Antibody-mediated hemolytic disease of the fetus and newborn, henceforth referred to as hemolytic disease, can pose a significant risk for anemia and severe postnatal hyperbilirubinemia. A positive maternal anti-erythrocyte antibody screen is often the first finding to herald the risk of hemolytic disease and prompt further evaluation including fetal surveillance for anemia and, if indicated, in utero red blood cell transfusion. 1 Liley H.G. Gardener G. Lopriore E. Smits-Wintjens V. Immune hemolytic disease. in: Orkin S. Nathan D. Ginsburg D. Look A.T. Fisher D. Lux S. Nathan and Oski's hematology and oncology of infancy and childhood. Elsevier Saunders, Philadelphia2015: 76-100 Google Scholar A positive maternal anti-erythrocyte antibody screen may also signal a risk for severe hyperbilirubinemia in the neonate, even in the absence of fetal anemia. In this regard, hemolytic disease remains an important cause of marked neonatal hyperbilirubinemia, acute bilirubin encephalopathy, and kernicterus. 2 Johnson L. Bhutani V.K. Karp K. Sivieri E.M. Shapiro S.M. Clinical report from the Pilot US Kernicterus Registry (1992 to 2004). J Perinatol. 2009; 29: S25-S45 Crossref Scopus (232) Google Scholar , 3 Christensen R.D. Agarwal A.M. George T.I. Bhutani V.K. Yaish H.M. Acute neonatal bilirubin encephalopathy in the State of Utah 2009-2018. Blood Cells Mol Dis. 2018; 72: 10-13 Crossref PubMed Scopus (24) Google Scholar , 4 Helal N.F. Ghany E.A. Abuelhamd W.A. Alradem A.Y. Characteristics and outcome of newborn admitted with acute bilirubin encephalopathy to a tertiary neonatal intensive care unit. World J Pediatr. 2019; 15: 42-48 Google Scholar , 5 Rennie J.M. Beer J. Upton M. Learning from claims: hyperbilirubinemia and kernicterus. Arch Dis Child Fetal Neonatal Ed. 2019; 104: F202-F204 Google Scholar Whether a positive maternal anti-erythrocyte antibody screen is detected at pregnancy registration, during gestation, or perinatally at the time of delivery hospitalization, it is incumbent on the newborn caretakers to be aware of the result. 6 Watchko J.F. Common hematologic problems in the newborn nursery. Pediatr Clin N Am. 2015; 62: 509-524 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar , 7 Intermountain Healthcare. Prenatal care for maternal anti-erythrocyte antibodies. 2017 Update. Intermountain Healthcare Patient and Provider Publications CPM043 – 07/17. https://intermountainhealthcare.org/ckr-ext/Dcmnt?ncid=521363279. Accessed December 1, 2018. Google Scholar We review the critical importance of a successful handoff of a positive maternal anti-erythrocyte antibody screen across the perinatal continuum to ensure the timely evaluation and management of the neonate. Although symptomatic ABO hemolytic disease is also an important cause of neonatal hyperbilirubinemia, maternal anti-A and anti-B antibodies are innately produced, that is, immune competent individuals who do not express the A or B protein produce antibody to the antigen. As such, anti-A and anti-B are not included in the maternal anti-erythrocyte antibody screen and ABO hemolytic disease is not addressed. Two case reports underscore the importance of the timely handoff of a positive maternal anti-erythrocyte antibody screen.