Andrew E. Czeizel

Population-based case control study of the safety of sulfasalazine use during pregnancy

We studied the human teratogenic risk of sulfasalazine because this drug interferes with folate metabolism.

Risk of specific congenital abnormalities in offspring of women with diabetes

Aimsu2003 To assess the extent to which the increased risk of congenital abnormalities seen in women with pre‐gestational insulin‐treated diabetes mellitus is unspecific or related to the embryology of specific organs.

Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population‐based case–control study

Objectiveu2002 To investigate whether folic acid supplementation in early pregnancy modifies the association between the prevalence of congenital abnormalities in the offspring and maternal use of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and primidone (PRI).

Augmentin treatment during pregnancy and the prevalence of congenital abnormalities: A population-based case-control teratologic study

OBJECTIVEnTo study the human teratogenic potential of augmentin (amoxicillin+clavulanic acid) treatment during pregnancy.nnnMATERIALS AND METHODSnPair analysis of cases with different congenital abnormalities and their matched controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, between 1991 and 1996.nnnRESULTSnThe case group included 6935 pregnant women who had offspring with congenital abnormalities, while the control group consisted of 10,238 pregnant women who had babies without any defects. The number (and rate) of pregnant women with augmentin treatment was 52 (0.75%) and 56 (0.55%) in the case and control groups, respectively (crude odds ratio (OR) with 95% confidence interval (CI) was 1.4, 0.9-2.0). The comparison of augmentin treatments during the second-third months of pregnancy (i.e. in the critical period for most major congenital abnormalities) in case-control pairs did not show a higher use of augmentin in any congenital abnormality group.nnnCONCLUSIONnAugmentin treatment of pregnant women in usual therapeutic doses is unlikely to increase the risk of congenital abnormalities in newborn infants. However, the number of cases and controls was limited, therefore, further multicenter-multinational studies are needed for the final risk assessment.

A population-based case-control teratologic study of oral erythromycin treatment during pregnancy.

The objective of the study was to evaluate the human teratogenic potential of oral erythromycin treatment during pregnancy in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Of 38,151 pregnant women who had newborn infants without any congenital abnormalities (population control group), 172 (0.5%) had received erythromycin, while of 22,865 pregnant women who had newborns or fetuses with congenital abnormalities, 113 (0.5%) had been treated with erythromycin (crude OR with 95% Cl = 1.1, 0.9-1.4). The case-control pair analysis did not indicate a teratogenic potential of erythromycin during the second through third months of gestation, i.e., in the critical period for most major congenital abnormalities. The frequency of maternal erythromycin treatments during the second-third months of pregnancy was also not higher in different congenital abnormality groups compared with the rate of the total control group as referent. Thus, treatment with oral erythromycin during pregnancy did not present detectable teratogenic risk to the fetus.

A Teratological Study of Aminoglycoside Antibiotic Treatment During Pregnancy

The aim of this study was to investigate the teratogenicity of aminoglycoside antibiotics, such as parenteral gentamicin, streptomycin, tobramycin and oral neomycin, during pregnancy. Pair analysis of cases with congenital abnormalities and matched healthy controls was carried out. The setting was the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-96. In total, 38,151 pregnant women who had newborn infants without any defects (control group) and 22,865 pregnant women who had foetuses or newborns with congenital abnormalities were included in the study. 38 (0.16%) and 42 (0.11%) pregnant women in the case and control groups, respectively, were treated with the aminoglycosides studied. A teratogenic potential of gentamicin and neomycin was not indicated by a comparison of the occurrence of aminoglycoside antibiotic treatments in the total control group as referent with the figures of different congenital abnormality groups. In addition, the case-control pair analysis during the second-third months of pregnancy did not show a teratogenic risk of gentamicin and neomycin. The conclusion of this study is that treatment with parenteral gentamicin and oral neomycin during pregnancy presents no detectable teratogenic risk to the foetus, when restricted to structural developmental disturbances.The aim of this study was to investigate the teratogenicity of aminoglycoside antibiotics, such as parenteral gentamicin, streptomycin, tobramycin and oral neomycin, during pregnancy. Pair analysis of cases with congenital abnormalities and matched healthy controls was carried out. The setting was the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-96. In total, 38,151 pregnant women who had newborn infants without any defects (control group) and 22,865 pregnant women who had foetuses or newborns with congenital abnormalities were included in the study. 38 (0.16%) and 42 (0.11%) pregnant women in the case and control groups, respectively, were treated with the aminoglycosides studied. A teratogenic potential of gentamicin and neomycin was not indicated by a comparison of the occurrence of aminoglycoside antibiotic treatments in the total control group as referent with the figures of different congenital abnormality groups. In addition, the case-control pair analysis during the second-third months of pregnancy did not show a teratogenic risk of gentamicin and neomycin. The conclusion of this study is that treatment with parenteral gentamicin and oral neomycin during pregnancy presents no detectable teratogenic risk to the foetus, when restricted to structural developmental disturbances.

The risk of limb deficiencies and other congenital abnormalities in children exposed in utero to calcium channel blockers

Aim. Calcium channel blockers given to pregnant rats have shown an increased prevalence of digital and limb defects and their safety in pregnant women has thus been questioned. We examined the risk of malformations following exposure in utero to calcium channel blockers.

Nitrofurantoin and congenital abnormalities.

OBJECTIVEnTo study human teratogenic potential of oral nitrofurantoin treatment during pregnancy.nnnMATERIALS AND METHODSnPair 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.nnnRESULTSnOf 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 Downs 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.nnnCONCLUSIONnTreatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus.

A population-based case–control teratologic study of oral chloramphenicol treatment during pregnancy

The objective of the study was to check the human teratogenic potential of oral chloramphenicol treatments during pregnancy. Pair analysis of cases with congenital abnormalities and matched population controls was performed in the large population-based dataset of the Hungarian Case–Control Surveillance of Congenital Abnormalities, 1980–1996. Of 38,151 pregnant women who had babies without any defects (control group), 51 (0.13%), while of 22,865 pregnant women who had newborn infants or fetuses with congenital abnormalities, 52 (0.23%) pregnant women were treated with oral chloramphenicol. The case–control pair analysis did not show any human teratogenic potential of chloramphenicol during the second–third months of pregnancy in the different groups of congenital abnormalities. The occurrence of chloramphenicol treatment in the total control group as referent was compared with the occurrence of chloramphenicol treatment in the different congenital abnormality groups during the second–third months of gestation (i.e., in the critical period for major congenital abnormalities) and a higher adjusted OR for this drug was found only in the group with undescended testis based on only two cases. At the evaluation of medically documented chloramphenicol treatment a higher OR was not found in any congenital abnormalities. Thus, chloramphenicol treatment during early pregnancy presents little, if any, teratogenic risk to the fetus in humans.

A population-based case-control teratologic study of nalidixic acid

Objective: Quinolones, mainly nalidixic acid, are frequently used in Hungary to treat bacterial infections in pregnant women, but so far no controlled epidemiological studies of congenital abnormalities among infants born to women treated with nalidixic acid during pregnancy have been reported. Methods: The analysis of oral nalidixic acid use during pregnancy in the mothers of cases with congenital abnormalities and in their matched population controls without congenital abnormality was carried out in the population‐based dataset of the Hungarian Case–Control Surveillance of Congenital Abnormalities between 1980 and 1996. The study included 22 865 women who had newborns or fetuses with congenital abnormalities, and 38 151 pregnant women who had newborn infants without any defects (controls). Results: In the case group, 242 (1.1%) and in the control group, 377 (1.0%) pregnant women were treated with nalidixic acid (crude OR: 1.1 with 95% CI: 0.9–1.3). Seventeen different congenital abnormality groups were evaluated and a higher prevalence of pyloric stenosis was found in seven case infants born to mothers who received nalidixic acid treatment during the last months of pregnancy (adjusted OR: 11.0 with 95% CI: 1.3–91.4). Conclusions: Treatment with nalidixic acid during pregnancy may increase the risk of pyloric stenosis, though the chance effects cannot be excluded.