-
1.
Vitamin D for Growth and Rickets in Stunted Children: A Randomized Trial.
Crowe, FL, Mughal, MZ, Maroof, Z, Berry, J, Kaleem, M, Abburu, S, Walraven, G, Masher, MI, Chandramohan, D, Manaseki-Holland, S
Pediatrics. 2021;(1)
Abstract
BACKGROUND AND OBJECTIVES Vitamin D is essential for healthy development of bones, but little is known about the effects of supplementation in young stunted children. Our objective was to assess the effect of vitamin D supplementation on risk of rickets and linear growth among Afghan children. METHODS In this double-blind, placebo-controlled trial, 3046 children ages 1 to 11 months from inner-city Kabul were randomly assigned to receive oral vitamin D3 (100 000 IU) or placebo every 3 months for 18 months. Rickets Severity Score was calculated by using wrist and knee radiographs for 631 randomly selected infants at 18 months, and rickets was defined as a score >1.5. Weight and length were measured at baseline and 18 months by using standard techniques, and z scores were calculated. RESULTS Mean (95% confidence interval [CI]) serum 25-hydroxyvitamin D (seasonally corrected) and dietary calcium intake were insufficient at 37 (35-39) nmol/L and 372 (327-418) mg/day, respectively. Prevalence of rickets was 5.5% (placebo) and 5.3% (vitamin D): odds ratio 0.96 (95% CI: 0.48 to 1.92); P = .9. The mean difference in height-for-age z score was 0.05 (95% CI: -0.05 to 0.15), P = .3, although the effect of vitamin D was greater for those consuming >300 mg/day of dietary calcium (0.14 [95% CI: 0 to 0.29]; P = .05). There were no between-group differences in weight-for-age or weight-for-height z scores. CONCLUSIONS Except in those with higher calcium intake, vitamin D supplementation had no effect on rickets or growth.
-
2.
Maternal Preconception Body Size and Early Childhood Growth during Prenatal and Postnatal Periods Are Positively Associated with Child-Attained Body Size at Age 6-7 Years: Results from a Follow-up of the PRECONCEPT Trial.
Nguyen, PH, Young, MF, Khuong, LQ, Tran, LM, Duong, TH, Nguyen, HC, Martorell, R, Ramakrishnan, U
The Journal of nutrition. 2021;(5):1302-1310
-
-
Free full text
-
Abstract
BACKGROUND Growth faltering is associated with adverse consequences during childhood and later life. However, questions remain on the relative importance of preconception maternal nutritional status (PMNS) and child growth during the first 1000 d of life. OBJECTIVES We examined associations between PMNS, gestational weight gain (GWG), and child growth during the first 1000 d with attained body size at age 6-7 y. METHODS We used data from a follow-up of a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam (n = 5011 women). The outcomes included offspring height-for-age z score (HAZ), BMI-for-age z score (BMIZ), and prevalence of stunting and overweight/obese at age 6-7 y (n = 1579). We used multivariable linear and Poisson regression models to evaluate the relative contributions of PMNS (height and BMI), GWG, and conditional growth in 4 periods: fetal, 0-6 mo, 6-12 mo, and 12-24 mo. RESULTS PMNS was positively associated with child-attained size at 6-7 y. For each 1-SD higher maternal height and BMI, offspring had 0.28-SD and 0.13-SD higher HAZ at 6-7 y, respectively. Higher maternal BMI and GWG were associated with larger child BMIZ (β: 0.29 and 0.10, respectively). Faster linear growth, especially from 6 to 24 mo, had the strongest association with child HAZ at 6-7 y (β: 0.39-0.42), whereas conditional weight measures in all periods were similarly associated with HAZ (β: 0.10-0.15). For BMIZ at 6-7 y, the magnitude of association was larger and increased with child age for conditional weight gain (β: 0.21-0.41) but smaller for conditional length gain. Faster growth in the first 2 y was associated with reduced risk of stunting and thinness but increased risk of overweight/obese at 6-7 y. CONCLUSIONS Interventions aimed at improving child growth while minimizing the risk of overweight during the school age years should target both women of reproductive age prior to conception through delivery and their offspring during the first 1000 d. The trial was registered at clinicaltrials.gov as NCT01665378.
-
3.
High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial.
Alburaki, W, Yusuf, K, Dobry, J, Sheinfeld, R, Alshaikh, B
The Journal of pediatrics. 2021;:16-23.e1
Abstract
OBJECTIVE To determine whether high early parenteral soybean oil lipid intake in very low birth weight (VLBW) infants in the first week after birth decreases the proportion of weight loss and subsequently the incidence of extrauterine growth restriction (EUGR). STUDY DESIGN This was a randomized controlled trial of appropriate for gestational- ge VLBW infants. Lipid intake in the control group started at 0.5-1 g/kg per day and increased daily by 0.5-1 g/kg per day till reaching 3 g/kg per day. The intervention group was started on 2 g/kg per day that increased to 3 g/kg per day the following day. RESULTS Of the 176 infants assessed for eligibility, 83 were included in the trial. Infants in the intervention group were started on lipid sooner (13.8 ± 7.8 vs 17.5 ± 7.8 hour; P = .03) and had higher cumulative lipid intake in the first 7 days of age (13.5 ± 4.2 vs 10.9 ± 3.5 g/kg per day; P = .03). Infants in the intervention group had a lower percentage of weight loss (10.4 vs 12.7%; P = .02). The mean triglyceride level was higher in the intervention group (1.91 ± 0.79 vs 1.49 ± 0.54 mmol/L; P = .01), however, hypertriglyceridemia was similar between the 2 groups. The incidence of EUGR was lower in the intervention group (38.6% vs 67.6%; P = .01). Head circumference z score was higher in the intervention group (-1.09 ± 0.96 vs -1.59 ± 0.98; P = .04). CONCLUSIONS In VLBW infants, provision of a high early dose of parenteral lipid in the first week of age results in less weight loss and lower incidence of EUGR. TRIAL REGISTRATION Clinicaltrials.gov: NCT03594474.
-
4.
Amino Acid Digestibility of Extruded Chickpea and Yellow Pea Protein is High and Comparable in Moderately Stunted South Indian Children with Use of a Dual Stable Isotope Tracer Method.
Devi, S, Varkey, A, Dharmar, M, Holt, RR, Allen, LH, Sheshshayee, MS, Preston, T, Keen, CL, Kurpad, AV
The Journal of nutrition. 2020;(5):1178-1185
-
-
Free full text
-
Abstract
BACKGROUND Legumes are an excellent plant source of the limiting indispensable amino acid (IAA) lysine in vegetarian, cereal-based diets. However, their digestibility is poor largely because of their antiprotease content. Extrusion can enhance digestibility by inactivating trypsin inhibitors and thus potentially improve the protein quality of legumes. OBJECTIVE We measured the digestibility of extruded chickpea and yellow pea protein with use of a dual stable isotope method in moderately stunted South Indian primary school children. METHODS Twenty-eight moderately stunted children (height-for-age z scores <-2.0 SD and >-3.0 SD) aged 6-11 y from low to middle socioeconomic status were randomly assigned to receive a test protein (extruded intrinsically [2H]-labeled chickpea or yellow pea) along with a standard of U-[13C]-spirulina protein to measure amino acid (AA) digestibility with use of a dual stable isotope method. Individual AA digestibility in the test protein was calculated by the ratios of AA enrichments in the test protein to the standard protein in the food and their appearance in blood plasma collected at 6 and 6.5 h during the experiment, representing a plateau state. RESULTS The mean AA digestibility of extruded chickpea and yellow pea protein in moderately stunted children (HAZ; -2.86 to -1.2) was high and similar in both extruded test proteins (89.0% and 88.0%, respectively, P = 0.83). However, lysine and proline digestibilities were higher in extruded chickpea than yellow pea (79.2% compared with 76.5% and 75.0% compared with 72.0%, respectively, P < 0.02). CONCLUSION Extruded chickpea and yellow pea protein had good IAA digestibility in moderately stunted children, which was 20% higher than an earlier report of their digestibility when pressure-cooked, measured by the same method in adults. Higher digestibility of lysine and proline highlights better retention of these AA in chickpea during extrusion-based processing. Extrusion might be useful for developing high-quality protein foods from legumes. This trial was registered at www.ctri.nic.in as CTRI/2018/03/012439.
-
5.
Study protocol to assess the impact of an integrated nutrition intervention on the growth and development of children under two in rural Bangladesh.
Ara, G, Sanin, KI, Khanam, M, Sarker, SA, Khan, SS, Rifat, M, Chowdhury, IA, Askari, S, Afsana, K, Ahmed, T
BMC public health. 2019;(1):1437
Abstract
BACKGROUND The period from birth to two years is the "critical window" for achieving optimal growth and development. An inadequate quality and quantities of complementary foods, poor child-feeding practices and infection negatively impact the growth of under-twos. Approximately one-third of under-fives in developing countries are stunted; many are also micronutrient deficient. An estimated 6% of mortalities among under-fives can be prevented by ensuring optimal complementary feeding. The objective of the study was to assess the ability of a 12-month integrated nutrition intervention to improve the nutritional status (length-for-age Z-score) of 6 to 12-month-old children in rural Bangladesh. METHODS In this community-based randomized controlled trial, the intervention group received a package of interventions that includes, food vouchers; to prepare egg-based nutritious snacks (suji firni for < 1-year-olds, suji halwa for > 1-year-olds), micronutrient powder to fortify children's food at home, child feeding counselling and water, sanitation and hygiene (WASH), behaviour change communication. The control group received routine health messages provided by the government. Baseline and endline surveys were conducted; Data collection was performed monthly on children's growth, food voucher utilization, child feeding and morbidity. In addition, we assessed the cognitive development of the children after 12 months of intervention. CONCLUSION This trial aims to explore whether an integrated nutrition intervention can mitigate childhood stunting during the critical window of opportunity in rural Bangladesh. The results may provide robust evidence to improve the linear growth of children in developing countries. TRIAL REGISTRATION The study was retrospectively registered on August 17, 2018 and is available online at ClinicalTrials.gov (ID: NCT02768181).
-
6.
Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.
Cheng, WD, Wold, KJ, Bollinger, LB, Ordiz, MI, Shulman, RJ, Maleta, KM, Manary, MJ, Trehan, I
The American journal of gastroenterology. 2019;(4):671-678
Abstract
INTRODUCTION Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.
-
7.
The impact of rickets on growth and morbidity during recovery among children with complicated severe acute malnutrition in Kenya: A cohort study.
Ngari, MM, Thitiri, J, Mwalekwa, L, Timbwa, M, Iversen, PO, Fegan, GW, Berkley, JA
Maternal & child nutrition. 2018;(2):e12569
-
-
Free full text
-
Abstract
The effects of rickets on children recovery from severe acute malnutrition (SAM) are unknown. Rickets may affect both growth and susceptibility to infectious diseases. We investigated the associations of clinically diagnosed rickets with life-threatening events and anthropometric recovery during 1 year following inpatient treatment for complicated SAM. This was a secondary analysis of clinical trial data among non-human immunodeficiency virus-infected Kenyan children with complicated SAM (2-59 months) followed for 1 year posthospital discharge (ClinicalTrials.gov ID NCT00934492). The outcomes were mortality, hospital readmissions, and growth during 12 months. The main exposure was clinically diagnosed rickets at baseline. Of 1,778 children recruited, 230 (12.9%, 95% CI [11.4, 14 .6]) had clinical signs of rickets at baseline. Enrolment at an urban site, height-for-age and head circumference-for-age z scores were associated with rickets. Rickets at study enrolment was associated with increased mortality (adjusted Hazard Ratio [aHR] 1.61, 95% CI [1.14, 2.27]), any readmission (aHR 1.37, 95% CI [1.09, 1.72]), readmission for severe pneumonia (aHR 1.37, 95% CI [1.05, 1.79]), but not readmission with diarrhoea (aHR 1.05, 95% CI [0.73, 1.51]). Rickets was associated with increased height gain (centimetres), adjusted regression coefficient 0.19 (95% CI [0.10, 0.28]), but not changes in head circumference, mid-upper arm circumference, or weight. Rickets was common among children with SAM at urban sites and associated with increased risks of severe pneumonia and death. Increased height gain may have resulted from vitamin D and calcium treatment. Future work should explore possibility of other concurrent micronutrient deficiencies and optimal treatment of rickets in this high-risk population.
-
8.
Environmental enteric dysfunction and systemic inflammation predict reduced weight but not length gain in rural Bangladeshi children.
Campbell, RK, Schulze, KJ, Shaikh, S, Raqib, R, Wu, LSF, Ali, H, Mehra, S, West, KP, Christian, P
The British journal of nutrition. 2018;(4):407-414
Abstract
Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15-24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18-24-month WLZ change (β -0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15-18-month WLZ change (β -0·03 (se 0·01) z score/month) and greater 15-month WLZ (β 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (β -0·04 (se 0·01) and β 0·02 (se 0·00) z score/month for 15-18 and 18-24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes.
-
9.
Effect of Differential Enteral Protein on Growth and Neurodevelopment in Infants <1500 g: A Randomized Controlled Trial.
Dogra, S, Thakur, A, Garg, P, Kler, N
Journal of pediatric gastroenterology and nutrition. 2017;(5):e126-e132
Abstract
OBJECTIVE The aim of the study was to determine whether higher enteral protein intake leads to improved head growth at 40 weeks postmenstrual age (PMA) in preterm infants <32 weeks or 1500 g. METHODS Randomized controlled trial in which 120 infants were assigned to either group A with higher enteral protein intake achieved by fortification with higher protein containing fortifier (1 g/100 mL expressed breast milk) or to group B with lower enteral protein intake where fortification was done with standard available protein fortifier (0.4 g /100 mL expressed breast milk). RESULTS The mean (standard deviation) protein intake was higher in group A as compared to group B; 4.2 (0.47) compared with 3.6 (0.37) g · kg · day, P < 0.001. At 40 weeks PMA, the mean (standard deviation) weekly occipitofrontal circumference gain was significantly higher in group A as compared to group B; 0.66 (0.16) compared with 0.60 (0.15) cm/week (mean difference 0.064, 95% confidence interval [0.004-0.123], [P = 0.04]). Weight growth velocity in group A was 11.95 (2.2) g · kg · day as compared to 10.78 (2.6) g · kg · day in group B (mean difference 1.10, 95% confidence interval [0.25-2.07], [P = 0.01]). No difference was observed in the length between the 2 groups. There was no difference in growth indices and neurodevelopmental outcomes at 12 to 18 months corrected age in the 2 groups. CONCLUSIONS Fortification of expressed human milk with fortifier containing higher protein results in better head growth and weight gain at 40 weeks PMA in preterm infants <32 weeks or 1500 g without any benefits on long-term growth and neurodevelopment at 12 to 18 months corrected age (CTRI/2014/06/004661).
-
10.
A Combined Intervention of Zinc, Multiple Micronutrients, and Albendazole Does Not Ameliorate Environmental Enteric Dysfunction or Stunting in Rural Malawian Children in a Double-Blind Randomized Controlled Trial.
Wang, AZ, Shulman, RJ, Crocker, AH, Thakwalakwa, C, Maleta, KM, Devaraj, S, Manary, MJ, Trehan, I
The Journal of nutrition. 2017;(1):97-103
-
-
Free full text
-
Abstract
BACKGROUND Environmental enteric dysfunction (EED) and linear growth stunting affect many rural agrarian children in the developing world and contribute to the persistently high rates of stunting that are observed worldwide. Effective interventions to consistently ameliorate EED are lacking. OBJECTIVE We tested whether a bundle of safe and affordable interventions would decrease EED and stunting over 12-24 wk in a cohort of rural Malawian children 12-35 mo old. METHODS This was a randomized, double-blind, placebo-controlled clinical trial in which the intervention group received a single dose of albendazole and 14 d of zinc at enrollment and after 20 wk. The intervention group also received a daily multiple micronutrient powder throughout the 24 wk of study. The primary outcomes were improvements in EED, as measured by the urinary lactulose-to-mannitol ratio (L:M ratio) from dual-sugar absorption testing, and linear growth. Urinary L:M ratios and anthropometric measurements were evaluated after 12 and 24 wk of intervention and compared with a placebo group that did not receive any of these interventions. RESULTS A total of 254 children were enrolled at a mean age of 24 mo; 55% were female. Their mean weight-for-age z score was -1.5, and their mean length-for-age z score was -0.9. After 12 and 24 wk of study, increases in the L:M ratio did not differ between the intervention group (0.071 and 0.088 units, respectively) and the placebo group (0.073 and 0.080 units, respectively) (P = 0.87 and 0.19, respectively). Relative changes in length and weight also did not differ significantly between groups at any time point. CONCLUSION The combined usage of albendazole, zinc, and a daily multiple micronutrient powder did not decrease EED or stunting in this population of agrarian children 12-35 mo old in rural Malawi. Alternative interventions to improve these diseases should be investigated. This trial was registered at clinicaltrials.gov as NCT02253095.