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1.
  • Butler, Eadaoin M., et al. (author)
  • Maternal bacteria to correct abnormal gut microbiota in babies born by C-section
  • 2020
  • In: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 99:30
  • Journal article (peer-reviewed)abstract
    • Introduction: There is evidence that caesarean section (CS) is associated with increased risk of childhood obesity, asthma, and coeliac disease. The gut microbiota of CS-born babies differs to those born vaginally, possibly due to reduced exposure to maternal vaginal bacteria during birth. Vaginal seeding is a currently unproven practice intended to reduce such differences, so that the gut microbiota of CS-born babies is similar to that of babies born vaginally. Our pilot study, which uses oral administration as a novel form of vaginal seeding, will assess the degree of maternal strain transfer and overall efficacy of the procedure for establishing normal gut microbiota development. Methods and analysis: Protocol for a single-blinded, randomized, placebo-controlled pilot study of a previously untested method of vaginal seeding (oral administration) in 30 CS-born babies. A sample of maternal vaginal bacteria is obtained prior to CS, and mixed with 5 ml sterile water to obtain a supernatant. Healthy babies are randomized at 1:1 to receive active treatment (3 ml supernatant) or placebo (3 ml sterile water). A reference group of 15 non-randomized vaginal-born babies are also being recruited. Babies' stool samples will undergo whole metagenomic shotgun sequencing to identify potential differences in community structure between CS babies receiving active treatment compared to those receiving placebo at age 1 month (primary outcome). Secondary outcomes include differences in overall gut community between CS groups (24 hours, 3 months); similarity of CS-seeded and placebo gut profiles to vaginally-born babies (24 hours, 1 and 3 months); degree of maternal vaginal strain transfer in CS-born babies (24 hours, 1 and 3 months); anthropometry (1 and 3 months) and body composition (3 months). Ethics and dissemination: Ethics approval by the Northern A Health and Disability Ethics Committee (18/NTA/49). Results will be published in peer-reviewed journals and presented at international conferences. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12618000339257).
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2.
  • Chiavaroli, Valentina, et al. (author)
  • Childhood obesity in New Zealand
  • 2019
  • In: World Journal of Pediatrics. - : ZHEJIANG UNIV SCH MEDICINE. - 1708-8569 .- 1867-0687. ; 15:4, s. 322-331
  • Research review (peer-reviewed)abstract
    • Background: Paediatric obesity has reached epidemic proportions globally, resulting in significant adverse effects on health and wellbeing. Early life events, including those that happen before, during, and after pregnancy can predispose children to later obesity. The purpose of this review is to examine the magnitude of obesity among New Zealand children and adolescents, and to determine their underlying risk factors and associated comorbidities.Data sources: PubMed, Web of Science, and Google Scholar searches were performed using the key terms "obesity", "overweight", "children", "adolescents", and "New Zealand".Results: Obesity is a major public health concern in New Zealand, with more than 33% of children and adolescents aged 2-14 years being overweight or obese. Obesity disproportionately affects Maori (New Zealand's indigenous population) and Pacific children and adolescents, as well as those of lower socioeconomic status. New Zealand's obesity epidemic is associated with numerous health issues, including cardiometabolic, gastrointestinal, and psychological problems, which also disproportionately affect Maori and Pacific children and adolescents. Notably, a number of factors may be useful to identify those at increased risk (such as demographic and anthropometric characteristics) and inform possible interventions.Conclusions: The prevalence of overweight and obese children and adolescents in New Zealand is markedly high, with a greater impact on particular ethnicities and those of lower socioeconomic status. Alleviating the current burden of pediatric obesity should be a key priority for New Zealand, for the benefit of both current and subsequent generations. Future strategies should focus on obesity prevention, particularly starting at a young age and targeting those at greatest risk.
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3.
  • Chiavaroli, Valentina, et al. (author)
  • Exercise in pregnancy : 1-year and 7-year follow-ups of mothers and offspring after a randomized controlled trial
  • 2018
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • There are limited data on long-term outcomes of mothers or their offspring following exercise interventions during pregnancy. We assessed long-term effects of an exercise intervention (home-based stationary cycling) between 20-36 weeks of gestation on anthropometry and body composition in mothers and offspring after 1 and 7 years. 84 women were randomised to intervention or usual activity, with follow-up data available for 61 mother-child pairs (38 exercisers) at 1 year and 57 (33 exercisers) at 7 years. At 1 year, there were no observed differences in measured outcomes between mothers and offspring in the two groups. At the 7-year follow-up, mothers were mostly similar, except that exercisers had lower systolic blood pressure (-6.2 mmHg; p = 0.049). However, offspring of mothers who exercised during pregnancy had increased total body fat (+3.2%; p = 0.034) and greater abdominal (+4.1% android fat; p = 0.040) and gynoid (+3.5% gynoid fat; p = 0.042) adiposity compared with controls. Exercise interventions beginning during pregnancy may be beneficial to long-term maternal health. However, the initiation of exercise during pregnancy amongst sedentary mothers may be associated with adverse effects in the offspring during childhood. Larger follow-up studies are required to investigate long-term effects of exercise in pregnancy.
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4.
  • Chiavaroli, Valentina, et al. (author)
  • Infants born large-for-gestational-age display slower growth in early infancy, but no epigenetic changes at birth
  • 2015
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
  • Journal article (peer-reviewed)abstract
    • We evaluated the growth patterns of infants born large-for-gestational-age (LGA) from birth to age 1 year compared to those born appropriate-for-gestational-age (AGA). In addition, we investigated possible epigenetic changes associated with being born LGA. Seventy-one newborns were classified by birth weight as AGA (10(th)-90(th) percentile; n = 42) or LGA (>90(th) percentile; n = 29). Post-natal follow-up until age 1 year was performed with clinical assessments at 3, 6, and 12 months. Genome-wide DNA methylation was analysed on umbilical tissue in 19 AGA and 27 LGA infants. At birth, LGA infants had greater weight (p < 0.0001), length (p < 0.0001), ponderal index (p = 0.020), as well as greater head (p < 0.0001), chest (p = 0.044), and abdominal (p = 0.007) circumferences than AGA newborns. LGA infants were still larger at the age of 3 months, but by age 6 months there were no more differences between groups, due to higher length and weight increments in AGA infants between 0 and 6 months (p < 0.0001 and p = 0.002, respectively). Genome-wide analysis showed no epigenetic differences between LGA and AGA infants. Overall, LGA infants had slower growth in early infancy, being anthropometrically similar to AGA infants by 6 months of age. In addition, differences between AGA and LGA newborns were not associated with epigenetic changes.
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5.
  • Chiavaroli, Valentina, et al. (author)
  • Lower insulin sensitivity remains a feature of children born very preterm
  • 2021
  • In: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 22:2, s. 161-167
  • Journal article (peer-reviewed)abstract
    • Background: The first report of children born very preterm (<32 weeks of gestation) having insulin resistance was made 16 years ago. However, neonatal care has improved since. Thus, we aimed to assess whether children born very preterm still have lower insulin sensitivity than term controls.Methods: Participants were prepubertal children aged 5 to 11 years born very preterm (<32 weeks of gestation; n = 51; 61% boys) or at term (37-41 weeks; n = 50; 62% boys). Frequently sampled intravenous glucose tolerance tests were performed, and insulin sensitivity was calculated using Bergman's minimal model. Additional clinical assessments included anthropometry, body composition using whole-body dual-energy X-ray absorptiometry scans, clinic blood pressure, and 24-hour ambulatory blood pressure monitoring.Results: Children born very preterm were 0.69 standard deviation score (SDS) lighter (P < .001), 0.53 SDS shorter (P = .003), and had body mass index 0.57 SDS lower (P = .003) than children born at term. Notably, children born very preterm had insulin sensitivity that was 25% lower than term controls (9.4 vs 12.6 x 10(-4) minutes(-1)center dot[mU/L]; P = .001). Other parameters of glucose metabolism, including fasting insulin levels, were similar in the two groups. The awake systolic blood pressure (from 24-hour monitoring) tended to be 3.1 mm Hg higher on average in children born very preterm (P = .054), while the clinic systolic blood pressure was 5.4 mm Hg higher (P = .002).Conclusions: Lower insulin sensitivity remains a feature of children born very preterm, despite improvements in neonatal intensive care. As reported in our original study, our findings suggest the defect in insulin action in prepubertal children born very pretermis primarily peripheral and not hepatic.
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6.
  • Chiavaroli, Valentina, et al. (author)
  • Partial remission in type 1 diabetes and associated factors : Analysis based on the insulin dose-adjusted hemoglobin A1c in children and adolescents from a regional diabetes center, Auckland, New Zealand
  • 2019
  • In: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 20:7, s. 892-900
  • Journal article (peer-reviewed)abstract
    • Background Partial remission (PREM) by the insulin dose-adjusted HbA1c (IDAA1c) method has not been evaluated for the combined associations of ethnicity and socioeconomic status in children and adolescents with type 1 diabetes (T1D). Objective To investigate prevalence and predictors of PREM defined by IDAA1c. Methods Six hundred fourteen of 678 children (aged <15 years) with new-onset T1D (2000-2013) from a regional pediatric diabetes service (Auckland, New Zealand). Results Overall rate of PREM at 3 months was 42.4%, and lower in Maori/Pacific children (28.6%; P = .006) and those of other ethnicities (28.8%; P = .030) compared with New Zealand Europeans (50.4%). Comparing the most and least deprived socioeconomic quintiles, the odds of PREM were lower among the most deprived (adjusted odds ratio [aOR] 0.44; P = .019). Lower rates of PREM were seen in children aged 0 to 4.9 years (23.8%) and 10 to 14 years (40.9%) than in children aged 5 to 9.9 years (57.4%; P < .05). Further predictors of lower rates of PREM were ketoacidosis at diagnosis (aOR 0.54 with DKA; P = .002) and diabetes duration (aOR 0.84 per month; P < .0001). Patient's sex, body mass index standard deviation score, or autoantibodies were not associated with PREM. PREM at 3 months was associated with lower HbA1c over 18 months compared with children not in PREM (65.0 vs 71.3 mmol/mol; P < .0001), independent of ketoacidosis. Conclusions This study on a regional cohort of youth with T1D showed social and ethnic disparities in rates of PREM defined by IDAA1c. Further research into reducing ketoacidosis rates at diagnosis and addressing factors associated with lower rates of PREM in non-European children are important health priorities.
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7.
  • Chiavaroli, Valentina, et al. (author)
  • The associations between maternal BMI and gestational weight gain and health outcomes in offspring at age 1 and 7 years
  • 2021
  • In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
  • Journal article (peer-reviewed)abstract
    • In secondary analyses of a randomised controlled trial of exercise during pregnancy, we examined associations between mid-pregnancy maternal body mass index (BMI) and excessive gestational weight gain (GWG) with offspring health. Follow-up data were available on 57 mother-child pairs at 1-year and 52 pairs at 7-year follow-ups. Clinical assessments included body composition and fasting blood tests. At age 1 year, increased maternal BMI in mid-gestation was associated with greater weight standard deviation scores (SDS) in the offspring (p = 0.035), with no observed associations for excessive GWG. At age 7 years, greater maternal BMI was associated with increased weight SDS (p < 0.001), BMI SDS (p = 0.005), and total body fat percentage (p = 0.037) in their children. Irrespective of maternal BMI, children born to mothers with excessive GWG had greater abdominal adiposity (p = 0.043) and less favourable lipid profile (lower HDL-C and higher triglycerides). At 7 years, maternal BMI and excessive GWG had compounded adverse associations with offspring adiposity. Compared to offspring of mothers with overweight/obesity plus excessive GWG, children of normal-weight mothers with adequate and excessive GWG were 0.97 and 0.64 SDS lighter (p = 0.002 and p = 0.014, respectively), and 0.98 and 0.63 SDS leaner (p = 0.001 and p = 0.014, respectively). Both greater maternal BMI in mid-pregnancy and excessive GWG were independently associated with increased adiposity in offspring at 7 years.
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9.
  • Derraik, Jose G. B., et al. (author)
  • Idiopathic short stature and growth hormone sensitivity in prepubertal children
  • 2019
  • In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 91:1, s. 110-117
  • Journal article (peer-reviewed)abstract
    • Objective: We compared growth hormone sensitivity to an insulin-like growth factor I (IGF-I) generation test in children with idiopathic short stature (ISS) and of normal stature (NS) across the birthweight range.Methods: Forty-six prepubertal children (~7.1 years) born at term were studied: ISS (n = 23; 74% boys) and NS (n = 23; 57% boys). Children underwent a modified IGF-I generation test with recombinant human growth hormone (rhGH; 0.05 mg/kg/d) over four consecutive days. Hormonal concentrations were measured at baseline and day 5.Results: Children with idiopathic short stature were 1.90 SDS lighter (P < 0.0001) but had 4.5% more body fat (P = 0.0007) than NS children. Overall, decreasing birthweight SDS across the normal range (-1.9 to +1.5 SDS) was associated with lower percentage IGF-I response to rhGH stimulation in univariable (r = 0.45; P = 0.002) and multivariable models (β = 24.6; P = 0.006). Plasma IGF-I concentrations rose in both groups with rhGH stimulation (P < 0.0001). GHBP levels (P = 0.002) were suppressed in ISS children (-19%; P = 0.029) but increased among NS children (+18%; P = 0.028), with contrasting responses also observed for leptin and IGFBP-1. Further, the increase in insulin concentrations in response to rhGH stimulation was ~3-fold greater in NS children (142% vs 50%; P = 0.006).Conclusions: A progressive decrease in birthweight SDS was associated with a reduction in GH sensitivity in both NS and ISS children. Thus, the lower IGF-I response to rhGH stimulation in association with decreasing birthweight indicates that the ISS children at the lower end of the birthweight spectrum may have partial GH resistance, which may contribute to their poorer growth.
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10.
  • Leong, Karen S. W., et al. (author)
  • Effects of Fecal Microbiome Transfer in Adolescents With Obesity The Gut Bugs Randomized Controlled Trial
  • 2020
  • In: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:12
  • Journal article (peer-reviewed)abstract
    • Importance Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.
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