Does the fortified milk with high iron dose improve the neurodevelopment of healthy infants? Randomized controlled trial.

BACKGROUND: Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron-fortified milk on the iron biochemical status and the neurodevelopment of children at 12 months of age. METHODS: Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered. RESULTS: Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 µg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose. CONCLUSION: Despite differences on the iron status were observed, there were no effects on neurodevelopment of well-nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow-up studies are needed to test for long-term neurodevelopmental improvement. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.

Adequate calcium intake during long periods improves bone mineral density in healthy children. Data from the Childhood Obesity Project.

BACKGROUND: Bone mineralization can be influenced by genetic factors, hormonal status, nutrition, physical activity and body composition. The association of higher calcium (Ca) intake or Ca supplementation with better bone mineral density (BMD) remains controversial. Furthermore, it has been speculated that maintaining long-term adequate Ca intake rather than having a brief supplementation period is more effective. The aim of the study was to prospectively analyse the influence of adequate Ca intake on BMD at 7 years of age in European children. METHODS: Data from the Childhood Obesity Project were analysed in a prospective longitudinal cohort trial. Dietary intake was recorded using 3-day food records at 4, 5 and 6 years of age. The probability of adequate intake (PA) of Ca was calculated following the American Institute of Medicine guidelines for individual assessments, with FAO, WHO and United Nations University joint expert consultation dietary recommendations. Children were categorised as having high Ca PA (PA >95%) or not (PA <95%). At 7 years, whole body (WB) and lumbar spine (LS) BMD were measured in the Spanish subsample by dual-energy x-ray absorptiometry. Internal BMD z-scores were calculated; BMD below -1 z-score were considered to indicate osteopenia, and BMD z-scores below -2, "low bone mineral density for age". RESULTS: BMD was measured in 179 children. Ca intake at 6 years was positively correlated with LS BMD at 7 years (R = 0.205, p = 0.030). A Ca increase of 100 mg/day explained 19.4% (p = 0.011) of the LS BMD z-score variation, modifying it by 0.089 (0.021, 0.157) units. Children with Ca PA >95% at 5 and 6 or from 4 to 6 years of age showed higher BMD z-scores at the LS and WB levels than children with Ca PA <95% (p < 0.001 and p < 0.05 for LS and WB BMD, respectively). Ca PA >95% maintained over 2 years explained 26.3% of the LS BMD z-score variation (p < 0.001), increasing it by 0.669 (0.202, 1.137). PA >95% maintained over 3 years explained 24.9% of the LS BMD z-score variation, increasing it by 0.773 (0.282, 1.264). The effects of Ca adequacy on WB BMD were similar. Children with PA >95% over 2 years had an Odds ratio of 13.84 and 12 for osteopenia at the LS and WB levels, respectively (p = 0.001). CONCLUSIONS: Long periods of adequate Ca intake in childhood increase BMD and reduce osteopenia risk. The Childhood Obesity Project clinical trial (CHOP) was registered at clinicaltrials.gov as NCT00338689.

The use of inulin-type fructans improves stool consistency in constipated children. A randomised clinical trial: pilot study.

BACKGROUND: Constipation is a common disorder in children. OBJECTIVE: The objective of this study is to assess the beneficial effects of a daily supplementation with Orafti® inulin-type fructans in 2-5 year old constipated children. METHODS: Double-blind, randomised, placebo-controlled parallel group trial where constipated children received two doses of 2 g Orafti® inulin-type fructans (OF:IN) or placebo (maltodextrin) for 6 weeks. Primary outcome was stool consistency. Secondary outcomes were stool frequency and gastrointestinal symptoms. RESULTS: Twenty-two children were included, 17 completed the study protocol (nine and eight for the control and the OF:IN group, respectively). Results showed that Orafti® inulin-type fructans supplemented children had softer stools (p = .003). The longitudinal analysis showed no significant changes in controls, whereas supplemented children increased their stool consistency from 2.2 to 2.6 on the modified Bristol scale for children (five items instead of seven) (p = .040). CONCLUSIONS: Prebiotic inulin-type fructans supplementation improves stool consistency in constipated 2-5-year old children. Clinicaltrials.gov, with number NCT02863848.

Associations of IGF-1 gene variants and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial.

OBJECTIVE: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied. DESIGN: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6 g/100 mL) or higher (HP: 2.05 and 3.2 g/100 mL) protein contents for the first 12 months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6 months were regressed on determined SNPs and feeding groups in 501 infants. RESULTS: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3 ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3 ng/mL and ~1.3 and decreased in BF infants by ~0.6 ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450 ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing. CONCLUSIONS: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth.

The model of Palliative Care in the perinatal setting: a review of the literature.

BACKGROUND: The notion of Palliative Care (PC) in neonatal and perinatal medicine has largely developed in recent decades. Our aim was to systematically review the literature on this topic, summarise the evolution of care and, based on the available data, suggest a current standard for this type of care. METHODS: Data sources included Medline, the Cochrane Library, CINAHL, and the bibliographies of the papers retrieved. Articles focusing on neonatal/perinatal hospices or PC were included. A qualitative analysis of the content was performed, and data on the lead author, country, year, type of article or design, and direct and indirect subjects were obtained. RESULTS: Among the 1558 articles retrieved, we did not find a single quantitative empirical study. To study the evolution of the model of care, we ultimately included 101 studies, most of which were from the USA. Fifty of these were comments/reflections, and only 30 were classifiable as clinical studies (half of these were case reports). The analysis revealed a gradual conceptual evolution of the model, which includes the notions of family-centered care, comprehensive care (including bereavement) and early and integrative care (also including the antenatal period). A subset of 27 articles that made special mention of antenatal aspects showed a similar distribution. In this subset, the results of the four descriptive clinical studies showed that, in the context of specific programmes, a significant number of couples (between 37 and 87%) opted for PC and to continue with the pregnancy when the foetus has been diagnosed with a lethal illness. CONCLUSIONS: Despite the interest that PC has aroused in perinatal medicine, there are no evidence-based empirical studies to indicate the best model of care for this clinical setting. The very notion of PC has evolved to encompass perinatal PC, which includes, among other things, the idea of comprehensive care, and early and integrative care initiated antenatally.

Effects of iron deficiency on neonatal behavior at different stages of pregnancy.

Animal and human studies have shown that prenatal and postnatal iron deficiency is a risk factor for behavioral, emotional and cognitive development. The aim of this study was to determine the associations between iron status of pregnant women and the behavior of their newborn, taking into account the timing in which the deficit occurs. This study was conducted in Spain (developed country) where: the general population is well-nourished; during pregnancy routine obstetrical checks are carried out; and pregnant women are systematically iron supplemented. A total of 216 healthy and well-nourished pregnant women and their term, normal weight newborn participated in this study. The neonatal behavior was assessed by the Neonatal Behavior Assessment Scale (NBAS). The results showed that in the first and second trimesters of pregnancy, iron deficiency was a weak and significant predictor of the NBAS autonomous nervous system cluster score, and in the third trimester, this condition predicted the NBAS motor and state organization clusters score and the NBAS robustness and endurance supplementary item. In conclusion, iron deficiency during pregnancy is related to the neonate's general autonomous response, motor performance and self regulation capabilities.

Pharmacological interventions for preventing complications in idiopathic hypercalciuria.

BACKGROUND: Idiopathic hypercalciuria is an inherited metabolic abnormality characterised by excessive amounts of calcium excreted into the urine in patients with normal serum levels of calcium. The morbidity of hypercalciuria is related to kidney stone disease and bone demineralization. In children, hypercalciuria can cause recurrent haematuria, frequency-dysuria syndrome, urinary tract infection and abdominal and lumbar pain. Several pharmacological treatments have been described that can decrease the levels of urinary calcium or its index of urinary crystallization. OBJECTIVES: To assess the benefits and harms of pharmacological interventions for preventing complications and decreasing urological symptoms in patients with idiopathic hypercalciuria. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), handsearched relevant conference proceedings and reference lists of articles. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTS that compared any pharmacological intervention for preventing complications in idiopathic hypercalciuria, with placebo, other pharmacological intervention or a different administration mode or dose of the same treatment given for a minimum duration of four months and had a follow-up period of at least six months. DATA COLLECTION AND ANALYSIS: Four authors assessed the studies for inclusion and extracted the data. Disagreements were resolved through discussion. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD). MAIN RESULTS: Five studies (316 adult patients) were included. Four compared thiazides with standard treatment (periodic clinical follow-up and increased water intake) or specific dietary recommendations and one analysed the effect of thiazide plus a neutral potassium salt. There was a significant decrease in the number of new stone recurrences in those treated with thiazides (RR 1.61, 95% CI 1.33 to 1.96), although the follow-up periods varied. The stone formation rate also showed a statistically significant decrease in the patients treated with diuretics (MD -0.18, 95% CI -0.30 to -0.06). Thiazides plus potassium salts significantly decreased calciuria and vitamin D levels. AUTHORS' CONCLUSIONS: There is some evidence that in patients with idiopathic hypercalciuria and recurrent stones, the addition of thiazides to a normal or modified diet for short to long periods (five months to three years) reduced the number of stone recurrences and decreased the stone formation rate. Thiazides and neutral potassium phosphate decreased calciuria in symptomatic patients with idiopathic hypercalciuria. There were no studies investigating the effect of pharmacological treatment on other clinical complications or asymptomatic idiopathic hypercalciuria.