In utero exposure to antibiotics and risk of congenital malformations: a population-based study
Per Damkier1, Louise M S Brønniche2, Johan F B Korch-Frandsen3
1Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Insights
This study found no increased risk of birth defects from 10 common antibiotics during early pregnancy when compared to penicillin use. Some minor risks were observed for specific antibiotics like pivmecillinam, sulfamethizole, and azithromycin versus no antibiotic exposure.
Area of Science:
- Obstetrics and Gynecology
- Pharmacology
- Pediatric Health
Background:
- Antibiotic use during pregnancy is common, with established safety for penicillins.
- Uncertainty exists regarding the safety of other frequently prescribed antibiotics during gestation.
Purpose of the Study:
- To assess the risk of congenital malformations after first-trimester exposure to 10 common antibiotics in Denmark.
- To compare risks against penicillin exposure and unexposed pregnancies.
Main Methods:
- A large cohort study in Denmark (2000-2015) linked healthcare and civic registries.
- Logistic regression analyzed malformation risks (any, major, cardiac) for 10 antibiotics versus safe penicillins and unexposed groups.
- Adjusted for maternal and socioeconomic factors.
Main Results:
- No increased risk of congenital malformations was linked to the 10 antibiotics compared to safe penicillins.
- Compared to no exposure, slight increases in major and cardiac malformations were noted for pivmecillinam, sulfamethizole, and azithromycin.
Conclusions:
- This study provides high-precision evidence of no increased congenital malformation risk from first-trimester exposure to 10 common systemic antibiotics.
- Findings support the generally safe use of these antibiotics during early pregnancy, with specific considerations for pivmecillinam, sulfamethizole, and azithromycin when compared to unexposed pregnancies.
Background:
Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with the use of other commonly prescribed antibiotics.
Objective:
To determine the risk of congenital malformations following first-trimester in utero exposure to 10 commonly prescribed antibiotics in Denmark.
Materials And Methods:
This was a cohort study comprising all singleton liveborn children in Denmark between 2000 and 2015. Data on malformations were collected through 2016. Merging validated and comprehensive populationwide Danish healthcare and civic registries, we merged data on pregnancy, prescription drugs purchases during first trimester and congenital malformations. Using logistic regression, we calculated the odds ratio for congenital malformations (any), major congenital malformations, and cardiac congenital malformations for the 10 most commonly prescribed antibiotics (excluding 4 penicillins that served as control). In the primary analysis, the exposed cohort was compared to a cohort exposed to any of 4 penicillins considered safe during pregnancy (ampicillin, pivampicillin, benzylpenicillin, and phenoxymethylpenicillin). In sensitivity analysis, the exposed cohort was compared to an unexposed cohort. Covariate adjustments were made for maternal age at delivery, year of delivery, parity, pre-pregnancy body mass index, smoking, educational status, employment status, and annual personal income.
Results:
We found no increased risk of congenital malformations to be related to first-trimester in utero exposure to the 10 most commonly prescribed antibiotics in Denmark compared to a cohort of pregnant women exposed to penicillins that are considered safe during pregnancy. Compared to unexposed pregnancies, small increased risks for major malformations and cardiac malformations were apparent for pivmecillinam (odds ratio, 1.13; confidence interval, 1.06-1.19; and odds ratio, 1.15; confidence interval, 1.04-1.28, respectively), sulfamethizole (odds ratio, 1.15; confidence interval, 1.07-1.24; and odds ratio, 1.22; confidence interval, 1.07-1.39, respectively), and azithromycin (odds ratio, 1.19, confidence interval, 1.03-1.38; and odds ratio, 1.29, confidence interval, 0.99-1.67, respectively).
Conclusion:
In this large populationwide cohort study, we found, with a high degree of precision, no increased risk of congenital malformations following first-trimester exposure to 10 commonly prescribed systemic antibiotics.
Related Concept Videos
00:57Antibiotic Selection
02:04Conservation of Small Populations
01:25What is Population Genetics?
00:57Population Growth
00:30What are Populations and Communities?
01:12Relative Risk