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Am J Obstet Gynecol. 2018 Oct;219(4):386.e1-386.e9. doi: 10.1016/j.ajog.2018.05.031. Epub 2018 Jun 2.

Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial.

Author information

1
Service de Gynécologie-Obstétrique, Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Colombes, France; Institut national de la santé et de la recherche médicale Iame-U1137, Paris, France; Université Paris-Diderot, Paris, France. Electronic address: laurent.mandelbrot@aphp.fr.
2
Service de Néonatalogie, Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris, France.
3
Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du Centre Hospitalier Universitaire de Bordeaux, Université Bordeaux, Bordeaux, France.
4
Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Clermond-Ferrand, Clermond-Ferrand, France.
5
Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
6
Centre Hospitalier d'Orléans, Orléans, France.
7
Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
8
Centre Hospitalier Universitaire de Rennes, Rennes, France.
9
Centre Hospitalier Universitaire de Reims, Reims, France.
10
Assistance Publique-Hôpitaux de Paris Hôpital Antoine Béclère, Clamart, France; Université Paris Sud, Kremlin-Bicêtre, Paris, France.
11
Centre Hospitalier Universitaire de Reims, Reims, France; Service de Gynécologie-Obstétrique, Assistance Publique-Hôpitaux de Paris Hôpital Necker, Paris; Université Paris-Descartes, Paris, France.
12
Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Tours, Tours, France.
13
Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris; Université Pierre et Marie Curie, Paris, France.
14
Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire d'Angers, Angers, France.
15
Pole Femmes-Parents-Enfants, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
16
Pole Femme-Mère-Nouveau-né, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire de Lille, Lille, France.
17
Laboratoire Parasitologie-Mycologie, Université Reims Champagne-Ardenne and Hôpital Maison Blanche, Reims, France; Centre National de Référence Toxoplasmose, Reims, France.
18
Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du Centre Hospitalier Universitaire de Bordeaux, Université Bordeaux, Bordeaux, France; Institut national de la santé et de la recherche médicale U1219 Bordeaux Population Health, Bordeaux, France.
19
Centre Hospitalier Universitaire de Clermont-Ferrand.
20
Centre Hospitalier Universitaire de Rouen.
21
Centre Hospitalier Universitaire de Nantes.
22
Centre Hospitalier Universitaire de Toulouse.
23
Centre Hospitalier Régional d'Orléans.
24
Centre Hospitalier Universitaire de Reims.
25
Centre Hospitalier Universitaire de Rennes.
26
Assistance Publique- Hôpitaux de Marseille.
27
Hôpital Antoine-Béclère, Clamart.
28
Hôpital Necker-Enfants Malades, Paris.
29
Centre Hospitalier Universitaire de Tours.
30
Centre Hospitalier Universitaire de Nice.
31
Centre Hospitalier Universitaire de Lille.
32
Hôpital Trousseau, Paris.
33
Laboratoire Pasteur-Cerba, St Ouen l'Aumone.
34
Centre Hospitalier du Mans.
35
Centre Hospitalier d'Avignon.
36
Centre Hospitalier Universitaire d'Angers.
37
Centre Hospitalier Universitaire de Montpellier.
38
Centre Hospitalier Universitaire de Poitiers.
39
Centre Hospitalier de Saint-Brieuc.
40
Hôpital Bichat.
41
Hôpital Robert-Debré, Paris.
42
Hôpital Cochin, Paris.
43
Hopital de Bicêtre, Kremlin-Bicêtre.
44
Centre Hospitalier Universitaire d'Amiens.
45
Centre Hospitalier de Pontoise.
46
Centre Hospitalier Universitaire de Saint Etienne.
47
Centre Hospitalier Universitaire de Grenoble.
48
Hôpital Louis-Mourier, Colombes.
49
Hôpital Jean-Verdier, Bondy.
50
Hopital Lariboisière, Paris.
51
Hôpital Pitié-Salpêtrière, Paris.
52
Centre Hospitalier Universitaire de Dijon.
53
Centre Hospitalier Universitaire de Limoges.
54
Centre Hospitalier de Chartres.

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.

KEYWORDS:

pregnancy; prenatal diagnosis; pyrimethamine-sulfadiazine; spiramycin; tolerance; toxoplasmosis

PMID:
29870736
DOI:
10.1016/j.ajog.2018.05.031

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