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Infants may present with a wide variety of clinical presentations, with almost every organ system at risk of injury. Further adding to the intricacy of the disease, the majority of infants will be asymptomatic at birth, but due to ongoing inflammation associated with the disease, there may be a myriad of delayed morbid effects that take years to manifest. Diagnosis and management is dependent on a combination of the presence or absence of overt symptoms of the infant, noninvasive serologic examinations of the infant and pregnant individual, certain radiographic images of the fetus in utero or infant postpartum, indirect blood and cerebrospinal fluid markers of the infant, and the timing and adequacy of treatment of the pregnant individual prior to the delivery. This review is meant to help navigate the complexities of the presentation, diagnostic pathways, and treatment decision making processes required for CS.<\/jats:p>","DOI":"10.1093\/cid\/ciaf504","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T11:58:02Z","timestamp":1757678282000},"page":"1023-1035","source":"Crossref","is-referenced-by-count":3,"title":["State-of-the-Art Review: Congenital Syphilis in the Modern Era: Current Strategies and Future Directions"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2323-1453","authenticated-orcid":false,"given":"John M","family":"Flores","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago Medicine , Chicago, Illinois ,","place":["USA"]},{"name":"Department of Pediatrics, Section of Pediatric Infectious Diseases, University of Chicago Comer Children's Hospital , Chicago, Illinois 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