Congenital syphilis (CS) has dramatically increased in the United States (US) in the past decade despite the widespread availability of penicillin. Once considered an infection on the verge of elimination, CS has re-emerged as a familiar neonatal pathogen in US hospitals. This rise in cases has prompted the evaluation of potential causes and updates in prevention and management guidelines. Following a structured narrative approach, we reviewed CS data reports, peer-reviewed research articles, and updated management guidelines from state health departments over the past two decades. Our main search criteria centered on the treatment and prevention of CS, with a focus on prenatal health disparities. We identified geographical regions reporting disproportionate rates of CS, examined state laws regarding maternal syphilis testing, and evaluated potential reasons for the recent rise in cases. This article examines the current epidemiology, screening, and management recommendations for perinatal and CS in the US. It also reviews pathogenesis and clinical features in perinatal and pediatric populations. Finally, it highlights the likely contributing factors to increased CS rates and identifies areas for future research. Dramatically rising CS cases in certain regions and racial groups reflect gaps in the prevention, timely diagnosis, treatment, and management of perinatal syphilis and CS. Healthcare providers attending to mothers and children should recognize the re-emergence of this pathogen and be familiar with new screening and management guidelines. Increased federal funding for targeted interventions and research that address vulnerable populations is critical to curbing the re-emergence of this infection.
