Does erythromycin have teratogenic properties?
The amount of information in the literature regarding the possible teratogenic effects of erythromycin treatment is insignificant. According to the results of the Perinatal Collaboration Project (a study conducted in the 1950s and early 1960s), only a few of these teratogenic effects have been reported with erythromycin. Among 79 children whose mothers took erythromycin during pregnancy, 8 had developmental defects (relative risk less than 1.5). The teratogenic properties of erythromycin used during pregnancy were not confirmed in a case-control study conducted in Hungary in 1980-1996, but an increased risk of cardiovascular malformations with erythromycin during any period of pregnancy has been found. (odds ratio 1.6, 95% confidence interval (CI) 1.1-2.4). About the same odds ratio was when using this drug at 2-3 months of pregnancy, but only 8 cases of malformations were recorded, and the increased risk was not statistically significant. Among women who have had children with cardiovascular defects, the odds ratio was 0.91 (95% CI 1.30-2.8).
It is known that the use of erythromycin in newborns at the beginning (3-13 days) of the postnatal period leads to an increased risk of pyloric stenosis. In this regard, it has also been suggested that the use of erythromycin by mothers during lactation may be a risk factor for the development of pyloric stenosis. There was no association between prenatal use of erythromycin and the development of pyloric stenosis, but this risk has been identified for other macrolides.
A study by Swedish scientists investigated the teratogenic effect of erythromycin. The study took into account the outcome of pregnancy after treatment of pregnant women at the start of pregnancy with erythromycin. All data were obtained from the Swedish Medical Birth Registry (SMBR). A similar analysis was also performed for penicillin.
SMBR contains medical information on childbirth, pregnancy and newborn babies for almost all infants in Sweden. Infants born between July 1, 1995 and late 2002, whose mothers took erythromycin during pregnancy, were selected from the SMBR. During this period, 677,028 newborns (666,046 births) were registered with the SMRB, of which 1,844 newborns (1,813 births) received erythromycin before the first visit to the prenatal clinic and the mothers in 1831 children (1806 births) after the first visit to the prenatal clinic.
The study compared the incidence of teratogenic effects of penicillin in the mothers of 9,110 newborns (8,980 births).
Among women who used erythromycin, 305 (17%) also used another antibacterial drug. In most cases (202 women), penicillins were used, in 33 patients - tetracyclines (23 of them - doxycycline), in 39 - cephalosporins (23 - cefadroxil), in 29 - clindamycin and 14 - metronidazole.
Of the 1,844 newborn babies whose mothers used erythromycin in early pregnancy, 103 were found to have birth defects (5.6%). The number of newborns with developmental disabilities whose mothers took penicillin was 420 (4.7%) out of 9110. The frequency of birth defects in all newborns was 4.6%. The odds ratio for birth defects after the mother used erythromycin, adjusted for year of birth, age of mother, number of children in family and smoking history was 1.24 (95% CI 1.01-1.51) and with penicillin 1.02 (95% CI 0.92-1.13). Among newborns with birth defects whose mothers took erythromycin in the early stages of pregnancy, 34 children (1.8%) had cardiovascular system defects (except for patients with chromosomal abnormalities, as well as newborns with open arterial duct or an umbilical artery). As for penicillin, malformations of the cardiovascular system were diagnosed in 86 neonates (0.9%), and a total of 6844 neonates were diagnosed with a similar diagnosis (1.0%).
Another malformation with a surprisingly high incidence was pyloric stenosis. This pathology was diagnosed in 4 newborn babies whose mothers took erythromycin (0.2%), in 6 children (0.06%) whose mothers received penicillin and in 458 newborns the population (0.06%). The estimated number of newborns with this diagnosis after mothers used erythromycin is 1.4, the risk ratio was 3.03 (95% CI 0.46-2.34) and the odds ratio was 1.92 (95% CI 1.37-2, 68). For penicillin, the first indicator was 5.8 and the risk ratio was 1.04 (95% CI 0.46–2.34). Thus, the study established the risk of an increased incidence of pyloric stenosis in newborns when mothers used erythromycin during pregnancy (risk ratio 3.0, 95% CI 1 , 1-8.5), and only a statistically significant risk was noted with the use of erythromycin in early pregnancy.
Compared to the prevailing opinion on the safety of erythromycin during pregnancy, this study confirms the teratogenic effect of this 14-member macrolide. An earlier study in Hungary found no teratogenic effects from erythromycin treatment, but found a high risk of cardiovascular abnormalities with erythromycin during different periods of pregnancy.
The teratogenic potential of erythromycin can be explained on the basis of studies showing that the undesirable effect of erythromycin at therapeutically significant concentrations is to block specific potassium channels in the heart (IKr) encoded by the related ether gene a-go-go human). This process results in the occurrence of a proarrhythmic effect and the risk of developing lethal arrhythmias in patients. Penicillin does not have similar proarrhythmic properties. It is possible that the hERG gene and, therefore, the potassium channels encoded by it play an important role in regulating the heart rate during the period of early embryogenesis, even before the innervation processes are completed in the heart. (at 5-9 weeks gestation). In animal studies, it has been found that drugs that block IKr are a class of drugs that have a teratogenic effect when used during the above period. Various malformations of the cardiovascular system, particularly interventricular septal abnormalities, were the most common malformations after a single use of drugs that block IKr during this period.