General

1. Korzeniowski OM. Antibacterial agents in pregnancy. Infect Dis Clin North Am 1995 Sep;9(3):639-51. Except for topical, nonabsorbable agents, any antibiotic chosen for use in pregnancy exposes the fetus as well as the mother to its effects. Therefore, initiation of antimicrobial therapy must be based on clear-cut necessity. Because the physiology of the maternal-fetal unit is complex and ethical consideration of potential fetal harm is pre-eminent, data on safety are derived from animal studies, incidental observations on individual women treated with an agent, or longitudinal tracing of groups of women who required treatment with a particular antimicrobial regimen. Consequently, a rating of absolute safety in pregnancy has never been assigned to any currently available antimicrobial agent. Decades of clinical experience with penicillins, cephalosporins, and erythromycins have documented the pharmacokinetics of these drugs in pregnant women as well as their overall safety for the fetus. These classes of drugs are those most favored for use in pregnancy for susceptible infections. Although aminoglycosides have known toxic effects on the fetus, they are safe to use if serum levels are carefully monitored in the mother. Agents in the quinolone, sulfonamide, and tetracycline categories should be avoided unless maternal necessity for their use justifies the exposure of the fetus to their toxicity. Both clinical and experimental data are very limited on the newer agents, such as the new macrolides, azithromycin and clarithromycin. The first-line agents for the treatment of TB (i.e., INH, rifampin, and ethambutol) are considered safe in pregnancy, but in the era of multidrug-resistant mycobacterial isolates, agents with known or suspected fetal toxicity may need to be used.

2. Duff P. Antibiotic selection in obstetric patients. Infect Dis Clin North Am 1997 Mar;11(1):1-12 (from the issue enterely devoted to “infections in obstetrics”)

3. Int J Gynaecol Obstet 1998 Jun;61(3):299-308 ACOG educational bulletin. Antimicrobial therapy for obstetric patients. Number 245, March 1998

Fluoroquinolones

1. Loebstein R, Addis A, et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother 1998 Jun;42(6):1336-9. We concluded that the use of fluoroquinolones during embryogenesis is not associated with an increased risk of major malformations. There were no clinically significant musculoskeletal dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of therapeutic abortions observed in quinolone-exposed women compared to that for their controls may be secondary to the misperception of a major risk related to quinolone use during pregnancy.

2. Loebstein R, Addis A, Ho E, Andreou R, et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study Antimicrob Agents Chemother 1998 Jun;42(6):1336-9 Concerns regarding the teratogenicity of fluoroquinolones have resulted in their restricted use during gestation. This is despite an increasing need for their use due to emerging bacterial resistance. The objectives of the present investigation were to evaluate pregnancy and fetal outcomes following maternal exposure to fluoroquinolones and to examine whether in utero exposure to quinolones is associated with clinically significant musculoskeletal dysfunctions. We prospectively enrolled and followed up 200 women exposed to fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin) during gestation. Pregnancy outcome was compared with that for 200 controls matched for age and for smoking and alcohol consumption habits. Controls were exposed to nonteratogenic, nonembryotoxic antimicrobial agents matched by indication, duration of therapy (+/- 3 days), and trimester of exposure. Rates of major congenital malformations did not differ between the group exposed to quinolones in the first trimester (2.2%) and the control group (2.6%) (relative risk, 0.85; 95% confidence interval, 0.21 to 3.49). Women treated with quinolones had a tendency for an increased rate of therapeutic abortions compared with the rate among women exposed to nonteratogens (relative risk, 4.50; 95% confidence interval, 0.98 to 20.57), resulting in lower live-birth rates (86 versus 94%; P = 0.02). The rates of spontaneous abortions, fetal distress, and prematurity and the birth weight did not differ between the groups. Gross motor developmental milestone achievements did not differ between the children of the mothers in the two groups. We concluded that the use of fluoroquinolones during embryogenesis is not associated with an increased risk of major malformations. There were no clinically significant musculoskeletal dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of therapeutic abortions observed in quinolone-exposed women compared to that for their controls may be secondary to the misperception of a major risk related to quinolone use during pregnancy.

Cephalosporins

1. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: a population-based, case-control study. Am J Obstet Gynecol. 2002 Sep;187(3):817; discussion 817

2. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: a population-based, case-control study. Am J Obstet Gynecol 2001 May;184(6):1289-96 Comment in: Am J Obstet Gynecol. 2002 Sep;187(3):817; discussion 817. OBJECTIVE: Our purpose was to study the human teratogenic potential of cephalosporin treatment during pregnancy. STUDY DESIGN: Pair analysis of cases with congenital abnormalities and matched controls without congenital abnormalities was performed. The population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, was used. The participants included 22,865 pregnant women who had fetuses or newborn infants with congenital abnormalities, 38,151 pregnant women who had infants without any defects (population control group), and 812 mothers who were delivered of babies affected with Down syndrome (patient controls). RESULTS: In the case group, 308 (1.35%) pregnant women were treated with cephalosporin. In the population and patient control groups, 440 (1.15%) and 16 (1.97%) pregnant women had similar treatments. The somewhat higher use of cephalosporins, mainly oral cephalexin, in the case and patient control groups was explained by recall bias. The comparison of the occurrence of medically documented cephalosporin treatments during the second to third months of gestation (ie, the critical period for major congenital abnormalities) in different congenital abnormality groups with the referent data of the total population control group and the patient control group did not indicate a detectable human teratogenic potential of the studied drug. CONCLUSION: Treatment with the studied cephalosporins during pregnancy does not seem to present a detectable teratogenic risk to the fetus. However, further studies are needed to clarify the teratogenic and fetal toxic effects of different cephalosporins separately.

3. Berkovitch M, Merlob P. Use of cephalosporins during pregnancy and in the presence of congenital abnormalities. Am J Obstet Gynecol 2002 Sep;187(3):817; author reply 817.

Sulfonamides

1. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Reprod Toxicol 2001 Nov;15(6):637- Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfamethoxazole (cotrimoxazole) and trimethoprim-sulfamethazine during pregnancy. These agents have antifolate effects and other antifolate agents can induce multiple congenital abnormalities, neural-tube defects, cardiovascular, and other malformations in animal experiments and in humans.Design: Pair analysis of cases with congenital abnormalities and matched healthy controls in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996.Participants: 38,151 pregnant women who had newborn infants without any congenital abnormalities (control group) and 22,865 case pregnant women who had newborns or fetuses with congenital abnormalities.Main Outcome: Prevalence of drug use in matched case-control pairs to study the possible association with congenital abnormalities.Results: In the case group 351 (1.5%) and in the control group 443 (1.2%) pregnant women were treated with cotrimoxazole (crude OR 1.3 with 95% CI 1.1-1.5). In addition 45 (0.2%) case and 39 (0.1%) control pregnant women had trimethoprim-sulfamethazine treatment (crude OR 1.9 with 95% CI 1.3-3.0). A higher rate of multiple congenital abnormalities (including mainly urinary tract and cardiovascular abnormalities) was found in case infants born to mothers with cotrimoxazole treatment during the second-third months of pregnancy. In addition, a higher rate of cardiovascular malformations occurred in cases born to mothers with cotrimoxazole treatment and trimethoprim-sulfamethazine treatment during the second-third months of pregnancy, respectively.Conclusion: Treatment with cotrimoxazole during pregnancy may increase the risk of cardiovascular malformations, and particularly multiple congenital abnormalities including defects of the urinary tract and cardiovascular system. A higher rate of cardiovascular malformations was also found after treatment with trimethoprim-sulfamethazine in the second-third months of pregnancy.

Penicillins

2. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. A population-based case-control teratologic study of ampicillin treatment during pregnancy. Am J Obstet Gynecol 2001 Jul;185(1):140- OBJECTIVE: This was a study of the association between ampicillin treatment during pregnancy and prevalence of different congenital abnormalities. STUDY DESIGN: The paired analysis of case patients with congenital abnormalities and matched population control subjects was performed in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 38,151 pregnant women who had babies without any defects (population control group), 2632 (6.9%) had been treated with ampicillin. Of 22,865 pregnant women who had offspring with congenital abnormalities (case patients), 1643 (7.2%) had been treated with ampicillin (crude odds ratio, 1.0; 95% confidence interval, 0.7-1.2). Of 812 mothers who were delivered of babies affected by Down syndrome (patient control subjects), 61 (7.5%) had ampicillin treatment, and these were also compared with the case group. RESULTS: The prevalence of ampicillin use during the second and third months of gestation, which is the critical period for most major congenital abnormalities, showed significant difference in the case-control pair analysis only for cleft palate (odds ratio, 4.2; 95% confidence interval, 1.4-16.3). This possible association was confirmed by the analysis of medically recorded ampicillin use and by the comparison of ampicillin treatment between the group with cleft palate and the patient control subjects. CONCLUSION: Treatment with ampicillin during pregnancy may pose little if any teratogenic risk in human beings. Only a higher prevalence of cleft palate was found after the ampicillin treatment during the second and third months of gestation. The lack of an experimental animal model and the lack of consistency with previous epidemiologic studies may indicate that even this apparent risk is not real and instead is a chance association; further investigation is therefore necessary.

3. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. Augmentin treatment during pregnancy and the prevalence of congenital abnormalities: a population-based case-control teratologic study. Eur J Obstet Gynecol Reprod Biol 2001 Aug;97(2):188-92 OBJECTIVE: To study the human teratogenic potential of augmentin (amoxicillin+clavulanic acid) treatment during pregnancy. MATERIALS AND METHODS: Pair 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. RESULTS: The 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. CONCLUSION: Augmentin 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.

Macrolides

1. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. A population-based case-control teratologic study of oral erythromycin treatment during pregnancy. Reprod Toxicol 1999 Nov-Dec;13(6):531-6 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.

2. Cooper WO, Ray WA, Griffin MR. Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis. Obstet Gynecol 2002 Jul;100(1):101-6. OBJECTIVE: To assess the association between prenatal antibiotics, including erythromycin, and infantile hypertrophic pyloric stenosis in a large cohort of infants. METHODS: This was a retrospective cohort study of births to women enrolled in Tennessee Medicaid/TennCare, 1985-1997. Prescriptions for erythromycin, nonerythromycin macrolides, and other antibiotics were identified from pharmacy files linked with birth certificate files. The primary study outcome was development of pyloric stenosis in the infant, identified from linked hospital discharge diagnosis and surgical procedure codes. RESULTS: The cohort included 260,799 mother/infant pairs. Among these women, 13,146 filled prescriptions for erythromycin (50.4 per 1000), and 621 filled prescriptions for nonerythromycin macrolides (2.4 per 1000). There was no association with prenatal erythromycin prescription and infantile hypertrophic pyloric stenosis either after 32 weeks' gestation (adjusted odds ratio 1.17, 95% confidence interval, 0.84, 1.64, P =.33) or at any time during pregnancy (adjusted odds ratio 1.15, 95% confidence interval 0.84, 1.56, P =.36). There was an association between maternal prescriptions for nonerythromycin macrolides and infantile hypertrophic pyloric stenosis (adjusted odds ratio 2.77, 95% confidence interval 1.22, 6.30, P =.01). CONCLUSION: The hypothesized association between erythromycin and infantile pyloric stenosis was not seen. Causal inference from the association between prenatal nonerythromycin macrolides and infantile hypertrophic pyloric stenosis is limited by the small number of affected children and the evidence of other differences between users of nonerythromycin macrolides and controls.

3. Einarson A, Phillips E, Mawji F, D'Alimonte D, Schick B, Addis A, Mastroiacova P, Mazzone T, Matsui D, Koren G. A prospective controlled multicentre study of clarithromycin in pregnancy. Am J Perinatol 1998;15(9):523-5. Clarithromycin is a relatively new macrolide antibiotic with an action spectrum similar to that of erythromycin. Its main indications for use are for upper and lower respiratory and skin and soft tissue infections. Little is known about its safety in pregnancy, although animal reproductive studies found an increased rate of cardiovascular anomalies, cleft palate, and embryonic loss. Human data, limited to case reports and one small uncontrolled study, cannot allow evidence based counseling of pregnant women who were exposed to the drug before finding out they were pregnant. Pregnant women who had been counseled on the use of clarithromycin by five centers, were matched for age, smoking, and alcohol use with a control group of pregnant women who were exposed to nonteratogenic antibiotics. A total of 157 women were followed up. Of these, 122 were exposed to the drug in the first trimester. There were no significant differences found between the two groups in the rates of major and minor malformations; 2.3 versus 1.4% for major (p = 0.86) and 5.4 versus 4.9% for minor (p = 0.96). Spontaneous abortion rates in the exposed group was significantly different, higher (14%) than in the control group (7%) (p = 0.04). This first prospective controlled study of exposure to clarithromycin in pregnancy suggests that this agent does not increase the rate of major malformations above the baseline risk of 1-3%. The higher rate of reported spontaneous abortions, although still within the expected baseline rate, may warrant further study.

4. Drinkard CR, Shatin D, Clouse J. Postmarketing surveillance of medications and pregnancy outcomes: clarithromycin and birth malformations. Pharmacoepidemiol Drug Saf 2000 Dec;9(7):549-56. PURPOSE: This retrospective surveillance study used linked administrative claims data and medical records to determine the rate and types of birth malformations in infants born to women exposed to the antibiotic, clarithromycin (Biaxin), during the first trimester of pregnancy. METHODS: Pharmacy and hospital claims from eight geographically diverse health plans were used to identify women who had a delivery claim within 270 days of a clarithromycin prescription over a 5-year period (1991-1995). Hospital delivery admission medical records for 143 mothers and their 149 infants were abstracted to identify birth malformations. RESULTS: Five infants were identified with major malformations, three with minor malformations, and four with undescended testicles likely to resolve with time. The observed rate of 3.4% (95% CI, 0.5, 6.3) for major malformations was not statistically significantly different compared to an expected rate of 2.8% based on earlier national data. There was no consistency across types of major malformations. CONCLUSIONS: These results provide no evidence that clarithromycin is a likely major teratogen in humans. Use of claims data is one way to evaluate quickly and efficiently the safety of prescription medications in humans during pregnancy, especially when both exposure and outcome are rare.

5. Cooper WO, Griffin MR, Arbogast P, Hickson GB, Gautam S, Ray WA. Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Arch Pediatr Adolesc Med 2002 Jul;156(7):647-50. OBJECTIVE: To assess the link between very early erythromycin exposure and pyloric stenosis in young infants. DESIGN: Retrospective cohort study. PARTICIPANTS AND METHODS: Medicaid or TennCare (Tennessee's program for Medicaid enrollees and uninsured individuals) births in Tennessee from 1985 to 1997. Cases of infants with a hospital discharge diagnosis of pyloric stenosis and an associated surgical procedure code were used. Erythromycin exposure and other antibiotic exposure between 3 and 90 days of life were identified from prescription files. MAIN OUTCOME MEASURES: Hospital discharge diagnosis of pyloric stenosis, and an associated surgical procedure code. RESULTS: Of 933 239 births in Tennessee during the study period, 314 029 were enrolled in Medicaid. Among these infants, 804 (2.6/1000 infants) met the criteria for pyloric stenosis. Very early exposure to erythromycin (between 3 and 13 days of life) was associated with a nearly 8-fold increased risk of pyloric stenosis (adjusted incident rate ratio, 7.88; 95% confidence interval, 1.97-31.57). No increased risk of pyloric stenosis was seen in infants exposed to erythromycin after 13 days of life or in infants exposed to antibiotics other than erythromycin. CONCLUSIONS: The significant increase in pyloric stenosis in children with very early exposure to erythromycin is consistent with reports of other investigators. The risks and benefits of erythromycin should be weighed carefully prior to initiating such therapy in young infants.

6. Kacmar J, Cheh E, Montagno A, Peipert JF. A randomized trial of azithromycin versus amoxicillin for the treatment of Chlamydia trachomatis in pregnancy. Infect Dis Obstet Gynecol 2001;9(4):197-202. OBJECTIVE: To compare the compliance, side effects and efficacy of amoxicillin and azithromycin for the treatment of Chlamydia trachomatis infection in pregnancy. METHODS: This is a randomized single-blind trial of women diagnosed with C. trachomatis before 33 weeks gestation. Women were randomlyassigned either 500 mg amoxicillin orally three times per dayfor 7 days or a single dose of 1 g azithromycin orally. Patients were interviewed by telephone approximately 3-7 days following therapy to assess compliance and side effects. Test of cure was performed at a follow-up visit 4-6 weeks following completion of therapy. RESULTS: Thirty-nine patients were randomized with 19 receiving amoxicillin and 20 receiving azithromycin. There were no differences in baseline data between the two groups, and there were no statistically significant differences in side effects, compliance or efficacy. In the amoxicillin group 84% of women took all pills, while 100% completed the single 1 g dose of azithromycin. Side effects were common in both groups (38% overall), with 40% of the azithromycin group reporting moderate to severe gastrointestinal side effects compared to 17% in the amoxicillin group (p = 0.11). Of patients who returned for follow-up test of cure, 3 of 15 (20%) in the amoxicillin group were positive compared with 1 of 19 (5%) in the azithromycin group (p = 0.3). CONCLUSIONS: Side effects of therapy for C. trachomatis in pregnancy are common. Amoxicillin was slightly better tolerated than azithromycin. Compliance and cure rates with both regimens was high.

7. Louik C, Werler MM, Mitchell AA. Erythromycin use during pregnancy in relation to pyloric stenosis. Am J Obstet Gynecol 2002 Feb;186(2):288-90. OBJECTIVE: Newborn infants treated with erythromycin may be at risk for developing pyloric stenosis. Because erythromycin is known to cross the placenta and is a recommended treatment for chlamydia and other infections in pregnancy, we explored whether erythromycin taken during pregnancy might similarly lead to an increase in risk of pyloric stenosis. STUDY DESIGN: We used data collected between 1976 and 1998 as part of an ongoing case-control surveillance program. Cases were 1044 infants with a diagnosis of pyloric stenosis. Two control groups were used: 1704 nonmalformed infants and 15,356 infants with a wide range of other malformations. Odds ratios and 95% CIs were calculated by using data from each control group. RESULTS: All odds ratio estimates are close to 1.0, all CIs include 1, and all upper 95% confidence bounds are less than 2.0. CONCLUSION: We found no evidence of an increased risk of pyloric stenosis among infants born to mothers exposed to erythromycin during pregnancy.

8. Mahon BE, Rosenman MB, Kleiman MB. Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis. J Pediatr 2001 Sep;139(3):380-4. OBJECTIVES: To evaluate the risk for infantile hypertrophic pyloric stenosis (IHPS) among infants prescribed systemic erythromycin, infants prescribed a course of erythromycin ophthalmic ointment, and infants whose mothers were prescribed a macrolide antibiotic during pregnancy. STUDY DESIGN: Retrospective cohort study of infants born at an urban hospital from June 1993 through December 1999. RESULTS: Of 14,876 eligible infants, 43 (0.29%) developed IHPS. Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66). Erythromycin ophthalmic ointment for conjunctivitis was not associated with increased risk of IHPS. Maternal macrolide antibiotics within 10 weeks of delivery may have been associated with higher risk of IHPS but the data were not conclusive. CONCLUSIONS: This study confirms an association between systemic erythromycin in infants and subsequent IHPS, with the highest risk in the first 2 weeks of age. No association was found with erythromycin ophthalmic ointment. A possible association with maternal macrolide therapy in late pregnancy requires further study. Systemic erythromycin should be used with prudence in early infancy.

Aminoglycosides

1. Fernandez H, Bourget P, Delouis C, Demirdjian S. [The administration of tobramycin in the 2nd and 3rd trimester of pregnancy: contribution to a pharmacokinetic study for the adaptation of posology] [Article in French] J Gynecol Obstet Biol Reprod (Paris) 1991;20(1):107-15. Aminoglycosides are currently used during pregnancy for the treatment of Staphylococcus, Enterobacteriaceae, Listeria monocytogenes, and Pseudomonas aeruginosa infections. The pharmacokinetics of tobramycin, an aminoglycoside antibiotic, was investigated after a 2.5 mg/kg short intravenous infusion and a once-daily dose regime in 18 pregnant women divided into 2 groups of 9 during the second (Group I: from 20 to 28 weeks of amenorrhoea) and the third (Group II: greater than or equal to 28 weeks of amenorrhoea) trimesters of pregnancy (during these period, risks of infectious diseases are increased). Plasma concentrations of tobramycin were measured by fluorescence polarization immunoassay (FPIA). The decrease of clearance (decrement of 27.6%), at 28 weeks and more gestation leads to an increase in the half-life and the MRT observed in the second group (increment of 49% and 41% respectively), whereas the volume of distribution remained unchanged in the two groups. No accumulation of the drug was observed in pregnant women. Pharmacokinetic disorders are correlated with the duration and moreover with the weight deviation of the women i.e., the growth of the conceptus. In 10 cases, a feto-maternal concentration ratio was calculated at delivery using an umbilical cord blood sample. This findings suggest a phenomenon of accumulation in the conceptus. To limit the potential nephrotoxicity and ototoxicity of tobramycin for the mother and the fetus, a once-daily dose regime seems to be an advanced solution for treatment of nonneutropenic pregnant women.

2. Czeizel AE, Rockenbauer M, Olsen J, Sorensen HT. A teratological study of aminoglycoside antibiotic treatment during pregnancy. Scand J Infect Dis 2000;32(3):309-13. 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.