Medically Assisted Reproduction and Risk of Cancer Among Offspring.

Importance: Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations. Objective: To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally. Design, Setting, and Participants: For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023. Exposure: Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI). Main Outcomes and Measures: The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth. Results: This study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years). Conclusions and Relevance: The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.

Trends in anti-infective use during pregnancy in France between 2010 and 2019: a nationwide population-based study.

AIMS: To describe the trends in anti-infective use during pregnancy between 2010 and 2019 and determine whether they were prescribed according to drug foetal safety international classification systems. METHODS: We conducted a population-based, nationwide study using the French national health data system including all pregnancies ended between 2010 and 2019. Anti-infective agents were considered according to their pharmacological group and potential harmful risk using the Australian and Swedish classification systems. Prevalence rate was estimated annually and by trimester. Average annual percent change (AAPC) and 95% confidence intervals (CIs) were calculated using Joinpoint regression. RESULTS: Among 7 571 035 pregnancies, 3 027 031 (40.0%) received ≥1 antibacterial. This proportion decreased significantly from 41.5% in 2010 to 36.1% in 2019 (AAPC = -1.7%, [95%CI, -2.5 to -1.0%]). Conversely, use of antiviral agents increased during the 10-year study period for anti-herpes simplex virus agents (AAPC = 4.4%, [3.7-5.2%]), influenza agents (AAPC = 25.4%, [6.2-48.1%]) and for HIV-antiretroviral agents (AAPC = 1.3%, [0.6-2.0%]). Use of influenza vaccine increased from 0.2% in 2010 to 4.2% in 2019 (AAPC = 49.7%, [39.3-60.9%]). Among all pregnancies, 0.9% had been exposed to a potentially harmful anti-infective agent increasing from 0.7% in 2010 to 1.2% in 2019 (AAPC = 6.4%, [4.4-8.5%]). CONCLUSION: Based on >7 million pregnancies identified from French nationwide data, this study showed that antibacterials are frequently prescribed during pregnancy although their use has decreased over the past 10 years. Our results suggest that anti-infective agents are generally prescribed in accordance with recommendations, although with a potential for improvement in influenza vaccination.

Risk of Inflammatory Bowel Disease in Patients With Psoriasis and Psoriatic Arthritis/Ankylosing Spondylitis Initiating Interleukin-17 Inhibitors: A Nationwide Population-Based Study Using the French National Health Data System.

OBJECTIVE: To investigate whether the initiation of treatment with an interleukin-17 inhibitor (IL-17i) in real life is associated with a higher risk of inflammatory bowel disease (IBD) in patients who had both psoriasis (PsO) and psoriatic arthritis (PsA)/ankylosing spondylitis (AS). METHODS: This nationwide cohort study was conducted using the French National Health Data System database. All adult patients with PsO and PsA/AS who were identified as having newly initiated treatment with an IL-17i during 2016-2019 were included. As controls, patients with PsO and PsA/AS who had newly initiated either 1) apremilast or 2) etanercept (ETN) during this period but had not received IL-17i were included. The follow-up end date was September 30, 2019. The primary end point was the risk of occurrence of IBD associated with exposure to an IL-17i compared to exposure to the other treatments, as determined in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray proportional hazards models. RESULTS: The study included a total of 16,793 new IL-17i users (mean ± SD age 48.4 ± 13 years, 45% men), 20,556 new apremilast users (age 52.6 ± 15 years, 54% men), and 10,294 new ETN users (age 46.3 ± 15 years, 44% men). New IL-17i users and new ETN users had received more biologics for their underlying disease compared to new apremilast users. IBD occurred in 132 patients: 72 new IL-17i users (0.43%), 11 new apremilast users (0.05%), and 49 new ETN users (0.48%). Most IBD cases occurred after 6 months of exposure (82%, 55%, and 76%, respectively). After propensity score weighting, the risk of IBD was significantly greater among patients initiating an IL-17i compared to those initiating apremilast (weighted hazard ratio [HR] 3.8 [95% confidence interval (95% CI) 2.1-6.8]). No difference in the risk of IBD between new IL-17i users and new ETN users was observed (weighted HR 0.8 [95% CI 0.5-1.2]). CONCLUSION: Patients with PsO and PsA/AS who initiate treatment with an IL-17i do not have a higher risk of developing IBD when compared to patients initiating ETN who display the same severity of underlying disease. These results need to be confirmed in other large studies of patients with PsO and PsA/AS.

Antihypertensive Drugs and COVID-19 Risk: A Cohort Study of 2 Million Hypertensive Patients.

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.