Protocol for the Australian Type 1 Diabetes National Screening Pilot: Assessing the feasibility and acceptability of three general population screening models in children.

AIM: One third of Australian children diagnosed with type 1 diabetes present with life-threatening diabetic ketoacidosis (DKA) at diagnosis. Screening for early-stage, presymptomatic type 1 diabetes, with ongoing follow-up, can substantially reduce this risk (<5% risk). Several screening models are being trialled internationally, without consensus on the optimal approach. This pilot study aims to assess three models for a routine, population-wide screening programme in Australia. METHODS: An implementation science-guided pilot study to evaluate the feasibility, acceptability and costs of three screening models in children will be conducted between July 2022 and June 2024. These models are as follows: (1) Genetic risk-stratified screening using newborn heel prick dried bloodspots, followed by autoantibody testing from 11 months of age; (2) genetic risk-stratified screening of infant (6-12 months) saliva followed by autoantibody testing from 10 months of age; and (3) autoantibody screening using capillary dried bloodspots collected from children aged 2, 6 or 10 years. Cohorts for each model will be recruited from targeted geographic areas across Australia involving ≥2 states per cohort, with a recruitment target of up to 3000 children per cohort (total up to 9000 children). The primary outcome is screening uptake for each cohort. Secondary outcomes include programme feasibility, costs, parental anxiety, risk perception, satisfaction, well-being and quality of life, and health professional attitudes and satisfaction. CONCLUSIONS: This pilot is the first direct comparison of three screening implementation models for general population screening. Findings will provide evidence to inform a potential national screening programme for Australian children. TRIAL REGISTRATION: ACTRN12622000381785.

Prescription retinoid and contraception use in women in Australia: A population-based study.

BACKGROUND/OBECTIVES: Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood. The objectives were to determine trends in the use of prescription retinoids among Australian reproductive-aged women and whether women dispensed oral retinoids used contraception concomitantly. METHODS: This was a population-based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15-44-year-old Australian women, 2013 - 2021. We described rates and annual trends in dispensing claims for PBS-listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level. RESULTS: There were 1,545,800 retinoid dispensings to reproductive-aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive-aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021. CONCLUSIONS: Rates of oral retinoid dispensing have doubled among reproductive-aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.

Opioid analgesic exposure during the first trimester of pregnancy and the risk of major congenital malformations in infants: a systematic review and meta-analysis†.

BACKGROUND: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta-analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. METHODS: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first-trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non-Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random-effects meta-analysis. RESULTS: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98-1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96-1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92-1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38-5.16) and cleft palate (relative risk 1.57, 95%CI 0.48-5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05-1.36) following codeine exposure. CONCLUSIONS: Although the meta-analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field.