Background: Rising substance use during pregnancy is a major global health concern associated with adverse maternal and neonatal outcomes. Despite growing international literature, Italian real-world multicenter data remain limited. Methods: We conducted a retrospective descriptive analysis of 31 women who reported substance use during a current or previous pregnancy across four Italian clinical centers using data collected between January 2024 and October 2025. Each participant contributed one index pregnancy to the maternal and neonatal outcome analysis. The 54 pregnancies recorded for the overall cohort represented cumulative obstetric history and were not treated as independent observations. Collected variables included type of substance, maintenance therapy, psychiatric diagnosis, infectious serology, neonatal outcomes, obstetric history, and partner relationship quality. Results: Opioid use (alone or in combination) was present in 77.4% of participants, cocaine/crack in 54.8%, and cannabis in 22.6%. Polysubstance use was common. Prematurity occurred in 13 of 31 index pregnancies (41.9%), and neonatal abstinence syndrome was documented in 10 of 31 index pregnancies (32.3%), all of which were opioid-exposed. Human immunodeficiency virus (HIV) positivity was present in 29.0% of participants and Hepatitis C Virus in 16.1%, exclusively among opioid-exposed women. Conflictual or unstable partner relationships were reported in 45.2% of participants. Conclusions: In this small, selected Italian multicenter clinical sample, substance use during pregnancy was heterogeneous and frequently associated with medical, psychiatric, and psychosocial vulnerability. Opioid exposure predominated, and all cases of neonatal abstinence syndrome occurred among opioid-exposed index pregnancies, while cocaine/crack and cannabis use were also frequently documented. Given the descriptive design and small sample size, these findings should not be interpreted as population-level prevalence estimates or as evidence of causal relationships between individual substances and pregnancy outcomes.




