Vitamin D supplementation for improving bone density in vitamin D-deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D-deficient children are unclear. OBJECTIVES: This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D-deficient individuals. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1-19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. RESULTS: Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. CONCLUSIONS: Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets). This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772.

Early Nutrition and Its Effect on Growth, Body Composition, and Later Obesity.

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Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes.

Background: Appetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants' milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad. Objective: We aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively. Materials and methods: Maternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations. Results: A positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (p interaction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes. Conclusion: Our main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition. Clinical trials registry number: NCT03254329.

Similar effects of milk protein and blends of milk and plant-based protein on appetite-related hormones in 7- to 8-year-old healthy Danish children: secondary analyses from the PROGRO randomised trial.

AIM: The effect of different protein sources on the appetite-related hormones in children is largely unknown. We investigated the effect of milk protein versus blends of milk and rapeseed protein on plasma leptin and adiponectin in children. METHODS: We included 88 Danish 7- to 8-year-old children randomised to receive 35 g protein/day for 4 weeks in 2018 as either milk protein or blends of milk and rapeseed protein (ratio 54:46 or 30:70). Outcomes included absolute and fat mass-adjusted adiponectin and leptin measured at baseline, Weeks 1 and 4. RESULTS: There was no difference in changes in absolute and fat mass-adjusted adiponectin and leptin after 1 or 4 weeks between the three groups (p ≥ 0.100). Leptin increased within all groups (p ≤ 0.046). Combining the three groups, leptin and fat mass-adjusted leptin increased by 23% (95% CI 11;35) and 17% (6.4;29) during the intervention respectively (both p ≤ 0.001). Adiponectin variables did not change during the intervention period. CONCLUSION: There were no differences between milk protein and blends of milk and rapeseed protein on absolute and fat mass-adjusted leptin and adiponectin in healthy children with a habitual intake of milk. However, leptin increased within all three groups. Future studies should further investigate effect on appetite-related hormones of rapeseed protein alone.

Plasma vitamin B12 concentration is positively associated with cognitive development in healthy Danish 3-year-old children: the SKOT cohort studies.

Adequate vitamin B12 (B12) and folate concentrations are essential for neural development in early childhood, but studies in well-nourished children are lacking. We investigated the relation between plasma B12 and folate at 9 and 36 months and psychomotor development at 36 months in well-nourished Danish children. Subjects from the SKOT cohorts with B12 measurement and completed Ages and Stages Questionnaire, 3rd edition (ASQ-3) at 36 months were included (n 280). Dietary intake, B12 and folate concentrations were collected at 9 and 36 months, and ASQ-3 was assessed at 36 months. Associations between B12 and folate at 9 and 36 months and ASQ-3 were analysed using regression models. Associations between diet and B12 were also investigated. No children had insufficient B12 (<148 pmol/l) at 36 months. B12 at 36 month was positively associated with total ASQ-3 corresponding to an increase of 100 pmol/l B12 per 1·5 increase in total ASQ-3 score (P = 0·019) which remained significant after adjustment for potential confounders including 9 months values. B12 at 9 months or folate at any time point was not associated with total ASQ-3. Intake of milk products was associated with B12 at 36 months (P = 0·003) and showed a trend at 9 months (P = 0·069). Intake of meat products was not associated with B12. In conclusion, B12 was positively related to psychomotor development at 3 years in well-nourished children, indicating that the impact of having marginally low B12 status on psychomotor development in well-nourished children should be examined further.

Effects of vitamin D and high dairy protein intake on bone mineralization and linear growth in 6- to 8-year-old children: the D-pro randomized trial.

BACKGROUND: Vitamin D and dairy protein may stimulate bone mineralization and linear growth in children, but previous studies show inconsistent results and have not examined their combined effects. OBJECTIVES: To investigate combined and separate effects of vitamin D supplementation and high-protein (HP) compared with normal-protein (NP) yogurt intake on children's bone mineralization and linear growth. METHODS: In a 2 × 2-factorial trial, 200 healthy, 6- to 8-year-old, Danish, children with light skin (55°N) were randomized to 20 µg/d vitamin D3 or placebo and to substitute 260 g/d dairy with HP (10 g protein/100 g) or NP (3.5 g protein/100 g) yogurt for 24 weeks during an extended winter. Outcomes were total body less head (TBLH) and lumbar spine bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) by dual-energy X-ray absorptiometry, height, and biomarkers of bone turnover and growth. The primary outcome was TBLH BMD. RESULTS: In total, 184 children (92%) completed the study. The baseline serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased by 7.2 ± 14.1 nmol/L and decreased by 32.3 ± 17.5 nmol/L with vitamin D and placebo, respectively. The baseline protein intake was 15.4 ± 2.4 energy percentage (E%), which increased to 18.3 ± 3.4 E% with HP. There were no vitamin D-yogurt interactions and no main effects of either intervention on TBLH BMD. However, vitamin D supplementation increased lumbar spine BMD and TBLH BMC compared to placebo, whereas HP groups showed lower increments in lumbar spine BMD, TBLH BMC and BA, and plasma osteocalcin compared to NP groups. Height, growth factors, and parathyroid hormone levels were unaffected. CONCLUSIONS: Although there were no effects on whole-body BMD, vitamin D increased bone mass and spinal BMD, whereas high compared with normal dairy protein intake had smaller incremental effects on these outcomes. This supports a recommended vitamin D intake of around 20 µg/d during winter but not use of HP dairy products for improved bone mineralization among healthy, well-nourished children. This trial was registered at clinicaltrials.gov as NCT03956732.

The effect of milk and rapeseed protein on growth factors in 7-8 year-old healthy children - A randomized controlled trial.

OBJECTIVE: Milk protein may stimulate linear growth through insulin-like growth factor-1 (IGF-1). However, the effect of plant proteins on growth factors is largely unknown. This study assesses the effect of combinations of milk and rapeseed protein versus milk protein alone on growth factors in children. DESIGN: An exploratory 3-armed randomized, double-blind, controlled trial was conducted in 129 healthy 7-8 year-old Danish children. Children received 35 g milk and rapeseed protein (ratio 54:46 or 30:70) or 35 g milk protein per day for 4 weeks. The primary outcome was difference in IGF-1 changes between intervention groups after 4 weeks. Secondary outcomes included changes in IGF-1 after 1 week and changes in insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3, insulin, height, weight and body composition after 1 and 4 weeks. Results were analysed by multiple linear mixed-effect models. RESULTS: There were no differences in changes of plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio or insulin between groups after 1 or 4 weeks based on 89 complete cases (P > 0.10). IGF-1 increased by 13.7 (95% CI 9.7;17.7) ng/mL and 18.0 (14.0;22.0) ng/mL from baseline to week 1 and 4, respectively, a 16% increase during the intervention. Similarly, insulin increased by 31% (14; 50) and 33% (16; 53) from baseline to week 1 and 4. Fat-free mass index (FFMI) increments were higher with milk alone than rapeseed blends (P < 0.05), coinciding with a trend towards a lower height increment. Body mass index increased within all groups (P < 0.05), mainly due to an increase in FFMI (P < 0.01). CONCLUSION: There were no differences in changes of growth factors between the combinations of milk and rapeseed protein and milk protein alone in healthy, well-nourished children with a habitual intake of milk. Within groups, growth factors increased considerably. Future studies are needed to investigate how intakes of plant and animal proteins affect childhood growth.

Dietary intake of carbohydrates in pregnant women with type 1 diabetes-A narrative review.

In pregnant women with type 1 diabetes, a low but sufficient, intake of carbohydrates is important to aim for near normal glycemic control. However, knowledge about the carbohydrate intake in this group is limited. To assess the average quantity and quality of carbohydrate intake in pregnant women with type 1diabetes compared to healthy pregnant women and current dietary reference intakes. A narrative literature search was performed in PubMed, Embase, and Cochrane Library and by using a snow-ball search technique to identify papers published on studies conducted in industrialized countries within the last 20 years. Intakes of carbohydrate were assessed qualitatively in relation to the Dietary Reference Intakes recommended by the American Diabetes Association and quantitatively as mean intake of dietary fiber. Five observational studies including 810 pregnant women with type 1 diabetes and 15 observational studies with a total of 118,246 healthy pregnant women were identified. The mean total carbohydrate intake was within the Acceptable Macronutrient Distribution Range (45%-64% of energy intake) in both groups. In pregnant women with type 1 diabetes, the average total intake was 218 ± 19 g/day, which was 20% (53 g/day) lower than in healthy pregnant women. Mean intake of dietary fiber in women with diabetes was lower than the recommended adequate intake for healthy women. With the limitations of pronounced heterogeneity across the included studies, pregnant women with type 1 diabetes reported a mean total carbohydrate intake, which was lower than in healthy pregnant women but still within the recommended range.

Effect of probiotics on thymus size and markers of infection in late infancy: a randomized controlled trial.

BACKGROUND: Probiotics are known to stimulate the immune system but the effect on thymus size in late infancy is unknown. We examined the effect of probiotics on thymus size and C-reactive protein (CRP) in healthy Danish infants starting daycare. We further examined associations between thymus size, CRP and recent infections. METHODS: The study included 186 children randomized to a combination of Lactobacillus rhamnosus, LGG® and Bifidobacterium animalis spp. lactis, BB-12® or placebo for 6 months. Thymus size, assessed as thymus index (TI) and thymus weight index (TWI), was measured by ultrasound at baseline and at endpoint. Blood samples were drawn to measure CRP. Infections were parent-reported. RESULTS: There was no significant difference in thymus size between the probiotic group and placebo (p ≥ 0.248) but TWI tended to be higher in the probiotic group corresponding to 5% higher than placebo (p = 0.068) in an adjusted model. There was no effect of probiotics on CRP (p = 0.331). At the endpoint, thymus size was inversely associated with CRP (p ≤ 0.040), diarrhea (p ≤ 0.050), and TI was also associated with the absence from daycare due to respiratory or gastrointestinal infections (p = 0.010). CONCLUSION: The probiotic intervention had no effect on thymus size or CRP in Danish children at the age of starting daycare. IMPACT: Overall there was no effect on thymus size of a combination of Lactobacillus rhamnosus, LGG® and Bifidobacterium animalis spp. lactis, BB-12® administered to Danish children starting daycare. This study examines the effect of probiotics on thymus size in healthy children when they start daycare thus exposed for infections while their immune system is still developing. This has to our knowledge not been described before. We found no significant difference in thymus size between the probiotic and placebo groups, but for thymus weight index, there was a trend. This should be investigated further in studies designed for this as primary outcome.

Maternal milk microbiota and oligosaccharides contribute to the infant gut microbiota assembly.

Breastfeeding protects against diseases, with potential mechanisms driving this being human milk oligosaccharides (HMOs) and the seeding of milk-associated bacteria in the infant gut. In a cohort of 34 mother-infant dyads we analyzed the microbiota and HMO profiles in breast milk samples and infant's feces. The microbiota in foremilk and hindmilk samples of breast milk was compositionally similar, however hindmilk had higher bacterial load and absolute abundance of oral-associated bacteria, but a lower absolute abundance of skin-associated Staphylococcus spp. The microbial communities within both milk and infant's feces changed significantly over the lactation period. On average 33% and 23% of the bacterial taxa detected in infant's feces were shared with the corresponding mother's milk at 5 and 9 months of age, respectively, with Streptococcus, Veillonella and Bifidobacterium spp. among the most frequently shared. The predominant HMOs in feces associated with the infant's fecal microbiota, and the dominating infant species B. longum ssp. infantis and B. bifidum correlated inversely with HMOs. Our results show that breast milk microbiota changes over time and within a feeding session, likely due to transfer of infant oral bacteria during breastfeeding and suggest that milk-associated bacteria and HMOs direct the assembly of the infant gut microbiota.

Intestinal Enterococcus abundance correlates inversely with excessive weight gain and increased plasma leptin in breastfed infants.

Epidemiological evidence indicates that breastfeeding provides protection against development of overweight/obesity. Nonetheless, a small subgroup of infants undergo excessive weight gain during exclusive breastfeeding, a phenomenon that remains unexplained. Breast milk contains both gut-seeding microbes and substrates for microbial growth in the gut of infants, and a large body of evidence suggests a role for gut microbes in host metabolism. Based on the recently established SKOT III cohort, we investigated the role of the infant gut microbiota in excessive infant weight gain during breastfeeding, including 30 exclusively breastfed infants, 13 of which exhibited excessive weight gain and 17 controls which exhibited normal weight gain during infancy. Infants undergoing excessive weight gain during breastfeeding had a reduced abundance of gut Enterococcus as compared with that observed in the controls. Within the complete cohort, Enterococcus abundance correlated inversely with age/gender-adjusted body-weight, body-mass index and waist circumference, body fat and levels of plasma leptin. The reduced abundance of Enterococcus in infants with excessive weight gain was coupled to a lower content of Enterococcus in breast milk samples of their mothers than seen for mothers in the control group. Together, this suggests that lack of breast milk-derived gut-seeding Enterococci may contribute to excessive weight gain in breastfed infants.

Circulating Insulin-Like Growth Factor-1 Is Positively Associated with Growth and Cognition in 6- to 9-Year-Old Schoolchildren from Ghana.

BACKGROUND: Milk intake stimulates linear growth and improves cognition in children from low-income countries. These effects may be mediated through insulin-like growth factor-1 (IGF-1). OBJECTIVE: The objective was to assess the effect of milk supplement on circulating IGF-1 and to assess IGF-1 as a correlate of growth and cognition in children. METHODS: Secondary data on blood spot IGF-1 from a randomized, double-blind, controlled trial in 6-9-y-old children from rural Ghana were analyzed. Intervention groups received porridge with non-energy-balanced supplements: 8.8 g milk protein/d, 100 kcal/d (Milk8); 4.4 g milk and 4.4 g rice protein/d, 100 kcal/d (Milk/rice); 4.4 g milk protein/d, 48 kcal/d (Milk4); or a control (no protein, 10 kcal/d). IGF-1, length, body composition, and Cambridge Neuropsychological Test Automated Battery (CANTAB) were measured at 3.5 or 8.5 mo. Linear regressions were used to assess the effect of milk interventions on IGF-1 and IGF-1 as a correlate of growth and cognition. RESULTS: The increase in IGF-1 was 15.3 (95% CI: 3.3, 27.3) ng/mL higher in children receiving Milk8 compared with the control. The IGF-1 increases in the isonitrogenous, isoenergetic Milk/rice or the Milk4 groups were not different from the control (P ≥ 0.49). The increase in IGF-1 was associated with improvements in 4 out of 5 CANTAB domains. The strongest associations included reductions in "mean correct latency" from Pattern Recognition Memory and "pre-extradimensional (pre-ED) shift errors" from Intra/Extradimensional Set Shift (P ≤ 0.005). In addition, change in IGF-1 was positively associated with changes in height, weight, and fat-free mass (P ≤ 0.001). CONCLUSIONS: Intake of skimmed milk powder corresponding to one, but not half a glass of milk on school days stimulates IGF-1 in 6-9-y-old Ghanian children. IGF-1 seems to mediate the effect of milk intake on growth and cognition. The association between IGF-1 and cognition in relation to milk intake is novel and opens possibilities for dietary interventions to improve cognition.

Role of Milk and Dairy Products in Growth of the Child.

Cow's milk and dairy products intake increase linear growth in children and result in increased adult stature. This is supported by observational and intervention studies mainly from low- and middle-income countries. However, recent reviews primarily based on studies from well-nourished populations question the relation. The probable effects seem to be mediated by insulin-like growth factor-1 and insulin and to be more pronounced during periods of high growth velocity. Several components of cow's milk are suggested to stimulate growth: a high protein quality, bioavailable minerals that are important for growth, and perhaps lactose. Higher adult stature is associated with both positive and negative health effects. Growth stimulation is important in populations with undernutrition, but in well-nourished populations, it might not be important. A high intake of cow's milk and thereby a high protein intake early in life can increase the risk of later overweight and obesity, while a high protein intake later in childhood seems to be associated with a lower BMI later in childhood. A high dairy intake can limit the diversity of the diet and result in iron deficiency. Therefore, milk intake should not exceed 500 mL/day in young children. Most products for the treatment of undernutrition include dairy protein because of the well-documented effects on growth and recovery. However, as dairy is an expensive ingredient, the amount needed and the effects of alternative plant-based protein sources are considered.

Thymus size is associated with breastfeeding and having pets in a sex-specific manner.

AIM: The aim was to examine associations between thymus size and anthropometric measurements, sex, age, breastfeeding status, presence of siblings, household pets, and infections and allergies since birth in 8- to 13-month-old healthy Danish infants. METHODS: Data collected from 256 healthy infants enrolled in the ProbiComp study were used. Thymus size was assessed using sonographic measures, and thymic index (TI) and thymus weight index (TWI) was used as an absolute and a relative volume estimate, respectively. RESULTS: In terms of TI and TWI, boys had approximately 15% and 5% larger thymus than girls (P < .001 and P < .02, respectively). TWI was larger in girls who were still breastfed than girls who were no longer breastfed (ß: 0.16 cm3 /kg; 95% CI: 0.004, 0.29; P = .01), but no difference was observed for boys. Having household pets was associated with a larger TI (P = .02), which seemed to be driven by associations for boys (ß: 1.38 cm3 ; 95% CI: 0.02, 2.74). No other factors associated with thymus size were identified. CONCLUSION: Thymus size was associated with current breastfeeding in girls and with having household pets in boys. Sex-specific associations should be further explored in future studies on factors associated with thymus size.

Breastmilk Lipids and Oligosaccharides Influence Branched Short-Chain Fatty Acid Concentrations in Infants with Excessive Weight Gain.

SCOPE: The aim is to identify breastmilk components associated with fecal concentration of SCFAs and to investigate whether they differ between infants with high weight gain (HW) and normal weight gain (NW). METHODS AND RESULTS: Breastmilk and fecal samples are collected from mother-infant dyads with HW (n = 11) and NW (n = 15) at 5 and 9 months of age. Breastmilk is profiled on ultra-performance LC-quadrupole TOF-MS platform. Fecal SCFAs are quantified using an isotope-labeled chemical derivatization method. Human milk oligosaccharides (HMOs) are quantified using HPLC after fluorescent derivatization. Lower levels of α-linolenic acid, oleic acid, 3-oxohexadecanoic acid, LPE (P-16:0), LPC (16:0), LPC (18:0), PC (36:2) in breastmilk from mothers from the HW-group at 5 months of age is found. Fecal SCFA concentrations are increased during the transition period from breastfeeding to complementary feeding. Fecal butyrate concentration is higher in the NW-group at 9 months of age. Fecal branched SCFAs are positively associated with breastmilk phospholipid levels, free-fatty acid levels, HMO-diversity, sialylated-HMOs, 6'-sialyllactose, and disialyl-lacto-N-hexaose. CONCLUSION: Fecal branched SCFA concentrations seem to be affected by breastmilk lipid and HMO composition. These differences in breastmilk metabolites may partially explain the excessive weight gain in early life.

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: a Mendelian randomization analysis.

BACKGROUND: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear. OBJECTIVE: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization. METHODS: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y. RESULTS: WHRadjBMI GRS was associated with higher WHRadjBMI (ß = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: ß = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: ß = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: ß = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (ß = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (ß = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal. CONCLUSIONS: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

Human Milk Oligosaccharide Composition Is Associated With Excessive Weight Gain During Exclusive Breastfeeding-An Explorative Study.

Background: Some infants experience excessive weight gain during exclusive breastfeeding. The cause is unknown, but variation in human milk composition might play a role. Several human milk koligosaccharides (HMOs) have been associated with growth velocity in breastfed infants, and it has been suggested that the mechanism could be through an effect on infant gut microbiota composition. Objective: The purpose of this exploratory study was to evaluate if HMO composition was different in milk fed to infants with excessive weight gain compared to infants with normal weight gain. Furthermore, we aimed to examine if HMO composition was associated with growth velocity and change in body composition and if there were maternal determinants of HMO composition. Materials and Methods: We recruited 13 high weight-gain (HW) and 17 normal weight-gain (NW) breastfed infants, collected human milk and anthropometry data at 5 and 9 months, and analyzed HMO composition by high performance liquid chromatography. Results: In the HW group eight out of 11 infants received milk from secretor mothers and in the NW group 15 out of 17. Comparing milk from Secretor mothers only, four HMO's were significantly different between the HW and NW group at 5 months and two remained significant at 9 months. Total HMO concentrations as well as total HMO-bound fucose at 5 months were positively associated with both fat mass index (FMI) and weight velocity from 0 to 5 months (all p < 0.025). 2'-fucosyllactose (2'-FL) was positively associated with weight velocity from 0 to 5 months and FMI at 5 months. In contrast, lacto-N-neotetraose was lower in the HW group (p = 0.012) and negatively associated with height-for-age Z-scores (p = 0.008), weight velocity from 0 to 5 months (p = 0.009) and FMI (p = 0.033). Maternal BMI at 5 months was negatively associated with 6'-sialyllactose and sialyl-lacto-N-tetraose (LSTb) and positively with 2'-FL, total HMO and total HMO-bound fucose (all p ≤ 0.03). Conclusion: In a small cohort, we found significantly different HMO concentrations in milk to exclusively breastfed infants with excessive weight gain, suggesting that some HMOs, including 2'-FL, which is the most abundant HMO and currently added to some infant formula, could be part of the cause for the excessive weight gain.

Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents.

BACKGROUND: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children. METHODS: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years. RESULTS: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536). CONCLUSIONS: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.