Protein Intake, IGF-1 Concentrations, and Growth in the Second Year of Life in Children Receiving Growing Up Milk - Lite (GUMLi) or Cow's Milk (CM) Intervention.

The relationship of protein intake with insulin-like growth factor 1 (IGF-1) concentrations in well-nourished children during the second year of life is poorly understood. The aim of this study was to explore the effect of a reduced-protein Growing Up Milk Lite (GUMLi) or unfortified cow's milk (CM) on protein intake, growth, and plasma IGF-1 at 2 y. An exploratory analysis of a sub-sample of Auckland-based children (n = 79) in the GUMLi trial (a double-blind, randomised control trial, N = 160) completed in Auckland and Brisbane (2015-2017) was conducted. One-year old children were randomised to receive a reduced-protein GUMLi (1.7 g protein/100 mL) or a non-fortified CM (3.1 g protein/100 mL) for 12 months. Blood sampling and anthropometric measurements were made at 1 and 2 y. Diet was assessed using a validated food frequency questionnaire. Total protein intake (g/d) from all cow's milk sources was 4.6 g (95% CI: -6.7, -2.4; p < 0.005) lower in the GUMLi group after 12 months of the intervention, with a significant group-by-time interaction (p = 0.005). Length-for-age (LAZ) and weight-for-length (WLZ) z-scores did not differ between groups, however, mean body fat % (BF%) was 3.2% (95%CI: -6.2, -0.3; p = 0.032) lower in the GUMLi group at 2 y. There was no difference between the intervention groups in relation to IGF-1 and IGF-BP3 (p = 0.894 and 0.698, respectively), with no group-by-sex interaction. After combining the groups, IGF-1 concentration at 2 y was positively correlated with parameters of growth (all p < 0.05), total cow's milk intake (p = 0.032) after adjusting for sex, breastfeeding status, and gestation. Randomisation to a reduced protein GUMLi resulted in small reduction in %BF and lower total protein intakes but had no effect on growth. Plasma IGF-1 concentrations were independently associated with total protein intake from cow's milk at 2 y, highlighting a potential area of the diet to target when designing future protein-related nutrition interventions. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry number: ACTRN12614000918628. Date registered: 27/08/2014.

Validation and calibration of the Eating Assessment in Toddlers FFQ (EAT FFQ) for children, used in the Growing Up Milk - Lite (GUMLi) randomised controlled trial.

The Eating Assessment in Toddlers FFQ (EAT FFQ) has been shown to have good reliability and comparative validity for ranking nutrient intakes in young children. With the addition of food items (n 4), we aimed to re-assess the validity of the EAT FFQ and estimate calibration factors in a sub-sample of children (n 97) participating in the Growing Up Milk - Lite (GUMLi) randomised control trial (2015-2017). Participants completed the ninety-nine-item GUMLi EAT FFQ and record-assisted 24-h recalls (24HR) on two occasions. Energy and nutrient intakes were assessed at months 9 and 12 post-randomisation and calibration factors calculated to determine predicted estimates from the GUMLi EAT FFQ. Validity was assessed using Pearson correlation coefficients, weighted kappa (κ) and exact quartile categorisation. Calibration was calculated using linear regression models on 24HR, adjusted for sex and treatment group. Nutrient intakes were significantly correlated between the GUMLi EAT FFQ and 24HR at both time points. Energy-adjusted, de-attenuated Pearson correlations ranged from 0·3 (fibre) to 0·8 (Fe) at 9 months and from 0·3 (Ca) to 0·7 (Fe) at 12 months. Weighted κ for the quartiles ranged from 0·2 (Zn) to 0·6 (Fe) at 9 months and from 0·1 (total fat) to 0·5 (Fe) at 12 months. Exact agreement ranged from 30 to 74 %. Calibration factors predicted up to 56 % of the variation in the 24HR at 9 months and 44 % at 12 months. The GUMLi EAT FFQ remained a useful tool for ranking nutrient intakes with similar estimated validity compared with other FFQ used in children under 2 years.

A multicenter, double-blind, randomized, placebo-controlled trial to evaluate the effect of consuming Growing Up Milk "Lite" on body composition in children aged 12-23 mo.

BACKGROUND: Growing Up Milk (GUM) was developed to assist young children in meeting their nutritional requirements during the second year of life. However, there is limited evidence that GUM improves nutritional status and growth in young children. OBJECTIVES: To evaluate the effect of consuming Growing Up Milk "Lite" (GUMLi) (reduced protein with synbiotics and micronutrients added) compared with standard cow milk as part of a whole diet for 1 y on body composition at 2 y of age. METHODS: GUMLi Trial was a multicenter, double-blind, randomized placebo-controlled trial conducted in Auckland and Brisbane. Healthy 1-y-olds were recruited and randomly assigned to receive either GUMLi or standard cow milk for 12 mo as part of a whole diet. The primary outcome was percentage body fat at 2 y of age measured by bioelectrical impedance. All regression models adjusted for baseline outcome and study center. RESULTS: 160 children (80 per arm) were randomly assigned, and 134 (67 per arm) were included in the modified intention-to-treat analyses. The mean percentage body fat at 12 mo was 23.3% (SD 7.9) in the GUMLi group and 25.7% (SD 7.2) in the cow milk group. After adjusting for baseline outcome and study location, the estimated mean difference in percentage body fat between the intervention and control at 12 mo was -2.19% (95% CI: -4.24, -0.15; P = 0.036). Per-protocol analysis showed a similar effect (mean difference: -2.09%; 95% CI: -4.16, -0.03; P = 0.047). Both fat mass and the fat mass index were significantly lower in the GUMLi group at 12 mo than in the cow milk group. CONCLUSIONS: At 2 y of age, children who consumed a GUM with a lower protein content than cow milk over 12 mo had a lower percentage of body fat. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12614000918628.

A comparison of the effect of a Growing Up Milk - Lite (GUMLi) v. cows' milk on longitudinal dietary patterns and nutrient intakes in children aged 12-23 months: the GUMLi randomised controlled trial.

The second year of life is a period of nutritional vulnerability. We aimed to investigate the dietary patterns and nutrient intakes from 1 to 2 years of age during the 12-month follow-up period of the Growing Up Milk - Lite (GUMLi) trial. The GUMLi trial was a multi-centre, double-blinded, randomised controlled trial of 160 healthy 1-year-old children in Auckland, New Zealand and Brisbane, Australia. Dietary intakes were collected at baseline, 3, 6, 9 and 12 months post-randomisation, using a validated FFQ. Dietary patterns were identified using principal component analysis of the frequency of food item consumption per d. The effect of the intervention on dietary patterns and intake of eleven nutrients over the duration of the trial were investigated using random effects mixed models. A total of three dietary patterns were identified at baseline: 'junk/snack foods', 'healthy/guideline foods' and 'breast milk/formula'. A significant group difference was observed in 'breast milk/formula' dietary pattern z scores at 12 months post-randomisation, where those in the GUMLi group loaded more positively on this pattern, suggesting more frequent consumption of breast milk. No difference was seen in the other two dietary patterns. Significant intervention effects were seen on nutrient intake between the GUMLi (intervention) and cows' milk (control) groups, with lower protein and vitamin B12, and higher Fe, vitamin D, vitamin C and Zn intake in the GUMLi (intervention) group. The consumption of GUMLi did not affect dietary patterns, however, GUMLi participants had lower protein intake and higher Fe, vitamins D and C and Zn intake at 2 years of age.

Evaluation of the Effect of a Growing up Milk Lite vs. Cow's Milk on Diet Quality and Dietary Intakes in Early Childhood: The Growing up Milk Lite (GUMLi) Randomised Controlled Trial.

scores provide an alternative approach to measuring dietary quality. The Growing Up Milk-Lite (GUMLi) Trial was a multi-centre, double-blinded, randomised controlled trial of children randomised to receive a reduced protein GUM (GUMLi) or unfortified cow's milk (CM). In a secondary analysis of the GUMLi Trial, we used the Probability of Adequate Nutrient Intake (PANDiet) to determine the nutritional adequacy of the diets of participating children living in Auckland. The PANDiet was adapted to the New Zealand Nutrient Reference Values and data from four 24 h Recalls (24HR) collected at months 7, 8, 10, and 11 post-randomisation were used. Differences between randomised groups (GUMLi vs. CM) of the PANDiet and its components were made. Eighty-three Auckland participants were included in the study (GUMLi n = 41 vs. CM n = 42). Total PANDiet scores were significantly higher in the GUMLi group (p < 0.001), indicating better overall nutrient adequacy and diet quality. Dietary intakes of children in both groups met the recommendations for fat, total carbohydrates and most micronutrients; however, protein intakes exceeded recommendations. Consumption of GUMLi was associated with higher nutritional adequacy, with an increased likelihood of meeting nutrient requirements; however, the impact of the family diet and GUMLi on dietary diversity requires further evaluation.

Compared with Cow Milk, a Growing-Up Milk Increases Vitamin D and Iron Status in Healthy Children at 2 Years of Age: The Growing-Up Milk-Lite (GUMLi) Randomized Controlled Trial.

Background: Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally. Objective: We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age. Methods: The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center. Results: GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group. Conclusion: In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628.

Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy.

BACKGROUND: Human milk is typically low in vitamin D activity (VDA). Whether the vitamin D content of breast milk at birth can be increased by supplementing the mother during pregnancy has not been reported to the best of our knowledge. OBJECTIVE: We examined the effect of vitamin D supplementation during pregnancy on breast-milk VDA in the first 2 mo of lactation. DESIGN: Breast-milk samples were obtained from women who were enrolled in a randomized, double-blinded, placebo-controlled trial of vitamin D supplementation during pregnancy. Pregnant women were enrolled at 27 wk of gestation and randomly assigned to the following 3 groups: a placebo group, a group who received one dosage of daily oral vitamin D3 (1000 IU), or a group who received 2 dosages of daily oral vitamin D3 (2000 IU). Serum 25-hydroxyvitamin D [25(OH)D] was measured at enrollment, at 36 wk of gestation, and in cord blood at birth. Study participants who were breastfeeding were invited to provide breast-milk samples for VDA measurement [concentration of vitamin D2, vitamin D3, 25(OH)D2, and 25(OH)D3] at 2 wk and 2 mo postpartum. A linear mixed model was used to compare breast-milk VDA between the 3 study groups. RESULTS: A total of 75 women provided breast-milk samples (44 women provided breast-milk samples at both 2 wk and 2 mo postpartum). The mean (95% CI) VDA at age 2 wk was 52 IU/L (12, 217 IU/L) in the placebo group, 51 IU/L (17, 151 IU/L) in the 1000-IU group, and 74 IU/L (25, 221 IU/L) in the 2000-IU group; and at age 2 mo, the mean (95% CI) VDA was 45 IU/L (16, 124 IU/L), 43 IU/L (18, 103 IU/L), and 58 IU/L (15, 224 IU/L), respectively. There was no significant interaction in VDA between the sample-collection time and treatment (P = 0.61), but there was a difference between lower- and higher-dosage treatment groups (P = 0.04). CONCLUSION: Maternal vitamin D supplementation during pregnancy of 2000 IU/d (compared with 1000 IU/d and with a placebo) results in a higher VDA of breast milk ≥2 mo postpartum. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000483055.

The impact of primary care on emergency department presentation and hospital admission with pneumonia: a case-control study of preschool-aged children.

BACKGROUND: In children, community-acquired pneumonia is a frequent cause of emergency department (ED) presentation and hospital admission. Quality primary care may prevent some of these hospital visits. AIMS: The aim of this study was to identify primary care factors associated with ED presentation and hospital admission of preschool-aged children with community-acquired pneumonia. METHODS: A case-control study was conducted by enrolling three groups: children presenting to the ED with pneumonia and admitted (n = 326), or discharged home (n = 179), and well-neighbourhood controls (n = 351). Interviews with parents and primary care staff were conducted and health record review was performed. The association of primary care factors with ED presentation and hospital admission, controlling for available confounding factors, was determined using logistic regression. RESULTS: Children were more likely to present to the ED with pneumonia if they did not have a usual general practitioner (GP) (odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.67-3.70), their GP worked ⩽ 20 h/week (OR = 1.86, 95% CI = 1.10-3.13) or their GP practice lacked an immunisation recall system (OR = 5.44, 95% CI = 2.26-13.09). Lower parent ratings for continuity (OR=1.63, 95% CI = 1.01-2.62), communication (OR = 2.01, 95% CI = 1.29-3.14) and overall satisfaction (OR = 2.16, 95% CI = 1.34-3.47) increased the likelihood of ED presentation. Children were more likely to be admitted when antibiotics were prescribed in primary care (OR = 2.50, 95% CI = 1.43-4.55). Hospital admission was less likely if children did not have a usual GP (OR = 0.22, 95% CI = 0.11-0.40) or self-referred to the ED (OR = 0.48, 95% CI = 0.26-0.89). CONCLUSIONS: Accessible and continuous primary care is associated with a decreased likelihood of preschool-aged children with pneumonia presenting to the ED and an increased likelihood of hospital admission, implying more appropriate referral. Lower parental satisfaction is associated with an increased likelihood of ED presentation.

Vitamin D during pregnancy and infancy and infant serum 25-hydroxyvitamin D concentration.

OBJECTIVE: To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D (25(OH)D) concentration ≥ 20 ng/mL during infancy. METHODS: A randomized, double-blind, placebo-controlled trial in New Zealand. Pregnant mothers, from 27 weeks' gestation to birth, and then their infants, from birth to age 6 months, were randomly assigned to 1 of 3 mother/infant groups: placebo/placebo, vitamin D3 1000/400 IU, or vitamin D3 2000/800 IU. Serum 25(OH)D and calcium concentrations were measured at enrollment, 36 weeks' gestation, in cord blood, and in infants at 2, 4, and 6 months of age. RESULTS: Two-hundred-and-sixty pregnant women were randomized. At enrollment, the proportions with serum 25(OH)D ≥ 20 ng/mL for placebo, lower-dose, and higher-dose groups were 54%, 64%, and 55%, respectively. The proportion with 25(OH)D ≥ 20 ng/mL was larger in both intervention groups at 36 weeks' gestation (50%, 91%, 89%, P < .001). In comparison with placebo, the proportion of infants with 25(OH)D ≥ 20 ng/mL was larger in both intervention groups to age 4 months: cord blood (22%, 72%, 71%, P < .001), 2 months (50%, 82%, 92%, P < .001), and 4 months (66%, 87%, 87%, P = .004), but only in the higher-dose group at age 6 months (74%, 82%, 89%, P = .07; higher dose versus placebo P = .03, lower dose versus placebo P = .21). CONCLUSIONS: Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥ 20 ng/mL, with the higher dose sustaining this increase for longer.

Risk factors for community-acquired pneumonia in pre-school-aged children.

AIM: To identify risk factors for children developing and being hospitalised with community-acquired pneumonia. METHODS: Children <5 years old residing in urban Auckland, New Zealand were enrolled from 2002 to 2004. To assess the risk of developing pneumonia, children hospitalised with pneumonia (n= 289) plus children with pneumonia discharged from the Emergency Department (n= 139) were compared with a random community sample of children without pneumonia (n= 351). To assess risk of hospitalisation, children hospitalised with pneumonia were compared with the children discharged from the Emergency Department. Adjusted odds ratio (OR) with 95% confidence intervals (CIs) were used to estimate the risk of pneumonia and hospitalisation with pneumonia. RESULTS: After adjustment for season, age and ethnicity there was an increased risk of pneumonia associated with lower weight for height (OR 1.28, 95% CI 1.10-1.51), spending less time outside (1.96, 1.11-3.47), previous chest infections (2.31, 1.55-3.43) and mould in the child's bedroom (1.93, 1.24-3.02). There was an increased risk of pneumonia hospitalisation associated with maternal history of pneumonia (4.03, 1.25-16.18), living in a more crowded household (2.87, 1.33-6.41) and one with cigarette smokers (1.99, 1.05-3.81), and mould in the child's bedroom (2.39, 1.25-4.72). CONCLUSIONS: Lower quality living environments increase the risk of pneumonia and hospitalisation with pneumonia in New Zealand. Poorer nutritional status may also increase the risk of pneumonia. Improving housing quality, decreased cigarette smoke exposure and early childhood nutrition may reduce pneumonia disease burden in New Zealand.