This nationwide cohort study provides a comprehensive overview of maternal and perinatal outcomes associated with sickle cell disease (SCD) during pregnancy. Using the French national health database, all singleton pregnancy-related hospital discharges from 2013 to 2020 in women aged 15-55 (n = 5 752 080) were selected. Of these, 1022 births were to women with SCD, 308 of whom were on long-term treatment, that is, hydroxyurea (HU) and/or transfusion programme. Pregnancies with SCD were more likely to involve pre-eclampsia (9.6% vs. 1.7%
p <
0.001), pulmonary embolism (0.70% vs. 0.02%
p <
0.001), caesarean sections (52.8% vs. 18.2%
p <
0.001) and postpartum haemorrhage (8.3% vs. 4.1%
p <
0.001) compared to pregnancies without SCD. Preterm birth (<
37 weeks) was much more common in women with SCD (28.5% vs. 5.6%). Infants born to women with SCD faced greater adverse neonatal outcomes (22.4% vs. 8.0%
p <
0.001). Although untreated SCD was linked to fewer complications than long-term treated SCD, both conditions presented greater risks compared with pregnancies without SCD. Unexpectedly, babies born to women with SCD had a higher incidence of congenital abnormalities (6.3% vs. 3.4%
p <
0.001), not attributed to HU use. Overall, despite advances in SCD management, pregnancy in SCD remains a high-risk condition, for both mothers and babies.