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Background Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors. Methods We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients’ gut microbiomes. Results Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. Conclusion Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. Trial registration The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001351505). Trial protocol The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174.

This report highlights the importance for neonatologists/pediatricians of considering Marcus Gunn jaw‐winking syndrome among differential diagnoses of ptosis. A detailed clinical assessment is crucial to promptly recognize and appropriately manage it.

The clinical approach plays a pivotal role in neonates with evidence of a skull mass, together with the need of monitoring unclear cases. Indeed, apparently transient alterations of the skull may be neural tube defects, which need prompt treatment.

Congenital diaphragmatic hernia is a rare condition associated with pulmonary complications as the abdominal viscera herniated into the chest may affect lungs development. We present the case of a male newborn baby with a prenatal diagnosis of a posterolateral defect (Bochdalek hernia) involving the right side. The infant underwent surgical repair at 3 days of life, and the post-surgery chest X-ray did not reveal morpho-structural alterations of the lungs and diaphragmatic profile. Our clinical case shows that patients may have a better lung outcome despite an initial unfavorable picture. Prenatal diagnosis is essential in identifying infants with congenital diaphragmatic hernia, especially those cases at higher risk for the worse outcomes, to optimize their clinical and surgical management.

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

Background Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257). Methods Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events. Findings Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment. Interpretation Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome. Funding Health Research Council of New Zealand, A Better Start – National Science Challenge.

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

Background Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment has not yet been assessed in the context of multiple donors. Methods We conducted a double-blinded randomised control trial of FMT in 42 adolescents with obesity. Participants were randomised to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6-, 12-, and 26-weeks post-treatment were analysed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients’ gut microbiomes. Results Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterised by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardise FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. Conclusion Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harboured diverse microbial species and genes, and were characterised by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. Trial registration The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001351505)

BACKGROUND The first report of children born very preterm (

Metabolic diseases are increasing among adolescents with obesity. Although the reported prevalence of metabolic syndrome is approximately 30% worldwide, its prevalence is largely unknown among New Zealand adolescents. Therefore, we assessed the health of adolescents with obesity (BMI ≥ 30 kg/m2) enrolled in a randomised clinical trial (Gut Bugs Trial), to identify the prevalence of undiagnosed comorbidities. Assessments included anthropometry, 24-h ambulatory blood pressure monitoring, and insulin sensitivity. We report on baseline data (pre-randomisation) on 87 participants (14–18 years; 59% females), with mean BMI 36.9 ± 5.3 kg/m2 (BMI SDS 3.33 ± 0.79). Approximately 40% of participants had undiagnosed metabolic syndrome, which was twice as common among males. Half (53%) had pre-diabetes and 92% a reduction in insulin sensitivity. Moreover, 31% had pre-hypertension/hypertension, 69% dyslipidaemia, and 25% abnormal liver function. Participants with class III obesity had a greater risk of metabolic syndrome than those with classes I/II [relative risk 1.99 (95% CI 1.19, 3.34)]. Risks for pre-hypertension/hypertension and inflammation were also greater among those with class III obesity. We identified a high prevalence of undiagnosed comorbidities among adolescents with obesity in New Zealand. As adolescent obesity tracks into adulthood, early interventions are needed to prevent progression to overt cardiometabolic diseases.

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).

Key Points Question Will fecal microbiome transfer (FMT) lead to weight loss among adolescents with obesity? Findings In this randomized clinical trial of 87 adolescents with obesity, FMT alone did not lead to weight loss at 6 weeks. FMT alone was associated with a reduction in android-to-gynoid-fat ratio sustained for at least 26 weeks, particularly in female adolescents; changes in the overall gut microbiome composition; and a resolution of metabolic syndrome by 26 weeks in participants who had this undiagnosed condition at baseline. Meaning FMT alone is not an effective treatment for weight loss but may reduce visceral adiposity and improve health., This randomized, double-masked, placebo-controlled clinical trial of 87 adolescents assesses the effect of fecal microbiome transfer on weight loss. Follow-up examination was conducted for the primary outcome at 6 weeks with intention-to-treat analyses, and was measured by body mass index standard deviation score., 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. Trial Registration Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505

We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring.Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques. Cord blood was collected at birth. Maternal and offspring body composition was assessed using DXA ~2 weeks after delivery.Nulliparous women had higher HbA1c in the third trimester of pregnancy than multiparous women (5.48% vs 5.29%; P=.002) and were more insulin-resistant based on the surrogate marker sex hormone-binding globulin (354 vs 408 nmol/L; P=.047). Nulliparous women also had higher levels of the inflammatory marker tumour necrosis factor-alpha (4.74 vs 3.62 pg/mL; P=.025). At birth, the offspring of nulliparous women were on average 340 g (P=.013) and 0.69 standard deviation scores (P=.026) lighter than those born of multiparous women. Cord blood data showed lower insulin-like growth factor-II (P=.026) and higher IGF binding protein-1 (P=.002) levels in the offspring of nulliparous women. In addition, a less favourable metabolic profile was observed in the offspring of nulliparous women, as indicated by higher triglyceride (P.001) and interleukin-6 (P=.039) concentrations.Infants born of nulliparous overweight and obese women appear to be exposed to a less favourable metabolic environment in utero, with evidence of subtle adverse metabolic outcomes at birth compared to infants of overweight/obese multiparous women.

Aim Perinatal factors seem to influence the onset of puberty, but there is limited information on the potential effect of large size at birth on pubertal growth. This study evaluated pubertal growth in children born large for gestational age (LGA) compared to children born appropriate for gestational age (AGA). Methods Longitudinal growth data collected from 70 children – 40 AGA and 30 LGA – were analysed. The ages at take-off, peak height velocity, final height and pubertal growth spurts were calculated using the Preece–Baines model I. Results Large for gestational age children showed an earlier age at take-off compared to AGA children (10.1 ± 1.2 versus 11.0 ± 1.4 years, p = 0.007), whereas the age at peak height velocity and at final height was similar. LGA children showed a longer growth spurt duration (2.5 ± 1 versus 1.5 ± 1.2 years, p < 0.001) and total pubertal duration (5.3 ± 1.2 versus 4.6 ± 1.2 years, p = 0.036) than AGA children. Results were similar when stratified by sex. Conclusion Being born LGA was associated with an earlier pubertal take-off and longer growth duration. These unique findings, due to the lack of studies on pubertal growth patterns in LGA children, might lead the way to novel research and a different approach to LGA children at the onset of pubertal growth.

IntroductionAnimal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents.Methods and analysisA two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m2] adolescents (males and females, aged 14–18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18–28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat.Ethics and disseminationEthics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences.Trial registration numberACTRN12615001351505; Pre-results.

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

PURPOSE: Obese adults with normal glucose tolerance (NGT) but with 1-hour post-load plasma glucose (1hPG) ≥ 155 mg/dl are at higher risk of developing type 2 diabetes (T2D) and cardiometabolic complications. Little information is available for the pediatric population, where recently, a lower cutoff, 132.5 mg/dl, has been suggested as being more sensitive to identify subjects at risk of T2D. Our aim was to assess whether obese Caucasian youth with 1hPG ≥ 132.5 mg/dl have worse insulin sensitivity and secretion and a worse cardiometabolic profile compared to obese youth with 1hPG < 132.5 mg/dl. METHODS: Medical records of 244 (43% male; age: 11.1 ± 2.7years) overweight/obese children and adolescents, who had undergone an oral glucose tolerance test (OGTT), were retrieved. Anthropometric and biochemical data were collected from the hard copy archive. Indexes of insulin resistance (HOMA-IR), insulin sensitivity (WBISI), and insulin secretion (Insulinogenic Index, Disposition Index) were calculated. RESULTS: Of the 244 records analyzed, 215 fulfilled criteria for NGT and had complete biochemical data. Among NGT patients, 42 (19.5%) showed 1hPG ≥ 132.5 mg/dL (high-NGT), while the remaining had 1hPG < 132.5 mg/dL (low-NGT). The high-NGT group showed a higher male prevalence (59.5 vs 37%), lower Disposition Index (0.54 [0.39-0.71] vs 0.79 [0.47-1.43]), and WBISI (0.24 [0.18-0.35] vs 0.33 [0.23-0.50]) than the low-NGT group. High-NGT subjects also showed a trend towards lower HDL-cholesterol and higher triglycerides/HDL-cholesterol ratio (2.13 [1.49-3.41] vs 1.66 [1.24-2.49]). CONCLUSIONS: In overweight/obese NGT Caucasian youth a 1hPG ≥ 132.5 mg/dL was able to identify those with impaired insulin sensitivity and secretion and a trend towards a worse cardio-metabolic profile, a group likely at risk for future T2D.

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. PubMed, Web of Science, and Google Scholar searches were performed using the key terms “obesity”, “overweight”, “children”, “adolescents”, and “New Zealand”. 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 Māori (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 Māori 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. 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.

Background To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. Methods A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: −0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). Results Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460–1.033) µg/mL; MPO: 136.6 (69.7–220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507–0.990) µg/mL; MPO: 139.5 (51.0–321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272–0.596) µg/mL MPO: 41.3 (39.7–106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p

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.

Hypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA). Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed. At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 μmol/l, p

Aims: To investigate whether short children born very preterm (Methods: We studied 26 prepubertal children (aged 7.0 ± 2.0 years) with short stature (height adjusted for parents' heights Results: At baseline, preterm children had lower IGF-binding protein 1 (IGFBP-1; -22%; p = 0.049) and IGFBP-3 (-24%; p = 0.013) concentrations than term children. Preterm children also had insulin concentrations that tended to be 39% higher (p = 0.059) than term peers. After stimulation, IGF-1 and IGFBP-3 concentrations increased similarly in term and preterm groups, while GH-binding protein (GHBP) concentrations decreased in both groups. Preterm children had higher GHBP (+50%; p = 0.049), insulin (+86%; p = 0.005), and leptin (+107%; p = 0.020) but lower IGFBP-1 (-47%; p = 0.006) concentrations than term children following rhGH stimulation. Conclusions: Preterm children who are short for genetic height potential show no evidence of GH resistance that would explain their short stature. However, there was indirect evidence of insulin resistance in the preterm children, as previously described in this group.

ObjectiveTo investigate whether there is an association of the triglyceride-to-HDL cholesterol (TG:HDL-C) ratio with cardiovascular risk factors and early signs of vascular damage in obese prepubertal children.Design and methodsIn 50 obese (27 boys, 7.8±1.4 years) and 37 normal-weight (20 boys; 7.3±1.5 years) prepubertal children, anthropometric measurements, oxidative stress markers (urinary isoprostanes (PGF2α (prostaglandin F2α)), soluble receptor for advanced glycation end-products (sRAGE)) and insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (WBISI)) were evaluated. Lipids profile was assessed and the TG:HDL-C ratio was calculated. In addition, high-resolution ultrasound was performed to assess carotid intima-media thickness (cIMT).ResultsObese children showed significantly higher values of the TG:HDL-C ratio (1.9±1.1 vs 1.2±0.6, P=0.002) compared with controls. After dividing the population in tertiles of the TG:HDL-C ratio (1.67), cIMT (P=0.0003), and HOMA-IR (P=0.0001) progressively increased from the lower to the upper tertile, whereas WBISI (P=0.0003) and sRAGE (P=0.05) progressively decreased. In a regression model, the TG:HDL ratio was significantly and positively associated with cIMT (r=0.493; P=0.0005). A cutoff point for TG:HDL-C ratio of 1.12 had 81% sensitivity and 49% specificity in the identification of children with cIMT values in the upper quartile (Area under the curve values from receiver operating characteristic curves=0.633±0.065, P=0.045).ConclusionThis study confirms the reliability of the TG:HDL-C ratio as a useful marker of cardiovascular risk. Interestingly, our results underline that the TG:HDL-C ratio is directly related with early signs of vascular damage already present in prepubertal children.

The Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima-media thickness (cIMT) in pre-pubertal hypercholesterolaemic children.We performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p0.05).The Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.

SummaryWhat is already known about this subject There is emerging evidence suggesting that childhood obesity may influence the timing/tempo of puberty and growth patterns. An earlier onset of puberty generally occurs in obese girls, whereas conflicting data are available for boys. Obese children tend to be taller during pre-puberty but lose this growth advantage during puberty. What this study adds Obese boys and girls present an earlier onset of puberty and completion of puberty, with a shorter duration of puberty compared to normal-weight peers. Obese children tend to have a similar adult height compared to normal-weight children. Background There is emerging evidence suggesting that childhood obesity may influence the timing of puberty and growth patterns. However, there are scant and controversial data in this field. Objective To assess whether puberty and physical growth vary in obese when compared to normal-weight children. Methods One hundred obese pre-pubertal children (44 boys; mean age (±SD): 9.01 ± 0.62 years; 56 girls; 8.70 ± 0.57 years) were compared to 55 normal-weight controls (27 boys; 9.17 ± 0.26 years; 28 girls; 8.71 ± 0.62 years). All study participants were followed prospectively with 6-monthly follow-up visits. At each study visit, height, weight, body mass index (BMI) and pubertal stage were assessed. Results Obese children entered puberty and achieved later stages of puberty earlier than controls (onset of puberty: boys: 11.66 ± 1.00 vs. 12.12 ± 0.91 years, P = 0.049; girls: 9.90 ± 0.78 vs. 10.32 ± 1.70, P = 0.016; late puberty: boys: 13.33 ± 0.71 vs. 14.47 ± 1.00 years, P

Key Points The microbiome has been implicated in the development of obesity. Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications. Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an “endocrine” organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.

We report the clinical and molecular investigations in a girl with 46,X,-X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype characterized by mental retardation and facial dysmorphisms in combination with short stature. The structure of the derivative X chromosome was studied using BAC array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene and the presence of the Yq11.1qter chromosome. It is common that females with Xp;Yq translocations present only short stature and are normal in every other aspect. Thus, this would be the first case in which a girl with Xp;Yq translocation presents an unusual phenotype with intermediate male clinical features with Xp;Yq translocations. The risk of developing gonadoblastoma in females with Y chromosome material is also discussed and, to this effect, different explanations related to this apparent variation are also presented.

Structural traumatic brain injury (TBI) can result in late-occurring health sequelae, consisting mainly of neuroendocrine dysfunctions. Studies have suggested that hypopituitarism is relatively common following TBI in childhood, but recent evidence suggests that the incidence appears to be frequently over-estimated. We recently showed that permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. This article is protected by copyright. All rights reserved. Language: en