to evaluate their effectiveness in terms of maternal mental health, pregnancy and birth outcomes. Method: The protocol for this review is published on PROSPERO with registration number CRD42020187443. A systematic search of major databases was conducted. Primary outcomes were maternal mental health problems (stress, anxiety, depression), and pregnancy (gestational age, labour duration, delivery mode) and birth outcomes (birth weight, Apgar score, preterm birth). Randomized controlled trials or quasi-experimental studies were eligible. Meta-analyses using a random-effects model was conducted for outcomes with sufficient data. For other outcomes a narrative review was undertaken. Result: We reviewed 32 studies comprising 3,979 pregnant women aged 18 to 40 years. Relaxation interventions included yoga, music, Benson relaxation, progressive muscle relaxation (PMR), deep breathing relaxation (BR), guided imagery, mindfulness and hypnosis. Intervention duration ranged from brief experiment (~10 minutes) to 6 months of daily relaxation. Meta-analyses showed relaxation therapy reduced maternal stress (-4.1 points; 95% Confidence Interval (CI): -7.4, -0.9; 9 trials; 1113 participants), anxiety (-5.04 points; 95% CI: -8.2, -1.9; 10 trials; 1965 participants) and depressive symptoms (-2.3 points; 95% CI: -3.4, -1.3; 7 trials; 733 participants). Relaxation has also increased offspring birth weight (80 g, 95% CI: 1, 157; 8 trials; 1239 participants), explained by PMR (165g, 95% CI: 100, 231; 4 trials; 587 participants) in sub-group analysis. In five trials evaluating maternal physiological responses, relaxation therapy optimized blood pressure, heart rate and respiratory rate. Four trials showed relaxation therapy reduced duration of labour. Apgar score only improved significantly in two of six trials. One of three trials showed a significant increase in birth length, and one of three trials showed a significant increase in gestational age. Two of six trials examining delivery mode showed significantly increased spontaneous vaginal delivery and decreased instrumental delivery or cesarean section following a relaxation intervention. Discussion: We found consistent evidence for beneficial effects of relaxation interventions in reducing maternal stress, improving mental health, and some evidence for improved maternal physiological outcomes. In addition, we found a positive effect of relaxation interventions on birth weight and inconsistent effects on other pregnancy or birth outcomes. High quality adequately powered trials are needed to examine impacts of relaxation interventions on newborns and offspring health outcomes. Conclusion: In addition to benefits for mothers, relaxation interventions provided during pregnancy improved birth weight and hold some promise for improving newborn outcomes; therefore, this approach strongly merits further research. [ABSTRACT FROM AUTHOR]

Impaired linear growth and slower pubertal growth can be associated with perinatal HIV infection. We characterised growth relative to population norms, among the full adolescent period in southern Africa to better understand processes leading to morbidity in adulthood. We conducted a secondary analysis of 945 adolescents aged 8–20 years from urban Malawi and Zimbabwe; we included children with HIV (CWH), an uninfected comparison group from a cohort study, and CWH with co-morbid chronic lung disease (CLD) from a randomised controlled trial. We used latent class analysis of anthropometric Z-scores generated from British 1990 reference equations at two annual time-points, to identify growth trajectory profiles and used multinomial logistic regression to identify factors associated with growth profiles. Growth faltering (one or more of weight-for-age, height-for-age, or BMI-for-age Z-scores < −2) occurred in 38% (116/303) of CWH from the cohort study, 62% (209/336) of CWH with CLD, and 14% (44/306) of HIV-uninfected participants. We identified seven different growth profiles, defined, relatively, as (1) average growth, (2) tall not thin, (3) short not thin, (4) stunted not thin, (5) thin not stunted, (6) thin and stunted and (7) very thin and stunted. Females in profile 3 exhibited the highest body fat percentage, which increased over 1 year. Males at older age and CWH especially those with CLD were more likely to fall into growth profiles 4–7. Improvements in height-for-age Z-scores were observed in profiles 6–7 over 1 year. Interventions to target those with the worst growth faltering and longer-term follow-up to assess the impact on adult health are warranted. [ABSTRACT FROM AUTHOR]