Objective: To describe long-term changes in Cesarean Delivery (CD) and estimate CD recurrence risk across five decades. Design: Population-based cohort study Setting: Norway, 1967-2014 Sample: A total of 951,895 nulliparous women with their singleton, cephalic, term deliveries were followed through their first and second births. Methods: Data from the Medical Birth Registry of Norway was used to describe CD by maternal age (years): <20 (reference), 20-24, 25-29, 30-34, 35-39 and >=40 and onset of labor: spontaneous (reference), induced and pre-labor CD. Based on seven risk factors, women were grouped as lower (no factors) - and higher-risk (one or more factors). Risk estimates were stratified by periods: 1967-1982, 1983-1998 and 1999-2014. Multivariable regression models were used to estimate relative risk (RR) with 95% confidence interval (CI). Results: CD in the first birth increased across periods from 3.3% to 10.2% and from 8% to 20.5% in lower- and higher-risk women, respectively. The increase in CD was only found among women < 35 years. Compared to women with spontaneous onset, the RR of CD in lower-risk women with induced onset of labor increased from 3.8 (95% CI 3.6-4.0) to 5.9 (95% CI 5.7-6.2) across periods. Overall CD recurrence risk was 57.9%, but relative recurrence risk was lower in the last than in the first period. Conclusion: Overall CD risk increased over time in Norwegian women <35 years both in lower- and higher- risk groups, while it was stable or decreased in older women. CD recurrence risk declined across 47 years in Norway.

Objective To investigate the risk of congenital heart defects (CHD) and other congenital anomalies (CA) associated with first trimester use of macrolides. Design Population-based case-malformed control study. Setting Thirteen European countries. Population Data on 145,936 livebirths, stillbirths and terminations of pregnancy for CA from 15 EUROCAT registries, covering 9 million births 1995–2012. Methods Cases were babies with CHD, anencephaly, orofacial clefts, genital and limb reduction anomalies associated with antibiotic exposure in the literature. Controls were babies with other CA or genetic conditions. A meta-analysis of the literature, including this study, was conducted for CHD. Main outcome Odds ratios adjusted (AOR) for maternal age and registry, with 95% Confidence Intervals (95%CI). Results Macrolide exposure was recorded for 307 cases, 72 non-genetic controls, 57 genetic controls. AOR for CHD was not significantly raised (AOR 0.94, 95%CI: 0.70 – 1.26 vs non-genetic controls; AOR 1.01, 95%CI: 0.73 – 1.41 vs genetic controls), nor significantly raised for any specific macrolide. The risk of atrioventricular septal defect was significantly raised with exposure to any macrolide (AOR 2.98; 95%CI: 1.48 – 6.01), erythromycin (AOR 3.68, 95%CI: 1.28 – 10.61), and azithromycin (AOR 4.50, 95%CI: 1.30 – 15.58). Erythromycin, clarithromycin, azithromycin and clindamycin, were also associated with an increased risk of at least one other CA. Meta-analysis gave an overall CHD OR 1.14, 95%CI 0.90 –1.49 for macrolides. Conclusions Guidelines for macrolide use in pregnancy should consider the increased risk of specific CA. This is relevant for the potential use of azithromycin in the treatment of COVID-19.