Antibiotics in pregnancy : utilization, determinants and safety

Antibiotics are indispensable in maternal health. Crucial for treating and preventing bacterial infections ranging from common ailments to life-threatening conditions, antibiotics are inevitably prescribed to pregnant women frequently. This thesis aimed to advance knowledge on antibiotic use during pregnancy, by examining utilization and its underlying factors; and by addressing safety concerns regarding prenatal exposures on the foetus.

In Study I, we comprehensively described trends and patterns in antibiotic use among women who gave birth in Sweden through a population-based drug utilization study. Prescriptions for systemic antibiotics were filled in 20.7% of 1434431 pregnancies overall, decreasing from 24.7% in 2007 to 18.0% in 2019. Phenoxymethylpenicillin, nitrofurantoin, amoxicillin and cefadroxil use were most prevalent. Intravaginal and intestinal antibiotic preparations were used to a substantially lower extent than systemic antibiotics.

In Study II, we conducted a population-based cohort study to evaluate how sociodemographic, medical, obstetric and healthcare utilization characteristics predicted antibiotic use during pregnancy. While the magnitude of associations was found to be modest for the majority of these characteristics, pre-existing morbidities, preconception polypharmacy and maternal age below 20 years most strongly predicted the use of systemic antibiotics, broad-spectrum antibiotics and multiple antibiotic courses.

In Study III, we investigated the association between first trimester tetracycline exposure and risks of major congenital malformations. In this population-based cohort study including 6340 exposed infants, we found that the risks of major congenital malformations (MCMs) overall, for all 12 organ system subgroups, and the 16 individual malformations selected based on prior safety signals and/or fulfilment of prespecified statistical power criteria, were not significantly higher than among propensity score-matched unexposed controls.

In Study IV, using a population-based cohort design, we investigated the associations between prenatal antibiotic exposure and infections during infancy, and whether such associations differed by antibiotic class. Compared to 1052361 unexposed infants, 294654 infants prenatally exposed to antibiotics had slightly higher rates of antimicrobial prescription fills, incident infections in specialist care and infection-related deaths, but these associations were attenuated in the sibling analyses. No differential associations with infections were found for antibiotics commonly used during pregnancy.

In conclusion, this thesis found no concerning patterns in antibiotic utilization among pregnant women in Sweden, nor in their safety. Tetracyclines and any antibiotic use were associated with no increased risks of MCMs and with minimal infection risks in infancy, respectively. Antibiotic prescribing for pregnant women should, nonetheless, be guided by risk-benefit assessments and the latest evidence to ensure optimal perinatal outcomes.

List of scientific papers

I. Nakitanda AO, Odsbu I, Pasternak B, Karlsson P, Pazzagli L. Antibiotic use during pregnancy in Sweden: a nationwide utilization study covering 2007-2019. Acta Obstetricia et Gynecologica Scandinavica. 2024;103(3):531-539.
https://doi.org/10.1111/aogs.14741

II. Nakitanda AO, Pazzagli L, Pasternak B, Odsbu I. Predictors of antibiotic use during pregnancy in Sweden: a population-based cohort study. [Submitted]

III. Nakitanda AO, Odsbu I, Cesta CE, Pazzagli L, Pasternak B. First trimester tetracycline exposure and risk of major congenital malformations: a population-based cohort study. [Submitted]

IV. Nakitanda AO, Kieler H, Odsbu I, Rhedin S, Almqvist C, Pasternak B, Pazzagli L. In-utero antibiotic exposure and subsequent infections in infancy: a registerbased cohort study with sibling analysis. American Journal of Obstetrics & Gynecology MFM. 2023;5(4):100860.
https://doi.org/10.1016/j.ajogmf.2023.100860