Transplacental pharmacokinetics and developmental toxicity of chemotherapeutic agents: a comparative analysis of fetal and pediatric exposure profiles

INTRODUCTION: Administering chemotherapy during pregnancy poses significant clinical challenges, requiring careful balance between effective maternal cancer treatment and protection of the developing fetus. Understanding fetal toxicity patterns from transplacental drug exposure is essential for the safe management of pregnancy-associated malignancies. AREAS COVERED: This review examines transplacental chemotherapy exposure and associated fetal toxicity. A systematic search of PubMed/MEDLINE, EMBASE, and the Cochrane Library (inception to March 2025) was conducted. Contemporary literature was synthesized to evaluate pharmacokinetic characteristics of placental drug transfer, developmental vulnerabilities across gestational stages, and documented adverse outcomes. The analysis emphasizes organ-specific toxicities, long-term developmental consequences, and mechanistic differences in fetal drug metabolism compared to postnatal populations. EXPERT OPINION: Transplacental chemotherapy exposure generates distinct risk patterns driven by unique placental pharmacokinetics, gestational age-dependent susceptibilities, and inability to optimize dosing or implement direct fetal monitoring. Evidence suggests fetuses may face elevated risks for specific adverse outcomes due to critical developmental timing and limited capacity for standard supportive interventions. However, comprehensive risk assessment remains challenging due to limited long-term follow-up data, heterogeneous exposure scenarios, and methodological constraints in outcome measurement.