부산대학교 도서관

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.ajog.2018.05.031 Byline: Laurent Mandelbrot, MD [laurent.mandelbrot@aphp.fr] (a,b,c,*), Francois Kieffer, MD (d), Remi Sitta, MSc (e), Helene Laurichesse-Delmas, MD (f), Norbert Winer, MD, PhD (g), Louis Mesnard, MD (h), Alain Berrebi, MD (i), Gwenaelle Le Bouar, MD (j), Jean-Paul Bory, MD (k), Anne-Gaelle Cordier, MD (l,m), Yves Ville, MD, PhD (k,n,o), Franck Perrotin, MD, PhD (p), Jean-Marie Jouannic, MD, PhD (q,r), Florence Biquard, MD (s), Claude d'Ercole, MD, PhD (t), Veronique Houfflin-Debarge, MD, PhD (u), Isabelle Villena, MD, PhD (v,w), Rodolphe Thiebaut, MD, PhD (e,x), Helene Laurichesse-Delmas (1), Denis Pons (36), C. Nourrisson (1), Norbert Winer (2), Rose-Anne Lavergne (2), Alain Berrebi (3), Judith Fillaux (3), Corinne Assouline (3), Louis Mesnard (4), Isabelle Villena (5), Jean-Paul Bory (5), Gwenaelle Le Bouar (6), Florence Robert-Gangneux (6), Claude d'Ercole (7), Coralie L'Ollivier (7), Florence Bretelle (7), Beatrice Guidicelli (7), Patricia Garcia (7), Anne-Gaelle Cordier (8), Alexandra Benachi (8), Christelle Vauloup-Fellous (8), Emmanuelle Letamendia (8), Yves Ville (9), Marie-Elisabeth Bougnoux (9), Franck Perrotin (10), Nathalie Van Langendonck (10), Jerome Potin (10), Pierre Marty (11), Christelle Pomares (11), Cynthia Trastour (11), Veronique Houfflin-Debarge (12), Anne Sophie Deleplancque (12), Francois Kieffer (13), Jean-Marie Jouannic (13), Jean-Marc Costa (14), Marie-Therese Cheve (15), Jean-Yves Col (16), Florence Biquard (17), Bernard Cimon (17), Y. Sterkers (18), Laurence Lachaud (18), Gilles Burlet (18), Martine Marechaud (19), Estelle Perraud (19), Anne-Gaelle Grebille (20), Morgane Valentin (21), Sandrine Houze (21), Sophie Omnes (21), Yvon Chitrit (22), Christine Boissinot (22), Helene Yera (23), Olivia Anselem (23), Vassilis Tsatsaris (23), Marie-Victoire Senat (24), Florent Fuchs (24), Adela Angoulvant (24), Charles Muszynski (25), Anne Totet (25), Catherine Noel (26), Laurent Bidat (26), Tiphaine Barjat (27), Pierre Flori (27), Herve Pelloux (28), Marie-Pierre Brenier-Pinchart (28), Catherine Thong-Vanh (28), Laurent Mandelbrot (29), Corinne Floch (29), Lionel Carbillon (30), Eric Lachassine (30), Aude Ricbourg (31), Luc Paris (32), Marc Dommergues (32), Thierry Rousseau (33), Frederic Dalle (33), Marie Laure Darde (34), Veronique Aubard (34), Camille Olivier (35), Eric Verspyk (36), Loic Favennec (36) Key words pregnancy; prenatal diagnosis; pyrimethamine-sulfadiazine; spiramycin; tolerance; toxoplasmosis Background The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis. Objective We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission. Study Design This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion. Results In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23--1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00--1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine. Conclusion There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis. Author Affiliation: (1) Centre Hospitalier Universitaire de Clermont-Ferrand (2) Centre Hospitalier Universitaire de Nantes (3) Centre Hospitalier Universitaire de Toulouse (4) Centre Hospitalier Regional d'Orleans (5) Centre Hospitalier Universitaire de Reims (6) Centre Hospitalier Universitaire de Rennes (7) Assistance Publique- Hopitaux de Marseille (8) Hopital Antoine-Beclere, Clamart (9) Hopital Necker-Enfants Malades, Paris (10) Centre Hospitalier Universitaire de Tours (11) Centre Hospitalier Universitaire de Nice (12) Centre Hospitalier Universitaire de Lille (13) Hopital Trousseau, Paris (14) Laboratoire Pasteur-Cerba, St Ouen l'Aumone (15) Centre Hospitalier du Mans (16) Centre Hospitalier d'Avignon (17) Centre Hospitalier Universitaire d'Angers (18) Centre Hospitalier Universitaire de Montpellier (19) Centre Hospitalier Universitaire de Poitiers (20) Centre Hospitalier de Saint-Brieuc (21) Hopital Bichat (22) Hopital Robert-Debre, Paris (23) Hopital Cochin, Paris (24) Hopital de BicA*tre, Kremlin-BicA*tre (25) Centre Hospitalier Universitaire d'Amiens (26) Centre Hospitalier de Pontoise (27) Centre Hospitalier Universitaire de Saint Etienne (28) Centre Hospitalier Universitaire de Grenoble (29) Hopital Louis-Mourier, Colombes (30) Hopital Jean-Verdier, Bondy (31) Hopital Lariboisiere, Paris (32) Hopital Pitie-SalpA*triere, Paris (33) Centre Hospitalier Universitaire de Dijon (34) Centre Hospitalier Universitaire de Limoges (35) Centre Hospitalier de Chartres (36) Centre Hospitalier Universitaire de Rouen (a) Service de Gynecologie-Obstetrique, Assistance Publique-Hopitaux de Paris, Hopital Louis Mourier, Colombes, France (b) Institut national de la sante et de la recherche medicale Iame-U1137, Paris, France (c) Universite Paris-Diderot, Paris, France (d) Service de Neonatalogie, Assistance Publique-Hopitaux de Paris, Hopital Trousseau, Paris, France (e) Unite de Soutien Methodologique a la Recherche Clinique et Epidemiologique du Centre Hospitalier Universitaire de Bordeaux, Universite Bordeaux, Bordeaux, France (f) Service de Gynecologie-Obstetrique, Centre Hospitalier Universitaire de Clermond-Ferrand, Clermond-Ferrand, France (g) Service de Gynecologie-Obstetrique, Centre Hospitalier Universitaire de Nantes, Nantes, France (h) Centre Hospitalier d'Orleans, Orleans, France (i) Centre Hospitalier Universitaire de Toulouse, Toulouse, France (j) Centre Hospitalier Universitaire de Rennes, Rennes, France (k) Centre Hospitalier Universitaire de Reims, Reims, France (l) Assistance Publique-Hopitaux de Paris Hopital Antoine Beclere, Clamart, France (m) Universite Paris Sud, Kremlin-BicA*tre, Paris, France (n) Service de Gynecologie-Obstetrique, Assistance Publique-Hopitaux de Paris Hopital Necker, Paris (o) Universite Paris-Descartes, Paris, France (p) Service de Gynecologie-Obstetrique, Centre Hospitalier Universitaire de Tours, Tours, France (q) Assistance Publique-Hopitaux de Paris, Hopital Trousseau, Paris (r) Universite Pierre et Marie Curie, Paris, France (s) Service de Gynecologie-Obstetrique, Centre Hospitalier Universitaire d'Angers, Angers, France (t) Pole Femmes-Parents-Enfants, Assistance Publique-Hopitaux de Marseille, Marseille, France (u) Pole Femme-Mere-Nouveau-ne, Hopital Jeanne de Flandre, Centre Hospitalier Universitaire de Lille, Lille, France (v) Laboratoire Parasitologie-Mycologie, Universite Reims Champagne-Ardenne and Hopital Maison Blanche, Reims, France (w) Centre National de Reference Toxoplasmose, Reims, France (x) Institut national de la sante et de la recherche medicale U1219 Bordeaux Population Health, Bordeaux, France * Corresponding author: Laurent Mandelbrot, MD. Article History: Received 16 January 2018; Revised 15 May 2018; Accepted 24 May 2018 (footnote) Supported by a grant from the French Ministry of Health, Program for Hospital Clinical Research (national AOM09182). (footnote) The authors report no conflict of interest. (footnote) Cite this article as: Mandelbrot L, Kieffer F, Sitta R, et al. Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial. Am J Obstet Gynecol 2018;219:386.e1-9.