Perinatal outcomes after a prenatal diagnosis of a fetal copy number variant: a retrospective population-based cohort study.

BACKGROUND: There are no established guidelines for the follow up of infants born after a prenatal diagnosis of a genomic copy number variant (CNV), despite their increased risk of developmental issues. The aims of this study were (i) to determine the perinatal outcomes of fetuses diagnosed with and without a CNV, and (ii) to establish a population-based paediatric cohort for long term developmental follow up. METHODS: An Australian state-wide research database was screened for pregnant individuals who had a prenatal chromosomal microarray (CMA) between 2013-2019 inclusive. Following linkage to laboratory records and clinical referrer details, hospital records were manually reviewed for study eligibility. Eligible participants were mother-child pairs where the pregnancy resulted in a livebirth, the mother was able to provide informed consent in English (did not require a translator) and the mother was the primary caregiver for the child at hospital discharge after birth. Research invitations were sent by registered post at an average of six years after the prenatal diagnostic test. Statistical analysis was performed in Stata17. RESULTS: Of 1832 prenatal records examined, 1364 (74.5%) mother-child pairs were eligible for recruitment into the follow up cohort. Of the 468 ineligible, 282 (60.3%) had 'no live pregnancy outcome' (209 terminations of pregnancy (TOP) and 73 miscarriages, stillbirths, and infant deaths), 157 (33.5%) required a translator, and 29 (6.2%) were excluded for other reasons. TOP rates varied by the type of fetal CNV detected: 49.3% (109/221) for pathogenic CNVs, 18.2% (58/319) for variants of uncertain significance and 3.3% (42/1292) where no clinically significant CNV was reported on CMA. Almost 77% of invitation letters were successfully delivered (1047/1364), and the subsequent participation rate in the follow up cohort was 19.2% (201/1047). CONCLUSIONS: This study provides Australia's first population-based data on perinatal outcomes following prenatal diagnostic testing with CMA. The relatively high rates of pregnancy loss for those with a prenatal diagnosis of a CNV presented a challenge for establishing a paediatric cohort to examine long term outcomes. Recruiting a mother-child cohort via prenatal ascertainment is a complex and resource-intensive process, but an important step in understanding the impact of a CNV diagnosis in pregnancy and beyond. TRIAL REGISTRATION: ACTRN12620000446965p; Registered on April 6, 2020.

The impact of codeine rescheduling on non-opioid analgesic use by people who regularly use codeine: a prospective cohort study.

BACKGROUND: Codeine was rescheduled in Australia to prescription only in February 2018. Initial studies reported an increase in population level paracetamol and ibuprofen sales following codeine upscheduling. However, to date no study has been able to investigate changes in non-opioid analgesic use at the individual patient level to determine if sales data reflect actual consumption patterns. AIM: To address this gap, we aimed to determine the impact of codeine rescheduling on non-opioid analgesic use in people who regularly used over-the-counter codeine, primarily for pain, prior to the rescheduling change. METHOD: We conducted a prospective cohort study with 260 participants who reported regular over-the-counter codeine consumption at cohort entry. Surveys were completed at baseline (November 2017, 3 months before rescheduling) and at 1 month (February 2018), 4 months (June 2018), and 12 months (February 2019), following rescheduling. The primary outcomes were mean daily doses of non-opioid analgesics, captured through a 7 day medication diary. RESULTS: The mean daily paracetamol dose decreased from 1754.4 mg (95% CI 1300.5-2208.3) at baseline to 1023.8 mg (95% CI 808.5-1239.1) at the final time-point (+ 12 months) (p = .009). The mean daily ibuprofen dose decreased from 305.1mg (95% CI 217.9-392.4) at baseline to 161.2 mg (95% CI 98.5-224.0) 12 months after rescheduling (p = .03). No significant change in doses of other medications remained was found. CONCLUSION: In people who regularly consumed over-the-counter codeine, doses of non-opioid analgesics either reduced or remained stable following codeine rescheduling, suggesting concerns of medication substitution or overuse following the change were not realised.