ORIGINAL ARTICLE Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy P Valentini 1 , D Buonsenso 1 , G Barone 1 , D Serranti 2 , R Calzedda 1 , M Ceccarelli 1 , D Speziale 3 , R Ricci 3 and L Masini 4 OBJECTIVE: To compare the effectiviness of spiramycin/cotrimoxazole (Sp/C) versus pyrimethamine/sulfonamide (Pyr/Sul) and spiramycin alone (Spy) on mother-to-child transmission of toxoplasmosis infection in pregnancy. STUDY DESIGN: Retrospective study of pregnant women evaluated for suspected toxoplasmosis between 1992 and 2011. RESULT: A total of 120 mothers and their 123 newborns were included. Prenatal treatment consisted of spiramycin in 43 mothers (35%), spiramycin/cotrimoxazole in 70 (56.9%) and pyrimethamine/sulfonamide in 10 (8.1%). A trend toward reduction in toxoplasmosis transmission was found when Sp/C was compared with Pyr/Sul and particularly with Spy alone (P = 0.014). In particular, Spy increased the risk of congenital infection when compared with Sp/C (odds ratio (OR) 4.368; 95% CI: 1.253 to 15.219), but there was no significant reduction when Sp/C was compared with Pyr/Sul (OR 1.83; 95% CI: 0.184 to 18.274). CONCLUSION: The treatment based on Sp/C has significant efficacy in reducing maternal-fetal transmission of Toxoplasma gondii when compared with Pyr/Sul and particularly to Spy. Randomized controlled trials would be required. Journal of Perinatology advance online publication, 11 September 2014; doi:10.1038/jp.2014.161 INTRODUCTION Congenital toxoplasmosis (CT) usually occurs when a woman first acquires Toxoplasmosis (TG) infection during pregnancy, rarely during reinfection or reactivation of a dormant toxoplasma pre- viously acquired. Because toxoplasmosis in pregnancy (TP) is usually asymptomatic, TP can only reliably be diagnosed by seroconver- sion (change from negative to positive toxoplasma-specific antibodies). 1,2 In general, about a third of infected mothers give birth to an infant with CT, 3,4 but the risk of transmission increases with the gestational age at maternal seroconversion (the later the appea- rance of the infection, the greater the chance of transmission). 5–8 Most children with CT have a normal development 9 but up to 4% die or can develop permanent neurological sequelae or visual impairment during the first years of life. 10,11 In many European countries, periodic serologic prenatal tests for TG is routinely offered to promptly discover and treat infected mothers to reduce the risk of mother-to-child transmission and, if fetal infection has occurred, to reduce the clinical sequelae in the newborn. 5,12 Nevertheless, the impact of prenatal therapy on the outcome for the newborn is still debated. 5,11 In fact, uncertainty about the benefits of prenatal treatment 13 and concern about potential teratogenic effects have led to different policies including no screening, neonatal screening 14,15 and prenatal screening with monthly or 3-monthly re-testing schedules, 16,17 as well as to different treatment regimens. In most centers, spiramycin (Spy) is prescribed immediately after diagnosis of maternal infection and changed to pyrimetha- mine-sulfonamide (Pyr/Sul) combination if fetal infection is diagnosed or if infection is acquired in late pregnancy. 4 In others, mothers are initially treated with Pyr/Sul (after 15 weeks of gestation), and changed to Spy if fetal diagnosis is negative. 4 In some Italian centers, because of difficulties in obtaining Pyr/Sul, an alternative protocol based on the association of spiramycin/ cotrimoxazole (Sp/C) have been developed, with promising results described in a previous retrospective study. 18,19 Because of these uncertainties, we performed this retrospective study aimed to evaluate the efficacy of three different regimens for the treatment of TP (Spy alone versus Pyr/Sul versus Sp/C) to reduce the mother-to-child transmission of TG, in a clinical cohort of patients identified during 19 years and followed-up until the age of 1 year in an academic hospital in Rome. METHODS Patients Between 1992 and 2011, 229 mothers were examined for suspected TP on the basis of serological test results performed at ‘A. Gemelli’ Hospital of Rome, a third-level academic referral center for infectious diseases in pregnancy. Their 232 infants (3 couples of twins), were screened to confirm or exclude the vertical transmission of the infection in utero. Mothers’ evaluation Repeated serum samples were collected monthly from every mother during the gestational period and were tested for the presence of anti-TG antibodies. The primary maternal infection was classified into five groups according to the probability of TP, using the classification of Lebech et al.: 20 1 Department of Pediatrics, Catholic University of the Sacred Heart, A. Gemelli Hospital, Rome, Italy; 2 Department of Pediatrics, Meyer Pediatric Hospital, Florence, Italy; 3 Department of Microbiology, Catholic University of Sacred Heart, A. Gemelli Hospital, Rome, Italy and 4 Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, A. Gemelli Hospital, Rome, Italy. Correspondence: Dr D Buonsenso, Department of Pediatrics; Gemelli Hospital, Largo Gemelli, Rome 1-00168, Italy. E-mail: danilobuonsenso@gmail.com Received 14 February 2014; revised 16 July 2014; accepted 25 July 2014 Journal of Perinatology (2014), 1 – 5 © 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp