Increased innate immune responses in adolescents with obesity and its relation to subclinical cardiovascular measures: An exploratory study.

Cardiometabolic risk accrues across the life course and childhood and adolescence are key periods for effective prevention. Obesity is associated with inflammation in adults, but pediatric data are scarce. In a cross-sectional and longitudinal study, we investigated immune cell composition and activation in 31 adolescents with obesity (41.9% male, BMIz>2.5, 14.4 years) and 22 controls with healthy weight (45.1% male, -1.5

Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children.

BACKGROUND: Severe childhood infection has a dose-dependent association with adult cardiovascular events and with adverse cardiometabolic phenotypes. The relationship between cardiovascular outcomes and less severe childhood infections is unclear. AIM: To investigate the relationship between common, non-hospitalised infections, antibiotic exposure, and preclinical vascular phenotypes in young children. DESIGN: A Dutch prospective population-derived birth cohort study. METHODS: Participants were from the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort. We collected data from birth to 5 years on antibiotic prescriptions, general practitioner (GP)-diagnosed infections, and monthly parent-reported febrile illnesses (0-1 years). At 5 years, carotid intima-media thickness (CIMT), carotid artery distensibility, and blood pressure (BP) were measured. General linear regression models were adjusted for age, sex, smoke exposure, birth weight z-score, body mass index, and socioeconomic status. RESULTS: Recent antibiotic exposure was associated with adverse cardiovascular phenotypes; each antibiotic prescription in the 3 and 6 months prior to vascular assessment was associated with an 18.1 µm (95% confidence interval, 4.5-31.6, p = 0.01) and 10.7 µm (0.8-20.5, p = 0.03) increase in CIMT, respectively. Each additional antibiotic prescription in the preceding 6 months was associated with an 8.3 mPa-1 decrease in carotid distensibility (-15.6- -1.1, p = 0.02). Any parent-reported febrile episode (compared to none) showed weak evidence of association with diastolic BP (1.6 mmHg increase, 0.04-3.1, p = 0.04). GP-diagnosed infections were not associated with vascular phenotypes. CONCLUSIONS: Recent antibiotics are associated with adverse vascular phenotypes in early childhood. Mechanistic studies may differentiate antibiotic-related from infection-related effects and inform preventative strategies.

The potential of intervening on childhood adversity to reduce socioeconomic inequities in body mass index and inflammation among Australian and UK children: A causal mediation analysis.

BACKGROUND: Lower maternal education is associated with higher body mass index (BMI) and higher chronic inflammation in offspring. Childhood adversity potentially mediates these associations. We examined the extent to which addressing childhood adversity could reduce socioeconomic inequities in these outcomes. METHODS: We analysed data from two early-life longitudinal cohorts: the Longitudinal Study of Australian Children (LSAC; n=1873) and the UK Avon Longitudinal Study of Parents and Children (ALSPAC; n=7085). EXPOSURE: low/medium (below university degree) versus high maternal education, as a key indicator of family socioeconomic position (0-1 year). OUTCOMES: BMI and log-transformed glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Mediator: multiple adversities (≥2/<2) indicated by family violence, mental illness, substance abuse and harsh parenting (LSAC: 2-11 years; ALSPAC: 1-12 years). A causal mediation analysis was conducted. RESULTS: Low/medium maternal education was associated with up to 1.03 kg/m2 higher BMI (95% CI: 0.95 to 1.10) and up to 1.69% higher GlycA (95% CI: 1.68 to 1.71) compared with high maternal education, adjusting for confounders. Causal mediation analysis estimated that decreasing the levels of multiple adversities in children with low/medium maternal education to be like their high maternal education peers could reduce BMI inequalities by up to 1.8% and up to 3.3% in GlycA. CONCLUSIONS: Our findings in both cohorts suggest that slight reductions in socioeconomic inequities in children's BMI and inflammation could be achieved by addressing childhood adversities. Public health and social policy efforts should help those affected by childhood adversity, but also consider underlying socioeconomic conditions that drive health inequities.

Change in adiposity is associated with change in glycoprotein acetyls but not hsCRP in adolescents with severe obesity.

BACKGROUND: Obesity-associated chronic inflammation mediates the development of adverse cardiometabolic outcomes. There are sparse data on associations between severe obesity and inflammatory biomarkers in adolescence; most are cross-sectional and limited to acute phase reactants. Here, we investigate associations between adiposity measures and inflammatory biomarkers in children and adolescents with severe obesity both cross-sectionally and longitudinally. METHODS: From the Childhood Overweight Biorepository of Australia (COBRA) study, a total of n = 262 participants, mean age 11.5 years (SD 3.5) with obesity had measures of adiposity (body mass index, BMI; % above the 95th BMI-centile, %>95th BMI-centile; waist circumference, WC; waist/height ratio, WtH; % total body fat, %BF; % truncal body fat, %TF) and inflammation biomarkers (glycoprotein acetyls, GlycA; high-sensitivity C-Reactive Protein, hsCRP; white blood cell count, WBC; and neutrophil/lymphocyte ratio, NLR) assessed at baseline. Ninety-eight individuals at mean age of 15.9 years (3.7) participated in a follow-up study 5.6 (2.1) years later. Sixty-two individuals had longitudinal data. Linear regression models, adjusted for age and sex for cross-sectional analyses were applied. To estimate longitudinal associations between change in adiposity measures with inflammation biomarkers, models were adjusted for baseline measures of adiposity and inflammation. RESULTS: All adiposity measures were cross-sectionally associated with GlycA, hsCRP and WBC at both time points. Change in BMI, %>95th BMI-centile, WC, WtH and %TF were associated with concomitant change in GlycA and WBC, but not in hsCRP and NLR. CONCLUSION: GlycA and WBC but not hsCRP and NLR may be useful in assessing adiposity-related severity of chronic inflammation over time.

Antibiotic Exposure and Dental Health: A Systematic Review.

CONTEXT: The use of antibiotics in young children is widespread and may lead to adverse effects on dental health, including staining, developmental defects, and dental caries. OBJECTIVE: To systematically review the effects of early childhood antibiotic exposure on dental health. DATA SOURCES: Medline (Ovid/PubMed), Embase (Ovid) and Cochrane databases. Study bias was assessed using the Newcastle-Ottawa Scale. STUDY SELECTION: English language articles that reported antibiotic exposure before 8 years of age and 1 or more of the relevant outcomes (dental caries, intrinsic tooth staining, or developmental defects of enamel) were included. DATA EXTRACTION: Data on study population, design, type of antibiotic, outcome measurement, and results were extracted from the identified studies. RESULTS: The initial search yielded 1003 articles of which 34 studies were included. Five of the 18 studies on tetracycline described a dose response relationship between exposure to tetracycline doses of > 20 mg/kg per day and dental staining. Early childhood exposure to doxycycline (at any dose) was not associated with dental staining. There was no clear association between any early childhood antibiotic exposure and dental caries or enamel defects. LIMITATIONS: In all included studies, the main limitations and sources of bias were the lack of comparison groups, inconsistent outcome measures, and lack of adjustment for relevant confounders. CONCLUSIONS: There was no evidence that newer tetracycline formulations (doxycycline and minocycline) at currently recommended dosages led to adverse effects on dental health. Findings regarding antibiotic exposure and developmental defects of enamel or dental caries were inconsistent. Further prospective studies are warranted.

Evidence for protein leverage in a general population sample of children and adolescents.

BACKGROUND/OBJECTIVES: The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents. SUBJECTS/METHODS: A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study. EXPOSURES: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates. OUTCOMES: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure. RESULTS: Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = -0.36 [-0.47 to -0.25]; L = -0.26 [-0.37 to -0.15]; L = -0.25 [-0.38 to -0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001). CONCLUSIONS: This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity.

Comparison of antibody responses to SARS-CoV-2 variants in Australian children.

There is limited understanding of antibody responses in children across different SARS-CoV-2 variants. As part of an ongoing household cohort study, we assessed the antibody response among unvaccinated children infected with Wuhan, Delta, or Omicron variants, as well as vaccinated children with breakthrough Omicron infection, using a SARS-CoV-2 S1-specific IgG assay and surrogate virus neutralization test (% inhibition). Most children infected with Delta (100%, 35/35) or Omicron (81.3%, 13/16) variants seroconverted by one month following infection. In contrast, 37.5% (21/56) children infected with Wuhan seroconverted, as previously reported. However, Omicron-infected children (geometric mean concentration 46.4 binding antibody units/ml; % inhibition = 16.3%) mounted a significantly lower antibody response than Delta (435.5 binding antibody untis/mL, % inhibition = 76.9%) or Wuhan (359.0 binding antibody units/mL, % inhibition = 74.0%). Vaccinated children with breakthrough Omicron infection mounted the highest antibody response (2856 binding antibody units/mL, % inhibition = 96.5%). Our findings suggest that despite a high seropositivity rate, Omicron infection in children results in lower antibody levels and function compared with Wuhan or Delta infection or with vaccinated children with breakthrough Omicron infection. Our data have important implications for public health measures and vaccination strategies to protect children.

Use of antibiotics and risk of type 2 diabetes, overweight and obesity: the Cardiovascular Risk in Young Finns Study and the national FINRISK study.

PURPOSE: To investigate whether exposure to systemic antibiotics influences the risk of developing type 2 diabetes and overweight/obesity. METHODS: The study sample comprised 2209 (110 with incident diabetes) participants from the population-based Cardiovascular Risk in Young Finns Study (YFS) aged 24-39 years in 2001. The exposure was national linked register data on purchased antibiotic courses between 1993 and 2001. Clinical examinations including BMI were conducted in 2001, 2007 and 2011. Participants with prevalent diabetes in 2001 were excluded. Data on type 2 diabetes was also obtained from two national registers until 2017. Data from four population-based National FINRISK studies were used for replication (N = 24,674, 1866 with incident diabetes). RESULTS: Prior antibiotic exposure (> 5 versus 0-1 antibiotic courses) was associated with subsequent type 2 diabetes in both YFS (OR 2.29; 95%CI 1.33-3.96) and FINRISK (HR 1.73; 95%CI 1.51-1.99). An increased risk for type 2 diabetes was observed in YFS (OR 1.043; 95%CI 1.013-1.074) and FINRISK (HR 1.022; 95%CI 1.016-1.029) per course. Exposure to antibiotics increased the risk of overweight/obesity (BMI > 25 kg/m2) after a 10-year follow-up in YFS (OR 1.043; 95%CI 1.019-1.068) and in FINRISK (OR 1.023; 95%CI 1.018-1.029) at baseline per antibiotic course. Adjustments for confounders from early life in YFS and at baseline in FINRISK, including BMI, socioeconomic status, smoking, insulin, blood pressure, and physical activity, did not appreciably alter the findings. CONCLUSION: Our results show that exposure to antibiotics was associated with increased risk for future type 2 diabetes and overweight/obesity and support judicious antibiotic prescribing.

Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in ApoE-/- Mice.

Bacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dosing schedule, and route of administration. We aimed to elucidate the effect of neonatal subcutaneous BCG vaccination­analogous to human BCG vaccination­on atherosclerosis development in ApoE−/− mice. At 2 days of age, a total of 40 ApoE−/− mice received either a weight-equivalent human dose of BCG, or saline, subcutaneously. From 4 weeks onwards, the mice were fed a Western-type diet containing 22% fat. At 16 weeks of age, mice were sacrificed for the assessment of atherosclerosis. Body weight, plasma lipids, atherosclerosis lesion size and collagen content were similar in both groups. Atherosclerosis lesion number was lower in mice that received BCG. Macrophage content was 20% lower in the BCG-vaccinated mice (p < 0.05), whereas plaque lipid content was increased by 25% (p < 0.01). In conclusion, neonatal BCG vaccination reduces atherosclerosis plaque number and macrophage content but increases lipid content in a murine model of atherosclerosis. Human epidemiological and mechanistic studies are warranted to investigate whether neonatal BCG vaccination is potentially atheroprotective.

Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: The relationship between childhood tobacco smoke exposure and cardiac structure and function in midlife is unclear. We investigated the association between parental smoking with cardiac structure and function in adulthood. METHODS: 1250 participants (56.5% female) from the Cardiovascular Risk in Young Finns Study who had data on parental smoking and/or serum cotinine, a biomarker of exposure to tobacco smoke, at baseline 1980 (age 3-18 years) and echocardiography performed in 2011. Parental smoking hygiene (i.e., smoking in the vicinity of children) was categorized by parental smoking and serum cotinine levels in offspring. Dimensions of the left ventricle, diastolic and systolic function, and cardiac remodeling were used as outcomes. Analyses were adjusted for sex, age, and covariates (blood pressure (BP), serum lipids, body mass index, socioeconomic status, smoking (only in adulthood)) in childhood and adulthood. RESULTS: Parental smoking was not associated with systolic or diastolic function in adulthood. Participants exposed to parental smoking (odds ratio (OR) 1.90, 95%CI 1.23-2.92), hygienic parental smoking (OR 1.74, 95%CI 1.12-2.71), and non-hygienic parental smoking (OR 1.88, 95%CI 1.02-3.45) had higher odds of concentric remodeling (relative wall thickness >85th sex-specific percentile without left ventricular hypertrophy). These associations were attenuated after adjustment for child and adult covariates in the non-hygienic parental smoking group. CONCLUSIONS: Exposure to parental smoking in childhood was associated with a higher likelihood of concentric remodeling and thicker left ventricular and interventricular septal walls in midlife, which was not improved by parents who smoked hygienically. Parental smoking was not related to systolic or diastolic function in this relatively young population.

Can adult polygenic scores improve prediction of body mass index in childhood?

BACKGROUND/OBJECTIVES: Modelling genetic pre-disposition may identify children at risk of obesity. However, most polygenic scores (PGSs) have been derived in adults, and lack validation during childhood. This study compared the utility of existing large-scale adult-derived PGSs to predict common anthropometric traits (body mass index (BMI), waist circumference, and body fat) in children and adults, and examined whether childhood BMI prediction could be improved by combining PGSs and non-genetic factors (maternal and earlier child BMI). SUBJECTS/METHODS: Participants (n = 1365 children, and n = 2094 adults made up of their parents) were drawn from the Longitudinal Study of Australian Children. Children were weighed and measured every two years from 0-1 to 12-13 years, and adults were measured or self-reported measurements were obtained concurrently (average analysed). Participants were genotyped from blood or oral samples, and PGSs were derived based on published genome-wide association studies. We used linear regression to compare the relative utility of these PGSs to predict their respective traits at different ages. RESULTS: BMI PGSs explained up to 12% of child BMI z-score variance in 10-13 year olds, compared with up to 15% in adults. PGSs for waist circumference and body fat explained less variance (up to 8%). An interaction between BMI PGSs and puberty (p = 0.001-0.002) suggests the effect of some variants may differ across the life course. Individual BMI measures across childhood predicted 10-60% of the variance in BMI at 12-13 years, and maternal BMI and BMI PGS each added 1-9% above this. CONCLUSION: Adult-derived PGSs for BMI, particularly those derived by modelling between-variant interactions, may be useful for predicting BMI during adolescence with similar accuracy to that obtained in adulthood. The level of precision presented here to predict BMI during childhood may be relevant to public health, but is likely to be less useful for individual clinical purposes.

Does being conceived by assisted reproductive technology influence adult quality of life?

Numerous studies have investigated the physical health and development of children and adolescents conceived with assisted reproductive technology (ART). Less is known about the quality of life of ART-conceived adults. This study explores the contributions of being conceived with ART and psychosocial cofactors present in young adulthood to the quality of life of adults aged 22-35 years. Young adults conceived through ART or natural conception (NC) completed questionnaires which included a standardized measure of quality of life (World Health Organization Quality of Life - Brief assessment (WHOQoL-BREF)) when aged 18-28 years (T1) and again when aged 22-35 years (T2). The WHOQoL-BREF has four domains: (i) Physical, (ii) Psychological, (iii) Social relationships and (iv) Environment. A total of 193 ART-conceived and 86 NC individuals completed both questionnaires. When accounting for other cofactors in multivariable analyses, being ART-conceived was strongly associated with higher scores (better quality of life) on the Social relationships, and Environment WHOQoL-BREF domains at T2. In addition, less psychological distress, a better relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more of the WHOQoL-BREF domains at T2. In conclusion, being ART-conceived can confer advantages in quality of life in adulthood, independent of psychosocial cofactors.

Comparison of Seroconversion in Children and Adults With Mild COVID-19.

Importance: The immune response in children with SARS-CoV-2 infection is not well understood. Objective: To compare seroconversion in nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion. Design, Setting, and Participants: This household cohort study of SARS-CoV-2 infection collected weekly nasopharyngeal and throat swabs and blood samples during the acute (median, 7 days for children and 12 days for adults [IQR, 4-13] days) and convalescent (median, 41 [IQR, 31-49] days) periods after polymerase chain reaction (PCR) diagnosis for analysis. Participants were recruited at The Royal Children's Hospital, Melbourne, Australia, from May 10 to October 28, 2020. Participants included patients who had a SARS-CoV-2-positive nasopharyngeal or oropharyngeal swab specimen using PCR analysis. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G (IgG) and cellular (T cell and B cell) responses in children and adults. Seroconversion was defined by seropositivity in all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] and 2 commercial assays: a SARS-CoV-2 S1/S2 IgG assay and a SARS-CoV-2 antibody ELISA) serological assays. Results: Among 108 participants with SARS-CoV-2-positive PCR findings, 57 were children (35 boys [61.4%]; median age, 4 [IQR, 2-10] years) and 51 were adults (28 women [54.9%]; median age, 37 [IQR, 34-45] years). Using the 3 established serological assays, a lower proportion of children had seroconversion to IgG compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P < .001). This result was not associated with viral load, which was similar in children and adults (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] vs 24.14 [8.47]; P = .09). In addition, age and sex were not associated with seroconversion within children (median age, 4 [IQR, 2-14] years for both seropositive and seronegative groups; seroconversion by sex, 10 of 21 girls [47.6%] vs 10 of 33 boys [30.3%]) or adults (median ages, 37 years for seropositive and 40 years for seronegative adults [IQR, 34-39 years]; seroconversion by sex, 18 of 24 women [75.0%] vs 14 of 18 men [77.8%]) (P > .05 for all comparisons between seronegative and seropositive groups). Symptomatic adults had 3-fold higher SARS-CoV-2 IgG levels than asymptomatic adults (median, 227.5 [IQR, 133.7-521.6] vs 75.3 [IQR, 36.9-113.6] IU/mL), whereas no differences were observed in children regardless of symptoms. Moreover, differences in cellular immune responses were observed in adults compared with children with seroconversion. Conclusions and Relevance: The findings of this cohort study suggest that among patients with mild COVID-19, children may be less likely to have seroconversion than adults despite similar viral loads. This finding has implications for future protection after SARS-CoV-2 infection in children and for interpretation of serosurveys that involve children. Further research to understand why seroconversion and development of symptoms are potentially less likely in children after SARS-CoV-2 infection and to compare vaccine responses may be of clinical and scientific importance.

Association of Prenatal Antibiotics and Mode of Birth With Otolaryngology Surgery in Offspring: A National Data Linkage Study.

BACKGROUND: Pediatric otolaryngology surgery is commonly performed after recurrent infections and allergy/atopy. Prenatal antibiotic exposure and cesarean section deliveries increase the risk of severe infection and allergy/atopy in the offspring, but the relationship with common, related surgical outcomes is unknown. This study measures the associations between prenatal antibiotic use and mode of birth with common pediatric otolaryngology surgery. METHODS: Data linkage analysis of all live-born, singleton children, born between 2008 and 2018 was done using Norwegian national health registry data. Exposures of interest were prenatal antibiotics and mode of birth. The primary outcome was common otolaryngology surgery before 10 years of age. Exposure-outcome associations were estimated through multivariable Cox proportional hazards models adjusting for predefined covariates. Interaction between exposures was explored. RESULTS: Of 539,390 children, 146,832 (27.2%) had mothers who were prescribed antibiotics during pregnancy, 83,473 (15.5%) were delivered via cesarean section, and 48,565 (9.0%) underwent an otolaryngology surgery during the study period. Prenatal antibiotic exposure [adjusted hazard ratio (aHR), 1.22; 95% CI: 1.20-1.24] and cesarean section (aHR, 1.14; 95% CI: 1.11-1.16) were each associated with otolaryngology surgery after mutual adjustment. There was some evidence of an interaction between the 2 exposures (P = 0.03). CONCLUSIONS: Antibiotic exposure in pregnancy and cesarean section may adversely affect early immune development and increase the risk of recurrent upper airway infections and allergy/atopy that may require otolaryngology surgery. Mechanistic studies are warranted to explore genetic and/or molecular pathways that explain these findings. This may identify potential therapeutic targets to reduce the burden of otolaryngology surgery.

Does an inflammatory diet affect mental well-being in late childhood and mid-life? A cross-sectional study.

Inflammatory diets are increasingly recognised as a modifiable determinant of mental illness. However, there is a dearth of studies in early life and across the full mental well-being spectrum (mental illness to positive well-being) at the population level. This is a critical gap given that inflammatory diet patterns and mental well-being trajectories typically establish by adolescence. We examined the associations of inflammatory diet scores with mental well-being in 11-12-year-olds and mid-life adults. Throughout Australia, 1759 11-12-year-olds (49 % girls) and 1812 parents (88 % mothers) contributed cross-sectional population-based data. Alternate inflammatory diet scores were calculated from a twenty-six-item FFQ, based on the prior literature and prediction of inflammatory markers. Participants reported negatively and positively framed mental well-being via psychosocial health, quality of life and life satisfaction surveys. We used causal inference modelling techniques via generalised linear regression models (mean differences and risk ratios (RR)) to examine how inflammatory diets might influence mental well-being. In children and adults, respectively, a 1 sd higher literature-derived inflammatory diet score conferred between a 44 % (RR 95 % CI 1·2, 1·8) to 57 % (RR 95 % CI 1·3, 2·0) and 54 % (95 % CI 1·2, 2·0) to 86 % (RR 95 % CI 1·4, 2·4) higher risk of being in the worst mental well-being category (i.e. <16th percentile) across outcome measures. Results for inflammation-derived scores were similar. BMI mediated effects (21-39 %) in adults. Inflammatory diet patterns were cross-sectionally associated with mental well-being at age 11-12 years, with similar effects observed in mid-adulthood. Reducing inflammatory dietary components in childhood could improve population-level mental well-being across the life course.

Prenatal antibiotic exposure and birth weight.

BACKGROUND/OBJECTIVES: Current research suggests an association between antibiotic use in early life and later obesity. Less is known about prenatal antibiotic exposure and foetal growth. We investigated the association between prenatal antibiotic exposure and birth weight. METHODS: Data from the Danish National Birth Cohort were linked to the Danish National Medical Birth Registry. Exposure was self-reported antibiotic use in pregnancy. Outcome was registered birth weight. Multivariable linear regression models were adjusted for confounders defined a priori. RESULTS: A total of 63 300 mother-child dyads from 1996 to 2002 were included. Overall, prenatal antibiotic exposure was not associated with birth weight (-8.90 g, 95%CI: -19.5- +1.64 g, p = 0.10). Findings were similar for those born term and preterm. Antibiotic exposure in second to third trimester, compared to no exposure, was associated with lower birth weight (-12.6 g, 95%CI: -24.1 to -1.1 g, p = 0.03). In sex-stratified analyses, there were no observed associations between antibiotics and birth weight. With further stratifications, prenatal antibiotic exposure and birth weight were associated in boys who were preterm (+91.0 g, 95%CI: +6.8 g- +175.2 g, p = 0.03) but not among girls who were preterm (-44.0 g, 95%CI: -128.1 to +40.0 g, p = 0.30). CONCLUSIONS: Prenatal antibiotic exposure is not consistently associated with birth weight.

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.

Changes in antibiotic prescribing following COVID-19 restrictions: Lessons for post-pandemic antibiotic stewardship.

AIMS: Public health responses to reduce SARS-CoV-2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID-19 restrictions on antibiotic dispensing in Australia. METHODS: We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face-to-face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. RESULTS: Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID-19 restrictions, we observed a sustained 36% (95% CI: 33-40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51-69%), whereas those recommended for non-respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April-October 2019 to 37.0 per 1000 for April-October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. CONCLUSION: In a setting with a low COVID-19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post-pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.

Goldilocks Days: optimising children's time use for health and well-being.

BACKGROUND: One size rarely fits all in population health. Differing outcomes may compete for best allocations of time. Among children aged 11-12 years, we aimed to (1) describe optimal 24-hour time use for diverse physical, cognitive/academic and well-being outcomes, (2) pinpoint the 'Goldilocks Day' that optimises all outcomes and (3) develop a tool to customise time-use recommendations. METHODS: In 2004, the Longitudinal Study of Australian Children recruited a nationally-representative cohort of 5107 infants with biennial follow-up waves. We used data from the cross-sectional Child Health CheckPoint module (2015-2016, n=1874, 11-12 years, 51% males). Time use was from 7-day 24-hour accelerometry. Outcomes included life satisfaction, psychosocial health, depressive symptoms, emotional problems, non-verbal IQ; vocabulary, academic performance, adiposity, fitness, blood pressure, inflammatory biomarkers, bone strength. Relationships between time use and outcomes were modelled using compositional regression. RESULTS: Optimal daily durations varied widely for different health outcomes (sleep: 8.3-11.4 hours; sedentary: 7.3-12.2 hours; light physical activity: 1.7-5.1 hours; moderate-to-vigorous physical activity (MVPA): 0.3-2.7 hours, all models p≤0.04). In general, days with highest physical activity (predominantly MVPA) and low sedentary time were optimal for physical health, while days with highest sleep and lowest sedentary time were optimal for mental health. Days with highest sedentary time and lowest physical activity were optimal for cognitive health. The overall Goldilocks Day had 10 hours 21 min sleep, 9 hours 44 min sedentary time, 2 hours 26 min light physical activity and 1 hour 29 min MVPA. Our interactive interface allows personalisation of Goldilocks Days to an individual's outcome priorities. CONCLUSION: 'Goldilocks Days' necessitate compromises based on hierarchies of priorities for health, social and economic outcomes.