Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial - 12/07/18
, François Kieffer, MD d, Rémi Sitta, MSc e, Hélène Laurichesse-Delmas, MD f, Norbert Winer, MD, PhD g, Louis Mesnard, MD h, Alain Berrebi, MD i, Gwenaëlle Le Bouar, MD j, Jean-Paul Bory, MD k, Anne-Gaëlle 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, Véronique Houfflin-Debarge, MD, PhD u, Isabelle Villena, MD, PhD v, w, Rodolphe Thiébaut, MD, PhD e, xand the
TOXOGEST Study Group
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : pregnancy, prenatal diagnosis, pyrimethamine-sulfadiazine, spiramycin, tolerance, toxoplasmosis
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| Supported by a grant from the French Ministry of Health, Program for Hospital Clinical Research (national AOM09182). |
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| The authors report no conflict of interest. |
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| 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;volume;x.ex-x.ex. |
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