The effects of incretin-based therapies on weight reduction and metabolic parameters in children with obesity: A systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that incretin-based therapies (IBTs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is) are effective and safe for treating pediatric obesity patients with or without type 2 diabetes. Therefore, we aimed to perform a systematic review and meta-analysis for updating current evidence. METHODS: We searched the PubMed, the Cochrane Library, and the EMBASE database for articles published until September 15, 2023, and limited to randomized control trials. The primary outcomes were changed from baseline in weight metrics and the cardiometabolic profile. A random effects model will be used, as high heterogeneity is expected. All analyses were performed using STATA 17.0. RESULTS: Fifteen trials with a total number of 1286 participants were included in our meta-analysis. Overall, the mean difference in weight change between the IBTs group and the control group was -2.89 kg (95% confidence interval, -5.12 to -0.65, p = 0.011). Additionally, IBTs significantly reduced the HbA1c level and fasting plasma glucose by 0.37% and 6.99 mg/dl, compared with control groups. IBTs showed a little increased risk of GI side effects and hypoglycemia events, but none of the severe hypoglycemia events were occurred in IBTs group. CONCLUSIONS: Our study results have proved that GLP-1 RAs are safe, acceptable, and effective in weight reduction and sugar control for children with obesity. In addition, DPP-4is seems to have no effect on glycemic control and weight loss in childhood obesity. Further research is needed to confirm these findings, especially in younger children.

Prenatal exposure to Per- and polyfluoroalkyl substances and adiposity measures of children at 4 and 6 years: A prospective birth cohort in China.

There is growing evidence that prenatal exposure to Per- and polyfluoroalkyl substances (PFAS) was associated with childhood obesity, but evidence on multiple adiposity measures including arm circumference (AC), and waist circumference (WC) among Chinese children is limited. We investigated the associations of prenatal exposure to PFAS with adiposity measures of children at 4 and 6 years of age in the Shanghai-Minhang Birth Cohort Study. A total of 573 mother-child pairs with maternal PFAS concentrations and at least one measurement of adiposity measures of children were included in the present study. Eleven PFAS were assessed in maternal fasting blood samples. Information on children's weight, height, AC, and WC was collected at follow-ups. Weight for age Z score (WAZ), body mass index for age Z score (BMIz), and children overweight were calculated based on the World Health Organization Child Growth Standards. Multivariate linear regression, Poisson regression with robust error variance, and Bayesian Kernel Machine Regression (BKMR) models were used to examine the associations of prenatal exposure to PFAS with children's adiposity measures. Eight PFAS with detection rates above 85 % were included in the analyses. In the multivariate linear regression models, maternal PFNA concentrations were associated with a greater AC (ß = 0.29, 95 % Confidence Interval (CI): 0.04-0.55) in 4-year-old children and with an increase in WAZ (ß = 0.26, 95 % CI: 0.06-0.46), BMIz (ß = 0.31, 95 % CI: 0.09-0.53), AC (ß = 0.49, 95 % CI: 0.08-0.90), and WC (ß = 1.47, 95 % CI: 0.41-2.52) in 6-year-old children. We also observed the associations of maternal concentrations of PFOS, PFNA, PFUdA, and PFTrDA with the increased risk of children overweight in 6-year-old children. BKMR models further supported the findings from multivariate linear regression and Poisson regression models, and identified PFNA as the most important contributor. Moreover, the associations described above were generally more pronounced in girls. In conclusion, prenatal exposure to PFAS was associated with an increased risk of children's adiposity with a sex-specific manner, and PFNA contributed most to the associations after controlling for the effect of co-exposure to other PFAS compounds, especially among girls at 6 years of age.

Urinary antibiotic levels and risk of overweight/obesity in preschool children: A biomonitoring-based study from eastern China.

There is limited evidence linking antibiotic exposure, particularly from contaminated food or drinking water, to childhood obesity. The study aimed to investigate the association between urinary antibiotic levels and overweight/obesity in preschool children. In the case-control study, 121 overweight/obese preschoolers and 242 controls (aged 3-6 years) from eastern China were enrolled in 2022 based on age, sex, and study site matching. Overweight/obesity was determined using body mass index (BMI) and weight for height (WFH) criteria derived from national data. A total of 50 antibiotics from 8 categories were analyzed using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). We identified major dietary patterns using principal component analysis (PCA) and examined the associations of antibiotic exposure with childhood overweight/obesity using multivariate logistic regression. Twenty-four individual antibiotics were detected in more than 10 % of the samples, and overall detection rates were up to 100 %. Overweight/obese children had a higher exposure to veterinary antibiotics (VAs) than normal weight children. PCA analysis showed that children who were overweight/obese had higher scores of "Aquatic products preferred dietary pattern" and "Cereals preferred dietary pattern" compared to children with normal weight. Multivariate logistic regression analyses indicated that exposure to elevated levels of deoxytetracycline (OR: 1.72; 95 %CI: 1.00-2.93) and quinolones (OR: 1.63; 95 %CI: 1.04-2.57) was significantly related to an increased risk of BMI-based overweight/obesity. Quinolones exposure was also significantly associated with WFH-based overweight/obesity, primarily in boys. After adjustment for all covariates, higher exposure to ofloxacin (of the quinolones) was significantly related to overweight/obesity in girls. Exposure to certain antibiotics, especially quinolones, may increase the risk of overweight/obesity in preschoolers. More prospective, well-designed studies are needed to clarify these findings.

Vitamin D Oral Replacement in Children With Obesity Related Asthma: VDORA1 Randomized Clinical Trial.

Children with asthma and obesity are more likely to have lower vitamin D levels, but the optimal replacement dose is unknown in this population. The objective of this study is identifying a vitamin D dose in children with obesity-related asthma that safely achieves serum vitamin D levels of ≥ 40 ng/mL. This prospective multisite randomized controlled trial recruited children/adolescents with asthma and body mass index ≥ 85% for age/sex. Part 1 (dose finding), evaluated 4 oral vitamin D regimens for 16 weeks to identify a replacement dose that achieved serum vitamin D levels ≥ 40 ng/mL. Part 2 compared the replacement dose calculated from part 1 (50,000 IU loading dose with 8,000 IU daily) to standard of care (SOC) for 16 weeks to identify the proportion of children achieving target serum 25(OH)D level. Part 1 included 48 randomized participants. Part 2 included 64 participants. In Part 1, no SOC participants achieved target serum level, but 50-72.7% of participants in cohorts A-C achieved the target serum level. In part 2, 78.6% of replacement dose participants achieved target serum level compared with none in the SOC arm. No related serious adverse events were reported. This trial confirmed a 50,000 IU loading dose plus 8,000 IU daily oral vitamin D as safe and effective in increasing serum 25(OH)D levels in children/adolescents with overweight/obesity to levels ≥ 40 ng/mL. Given the critical role of vitamin D in many conditions complicating childhood obesity, these data close a critical gap in our understanding of vitamin D dosing in children.

Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study.

BACKGROUND/OBJECTIVES: Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood. SUBJECTS: 373 eligible mother-infant pairs in the Healthy Start longitudinal cohort. METHODS: We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated. RESULTS: The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS. CONCLUSIONS: Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

Bisphenol A substitutes and childhood obesity at 7 years: a cross-sectional study in Shandong, China.

Bisphenol A (BPA) substitutes, such as bisphenol S (BPS) and bisphenol AF (BPAF), are increasingly used due to restrictions on BPA usage, a known endocrine disrupting chemical and putative obesogen. However, little is known about the obesogenic effects of exposure to BPA substitutes in children. A total of 426 children aged 7 years old originally recruited from Laizhou Wan Birth Cohort in Shandong, China, during 2010-2013 participated in the 2019-2020 survey. Urinary BPA and its substitutes including BPS, BPAF, bisphenol B (BPB), bisphenol AP (BPAP), bisphenol Z (BPZ), and bisphenol P (BPP) were determined. Anthropometric measures including height, weight, waist circumference, and body fat percentage were assessed, and overweight/obesity was defined as BMI z-score ≥ 85th percentile. Linear and logistic regressions were used on continuous and binary obesity measures, respectively, and weighted quantile sum (WQS) regression was further used to estimate the mixture effects of exposure to diverse bisphenols, and sex-stratified analysis was performed. BPA substitutes were widely detected (> 75%) in children's urine samples. A positive association with obesity measures was consistently observed for urinary BPS and BPAF, i.e., BMI z-score, waist circumference, and overweight/obesity. Further analysis from the WQS regression model demonstrated a positive association between bisphenol mixtures and all measures of obesity, with BPAF contributing the greatest weighing to the observed associations. Sex difference might exist as the positive associations were only significant in boys. No significant association was found between obesity and BPA or other BPA substitutes. Our study adds to mounting evidence that BPA substitutes BPS and BPAF are linked to obesity in children, especially in boys. Further longitudinal studies with larger sample size with continued biomonitoring these chemicals and their obesogenic effects are necessary.

Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. OBJECTIVES: The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity. METHODS: We used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (n=660), and b) OCs, PUFAs, and vitamins (n=558). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale. RESULTS: Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, pInteraction=0.02) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and ß-cryptoxanthin suggested a protective effect of the antioxidant on overweight/obesity risk. CONCLUSION: These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.

Inherited Epigenetic Hallmarks of Childhood Obesity Derived from Prenatal Exposure to Obesogens.

Childhood obesity has reached epidemic levels in developed countries and is becoming a major cause for concern in the developing world. The causes of childhood obesity are complex and multifactorial, involving the interaction between individual genetics and environmental and developmental factors. Among the environmental factors, there is a growing interest in understanding the possible relationship between the so-called environmental obesogens and the development of obesity in children. Exposure to these obesogens such as phthalates, bisphenol A, or parabens, has been identified as a promoter of obesity through different mechanisms such as the alteration of adipocyte development from mesenchymal progenitors, the interference with hormone receptors, and induced inflammation. However, less attention has been paid to the inheritance of epigenetic modifications due to maternal exposure to these compounds during pregnancy. Thus, the aim of this review is to summarize the current knowledge of epigenetic modifications due to maternal exposure to those obesogens during pregnancy as well as their potential implication on long-term obesity development in the offspring and transgenerational inheritance of epiphenotypes.

The mediating function of obesity on endocrine-disrupting chemicals and insulin resistance in children.

OBJECTIVES: To explore the association of endocrine-disrupting chemicals (EDCs) with insulin resistance (IR) in children as well as whether obesity played a mediation role between EDCs and IR. METHODS: In this cross-sectional study, the data of 878 subjects were included, and divided into the non-IR group (n=501) and IR group (n=377). The associations of EDC and IR, obesity, abdominal obesity were shown by restricted cubic spline (RCS). Univariate and multivariable logistic analysis were applied to explore the associations between EDCs and IR as well as EDCs and obesity, respectively. Bootstrap coefficient product was used to analyze the medication effect of obesity on EDCs and IR. RESULTS: RCS showed that increase of benzophenone-3 (BP-3) level was associated with increased risk of IR, obesity and abdominal obesity. After adjusting for confounders, BP-3>100 ng/mL was a risk factor for IR (OR=1.42, 95%CI: 1.11-1.81). In the adjusted model, we found BP-3>100 ng/mL was a risk factor for both obesity (OR=1.52, 95%CI: 1.13-2.04) and abdominal obesity (OR=1.68, 95%CI: 1.11-2.54). The indirect effect of obesity as a mediator on the relationship between BP-3 and IR was 0.038 (95%CI: 0.016-0.090) and the direct effect of obesity as a mediator on the relationship between BP-3 and IR was 0.077 (95%CI: 0.001-0.160). As for abdominal obesity, the indirect effect of it on the relationship between BP-3 and IR was 0.039 (95%CI: 0.007-0.070). CONCLUSIONS: BP-3 level might be a risk factor for IR and obesity in children, and obesity was a mediator on the relationship between BP-3 and IR in children.

Association between maternal antibiotic exposure during pregnancy and childhood obesity in the Japan Environment and Children's Study.

BACKGROUND: The association between maternal antibiotic exposure during pregnancy and childhood obesity is still unclear. OBJECTIVES: The study aimed to evaluate the association between prenatal exposure to antibiotics and obesity at age 3 years using data from a large Japanese birth cohort. METHODS: The Japan Environment and Children's Study is a nationwide birth cohort study. In this study, singleton vaginal full-term births were included. Obesity was defined as body mass index ≥95th percentile according to child growth standards. Prenatal antibiotic exposure was defined as antimicrobial agent use during pregnancy and was collected from maternal interviews and medical record transcripts. Logistic regression analysis was performed to evaluate the association of prenatal antibiotic exposure with child obesity at 3 years. RESULTS: In the crude and adjusted models with all children, maternal antibiotic exposure during pregnancy showed a marginal relationship with child obesity at 3 years. In the analyses according to exposure period and sex, exposure to antibiotics during the second/third trimester was significantly associated with obesity at the age of 3 years in female infants, but not in male infants, although the exposure during the first trimester was not in both sexes. CONCLUSION: Maternal antibiotic exposure during mid/late pregnancy may result in child obesity.

Antibiotic exposure and risk of overweight/obesity in school children: A multicenter, case-control study from China.

BACKGROUND: Although the use of antibiotics during early life has been associated with increased risk of adipogenesis, effect of antibiotic exposure from various sources, including food or drinking water, on adiposity in children is largely unknown. OBJECTIVE: To investigate associations between urinary biomarkers of multiple antibiotics and risk of adipogenesis in school children. METHODS: This case-control study recruited 410 overweight/obese school children aged 6-9 years and 410 controls from Shandong and Guangdong Province, China, matched on sex, age and school. Diagnosis of overweight and obesity was based on body mass index-based criteria derived from national data. Urinary concentrations of 45 antibiotics from 8 categories (macrolides, ß-lactams, tetracyclines, fluoroquinolones, sulfonamides, phenicols, lincosamides, and quinoxalines), including 6 human antibiotics (HAs), 6 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 17 antibiotics preferred as VA (PVAs), were measured by ultra-performance liquid chromatography coupled to triple-quadrupole tandem mass spectrometry. Conditional logistic regression analyses were used to assess odds ratios (ORs) of childhood overweight/obesity in relation to urinary antibiotic concentrations. RESULTS: A total of 32 antibiotics were found in urine samples with an overall detection frequency of 92.93 %. Children with overweight/obesity have higher veterinary antibiotic levels than those with normal weight. Compared with undetected levels of antibiotics, the multivariable-adjusted ORs (95 % confidence interval) of overweight/obesity for high levels of antibiotics divided according to median values were 1.63 (1.02, 2.62) for florfenicol, 1.62 (1.04, 2.54) for phenicols, and 1.41 (0.97, 2.04) for sum of VAs and PVAs. These associations predominantly existed in boys and remained significant in florfenicol after FDR multiple testing correction (FDR adjusted p < 0.05). CONCLUSION: Exposure to certain antibiotic for veterinary use mainly from food or drinking water was associated with an increased risk of adipogenesis in children. Further studies are needed to confirm our findings and clarify the underlying mechanisms.

Association between triclosan exposure and obesity measures among 7-year-old children in northern China.

BACKGROUND: Triclosan (TCS) is a widely used synthetic antibacterial compound with ubiquitous human exposure. Animal studies have suggested the obesogenic effect of TCS exposure, but knowledge regarding its impacts on childhood obesity was limited. OBJECTIVE: To investigate the associations of TCS exposure with childhood obesity in northern China. METHODS: This study included 423 children who participated in the 7-year-old follow-up visits of Laizhou Wan Birth Cohort in Shandong, northern China. Children's TCS exposure were determined in spot urine samples via high performance liquid chromatography-tandem mass. Their height, weight, waist circumference, body fat percentage, body mass index (BMI), and waist-to-height ratio (WHtR) were measured or calculated. BMI z-score ≥ 85th percentile was defined as overweight/obesity, and WHtR ≥ 0.5 was considered to be abdominal obesity. Multivariable linear regressions, generalized linear models (GLMs), and multivariable logistic regressions were performed to examine the associations between TCS exposure and obesity measures in children. RESULTS: Linear regressions showed that TCS concentrations, when treated as continuous variables, were positively associated with BMI z-score (ß = 0.12, 95% CI: 0.01, 0.24) and body fat percentage (ß = 0.82, 95% CI: 0.13, 1.52). When TCS concentrations were categorized as a four-level ordinal variable, the results of GLMs were similar those of continuous variables and both of the positive trends were significant (p-trend = 0.049 for BMI z-score; p-trend = 0.023 for body fat percentage). Moreover, the higher TCS levels versus reference group were associated with an approximate 2-3 fold increased risk of abdominal obesity (p-trend = 0.044). CONCLUSION: Exposure to TCS was positively associated with obesity measures among 7-year-old children in northern, China. Given to the cross-sectional study design, a large prospective study is warranted to confirm our findings.

The triponderal mass index as a measure of adiposity in pediatric survivors of acute lymphoblastic leukemia: a cross-sectional study.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Treatments of ALL predispose survivors to obesity, which increases the risk of cardiovascular disease and diabetes. The hallmark of obesity is excess fat mass, and adiposity is a superior predictor of cardiometabolic risk when compared to Body Mass Index (BMI), yet clinical measures of adiposity in children are lacking. The Tri-Ponderal Mass Index (TMI) (kg/m3) is a more accurate adiposity measure compared to BMI z-score in the general pediatric population. This cross-sectional study aimed to validate TMI as an adiposity measure against DEXA scan-derived adiposity, and to compare it to BMI z-score, in pediatric ALL survivors. This study was a retrospective chart review of pediatric ALL survivors diagnosed between 2004 and 2015 at McMaster Children's Hospital, a tertiary pediatric center in Ontario, Canada. One hundred and thirteen patients (Female n = 55, 48.70%) were included, and adiposity was measured using DEXA scans. Exploratory partial correlations and linear regression analyses were adjusted for age, sex, ethnicity, and ALL risk status. Both TMI and BMI z-score correlated with the DEXA-measured fat mass percentage (FM%) (partial correlation TMI versus FM% r = 0.56; p value < 0.0001; BMI z-score versus FM% r = 0.55; p value < 0.0001). In regression analyses, the association of TMI was not inferior to BMI z-score in assessing adiposity (TMI versus FM% estimated unstandardized B 0.80, 95% CI 0.56, 1.02; p value < 0.0001; BMI z-score versus FM% (unstandardized B 0.37, 95% CI 0.26, 0.49; p value < 0.0001). The TMI is a useful clinical adiposity-specific measure in survivors of pediatric ALL.

Prenatal exposure to antibiotics and risk of childhood overweight or obesity: A systematic review and meta-analysis.

Infant antibiotic use has been modestly associated with childhood overweight, while evidence on prenatal exposures remains less clear. A systematic review and meta-analysis were conducted to examine associations between maternal antibiotic exposure and subsequent risk of childhood overweight/obesity. Publications were retrieved from PubMed and Web of Science databases up to December 2019. A random effects model was used to summarize risk estimates, overall, and by period and frequency of exposure. Ten observational studies were included in the narrative synthesis. We did not observe a clear pattern of association between prenatal antibiotic use and childhood overweight/obesity. There were suggestive associations for repeated exposures (≥3 courses) and those taking place during the second trimester of gestation, which were also pointed out in our meta-analysis (relative risk, RR2T = 1.15 (95% CI 1.04; 1.28, I2  = 18%), and RR3courses = 1.31 (95% CI 1.03; 1.67, I2  = 65%), respectively). In most studies, however, confounding by underlying infections cannot be ruled out. Overall, current data do not conclusively support the hypothesis that prenatal exposure to antibiotics is a risk factor for childhood obesity/overweight. Further studies, controlling for underlying infections and exploring the association according to frequency, period (both prenatal and intrapartum) and type of antibiotic, are needed to clarify this association.

Birth with synthetic oxytocin and the risk of being overweight or obese during childhood.

BACKGROUND: Despite the importance of oxytocinergic signalling for satiety regulation and energy balance, the impact of exposure to synthetic oxytocin during childbirth on obesity during childhood remains unknown. OBJECTIVES: To examine the association between oxytocin exposure during labour and the risk of being overweight or obese during childhood. METHODS: Synthetic oxytocin exposure data of mothers from the Danish Medical Birth Registry were linked with self-reported anthropometric data of their children from the Danish National Birth Cohort (5 months-11 years of age). Multinomial logistic regression and latent class growth analyses were performed to determine the association between oxytocin exposure and obesity during childhood. RESULTS: With the exception of the normal weight-to-overweight group between ages 5 and 12 months, none of the other analyses revealed a significant association between synthetic oxytocin use and the risk of being overweight until the age of 11 years. Furthermore, latent class growth analysis did not reveal an association between oxytocin exposure at birth and the risk of being overweight or obese during childhood. CONCLUSIONS: Our analysis of a large cohort of children who varied in their synthetic oxytocin exposure status at childbirth did not reveal an association between oxytocin exposure and the risk of childhood overweight/obesity.

Prenatal and infant antibiotic exposure and childhood growth, obesity and cardiovascular risk factors: The Rhea mother-child cohort study, Crete, Greece.

BACKGROUND: Early-life antibiotic use has been hypothesized to promote weight gain and increase the risk of childhood obesity. OBJECTIVES: To examine the associations of prenatal and infant antibiotics with childhood growth, adiposity and cardiometabolic traits in the Greek Rhea cohort. METHODS: We used data from 747 mother-child pairs with anthropometric measurements drawn from medical records or measured at 4 and 6 years of age. Antibiotic exposure was assessed by maternal report during pregnancy and at the first year of life. Children were classified as exposed to antibiotics prenatally if the mother received at least one course of oral antibiotics during pregnancy and postnatally if the mother reported that the child received at least one oral antibiotic treatment during the first year of life. Outcomes included repeated weight, body mass index (BMI), waist circumference, body fat (%), total cholesterol and blood pressure. We applied mixed effects, linear and log-binomial regression models after adjusting for important covariates. RESULTS: Around 14.6% of the participating children were prenatally exposed to antibiotics and 32.4% received antibiotics during the first year of life. Prenatal exposure to antibiotics was associated with a twofold increase in the risk for obesity (risk ratio [RR]; 95% confidence interval [CI]: 2.09 [1.58, 2.76]) and abdominal obesity (RR [95% CI]: 2.56 [1.89, 3.47]) at 6 years. Postnatal exposure to antibiotics was associated with increased weight (beta [95% CI]: 00.25 [0.06, 0.44]) and BMI (beta [95% CI]: 0.23 [0.003, 0.45]) SD scores from 2 to 7 years of life. CONCLUSION: Early-life antibiotic use was associated with accelerated childhood growth and higher adiposity.

Metformin for pregnancy and beyond: the pros and cons.

CONTEXT AND AIM: Metformin has been used in pregnancy since the 1970s. It is cheap, widely available and is acceptable to women. Despite its increasing use, controversy remains surrounding its benefits and risks. Metformin effectively reduces hyperglycaemia for the mother during pregnancy and it reduces rates of macrosomia and neonatal hypoglycaemia. However, concern exists surrounding an increase in the rate of SGA births and obesity in childhood. We aim to review the evidence and expert opinion behind metformin in pregnancy through to the post-partum period. METHODS: We performed a literature review of relevant studies from online databases using a combination of keywords. We also searched the references of retrieved articles for pertinent studies. RESULTS: There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations. If used throughout pregnancy, it is likely to lead to reduced maternal weight gain and reduced insulin dose in women with type 2 diabetes. In infants, metformin reduces hypoglycaemia and macrosomia but may increase the rate of infants born SGA. There is some evidence of an increased risk of obesity and altered fat distribution in offspring. Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy. CONCLUSION: Due to increasing rates of maternal obesity, GDM and type 2 diabetes, metformin use in pregnancy is increasing. Overall, it appears safe and effective but further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies.

Dose-response association of early-life antibiotic exposure and subsequent overweight or obesity in children: A meta-analysis of prospective studies.

The objective of this study is to investigate the dose-response relationship between antibiotic exposure in early life and the risk of subsequent overweight or obesity. Electronic databases were searched from inception to December 2020. Prospective studies that reported the odds ratios (ORs) of childhood overweight or obesity for three or more quantitative categories of antibiotic exposure were identified. A random-effect model was used to pool the ORs and 95% confidence intervals (CIs). Generalized least squares and restricted cubic splines were used to explore the dose-response association. A total of 12 sets of results from 10 articles involving 427,453 participants were included in this meta-analysis. The pooled OR for increased risk of overweight or obesity was 1.30 in high-level antibiotic exposure (95% CI: 1.20 to 1.41) and 1.06 in low-level antibiotic exposure (95% CI: 1.02 to 1.10), as compared with children who never exposed to antibiotics. There was a logarithmic-curve relationship between early-life antibiotic exposure and the risk of subsequent overweight or obesity. The OR was 1.08 (95% CI: 1.06 to 1.11) for one prescription, 1.16 (95% CI 1.11 to 1.21) for two prescriptions, 1.24 (95% CI: 1.16 to 1.32) for three prescriptions, 1.30 (95% CI: 1.20 to 1.41) for four prescriptions, and less than a 5% increase for more prescriptions. Early-life antibiotic exposure is associated with the risk of childhood overweight or obesity in a dose-response manner. Further studies are needed to confirm our results.

Sugar-Sweetened Beverage Consumption Status and Its Association with Childhood Obesity among Chinese Children Aged 6-17 Years.

OBJECTIVE: There is a remarkable growth in sugar-sweetened (SSB) production and obesity prevalence among school-aged children in China. This paper describes SSB consumption and its association with obesity among Chinese children aged 6-17 years in 2012. METHODS: in total, 25,553 children aged 6~17 years enrolled in the China Nutrition and Health Surveillance 2010-2013 were included in this study. Data of SSB consumption frequency and quantity were obtained from a food frequency questionnaire, and the children's nutritional status was assessed. Multivariate logistic regression was used to evaluate the association between SSB consumption and obesity status. RESULTS: SSB intake was estimated as 181.0 g/day, occurring 2.2 times/week. Older children, males, children from urban areas, and children with higher socioeconomic status were more likely to consume SSBs. Children who consumed SSBs 1~<5 times/week (11.7%) and >5 times/week (12.9%) were more likely to be overweight/obesity than those who consumed SSBs less than once/week. CONCLUSION: SSB consumption was common among Chinese school-aged children, especially among males, older children, and children from urban areas. High consumption of SSBs was associated with a higher prevalence of overweight/obesity. Actions and plans are required to reduce SSB consumption and control childhood obesity in China.

Associations between Inhaled Corticosteroid Use in the First 6 Years of Life and Obesity-related Traits.

Rationale: Infants and young children might be particularly likely to experience the potential clinical side effects of inhaled corticosteroids (ICSs) on body mass index (BMI), adiposity rebound (AR), and body composition, but this has rarely been studied in long-term studies in this age group. Objectives: To determine the association between ICS exposure in the first 6 years of life and the BMI, AR, body composition, and blood lipid concentrations. Methods: Children from the two mother-child cohorts of the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) were included. ICS use was registered prospectively to age 6 years, and the cumulative dose was calculated. Multiple linear regression models were used for analysis. Measurements and Main Results: A total of 932 (84%) of the 1,111 children from the COPSAC cohorts had BMI data, 786 (71%) had dual-energy X-ray absorptiometry scan data at the age of 6 years, and 815 (73%) had an AR age calculated. Two hundred ninety-one children (31%) received a cumulative ICS dose higher than that from 10 weeks of standard treatment before the age of 6. ICS treatment during 0-6 years of age was associated with an increased BMI z-score (0.05 [95% confidence interval, 0.005 to 0.09] SDs per each year of standard treatment; P = 0.03) an earlier age at AR (-0.18 [95% confidence interval, -0.28 to -0.08] yr; P = 0.0006), and a 2% increased geometric mean android fat percentage (P = 0.05). ICS exposure and dual-energy X-ray absorptiometry scan data were not associated. Conclusions: ICS use in early childhood was associated with an increased BMI z-score at age 6, an earlier AR, and a trend of association with an increased android body fat percentage.