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Summary Background Given the high prevalence of early childhood overweight and obesity, more evidence is required to better understand the cost‐effectiveness of community‐wide interventions targeting obesity prevention in children aged 0–5 years. Objectives To assess the cost‐effectiveness of the Romp & Chomp community‐wide early childhood obesity prevention intervention if delivered across Australia in 2018 from a funder perspective, against a no‐intervention comparator. Methods Intervention costs were estimated in 2018 Australian dollars. The annual Early Prevention of Obesity in Childhood micro‐simulation model estimated body mass index (BMI) trajectories to age 15 years, based on end of trial data at age 3.5 years. Results from modelled cost‐effectiveness analyses were presented as incremental cost‐effectiveness ratios (ICERs): cost per BMI unit avoided, and cost per quality‐adjusted life year (QALY) gained at age 15 years. Results All Australian children aged 0–5 years (n = 1 906 075) would receive the intervention. Total estimated intervention cost and annual cost per participant were AUD178 million and AUD93, respectively, if implemented nationally. The ICERs were AUD1 126 per BMI unit avoided and AUD26 399 per QALY gained (64% probability of being cost‐effective measured against a AUD50 000 per QALY threshold). Conclusions Romp & Chomp has a fair probability of being cost‐effective if delivered at scale.

Background: Overweight and obesity in children is associated with poor health-related quality of life (HRQoL), but the nuances of this relationship across different age and socio-demographic groups are not well-established. The aim of this study is to examine how the association between weight status and HRQoL changes with age and socioeconomic position (SEP) throughout childhood and adolescence. Methods: We used data from the Longitudinal Study of Australian Children (LSAC); a cohort study in which children were interviewed biennially from ages 4-5 to 16-17. Measurements of HRQoL (using PedsQL TM), BMI, and sociodemographic characteristics were collected at each interview. Of the 4983 children recruited into the study, we included data from 4083 children (a total of 24 446 observations). We used generalised estimating equations to assess whether age and SEP modified the association between weight status and HRQoL, after controlling for sex, long-term medical condition, language spoken to child and maternal smoking status. Results: Age was a significant modifier of the association between weight status and HRQoL, with adjustment for known predictors of HRQoL (P<0.001). At age 4, children with obesity had, on average, a 0.99 (95% CI 0.02 to 1.96) point lower PedsQL total score than children at healthy weight. This difference became clinically important by age 9 at 4.50 (95% CI 3.86 to 5.13) points and increased to 6.69 (95% CI 5.74 to 7.64) points by age 17. There was no evidence that SEP modified the relationship between weight status and HRQoL (P>0.05). Conclusions: Our results demonstrate that the relationship between overweight and obesity status and poor HRQoL is strengthened with increasing age through childhood and adolescence, but is not affected by SEP. Paediatricians, researchers and carers of children with obesity should acknowledge HRQoL outcomes, particularly for older children and adolescents.

The TERT-CLPTM1L region of chromosome 5p15.33 is a multi-cancer susceptibility locus that encodes the reverse transcriptase subunit, hTERT, of the telomerase enzyme. Numerous cancer-associated single-nucleotide polymorphisms (SNPs), including rs10069690, have been identified within the hTERT gene. The minor allele (A) at rs10069690 creates an additional splice donor site in intron 4 of hTERT, and is associated with an elevated risk of multiple cancers including breast and ovarian carcinomas. We previously demonstrated that the presence of this allele resulted in co-production of full length (FL)-hTERT and an alternatively spliced, INS1b, transcript. INS1b does not encode the reverse transcriptase domain required for telomerase enzyme activity, but we show here that INS1b protein retains its ability to bind to the telomerase RNA subunit, hTR. We also show that INS1b expression results in decreased telomerase activity, telomere shortening, and an increased telomere-specific DNA damage response (DDR). We employed antisense oligonucleotides to manipulate endogenous transcript expression in favor of INS1b, which resulted in a decrease in telomerase activity. These data provide the first detailed mechanistic insights into a cancer risk-associated SNP in the hTERT locus, which causes cell type-specific expression of INS1b transcript from the presence of an additional alternative splice site created in intron 4 by the risk allele. We predict that INS1b expression levels cause subtle inadequacies in telomerase-mediated telomere maintenance, resulting in an increased risk of genetic instability and therefore of tumorigenesis.