What works? Interventions for maternal and child undernutrition and survival. Combined treatment with growth hormone and luteinizing hormone releasing hormone-analogue (LHRHa) of pubertal children with familial short stature. Clinical efficacy of group-based treatment for childhood obesity compared with routinely given individual counseling. An 18-month study of the effect of periodic anthelminthic treatment on the growth and nutritional status of pre-school children in Bangladesh. Randomised controlled trial of recombinant human growth hormone in prepubertal and pubertal renal transplant recipients. British Association for Pediatric Nephrology. Randomised trial of growth hormone in short normal girls. Randomized clinical trial of behavioral and nutrition treatment to improve energy intake and growth in toddlers and preschoolers with cystic fibrosis. A randomized clinical trial of home intervention for children with failure to thrive. Effect of zinc supplementation on growth and body composition in children with sickle cell disease. Remission induced by an elemental diet in small bowel Crohn's disease. Dietary intake and nutritional treatment in childhood Crohn's disease.
We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment. We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly assigned to clinical follow-up (group A), GH treatment alone (group B) and GH+LHRH analogue (LHRHa) treatment (group C). Height velocity increased significantly compared to baseline in groups A and B (4.7 +/- 0.4 vs 6.6 +/- 0.6 and 4.4 +/- 0.3 vs 8 +/- 1 respectively), but not in C (5 +/- 0.5 vs 6.5 +/- 0.4). Moreover in group B height and height prognosis standard deviation score SDS) also were higher (-2.2 +/- 0.2 vs -1.7 +/- 0.2 and 1.8 +/- 0.3 vs -1 +/- 0.2, respectively). Comparisons among the groups showed a significant increase in group B vs the other groups of height velocity SDS (3.9 +/- 1.3 vs 0.4 + 1 and 0.3 +/- 0.7) and of height prognosis SDS (-1 +/- 0.2 vs -2.4 +/- 0.3 and -2.4 +/- 0.3). In conclusion, after one-year treatment, GH seems to be more effective in stimulating growth than GH +/- LHRHa, even if studies of longer duration and/or follow-up are needed. The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity.
                Seventy obese children (weight for height 115-182%) aged 7-9 years were randomized either to routine counseling (two appointments for children) or to family-based group treatment (15 separate sessions for parents and children). These sessions included nutrition education, physical activity education and behavioral therapy.
                Children's weights and heights were measured at baseline, after the 6-month intervention and after the 6-month follow-up. The change of weight for height based on Finnish growth charts was used as the primary, and changes in body mass index (BMI) and BMI standard deviation scores (BMI-SDS) as secondary outcome measures.
                Children attending the group treatment lost more weight for height (6.8%) than children receiving routine counseling (1.8%) (P=0.001). The difference was significant when the data were analyzed in four groups by the cut-off limits of 0, -5 and -10% for the change in weight for height. The respective decreases in BMI were 0.8 vs 0.0 (P=0.003) and in BMI-SDS 0.3 vs 0.2 (P=0.022). The results remained similar in adjusted analyses. Both group and routine programs were feasible with a high, 87-99%, participation rate in sessions and appointments and very low, 3% or less, attrition rate from the programs. Six months after the intervention, beneficial effects were partly lost, but for changes in weight for height and BMI, the differences between the two treatment programs still were significant, and for BMI-SDS, there was a trend.
                Family-based group treatment that stresses a health-promoting lifestyle and is given separately for parents and children, offers an effective mode of therapy to treat obese school-aged children. An 18-month study was conducted from February 1989 to August 1990 to examine the effect of regular deworming on child growth and nutritional status. A sample of 1402 children, from 2 to 6 years old, were divided into a treatment group and a control group. The 688 children in the treatment group received a 500 mg single dose of mebendazole, while the 714 children in the control group were given a placebo. Height, weight and mid-upper arm circumference (MUAC) were measured on monthly household visits. Growth was measured in terms of the change in height-for-age, weight-for-age, weight-for-height and MUAC over 18 months. The initial prevalence of infection was estimated from a random sample of 96 children (49 treated, 47 control). The initial overall prevalence of Ascaris lumbricoides, Trichuris trichiura and hookworm was 71, 44 and 10% respectively. The final prevalence of infection, estimated from a random sample of 265 children, was A. lumbricoides 6%, T. trichiura 6% and hookworm 2% in the mebendazole group compared with 64, 18 and 19% respectively in the placebo group. Despite the successful treatment of helminths, there was no significant improvement in the growth of treated children compared with their untreated counterparts in terms of the change in z-scores of height-for-age, weight-for-age, weight-for-height and MUAC. The factors which may have contributed to this outcome are discussed. To evaluate the efficacy (height velocity (HV), change in height standard deviation score (delta HSDS)), and safety (glomerular filtration rate (GFR), incidence of rejection, and calcium and glucose metabolism) of recombinant human growth hormone (rhGH) treatment after renal transplantation.
                A two year randomised controlled trial.
                Fifteen prepubertal and seven pubertal children: mean (SD) age, 13.0 (2.6) and 15.2 (2.4) years, respectively; mean (SD) GFR, 51 (30) and 48 (17) ml/min/1.73 m2, respectively. Six prepubertal and three pubertal children were controls during the first year; all received rhGH in the second year.
                In the first year, mean (SE) HV and delta HSDS in the prepubertal treated group increased compared with controls: 8.1 (0.9) v 3.7 (0.6) cm/year and 0.6 (0.1) v -0.3 (0.2), respectively. In the pubertal treated group, mean (SE) HV and delta HSDS were also greater: 10.1 (0.6) v 3.9 (1.3) cm/year and 0.6 (0.1) v -0.1 (0.2), respectively. Comparing all treated and control children, there was no significant change in GFR: treated group, mean (SE) 9.9 (5.4) ml/min/1.73 m2 v control group, -1.6 (7.6) ml/min/1.73 m2. There were also no differences in the incidence of rejection in the first year: eight episodes in 13 patients v five episodes in nine patients, respectively. Phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and fasting insulin concentrations rose during the first year of treatment, but not thereafter. In the second year of treatment, HV remained above baseline.
                Treatment with rhGH improves growth in prepubertal and pubertal children with renal transplants, with no significant change in GFR or the incidence of rejection. Phosphate, ALP, PTH, and insulin increased during the first year of treatment. There are few data on the long-term outcome of growth-hormone treatment in short normal children. We assessed the impact of growth-hormone treatment on pubertal development and near-final height in girls.
                In a randomised controlled trial, we studied ten girls, with a mean age of 8.07 years and height 2 SDs or more below the mean for their age, and eight short untreated controls matched for age, and 20 short untreated girls who did not give consent for randomisation. The girls received either 30 IU/m2 somatropin per week as daily subcutaneous injections or no treatment. We assessed pubertal staging and height gain every 6 months.
                Eight treated girls completed a mean of 6.2 years' therapy. By a mean age of 16.4 years, their mean height SD score had changed significantly from -2.42 to -1.14 (p=0.008) and they were, on average, 7.5 cm taller than the girls in the control group (height SD scores did not change significantly from -2.55) and 6.0 cm taller than the non-consent group. The timing of each pubertal stage, and the age and amplitude of peak height velocity were similar for all groups.
                Growth-hormone therapy effectively increased height SD score among short normal girls started on treatment in early to mid childhood, with no untoward effect on pubertal progression. To conduct a randomized clinical trial comparing a behavioral and nutrition intervention (BEH) with a usual care control condition (CTL) for children (ages 18 months to 4 years) with cystic fibrosis (CF) and pancreatic insufficiency. This trial was designed to (1) evaluate a randomized comparison of BEH with CTL over 8 weeks, (2) provide a replication of the impact of BEH by inviting the CTL group to receive BEH after 8 weeks, and (3) examine the maintenance of BEH at 3- and 12-month follow-up.
                Of 14 eligible children, 10 were randomly assigned and initiated treatment (71% recruitment rate). Four participants were randomly assigned to BEH, and 6 were assigned to CTL (5 of whom chose to crossover to BEH). BEH included nutrition counseling to increase energy intake (via types of foods and addables/spreadables) and child behavioral management training to teach parents differential attention and contingency management skills. CTL was consistent with the 2002 CF Foundation Consensus Conference Guidelines for nutritional care.
                BEH led to greater increases in energy intake pre- to posttreatment than CTL as measured by calories per day (842 kcal/day vs -131 kcal/day change). On receiving BEH, the change in energy intake was replicated with the CTL group (892 kcal/day change). At 3- and 12-month follow-up, energy intake was maintained (672 kcal/day increase from baseline and 750 kcal/day increase from baseline, respectively). Children in this study met or exceeded normal weight and height velocities from pretreatment to the 3-month follow-up (mean weight: 1.4 kg/6 months; mean height: 5.1 cm/6 months) and from posttreatment to the 12-month follow-up (mean weight: 2.5 kg/12 months; mean height: 8.3 cm/12 months).
                Toddlers and preschoolers who have CF and received BEH were able to meet the energy intake recommendations for this disease and maintain these gains up to 12 months after treatment. In addition, these children demonstrated weight and height velocities from pretreatment to 12-month follow-up, consistent with the goal of normal growth. BEH is a promising, evidence-based, early nutritional intervention for children with CF. An upcoming multisite clinical trial will test BEH versus an attention control condition using a larger sample (N = 100), providing additional evidence about the efficacy of this treatment for energy intake and growth in young children with CF. To evaluate the efficacy of a home-based intervention on the growth and development of children with nonorganic failure to thrive (NOFTT).
                Randomized clinical trial.
                The NOFTT sample included 130 children (mean age, 12.7 months; SD, 6.4) recruited from urban pediatric primary care clinics serving low income families. All children were younger than 25 months with weight for age below the fifth percentile. Eligibility criteria included gestational age of at least 36 weeks, birth weight appropriate for gestational age, and no significant history of perinatal complications, congenital disorders, chronic illnesses, or developmental disabilities. Children were randomized into two groups: clinic plus home intervention (HI) (n = 64) or clinic only (n = 66). There were no group differences in children's age, gender, race, or growth parameters, or on any of the family background variables. Most children were raised by single, African-American mothers who received public assistance. Eighty-nine percent of the families (116 of 130) completed the 1-year evaluation.
                All children received services in a multidisciplinary growth and nutrition clinic. A community-based agency provided the home intervention. Families in the HI group were scheduled to receive weekly home visits for 1 year by lay home visitors, supervised by a community health nurse. The intervention provided maternal support and promoted parenting, child development, use of informal and formal resources, and parent advocacy.
                Growth was measured by standard procedures and converted to z scores for weight for height and height for age to assess wasting and stunting. Cognitive and motor development were measured with the Bayley Scales of Infant Development, and language development was measured by the Receptive/Expressive Emergent Language Scale. Both scales were administered at recruitment and at the 12-month follow-up. Parent-child interaction was measured by observing mothers and children during feeding at recruitment and at the 12-month follow-up, and the quality of the home was measured by the Home Observation Measure of the Environment 18 months after recruitment.
                Repeated-measures multivariate analyses of covariance were used to examine changes in children's growth and development and parent-child interaction. Analyses of covariance were used to examine the quality of the home. Independent variables were intervention status and age at recruitment (1.0 to 12.0 vs 12.1 to 24.9 months). Maternal education was a covariate in all analyses. When changes in developmental status and parent-child interaction were examined, weight for height and height for age at recruitment were included as covariates.
                Children's weight for age, weight for height, and height for age improved significantly during the 12-month study period, regardless of intervention status. Children in the HI group had better receptive language over time and more child-oriented home environments than children in the clinic-only group. The impact of intervention status on cognitive development varied as a function of children's ages at recruitment, with younger children showing beneficial effects of home intervention. There were no changes in motor development associated with intervention status. During the study period, children gained skills in interactive competence during feeding, and their parents became more controlling during feeding, but differences were not associated with intervention status.
                Findings support a cautious optimism regarding home intervention during the first year of life provided by trained lay home visitors. Early home intervention can promote a nurturant home environment effectively and can reduce the developmental delays often experienced by low income, urban infants with NOFTT: Subsequent investigations of home intervention should consider alternative options for toddlers with NOFTT: Poor growth and delayed maturation in children with sickle cell disease (SCD) may be due, in part, to mild zinc deficiency.
                The objective was to determine the effects of zinc supplementation on growth and body composition in children with SCD.
                Forty-two prepubertal children (20 girls and 22 boys) aged 4-10 y with SCD-SS were randomly assigned to receive 10 mg elemental Zn/d in cherry syrup (zinc group) or cherry syrup alone (control group). The 2 groups were stratified by sex and initial height status. Dietary intakes were evaluated and anthropometric, high-precision knee-height, and plasma zinc measurements were made at baseline and at 3, 6, and 12 mo. Body composition was determined every 6 mo with dual-energy X-ray absorptiometry, and z scores for anthropometric variables were computed from national reference data. Longitudinal-mixed-effects analysis was used to test for differences between the groups over the 12-mo observation period.
                Thirty-eight children completed the study. No significant differences were observed at baseline. After 12 mo, the zinc group had significantly greater mean (+/- SE) increases in height (0.66 +/- 0.29 cm/y), sitting height (0.97 +/- 0.40 cm/y), knee height (3.8 +/- 1.2 mm/y), and arm circumference z scores (0.27 +/- 0.12 cm/y). Height-for-age and weight-for-age z scores decreased significantly by 0.11 +/- 0.04 and 0.13 +/- 0.05, respectively, in the control group but did not change significantly in the zinc group.
                Prepubertal children with SCD-SS may have zinc deficiency and may benefit from zinc supplementation to improve linear growth and weight gain. Seventeen children with active Crohn's disease of the small intestine were entered into a randomised control trial comparing the efficacy of an elemental diet with that of a high dose steroid regimen. Eight children received an elemental diet (Flexical) through a nasogastric tube for six weeks, followed by reintroduction of food over six weeks during which the Flexical was stopped. Seven children were given intramuscular adrenocorticotrophic hormone followed by oral prednisolone with sulphasalazine. Two children were withdrawn from the trial. The elemental diet was equally effective in inducing an improvement in Lloyd-Still disease activity index, erythrocyte sedimentation rate, C reactive protein and albumin concentrations, and body weight as the high dose steroid regimen. Linear growth, assessed from height velocity over six months, was significantly greater in the children receiving an elemental diet. Dietary intake was assessed in 24 children with active Crohn's disease. Seventeen of the children were sex and height matched with healthy siblings of other patients. The mean energy intake was 1,764 KJ/day (420 kcal/day) lower in patients during relapse than controls (p < 0.05). All 24 children entered a randomised controlled trial of high-dose steroids compared to an elemental diet. The elemental diet was well tolerated orally in most cases; only one patient required nasogastric administration. There was a similar improvement in disease activity and duration of remission in both groups regardless of the site of disease. Subsequent growth velocity was significantly better in the group treated with the elemental diet despite a greater and more sustained increase in energy intake in the group treated with steroids. Reintroduction of specific foods in the elemental diet group initially caused symptoms in three children but were subsequently tolerated. During remission, there was no significant difference in energy intake, but vegetables were consumed significantly less frequently (p < 0.01) and confectionery significantly more frequently (p < 0.05) when patients were compared with their own siblings.
In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.