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.

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.

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.

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.

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.

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.

Probiotics in late infancy reduce the incidence of eczema: A randomized controlled trial.

BACKGROUND: Allergic diseases are common and represent a considerable health and economic burden worldwide. We aimed to examine the effect of a combination of two probiotic strains administered in late infancy and early childhood on the development of allergic diseases and sensitization. METHODS: In this double-blind, placebo-controlled intervention trial, participants were randomized to receive a daily mixture of Lactobacillus rhamnosus and Bifidobacterium animalis subsp lactis or placebo-starting prior to attending day care. The intervention period was 6 months, and the parents answered web-based questionnaires on allergic symptoms and doctor's diagnosed allergic disease monthly. IgE was measured at baseline and follow-up. RESULTS: A total of 290 participants were randomized: 144 in the probiotic group and 146 in the placebo group. Mean age at intervention start was 10.1 months. At follow-up (mean age 16.1 months), the incidence of eczema was 4.2% in the probiotic group and 11.5% in the placebo group (P = 0.036). The incidence of asthma and conjunctivitis did not differ between groups, and no children presented with rhinitis. Sensitization was equal in the two groups at intervention start (7.5% and 9.5%, respectively), and two children in each group were sensitized during the intervention. CONCLUSIONS: We observed a significantly lower incidence of eczema in the probiotic group compared to the placebo group. The probiotics were administered in late infancy-prior to attending day care-suggesting a broader window of opportunity using probiotics in the prevention of eczema. The incidence of asthma, rhinitis, conjunctivitis, and sensitization did not differ.

Risks for upper respiratory infections in infants during their first months in day care included environmental and child-related factors.

AIM: We examined the frequency and potential risk factors for respiratory infections, diarrhoea and absences in infants during their first months in day care. METHODS: This prospective cohort study comprised 269 Danish infants aged eight months to 14 months and was part of a study that examined how probiotics affected absences from day care due to respiratory and gastrointestinal infections. The risk factors examined were the household, child characteristics and type of day care facility. Parents registered upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), diarrhoea and day care absences on web-based questionnaires. RESULTS: Over a mean of 5.6 months in day care, 36% and 20% of the infants had at least one URTI or LRTI, and 60% had diarrhoeal episodes. The risk of at least one URTI was increased by previous respiratory infections, with an odds ratio (OR) of 2.65, but was inversely associated with having a pet (OR: 0.43), being cared for by registered child minders compared to day care centres (OR: 0.36), birthweight (OR 0.40) and age at day care enrolment (OR: 0.64). No significant risk factors for LRTIs and diarrhoea were found. CONCLUSION: Infection risks were associated with environmental factors and factors related to the child.

Administration of two probiotic strains during early childhood does not affect the endogenous gut microbiota composition despite probiotic proliferation.

BACKGROUND: Probiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous gut microbiota, however probiotic intervention studies in adults have failed to show significant effects on gut microbiota composition. The gut microbiota of young children is known to be unstable and more responsive to external factors than that of adults. Therefore, potential effects of probiotic intervention on gut microbiota may be easier detectable in early life. We thus investigated the effects of a 6 month placebo-controlled probiotic intervention with Bifidobacterium animalis subsp. lactis (BB-12®) and Lactobacillus rhamnosus (LGG®) on gut microbiota composition and diversity in more than 200 Danish infants (N = 290 enrolled; N = 201 all samples analyzed), as assessed by 16S rRNA amplicon sequencing. Further, we evaluated probiotic presence and proliferation by use of specific quantitative polymerase chain reaction (qPCR). RESULTS: Probiotic administration did not significantly alter gut microbiota community structure or diversity as compared to placebo. The probiotic strains were detected in 91.3% of the fecal samples from children receiving probiotics and in 1% of the placebo treated children. Baseline gut microbiota was not found to predict the ability of probiotics to establish in the gut after the 6 month intervention. Within the probiotics group, proliferation of the strains LGG® and BB-12® in the gut was detected in 44.7% and 83.5% of the participants, respectively. A sub-analysis of the gut microbiota including only individuals with detected growth of the probiotics LGG® or BB-12® and comparing these to placebo revealed no differences in community structure or diversity. CONCLUSION: Six months of probiotic administration during early life did not change gut microbiota community structure or diversity, despite active proliferation of the administered probiotic strains. Therefore, alteration of the healthy infant gut microbiota is not likely to be a prominent mechanism by which these specific probiotics works to exert beneficial effects on host health. TRIAL REGISTRATION: NCT02180581 . Registered 30 June 2014.

Dietary protein intake and quality in early life: impact on growth and obesity.

PURPOSE OF REVIEW: Obesity is an increasing problem and high-protein intake early in life seems to increase later risk of obesity. This review summarizes recent publications in the area including observational and intervention studies and publications on underlying mechanisms. RECENT FINDINGS: Recent observational and randomized controlled trials confirmed that high-protein intake in early life seems to increase early weight gain and the risk of later overweight and obesity. Recent studies have looked at the effect of different sources of protein, and especially high-animal protein intake seems to have an effect on obesity. Specific amino acids, such as leucine, have also been implicated in increasing later obesity risk maybe via specific actions on insulin-like growth factor I. Furthermore, additional underlying mechanisms including epigenetics have been linked to long-term obesogenic programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. SUMMARY: Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved and the role of different dietary protein sources and amino acids has increased, but intervention studies are needed to confirm the mechanisms. Avoiding high-protein intake in early life holds promise as a preventive strategy for childhood obesity.

Seasonal variations in growth and body composition of 8-11-y-old Danish children.

BACKGROUND: Earlier studies on seasonality in growth reported the largest height gains during spring and largest body weight gains during autumn. We examined seasonality in height, body weight, BMI, fat mass index (FMI), and fat-free mass index (FFMI) among contemporary Danish 8-11-y olds. METHODS: A total of 760 children from the OPUS School Meal Study provided >2,200 measurements on height, body weight, and composition between September and June. Average velocities were calculated using change-score analyses based on 3-mo intervals. As a complementary analysis, point velocities derived from estimated growth curves were fitted using semiparametric regression that included covariate adjustment and allowed flexible modeling of the time trend. RESULTS: Average velocities showed the following trends: height was higher than the average (6.10 cm/y) in January-April. Body weight was below the average (4.02 kg/y) in August-January and above in January-May; BMI (average: 0.49 kg/ m(2)/y) and FFMI (average: 0.17 kg/m(2)/y) showed similar trends. In contrast, FMI was above the average (0.38 kg/m(2)/y) in November-March. Similar trends were seen for point velocities. CONCLUSION: Our findings suggest seasonality in growth and body composition of Danish children. We recovered the well-known height velocity peak during spring time, but unlike earlier studies, we found coincident peaks in body weight, BMI, and FFMI velocities.

Free Amino Acids in Human Milk and Associations With Maternal Anthropometry and Infant Growth.

OBJECTIVES: Free glutamic acid has an appetite-regulating effect and studies with infant formula have suggested that free amino acids (FAA), especially glutamic acid, can downregulate intake. The content of glutamic acid and glutamine is high in breast milk but varies considerably between mothers. The aim was to investigate whether maternal anthropometry was associated with the content of the FAA glutamic acid or glutamine in breast milk and whether there was a negative association between these FAA and current size or early infant growth in fully breastfed infants. METHODS: From a subgroup of 78 mothers, of which 50 were fully breast feeding, from the Odense Child Cohort breast milk samples were collected 4 months after birth and analyzed for FAA. Information regarding breastfeeding status and infant weight and length was also recorded. RESULTS: There was a large variation in the concentration of the FAAs between mothers. Glutamic acid was positively correlated with mother's prepregnancy weight and height (P ≤ 0.028), but not body mass index. There was no negative correlation between the 2 FAA and infant weight or body mass index. Infant length at 4 months was, however, positively associated with glutamine, (P = 0.013) but the correlation was attenuated when controlling for birth length (P = 0.089). CONCLUSIONS: The hypothesis that a high content of glutamic acid and glutamine in breast milk could downregulate milk intake to a degree affecting early growth could not be confirmed. Maternal factors associated with the level of these FAA in milk and the potential effect on the infant should be investigated further.

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

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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 impact on the insulin-like growth factor axis and later health consequences.

PURPOSE OF REVIEW: There is increasing interest in the role of insulin-like growth factor-I (IGF-I) in the relation between early growth and later risk of noncommunicable diseases (NCDs). This review presents and discusses a selection of recent publications on this topic. RECENT FINDINGS: Nutrition during pregnancy and in preterm infants has an influence on IGF-I. Breastfeeding is associated with lower IGF-I values and the effect of early protein intake was confirmed in a large intervention study. IGF-I levels are associated with early obesity, but the relation is complex and differs with age. Further studies and reviews support that there is a programming of the IGF axis, with higher levels during early life being associated with lower levels in adulthood, which is likely to influence the risk of NCDs later in life. SUMMARY: Recent studies support that IGF-I plays an important role in the complex association between early diet, growth and later health, but more studies are needed to better understand the role of IGF-I, especially in the early development of obesity. Studies with data on how IGF-I is influenced by early diet in studies of preterm infants and young children with undernutrition from low-income countries will be helpful in recommending optimal diets.

Central adiposity and protein intake are associated with arterial stiffness in overweight children.

Being overweight is associated with vascular abnormalities, which are important in the development of atherosclerosis. However, little is known about dietary and lifestyle determinants of vascular function in overweight children. In adults, dietary protein and milk intake are associated with reduced blood pressure and reduced risk of metabolic syndrome. This study examined the associations between dietary protein, milk intake, physical activity, and adiposity on arterial stiffness in overweight children. In a cross-sectional study, overweight children with habitual milk intakes ≤ 250 mL/d were examined by DXA scans, pedometer counts, anthropometry, and metabolic variables. Dietary intake was registered for 4 d. The outcomes were arterial stiffness measured by pulse wave velocity (PWV) (n = 182) and augmentation index (Aix) (n = 183). The PWV (mean ± SD) was 4.78 ± 0.72 m/s and the Aix was -0.77 ± 9.44%. In multivariate models, the android fat:gynoid fat and android fat:body fat ratios were positively associated with PWV (ß = 1.49 and ß = 10.3, both P < 0.05) and Aix (ß = 28.3, P < 0.01 and ß = 153, P < 0.05), whereas the gynoid fat:body fat ratio was negatively associated with the Aix (ß = -134; P < 0.001). Protein intake (percentage energy) was positively associated with PWV (ß = 0.05; P < 0.01). Milk intake (L/d) tended to be negatively associated with PWV (ß = -0.64; P = 0.05). Pedometer counts were negatively associated with the Aix; however, the association became nonsignificant after controlling for HOMA, which was positively associated with the Aix (ß = 0.95; P < 0.01). In conclusion, central adiposity and protein intake are associated with increased arterial stiffness measured as PWV in overweight children independent of blood pressure and heart rate. The effect of protein intake may be caused by meat, because the milk intake was low.

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.

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.

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.

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.