Nitrofurantoin and congenital abnormalities

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Abstract

Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980–1996. Results: Of 38,151 pregnant women who had newborn infants without any congenital abnormalities (population control group), 774 (3.4%); of 22,865 case pregnant women who had newborns or fetuses with congenital abnormalities, 1079 (2.8%) and of 812 pregnant women who had newborns or fetuses with Down’s syndrome (patient controls), 23 (2.8%) pregnant women were treated with nitrofurantoin. The above differences between population controls and cases may be connected with recall bias, because the case-control pair analysis did not indicate a teratogenic potential of nitrofurantoin use during the second and the third months of gestation, i.e. in the critical period for major congenital abnormalities. Conclusion: Treatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus.

Introduction

Nitrofurantoin is an antimicrobial agent used for the treatment and prevention of urinary tract infections. About 4% of pregnant women with covert bacteriuria, acute cystitis and pyelonephritis were treated by nitrofurantoin in Hungary during the 1980s. Therapeutic doses of nitrofurantoin are unlikely to pose a substantial teratogenic risk, but the available data are insufficient to state that there is no risk [1], [2], [3]. We report data from the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) [4] on the safety of nitrofurantoin in pregnancy.

Section snippets

Materials and methods

The Hungarian Congenital Abnormality Registry (HCAR) is a national-based registry of cases with congenital abnormality (CA) [5]. Notification of CAs is mandatory for physicians, and most are reported by obstetricians (in Hungary practically all deliveries occur in inpatient obstetric clinics) and pediatricians (who are working in the neonatal units of inpatient obstetric clinics and various inpatient and outpatient pediatric clinics). Autopsy was obligatory for all infant deaths and usual in

Results

During the study period, 2,146,574 babies were born in Hungary, hence 38,151 population controls represented 1.8% of the Hungarian births. In the population control group, 1079 (2.8%) pregnant women had nitrofurantoin treatment. The case group consisted of 22,865 malformed offspring and 774 (3.4%) pregnant women were treated by nitrofurantoin during pregnancy (crude OR: 1.2 with 95% CI=1.1–1.3). Of 812 patient controls, 23 (2.8%) had mothers with nitrofurantoin treatment during pregnancy (crude

Discussion

We estimated the teratogenic effect of oral nitrofurantoin treatments during pregnancy in cases with CA and in their matched controls as well as in patient controls. The critical evaluation of our data did not indicate a detectable teratogenic risk of nitrofurantoin.

The strengths of the HCCSCA are (i) the large population-based dataset; (ii) including 1876 pregnant women with oral nitrofurantoin treatment because this drug was used frequently in Hungary for the treatment of urinary tract’s

Acknowledgements

This project was supported by the EuroMap concerted action in the Biomed 2 Work programme, Contract No. BMH4-97-2430 and the Danish Medical Research Council (Grant No. 9700 677).

References (15)

  • A Kis-Varga et al.

    A new approach to germinal mutation surveillance: pair-wise evaluation of component elements in unidentified multiple congenital abnormalities

    Mut. Res.

    (1990)
  • Friedman JM, Polifka JE. The effects of drugs on the fetus and nursing infant. Baltimore: Johns Hopkins University...
  • R Wise

    Antibiotics Br. Med. J.

    (1987)
  • Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 5th ed. Baltimore: Williams and Wilkins,...
  • A.E Czeizel et al.

    Evaluation of drug intake during pregnancy in the Hungarian Case-Control Surveillance of Congenital Anomalies

    Teratology

    (1990)
  • A.E Czeizel

    The first 25 years of the Hungarian Congenital Abnormality Registry

    Teratology

    (1997)
  • Czeizel AE, The role of pharmacoepidemiology in pharmacovigilance: rational drug use in pregnancy. Pharmacoepid Drug...
There are more references available in the full text version of this article.

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