Infancy weight faltering and childhood neurodevelopmental disorders: a general population birth-cohort study.

While it is known that intrauterine growth restriction is associated with later mental disorders, it is still unclear whether similar associations exists for postnatal weight faltering, also known as 'failure to thrive' in infancy. This study examined the potential connection between infancy weight faltering and mental disorders diagnosed in childhood focusing specifically on neurodevelopmental disorders. The Copenhagen Child Cohort (CCC2000) was used to explore weight gain in infancy assessed by community health nurses. Data from the Danish national registries were used to quantify ICD-10 mental disorders diagnosed between birth and 12 years of age, as well as potential child and family confounders. Of 4.476 children with sufficient weight data, 339 (7.3%) children were diagnosed with a mental disorder in childhood. Both any (weight gain < -1SD) and severe infancy weight faltering (weight gain < -2SD) were associated with psychomotor delays, while severe infancy weight faltering was also associated with intellectual impairments. Notably, no significant associations were found between weight faltering and autism spectrum disorders or attention deficit hyperactivity disorders. Weight faltering in infancy may be an early marker of neurodevelopmental delays. This possibility should be considered when assessing infants with slow weight gain, to early identification and treatment of co-occurring neurodevelopmental disorders.

Lipid-based nutrient supplement at initiation of antiretroviral therapy does not substitute energy from habitual diet among HIV patients - a secondary analysis of data from a randomised controlled trial in Ethiopia.

Introduction: Malnutrition is common among people with HIV in sub-Saharan Africa. Nutritional supplementation at initiation of antiretroviral treatment (ART) has shown beneficial effects, but it is not known if supplementation replaces or supplements the habitual energy intake in a context of food insecurity. Methods: As part of a randomised controlled trial among people with HIV initiating ART in Ethiopia, we assessed whether the provision of a lipid-based nutrient supplement (LNS) affected energy intake from the habitual diet. People with HIV aged ≥18 years with a body mass index (BMI) >17 were randomly allocated 2:1 to receive either early (month 1-3 after ART initiation) or delayed (month 4-6 after ART initiation) supplementation with LNS (≈4,600 kJ/day). Participants with BMI 16-17 were all allocated to early supplementation. The daily energy intake from the habitual diet (besides the energy contribution from LNS) was assessed using a 24-h food recall interview at baseline and at monthly follow-up visits. Linear mixed models were used to compare habitual energy intake in (1) early versus delayed supplementation groups and (2) supplemented versus unsupplemented time periods within groups. Results: Of 301 participants included, 67% of the participants were women, mean (±standard deviation [SD]) age was 32.9 (±8.9) years and 68% were living in moderately or severely food insecure households. Mean (±SD) reported habitual energy intake at baseline was 5,357 kJ/day (±2,246) for women and 7,977 kJ/day(±3,557) for men. Among all participants, there were no differences in mean habitual energy intake between supplemented and unsupplemented groups in neither the first 3 (P = 0.72) nor the following 3 months (P = 0.56). Furthermore, habitual energy intake did not differ within groups when comparing periods with or without supplementation (P = 0.15 and P = 0.20). The severity of food insecurity did not modify the effect of supplementation in habitual energy intake (P = 0.55). Findings were similar when participants with BMI 16-17 were excluded. Conclusion: Our findings indicate that the LNS provided after ART initiation supplement, rather than substitute, habitual energy intake among people with HIV, even among those who are food insecure. This supports the feasibility of introducing nutritional supplementation as part of HIV treatment.

Restitution of gut microbiota in Ugandan children administered with probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) during treatment for severe acute malnutrition.

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. Klebsiella spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., Veilonella dispar) and follow-up (e.g. Lactobacillus ruminis, Blautia spp., Faecalibacterium prausnitzii), reaching similar ß- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence ß-diversity upon discharge or follow-up, but it increased (p < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence (p < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.

Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda.

BACKGROUND: World Health Organization now recommends the transition from F-75 to ready-to-use therapeutic foods (RUTF) in the management of severe acute malnutrition (SAM). We described the transition from F-75 to RUTF and identified correlates of failed transition. METHODS: We conducted an observational study among children aged 6-59 months treated for SAM at Mulago hospital, Kampala, Uganda. Therapeutic feeding during transition phase was provided by first offering half of the energy requirements from RUTF and the other half from F-75 and then increasing gradually to RUTF as only energy source. The child was considered to have successfully transitioned to RUTF if child was able to gradually consume up to 135 kcal/kg/day of RUTF in the transition phase on first attempt. Failed transition to RUTF included children who failed the acceptance test or those who had progressively reduced RUTF intake during the subsequent days. Failure also included those who developed profuse diarrhoea or vomiting when RUTF was ingested. RESULTS: Among 341 of 400 children that reached the transition period, 65% successfully transitioned from F-75 to RUTF on first attempt while 35% failed. The median (IQR) duration of the transition period was 4 (3-8) days. The age of the child, mid-upper arm circumference, weight-for-height z-score and weight at transition negatively predicted failure. Each month increase in age reflected a 4% lower likelihood of failure (OR 0.96 (95% CI 0.93; 0.99). Children with HIV (OR 2.73, 95% CI 1.27; 5.85) and those rated as severely ill by caregiver (OR 1.16, 95% CI: 1.02; 1.32) were more likely to fail. At the beginning of the rehabilitation phase, the majority (95%) of the children eventually accepted RUTF while only 5% completed rehabilitation in hospital on F-100. CONCLUSION: Transition from F-75 to RUTF for hospitalized children with SAM by gradual increase of RUTF was possible on first attempt in 65% of cases. Younger children, severely wasted, HIV infected and those with severe illness as rated by the caregiver were more likely to fail to transit from F-75 to RUTF on first attempt.

Probiotics and Child Care Absence Due to Infections: A Randomized Controlled Trial.

OBJECTIVES: The risk of infections is higher in children attending child care compared with children cared for at home. This study examined the effect of a combination of probiotics on absence from child care because of respiratory and gastrointestinal infections in healthy infants aged 8 to 14 months at the time of enrollment in child care. METHODS: The ProbiComp study was a randomized, double-blind, placebo-controlled study. A total of 290 infants were randomly allocated to receive a placebo or a combination of Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus in a dose of 109 colony-forming units of each daily for a 6-month intervention period. Absence from child care, occurrence of infant symptoms of illness, and doctor visits were registered by the parents using daily and weekly Web-based questionnaires. RESULTS: Median absence from child care was 11 days (interquartile range: 6-16). Intention-to-treat analysis showed no difference between the probiotics and placebo groups (P = .19). Additionally, there was no difference in any of the secondary outcomes between groups; the number of children with doctor-diagnosed upper or lower respiratory tract infections, the number of doctor visits, antibiotic treatments, occurrence and duration of diarrhea, and days with common cold symptoms, fever, vomiting, or caregivers' absence from work. CONCLUSIONS: A daily administration of a combination of B animalis subsp lactis and L rhamnosus for 6 months did not reduce the number of days absent from child care in healthy infants at the time of enrollment in child care.

[Acute malnutrition in children].

The prevalence of malnutrition has declined significantly over the last 30 years. Despite this, malnutrition remains a major cause of illness and death among children worldwide, particularly in low- and medium-income countries. Marasmus and kwashiorkor are the most life-threatening forms of malnutrition. Treatment protocols enable effective treatment, but only a minority of malnourished children have access to treatment. Furthermore, treating children with complicated malnutrition requiring hospitalization remains a clinical challenge.

Effects of dietary protein and glycaemic index on biomarkers of bone turnover in children.

For decades, it has been debated whether high protein intake compromises bone mineralisation, but no long-term randomised trial has investigated this in children. In the family-based, randomised controlled trial DiOGenes (Diet, Obesity and Genes), we examined the effects of dietary protein and glycaemic index (GI) on biomarkers of bone turnover and height in children aged 5-18 years. In two study centres, families with overweight parents were randomly assigned to one of five ad libitum-energy, low-fat (25-30% energy (E%)) diets for 6 months: low protein/low GI; low protein/high GI; high protein/low GI; high protein/high GI; control. They received dietary instructions and were provided all foods for free. Children, who were eligible and willing to participate, were included in the study. In the present analyses, we included children with data on plasma osteocalcin or urinary N-terminal telopeptide of collagen type I (U-NTx) from baseline and at least one later visit (month 1 or month 6) (n 191 in total, n 67 with data on osteocalcin and n 180 with data on U-NTx). The level of osteocalcin was lower (29.1 ng/ml) in the high-protein/high-GI dietary group than in the low-protein/high-GI dietary group after 6 months of intervention (95% CI 2.2, 56.1 ng/ml, P=0.034). The dietary intervention did not affect U-NTx (P=0.96) or height (P=0.80). Baseline levels of U-NTx and osteocalcin correlated with changes in height at month 6 across the dietary groups (P<0.001 and P=0.001, respectively). The present study does not show any effect of increased protein intake on height or bone resorption in children. However, the difference in the change in the level of osteocalcin between the high-protein/high-GI group and the low-protein/high-GI group warrants further investigation and should be confirmed in other studies.

Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents.

In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.

Probiotics to adolescents with obesity: effects on inflammation and metabolic syndrome.

OBJECTIVES: The connections between gut microbiota, energy homeostasis, and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. We aimed to investigate the effect of the probiotic strain Lactobacillus salivarius Ls-33 on a series of biomarkers related to inflammation and the metabolic syndrome (MS) in adolescents with obesity. METHODS: The study was a double-blind placebo-controlled trial including 50 adolescents with obesity randomized to Ls-33 (10 CFU) or placebo daily for 12 weeks. RESULTS: The average body mass index-for-age z-score was 2.6 ±â€Š0.5. There were no differences in biomarkers of inflammation and parameters related to the MS at baseline between the probiotic and placebo groups. Furthermore, there were no differences in changes from baseline to 12-week intervention with regard to any anthropometric measures, blood pressure (systolic and diastolic), fasting glucose and insulin, homeostasis model assessment of insulin resistance, C-peptide, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, free fatty acids, C-reactive protein, interleukin-6, tumor necrosis factor alpha, or fecal calprotectin, despite the increased values of biomarkers of inflammation and of several parameters related to the MS at baseline when compared with normal-weight adolescents. The levels of L salivarius in fecal samples from the probiotic group in the present study were comparable with the levels reported for the other probiotic lactobacilli and bifidobacteria using quantitative polymerase chain reaction. CONCLUSIONS: It was not possible to detect any beneficial effect of the probiotic intervention with Ls-33 on inflammatory markers or parameters related to the MS in adolescents with obesity being in a state of low-grade systemic inflammation.

Obesity, inflammation and metabolic syndrome in Danish adolescents.

AIM: To describe biomarkers of inflammation and markers related to the metabolic syndrome (MS) in healthy obese Danish adolescent and compare to a normal-weight group. METHODS: Fifty-one obese and 30 normal-weight adolescents (12-15 years) were included. Anthropometry and blood pressure were measured, and blood was sampled. RESULTS: Obese adolescents had significantly higher blood pressure, insulin, homeostasis model assessment of insulin resistance, C-peptide, total cholesterol, low-density lipoprotein cholesterol (LDL), triglyceride, C-reactive protein (CRP), interleukin-6 and tumour necrosis factor alpha and lower high-density lipoprotein cholesterol values, compared with normal-weight adolescents, whereas there were no differences between the groups for glucose, free fatty acids or faecal calprotectin. Within the obese group insulin, low-density lipoprotein cholesterol, and CRP were positively associated with body mass index (BMI) Z-scores. The MS was present in 14% of obese adolescents. CRP was positively associated with most anthropometric measures within the obese group, and in multiple linear regression analysis both BMI Z-score and the sum of skin folds explained a considerable part (R(2) = 0.421) of the variation in CRP. CONCLUSION: Otherwise healthy Danish obese adolescents had marked low-grade inflammation, elevated biomarkers of the MS and high prevalence of the MS.

Dietary habits of partly breast-fed and completely weaned infants at 9 months of age.

OBJECTIVE: To test whether there are differences in diet diversity between children still being partly breast-fed at 9 months and those completely weaned at the same age. DESIGN: Cross-sectional study. SETTING: Cross-sectional study (SKOT cohort) in the area of Copenhagen, Denmark. SUBJECTS: Healthy term infants (n 312) at 9 months of age (mean 9·1 (SD 0·3) months). RESULTS: The infants partly breast-fed (n 168) at 9 months had significantly lower body weight (P < 0·0001), were significantly shorter (P = 0·0022) and were introduced to complementary foods significantly later (P < 0·0001) than completely weaned infants (n 141) of similar age. Furthermore, they had lower intake of energy, both in absolute amount (P < 0·0001) and per kilogram of body weight (P = 0·049). Significantly lower intakes of most energy-yielding nutrients, in absolute amounts and as energy percentages, were seen for the partly breast-fed compared with the completely weaned infants. These differences appear to be caused primarily by differences in the type and amount of milk consumed, as the energy derived from sources other than milk was similar except for fatty spread and vegetables as a side dish. Only small differences were found for absolute intakes of foods between feeding groups, although fatty spread had significantly higher intake rates and consumption (P = 0·031) among partly breast-fed compared with completely weaned infants. CONCLUSIONS: At 9 months the infants partly breast-fed did not eat a less diversified diet compared with those completely weaned at the same age. Despite later introduction to complementary foods compared with the completely weaned, their intake of foods was similar and no delay in their progression towards the family foods was noted.

Molecular fingerprints of the human fecal microbiota from 9 to 18 months old and the effect of fish oil supplementation.

OBJECTIVES: The aim of this study was to monitor changes in the fecal microbiota from 9 to 18 months and to investigate the effect of increasing dietary n-3 polyunsaturated fatty acids on the fecal microbiota. PATIENTS AND METHODS: In a double-blind controlled trial with random allocation to daily supplementation with 5 mL of fish oil (FO) or sunflower oil (SO) from 9 to 18 months of age, stool samples were collected from 132 healthy Danish infants. Molecular fingerprints of the bacterial DNA were obtained by terminal restriction fragment length polymorphism (T-RFLP). RESULTS: The T-RFLP profiles indicated that a few T-RFs became dominant with age (bp100 and 102, both presumed to be Bacteroidetes) concomitantly with an overall increase in the microbial diversity (P = 0.04). Breast-feeding influenced both the T-RFLP profiles at 9 months and the changes from 9 to 18 months, and breast-feeding cessation during the trial modified the response to the dietary oils. In the FO group, the increase in bp102 was significantly reduced among children weaned before compared with those weaned during the trial (P = 0.027), whereas the increase in bp100 was reduced in the preweaned children of the SO group relative to those weaned during the trial (P = 0.004). This was supported by intervention group differences in the changes in bp102 and bp100 among the earlier weaned children (P = 0.06 and P = 0.09, respectively). CONCLUSIONS: Cessation of breast-feeding played a dominant role relative to developmental changes in the fecal microbiota from 9 to 18 months. FO compared with SO supplementation affected changes in large bacterial groups, but only among children who had stopped breast-feeding before 9 months of age.

Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence.

BACKGROUND: Low birth weight followed by accelerated weight gain during early childhood has been associated with adverse metabolic and cardiovascular outcomes later in life. The aim of this study was to examine the impact of early infant weight gain on glucose metabolism and cardiovascular risk factors in adolescence and to study if the effect differed between adolescents born small for gestational age (SGA) vs. appropriate for gestational age (AGA). METHODOLOGY/PRINCIPAL FINDINGS: Data from 30 SGA and 57 AGA healthy young Danish adolescents were analysed. They had a mean age of 17.6 years and all were born at term. Data on early infant weight gain from birth to three months as well as from birth to one year were available in the majority of subjects. In adolescence, glucose metabolism was assessed by a simplified intravenous glucose tolerance test and body composition was assessed by dual-energy X-ray absorptiometry. Blood pressures as well as plasma concentrations of triglycerides and cholesterol were measured. Early infant weight gain from birth to three months was positively associated with the fasting insulin concentration, HOMA-IR, basal lipid levels and systolic blood pressure at 17 years. There was a differential effect of postnatal weight gain on HOMA-IR in AGA and SGA participants (P for interaction = 0.03). No significant associations were seen between postnatal weight gain and body composition or parameters of glucose metabolism assessed by the simplified intravenous glucose tolerance test. In subgroup analysis, all associations with early infant weight gain were absent in the AGA group, but the associations with basal insulin and HOMA-IR were still present in the SGA group. CONCLUSION: This study suggests that accelerated growth during the first three months of life may confer an increased risk of later metabolic disturbances--particularly of glucose metabolism--in individuals born SGA.

[Undernutrition in humanitarian crises]. / Underernaering ved humanitaere kriser.

Undernutrition is a major cause of morbidity and mortality in emergencies. The response depends on the extent and type of undernutrition in the affected population. Nutritional status is assessed by weight-for-height, mid-upper arm circumference and micronutrient deficiencies. Food aid is distributed in general or selective feeding programmes. Promotion of breastfeeding has been found to be one of the most efficient strategies to prevent undernutrition. There is a lack of evidence to support the optimal composition of food aid products, but there is an increasing focus on the importance of research in this field.

Infant weight gain, duration of exclusive breast-feeding and childhood BMI - two similar follow-up cohorts.

OBJECTIVE: To describe the association between duration of exclusive breast-feeding (EBF), weight gain in infancy and childhood BMI in two populations with a long duration of EBF. DESIGN: Cohort study with follow-up in childhood. Breast-feeding status was reported monthly during infancy. Weight and length were measured at birth, 2, 6 and 12 months of age, as well as in childhood at 6 or 10 years of age. SETTING: Iceland and Denmark. SUBJECTS: Randomly selected healthy newborns from Denmark (n 85) and Iceland (n 100). RESULTS: Infants exclusively breast-fed for < or =2 months gained 348 (95% CI 69, 626) g more weight from 2 to 6 months than infants exclusively breast-fed for 3-4 months (P = 0.009). Weight gain from 6 to 12 months was found to be greater among infants exclusively breast-fed for < or =2 months compared with those exclusively breast-fed for > or =5 months (P = 0.008). A greater weight change, in terms of Z-score, between the ages of 2 and 6 months was associated with higher Z-score of childhood BMI, adjusted for birth weight, country and duration of EBF (B = 0.49, se = 0.11, P < 0.001, adj. R2 = 0.15). However, the association was much stronger in the Icelandic cohort than the Danish one. CONCLUSIONS: Although duration of EBF was not associated with childhood BMI in the present study it may modulate growth rate in infancy, which is related to childhood BMI. However, other factors determinative for infant growth also need to be considered when assessing the relationship of early growth and nutrition to childhood overweight, as traditions in complementary food might differ between populations.

Effects of maternal micronutrient supplementation on fetal loss and under-2-years child mortality: long-term follow-up of a randomised controlled trial from Guinea-Bissau.

A number of trials on maternal multi-micronutrient supplementation (MMS) have found a benefical effect on birth weight, but few have demonstrated a beneficial effect on infant survival. We examined the effect of two different preparations of antenatal MMS on fetal loss and under-2-years child mortality, as compared with iron-folic acid supplementation among 2,100 pregnant women in Guinea-Bissau. Women receiving a 1xRDA MMS preparation (consisting of 14 vitamins and minerals) had a marginally reduced risk of fetal loss (Relative risk (RR) 0.65, 95% CI 0.40; 1.05), and women receiving a 2xRDA MMS preparation had a similar effect (RR 0.67, 95% CI 0.42; 1.08), the pooled effect being 0.66 (95% CI 0.44; 0.99). None of the supplements reduced under-2-years mortality or the combination of fetal loss and under-2-years mortality. There was a marginally negative effect of both the 1xRDA (RR 2.10, 95% CI 0.99; 4.46) and the 2xRDA (RR 2.02, 95% CI 0.95; 4.32) MMS preparation on mortality specifically between 92-365 days of age.