c Serology has a pivotal role in the diagnosis of congenital syphilis (CS), but problems arise because of the passive transfer of IgG antibodies across the placenta. The aim of this study was to assess the diagnostic value of a comparative Western blot (WB) method finalized to match the IgG immunological profiles of mothers and their own babies at birth in order to differentiate between passively transmitted maternal antibodies and antibodies synthesized by the infants against Treponema pallidum. Thirty infants born to mothers with unknown or inadequate treatment for syphilis were entered in a retrospective study, conducted at St. Orsola-Malpighi Hospital, Bologna, Italy. All of the infants underwent clinical, instrumental, and laboratory examinations, including IgM WB testing. For the retrospective study, an IgG WB assay was performed by blotting T. pallidum antigens onto nitrocellulose sheets and incubating the strips with serum specimens from mother-child pairs. CS was diagnosed in 11 out of the 30 enrolled infants; 9/11 cases received the definitive diagnosis within the first week of life, whereas the remaining two were diagnosed later because of increasing serological test titers. The use of the comparative IgG WB testing performed with serum samples from mother-child pairs allowed a correct CS diagnosis in 10/11 cases. The CS diagnosis was improved by a strategy combining comparative IgG WB results with IgM WB results, leading to a sensitivity of 100%. The comparative IgG WB test is thus a welcome addition to the conventional laboratory methods used for CS diagnosis, allowing identification and adequate treatment of infected infants and avoiding unnecessary therapy of uninfected newborns.T reponema pallidum infection in pregnant women can lead to stillbirth, early fetal death, low birth weight, preterm delivery, neonatal death, or congenital syphilis (CS) in their babies. The effectiveness of serological testing and treatment in preventing mother-to-child transmission of syphilis is well recognized (1). In 2007, the WHO launched its Initiative for the Global Elimination of Congenital Syphilis, with the goal that by 2015 at least 90% of pregnant women are being tested for syphilis and at least 90% of seropositive pregnant women are receiving adequate treatment (http://www.who.int/reproductivehealth/publications/rtis/97892 41595858/en/index.html). Despite that huge effort, CS persists as a public health problem (2, 3), and in recent years, CS cases have also been reported in high-income countries (4-6).The diagnosis of CS is complex and is based on a combination of maternal history and clinical and laboratory criteria in both mother and infant (4, 6). Infected infants may be asymptomatic or may have subtle and insidious findings or multiple-organ involvement. Even asymptomatic newborns may have early or late postnatal manifestations (7).Due to the frequent absence of specific signs of infection at birth, serology has a pivotal role in CS diagnosis: all infants born to mothers with reactive syphilis test resu...