Economic costs of childhood stunting to the private sector in low- and middle-income countries.

Background: Stunting during childhood has long-term consequences on human capital, including decreased physical growth, and lower educational attainment, cognition, workforce productivity and wages. Previous research has quantified the costs of stunting to national economies however beyond a few single-country datasets there has been a limited number of which have used diverse datasets and have had a dedicated focus on the private sector, which employs nearly 90% of the workforce in many low- and middle-income countries (LMICs). We aimed to examine (i) the impact of childhood stunting on income loss of private sector workforce in LMICs; (ii) to quantify losses in sales to private firms in LMICs due to childhood stunting; and (iii) to estimate potential gains (benefit-cost ratios) if stunting levels are reduced in select high prevalence countries. Methods: This multiple-methods study engaged multi-disciplinary technical advisers, executed several literature reviews, used innovative statistical methods, and implemented health and labor economic models. We analyzed data from seven longitudinal datasets (up to 30+ years of follow-up; 1982-2016; Peru, Ethiopia, India, Vietnam, Philippines, Tanzania, Brazil), 108 private firm datasets (spanning 2008-2020), and many global datasets including Joint Malnutrition Estimates, and World Development Indicators to produce estimates for 120+ LMICs (with estimates up to 2021). We studied the impact of childhood stunting on adult cognition, education, and height as pathways to wages/productivity in adulthood. We employed cloud-based artificial intelligence (AI) platforms, and conducted comparative analyses using three analytic approaches: traditional frequentist statistics, Bayesian inferential statistics and machine learning. We employed labour and health economic models to estimate wage losses to the private sector worker and firm revenue losses due to stunting. We also estimated benefit-cost ratios for countries investing in nutrition-specific interventions to prevent stunting. Findings: Across 95 LMICs, childhood stunting costs the private sector at least US$135.4 billion in sales annually. Firms from countries in Latin America and the Caribbean and East Asia and Pacific regions had the greatest losses. Totals sales losses to the private sector accumulated to 0.01% to 1.2% of national GDP across countries. Sectors most affected by childhood stunting were manufacturing (non-metallic mineral, fabricated metal, other), garments and food sectors. Sale losses were highest for larger sized private firms. Across regions (representing 123 LMICs), US$700 million (Middle East and North Africa) to US$16.5 billion (East Asia and Pacific) monthly income was lost among private sector workers. Investing in stunting reduction interventions yields gains from US$2 to US$81 per $1 invested annually (or 100% to 8000% across countries). Across sectors, the highest returns were in elementary occupations (US$46) and the lowest were among agricultural workers (US$8). By gender, women incurred a higher income penalty from childhood stunting and earned less than men; due to their relatively higher earnings, the returns for investing in stunting reduction were consistently higher for men across most countries studied. Interpretation: Childhood stunting costs the private sector in LMICs billions of dollars in sales and earnings for the workforce annually. Returns to nutrition interventions show that there is an economic case to be made for investing in childhood nutrition, alongside a moral one for both the public and private sector. This research could be used to motivate strong public-private sector partnerships to invest in childhood undernutrition for benefits in the short and long-term.

An examination of contributions of animal- and plant-based dietary patterns on the nutrient quality of diets of adult Canadians.

Dietary guidance and Canada's 2019 Food Guide encourage increased consumption of plant-based foods as a source of dietary protein. However, there is an absence of recent data on protein and nutrient intakes and quality of Canadian dietary patterns that might occur with increased plant protein intakes. This study compared food sources and nutrient intakes of Canadian adults within groups of increasing plant protein-containing diets. The CCHS 2015 Public-Use Microdata File of single 24-hour dietary recalls of males and females ≥19 years (n = 6498) or ≥70 years (n = 1482) were examined. Respondents were allocated into 4 groups defined by their protein intake percentage coming from plant-based foods (i.e., group 1: 0-24.9%, group 2: 25-49.9%, group 3: 50-74.9%, group 4: 75-100%). Protein intake in adults averaged 63.3% animal and 36.7% plant protein. Where plant protein contributed >50% protein, higher intakes of carbohydrate, dietary fibre, folate, dietary folate equivalents, iron and magnesium (p < 0.001) but lower intakes of total and saturated fat, protein, vitamin D, vitamin B12, riboflavin and niacin (p < 0.0001) were reported. In contrast, group 1 had higher total and saturated fat, protein, vitamin B12, thiamin, niacin, and zinc, but lower carbohydrate, dietary fibre, and magnesium. Balancing plant- with animal-based protein foods leads to healthier dietary patterns with more favourable nutritional properties when compared with diets based on either high animal or high plant protein content. Novelty: Combinations of animal- and plant-based proteins improve nutrient quality of Canadian diets. The source of protein influences diet quality.

Faba bean meal, starch or protein fortification of durum wheat pasta differentially influence noodle composition, starch structure and in vitro digestibility.

Faba bean (Vicia faba L.) flour, starch concentrate (60% starch), protein concentrate (~60% protein) and protein isolate (~85% protein) were added to replace one-quarter of durum wheat semolina to enrich the nutritional quality and physiological functions of durum wheat (Triticum turgidum L.) pasta. The raw pasta samples prepared with protein concentrate or isolate had higher (p ≤ 0.001) protein and lower (p ≤ 0.001) total starch concentrations, along with increased total dietary fiber and slowly digestible starch (p ≤ 0.001) than durum wheat semolina control or those with added whole faba-bean flour or isolated starch. The faba bean fortified pasta had altered starch with increased proportion of medium B-type glucan chains and long C-type glucan chains, reduced starch digestibility and were associated with glycaemia related effects in the human diet. The faba bean fortified pasta had increased protein and dietary fiber that influenced food intake and satiety. The results suggest differential contributions of food ingredients in human health outcomes.

The effect of increasing intakes of plant protein on the protein quality of Canadian diets.

The 2015 Canadian Community Health Survey was used to investigate the protein content and protein quality of the diets consumed by adults (≥19 years) when plant protein is increased. Individuals (n = 6498) were allocated to quartiles of increasing proportions of protein from plant foods (Quartile 1: 0-24.9%; Quartile 2: 25%-49.9%; Quartile 3: 50-74.9%; Quartile 4: 75-100%). The Protein Digestibility Corrected Amino Acid Score (PDCAAS) of diets were estimated using indispensable amino acid concentrations of foods and an assumed digestibility coefficient of 0.8. Corrected protein intakes were determined by aggregating foods consumed over 24 hours and as the sum of corrected protein consumed at eating events within six 4-hour time intervals. Most individuals (51%) consumed 25-49.9% of protein from plant foods. Cereal-based foods represented the majority of plant protein consumed. PDCAAS of diets remained ≥0.87 for quartiles 1-3, but decreased (p < 0.0001) to 0.71 ± 0.018 in quartile 4 vs. quartile 2 (0.96 ± 0.004). Corrected protein intakes in quartile 2 (80.66 ± 1.21 g/day; 1.07 ± 0.03 g protein/kg body weight) decreased to 37.13 ± 1.88 g/day (0.54 ± 0.03 g/kg body weight) in quartile 4 (p < 0.0001). Aggregated daily corrected protein intake strongly correlated (r = 0.99; p < 0.001) with the sum of corrected protein consumed within time intervals. Intra-time interval analysis revealed that the relative proportions of animal and plant proteins changed at eating events over 24 hours and did not reflect the allocation to quartiles based on the daily proportion of plant protein consumption. Various tools should be explored and developed to assist Canadians in effectively incorporating plant protein foods into dietary patterns. Novelty: Corrected protein intakes decreased as plant protein consumption increased. PDCAAS was ≥0.87 for diets with ≤74.9% plant protein.

Faba bean protein flours added to pasta reduce post-ingestion glycaemia, and increase satiety, protein content and quality.

The hypothesis that adding faba bean (FB) flour and its macronutrient concentrated flours to pasta reduces postprandial glycaemia and increases satiety was tested in 54 young adult males. Each consumed a serving of pasta made from durum wheat semolina (DWS) alone, or DWS flour with 25% of flours from whole FB (FBF), starch concentrate (FBS), protein concentrate (FBPC), or protein isolate (FBPI). Post-consumption measurements included postprandial blood glucose, insulin, C-peptide, GLP-1 and PYY, and subjective appetite, over 120 min. Second meal effects of treatments were assessed after participants consumed either an ad libitum or fixed size meal (12 kcal kg-1) at a pizza meal at 120 min. Additions of FB flours from FBPC and FBPI reduced postprandial glycaemia and appetite, increased protein content and quality of the pastas and PYY and C-peptide responses, but had no effect on plasma insulin or GLP-1. In conclusion, DWS pastas with added faba bean protein flour reduce postprandial BG and appetite and have higher nutritional quality. The clinical trial registry number is NCT02658591 .

Increased milk protein content and whey-to-casein ratio in milk served with breakfast cereal reduce postprandial glycemia in healthy adults: An examination of mechanisms of action.

This study describes the effects on glycemic response and the underlying mechanisms of action of increasing the protein concentration and decreasing the casein-to-whey ratio in milk when consumed with a high glycemic breakfast cereal. Twelve healthy men and women, aged 18 to 30 yr and with a body mass index of 20 to 24.9 kg/m2, consumed (in random order) milk beverages (250 mL) containing either 3.1 or 9.3% protein and casein-to-whey ratios of either 80:20 or 40:60. We measured postprandial appetite, glucose, regulatory hormones, and stomach emptying rate over 200 min, as well as food intake at an ad libitum meal at 120 min. Although pre-meal appetite was suppressed to a greater extent with milk beverages that had high (9.3%) compared with regular (3.1%) protein content, food intake was similar among all 4 treatments. Pre-meal mean blood glucose was lower with beverages that had high rather than regular milk protein content, with the lowest glucose peaks after the high milk protein treatment with the 40:60 casein-to-whey ratio. Pre-meal insulin and C-peptide levels were not affected by milk protein content or casein-to-whey ratio, but pre-meal glucagon-like peptide 1 was higher after the treatment containing high milk protein and the 40:60 casein-to-whey ratio, and pre-meal cholecystokinin was higher after the treatments containing high milk protein content. Plasma paracetamol response was also lower after the treatments containing high compared with regular milk protein content. When consumed with carbohydrate, milk beverages with high protein content and (to a lesser extent) a decreased casein-to-whey ratio lowered postprandial glycemia through insulin-independent mechanisms, primarily associated with delayed stomach emptying.

Acute decrease in plasma testosterone and appetite after either glucose or protein beverages in adolescent males.

OBJECTIVE: Chronic testosterone blood concentrations associate with food intake (FI), but acute effects of testosterone on appetite and effect of protein and glucose consumption on testosterone response have had little examination. METHODS: In a randomized, crossover study, twenty-three adolescent (12-18 years old) males were given beverages containing either: (a) whey protein (1 g/kg body weight), (b) glucose (1 g/kg body weight) or (c) a calorie-free control (C). Plasma testosterone, luteinizing hormone (LH), GLP-1 (active), ghrelin (acylated), glucose, insulin and subjective appetite were measured prior (0) and at 20, 35 and 65 minutes after the consumption of the beverage. FI at an ad libitum pizza meal was assessed at 85 minutes. RESULTS: Testosterone decreased acutely to 20 minutes after both protein and glucose with the decrease continuing after protein but not glucose to 65 minutes (P = 0.0382). LH was also decreased by both protein and glucose, but glucose had no effect at 20 minutes in contrast to protein (P < 0.001). Plasma testosterone concentration correlated positively with LH (r = 0.58762, P < 0.0001) and negatively with GLP-1 (r = -0.50656, P = 0.0003). No associations with appetite, ghrelin or glycaemic markers were found. Food intake was not affected by treatments. CONCLUSION: Protein or glucose ingestion results in acute decreases in both plasma testosterone and LH in adolescent males. The physiological significance of this response remains to be determined as no support for testosterone's role in acute regulation of food intake was found.

Maternal fat-soluble vitamins, brain development, and regulation of feeding behavior: an overview of research.

Recent research shows a link between vitamin intake during pregnancy and offspring health. Inadequate intakes of water-soluble vitamins during pregnancy lead to obesity and characteristics of the metabolic syndrome, concurrent with altered developments in food intake regulatory pathways. Few studies, however, have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the development of food intake regulatory pathways. The majority of studies to date have focused on associations between inadequate and high intakes of folic acid and vitamin D and neurocognitive development of the offspring. Hence, the objective of this review is to present an evaluation of the role of maternal vitamins A, D, E, and K in brain development and function of neural pathways that regulate feeding behaviors. PubMed and Google Scholar were searched from 1975 through September, 2016. Most studies supporting a role for fat-soluble vitamins in regulating brain development and associated behaviors have been conducted in animal and cell models, leaving uncertain their relevance to neurocognitive development and function in humans. Nevertheless, although current research on defining the role of maternal fat-soluble vitamins in offspring's brain development is limited, it is sufficient to warrant further investigations on their impact when intake amounts during pregnancy are not only inadequate but also exceed requirements.

Role of maternal vitamins in programming health and chronic disease.

Vitamin consumption prior to and during pregnancy has increased as a result of proactive recommendations by health professionals, wide availability of vitamin supplements, and liberal food-fortification policies. Folic acid, alone or in combination with other B vitamins, is the most recommended vitamin consumed during pregnancy because deficiency of this vitamin leads to birth defects in the infant. Folic acid and other B vitamins are also integral components of biochemical processes that are essential to the development of regulatory systems that control the ability of the offspring to adapt to the external environment. Although few human studies have investigated the lasting effects of high vitamin intakes during pregnancy, animal models have shown that excess vitamin supplementation during gestation is associated with negative metabolic effects in both the mothers and their offspring. This research from animal models, combined with the recognition that epigenetic regulation of gene expression is plastic, provides evidence for further examination of these relationships in the later life of pregnant women and their children.

High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring.

High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake.

A gestational diet high in fat-soluble vitamins alters expression of genes in brain pathways and reduces sucrose preference, but not food intake, in Wistar male rat offspring.

High intakes of multivitamins (HV) during pregnancy by Wistar rats increase food intake, body weight, and characteristics of the metabolic syndrome in male offspring. In this study, high-fat soluble vitamins were fed in combination during gestation to test the hypothesis that they partially account for the effects of the HV diet. Pregnant Wistar rats (14-16/group) were fed a recommended multivitamin diet (1-fold all vitamins) or high-fat soluble vitamin diet (HFS; 10-fold vitamins A, D, E, and K) during pregnancy. Offspring body weight, food intake, and preference as well as expression of selected genes in the hypothalamus and hippocampus were evaluated at birth, weaning, and 14 weeks postweaning. Body weight and food intake were not affected but sucrose preference decreased by 4% in those born to dams fed the HFS gestational diet. Gene expressions of the hypothalamic anorexogenic pro-opiomelanocortin (Pomc) and orexogenic neuropeptide Y (Npy) (∼30% p = 0.008, ∼40% p = 0.007) were increased in weaning and adult rats, respectively. Hippocampal dopaminergic genes (35%-50% p < 0.05) were upregulated at birth and 14 weeks postweaning. DNA hypermethylation (2% p = 0.006) was observed in the dopamine receptor 1 (Drd1) promoter region. We conclude that a gestational diet high in vitamins A, D, E, and K does not show the effects of the HV diet on body weight or food intake but may affect the development of higher hedonic regulatory pathways associated with food preference.

A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance.

High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance.

Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

SCOPE: High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms. METHODS AND RESULTS: Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction. CONCLUSION: Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects.

Increasing vitamin A in post-weaning diets reduces food intake and body weight and modifies gene expression in brains of male rats born to dams fed a high multivitamin diet.

High multivitamin gestational diets (HV, 10-fold AIN-93G levels) increase body weight (BW) and food intake (FI) in rat offspring weaned to a recommended multivitamin (RV), but not to a HV diet. We hypothesized that high vitamin A (HA) alone, similar to HV, in post-weaning diets would prevent these effects of the HV maternal diet consistent with gene expression in FI and reward pathways. Male offspring from dams fed HV diets were weaned to a high vitamin A (HA, 10-fold AIN-93G levels), HV or RV diet for 29 weeks. BW, FI, expression of genes involved in regulation of FI and reward and global and gene-specific DNA methylation of pro-opiomelanocortin (POMC) in the hypothalamus were measured. Both HV and HA diets slowed post-weaning weight gain and modified gene expression in offspring compared to offspring fed an RV post-weaning diet. Hypothalamic POMC expression in HA offspring was not different from either HV or RV, and dopamine receptor 1 was 30% (P<.05) higher in HA vs. HV, but not different from RV group. Hippocampal expression of serotonin receptor 1A (40%, P<.01), dopamine receptor 2 (40%, P<.05) and dopamine receptor 5 (70%, P<.0001) was greater in HA vs. RV fed pups and is 40% (P<.01), 50% (P<.05) and 40% (P<.0001) in HA vs. HV pups, respectively. POMC DNA methylation was lower in HA vs. RV offspring (P<.05). We conclude that high vitamin A in post-weaning diets reduces post-weaning weight gain and FI and modifies gene expression in FI and reward pathways.

High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring.

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

High folate gestational and post-weaning diets alter hypothalamic feeding pathways by DNA methylation in Wistar rat offspring.

Excess vitamins, especially folate, are consumed during pregnancy but later-life effects on the offspring are unknown. High multivitamin (10-fold AIN-93G, HV) gestational diets increase characteristics of metabolic syndrome in Wistar rat offspring. We hypothesized that folate, the vitamin active in DNA methylation, accounts for these effects through epigenetic modification of food intake regulatory genes. Male offspring of dams fed 10-fold folate (HFol) diet during pregnancy and weaned to recommended vitamin (RV) or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake and body weight were highest in offspring of HFol dams fed the RV diet. In contrast, the HFol pup diet in offspring of HFol dams reduced food intake (7%, p = 0.02), body weight (9%, p = 0.03) and glucose response to a glucose load (21%, p = 0.02), and improved glucose response to an insulin load (20%, p = 0.009). HFol alone in either gestational or pup diet modified gene expression of feeding-related neuropeptides. Hypomethylation of the pro-opiomelanocortin (POMC) promoter occurred with the HFol pup diet. POMC-specific methylation was positively associated with glucose response to a glucose load (r = 0.7, p = 0.03). In conclusion, the obesogenic phenotype of offspring from dams fed the HFol gestational diet can be corrected by feeding them a HFol diet. Our work is novel in showing post-weaning epigenetic plasticity of the hypothalamus and that in utero programming by vitamin gestational diets can be modified by vitamin content of the pup diet.

Beneficios de la terapia con hidroxiúrea en niños con anemia de células falciformes / Benefits of hidroxyurea therapy in children with sickle cell disease

Objetivo: describir la toxicidad y los beneficios de la hidroxiúrea (HU) en el tratamiento de niños con anemia de células falciformes (ACF). Materiales y métodos: estudio observacional descriptivo-retrospectivo de pacientes con ACF tratados con HU en el Hospital Pablo Tobón Uribe (HPTU) de Medellín, Colombia, entre mayo de 2004 y septiembre de 2009. Se trató con este medicamento a 16 pacientes menores de 15 años, 11 de ellos (68,8%) de sexo masculino. Todos los pacientes tenían anemia falciforme (Hb SS). Las variables se estudiaron antes y después del inicio de la HU. Resultados: se encontró una media de crisis dolorosas por ACF de 3,31 antes y 1,13 después de la HU (p = 0,006); la media de la necesidad de transfundir glóbulos rojos fue de 2,69 antes y 0,75 después (p = 0,112); los episodios de síndrome torácico agudo (STA) tuvieron una media de 0,19 antes y 0,13 después (p = 0,705); la media de la necesidad de hospitalización por ACF fue de 1,94 antes y 1,06 después de la HU (p = 0,155). Un paciente (6,3%) presentó toxicidad hematológica y dos (12,5%) tuvieron toxicidad hepática, pero no hubo casos de toxicidad renal; tres pacientes (18,8%) presentaron accidentes cerebrovasculares. No se encontraron neoplasias. Conclusión: la HU redujo significativamente la frecuencia de crisis dolorosas en los pacientes con ACF. La toxicidad fue en general aceptable. Se requieren estudios prospectivos, multicéntricos, doble ciego, controlados con placebo, para definir el papel de la HU en pacientes pediátricos.

Objective: To assess the toxicity and benefits of hydroxyurea (HU) in the management of children with sickle cell disease (SCD). Materials and methods: a descriptive observationalretrospective study of patients with SCD treated with HU was carried out at Hospital Pablo Tobón Uribe in Medellin, Colombia, from May 2004 to September 2009. Sixteen patients aged under 15 years were treated with this drug; out of them, 11 (68.8%) were male. All patients had sickle cell anemia (Hb SS). The variables were studied before and after initiation of HU. Results: Average number of painful crises was 3.31 before and 1.13 after HU (p = 0.006); average number of red blood cell transfusions was 2.69 before and 0.75 after HU (p = 0.112); average number of acute chest syndrome episodes was 0.19 before and 0.13 after HU (p = 0.705); average number of hospitalizations was 1.94 before and 1.06 after HU (p = 0.155). One patient (6.3%) had hematologic toxicity, two patients (12.5%) had liver toxicity, and three patients (18.6%) had strokes. Renal toxicity was not found. There were no malignancies. Conclusion: HU significantly reduced the frequency of painful crises in our patients with SCD. Toxicity was generally acceptable. Prospective multicenter, double-blind, placebo-controlled studies are required in order to define the role of HU in pediatric patients with SCD.