Pregnancy during pembrolizumab therapy for triple-negative breast cancer with onset of congenital hypothyroidism: Case report, literature review, and caution for clinical practice.

Cancer during pregnancy is rare but increasingly reported due to advanced maternal age and improvements in prenatal diagnostics leading to incidental detection. Immune checkpoint inhibitors (ICIs), such as pembrolizumab (Keytruda), are now used in oncology, particularly for triple-negative breast cancer (TNBC). As IgG antibodies, ICIs cross the placental barrier and may induce immune-mediated effects in the fetus. We report the first documented case of congenital hypothyroidism following inadvertent in-utero exposure to pembrolizumab. The patient, treated with chemotherapy followed by pembrolizumab for TNBC, was found to be pregnant at 24 weeks of gestation. Pembrolizumab was discontinued, and the pregnancy progressed without complications. On the third day of life, the neonate was diagnosed with congenital hypothyroidism caused by in-utero thyroiditis attributed to pembrolizumab. Levothyroxine treatment was initiated, and at 14 months the infant demonstrated normal psychomotor development under continued thyroid hormone supplementation. Endocrine immune-related adverse events, particularly thyroid disorders, are frequent in adults treated with ICIs, but their fetal impact is rarely described. A review of the literature and a query of the international pharmacovigilance database identified only a limited number of in-utero exposure cases, mainly in melanoma, with neonatal outcomes ranging from uneventful deliveries to immune-related complications. This case highlights the risk of endocrine toxicity in neonates exposed to ICIs during pregnancy and underscores the need for multidisciplinary care, appropriate contraceptive counseling during immunotherapy, and long-term follow-up of exposed children as the use of ICIs continues to expand.