International Journal of Gynecology and Obstetrics 83(2003) 305–306

0020-7292/03/$30.00� 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd.All rights reserved.doi:10.1016/S0020-7292(03)00259-5

Brief communication

Oral tinidazole treatment during pregnancy and teratogenesis

A.E. Czeizel*, Z. Kazy, P. Vargha

Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary

Received 18 March 2003; received in revised form 14 May 2003; accepted 20 May 2003

Keywords: Tinidazole; Human teratogenic potential; Congenital abnormalities; Case–control analysis

Placental transfer of tinidazole(Tinidazol,Polfa ), an anti-infective drug possesses tricho-�

monocidal and amoebicidal activity was proved inearly human pregnancyw1x, therefore it shouldnotbe given in the first trimester of pregnancyw2x.The teratogenic potential of tinidazole was eval-

uated in the large population-based data set of theHungarian Case–Control Surveillance of Congen-ital Abnormalitiesw3x. Cases with isolated congen-ital abnormalities(CAs) and multiple CAs wereselected from the Hungarian Congenital Abnor-mality Registry w4x between 1980 and 1996. Ascontrols, two newborn infants without CAs wereselected for every case from the National BirthRegistry of the Central Statistical Office matchingaccording to sex, week of birth, and district ofparents’ residence. The exposure data wereobtained prospectively through antenatal care log-books and other medical records, in addition ret-rospectively by questionnaires completed bymothers, finally all non-respondent case and 200non-respondent control families were visited athome by regional nurses to obtain necessary data.Exposure information was available for 85.5% of

*Corresponding author. 1026 Budapest, Torokvesz lejto 32,¨ ¨ ´Hungary. Tel.yfax: q36-1-394-4712.

E-mail address: czeizel@interware.hu(A.E. Czeizel).

cases(response: 73.6%; home visit: 11.9%) and69.3% (response: 68.9%; home visit: 0.4%) ofcontrols.Of 22 843 cases with CA, only 10(0.04%),

while of 38 151 controls, 16(0.04%) had motherswith oral tinidazole treatment(1–2 gyday for 6–7 days) during pregnancy(crude POR with 95%CI: 1.0; 0.7–1.3). Tinidazole was used mainly inthe second trimester(4 and 10 in the case andcontrol groups, respectively).Potential confounders and distribution of gesta-

tional months by treatment did not show a differ-ence between the two study groups.The McNemar analysis for case–control pairs

did not indicate a higher maternal tinidazole useduring the entire pregnancy or during the second–third months of gestation among cases in CA-groups on the basis of adjusted PORs with 95%CI for potential confounders using conditionallogistic regression model(Table 1).The first controlled epidemiological study failed

to demonstrate a higher rate of CAs in childrenborn to mothers who had received oral tinidazoletreatment during pregnancy. However, the numberwas limited, therefore further studies are neededfor the final conclusion.

306 A.E. Czeizel et al. / International Journal of Gynecology and Obstetrics 83 (2003) 305–306

Table 1Results of McNemar analysis of case–control pairs and adjusted prevalence odds ratios(POR) with 95% confidence interval(95%CI) of tinidazole treatment during pregnancy

Congenital abnormality Case–control pairs Entire pregnancy Second–third(CA) groups

No No Yes No No Yes Yes Yes Total POR 95% CImonths

POR 95% CI

Isolated CAsCardiovascular CAs 4476 (4477) 1 (1) 2 (1) 0 (0) 4479 0.8 0.1–8.9 1.0 0.1–16.0Pyloric stenosis 240 (240) 1 (1) 0 (0) 0 (0) 241 (3.0 0.1–73.7) 3.0 0.1–73.7Hypospadias 3034 (3038) 1 (0) 3 (0) 0 (0) 3038 0.4 0.0–4.1 –Undecended testis 2049(2050) 1 (1) 1 (0) 0 (0) 2051 0.8 0.1–12.8 3.0 0.1–73.7Clubfoot 2421 (2424) 1 (0) 2 (0) 0 (0) 2424 0.5 0.1–5.6 –Limb deficiencies 547 (548) 1 (0) 0 (0) 0 (0) 548 (3.0 0.1–73.7) –Polyysyndactyly 1739 (1744) 3 (0) 2 (0) 0 (0) 1744 0.7 0.1–5.2 –Other isolated CAs 6968 (6969) 0 (0) 1 (0) 0 (0) 6969 (0.3 0.0–8.2) –

Multiple CAs 1348 (1349) 1 (0) 0 (0) 0 (0) 1349 (3.0 0.1–73.7) –

Total 22 822 (22839) 10 (3) 11 (1) 0 (0) 22 843 1.0 0.4–2.4 3.0 0.3–28.8

The data of subgroups of the second–third month of gestation are shown in parentheses.

References

w1x Karhunan M. Placental transfer of metronidazole andtinidazole in early human pregnancy after a singleinfusion. Br J Clin Pharmacol 1984;18:254–257.

w2x Pagliaro AM, Pagliaro LA. Pharmacologic aspects ofnursing. St. Louis, MO: Mosby Co, 1986.

w3x Czeizel AE, Rockenbauer M, Siffel CS, Varga E.Description and mission evaluation of the HungarianCase-Control Surveillance of Congenital Abnormalities,1980–1996. Teratology 2001;63:176–185.

w4x Czeizel AE. The first 25 years of the Hungarian Con-genital Abnormality Registry. Teratology 1997;55:299–305.