Use of interrupted time-series analysis to characterise antibiotic prescription fills across pregnancy: a Norwegian nationwide cohort study

OBJECTIVES: Antibiotics are the most frequently prescribed medications for pregnant and breastfeeding women. We applied interrupted time-series analysis (ITSA) to describe antibiotic prescription fills patterns in pregnant women and examined recurrent antibiotic fills in subsequent pregnancies. DESIGNS: A population-based drug utilisation study. SETTING: Norwegian primary care. PARTICIPANTS: 653 058 pregnancies derived from Medical Birth Registry of Norway linked to the Norwegian Prescription Database (2006–2016). MAIN OUTCOME MEASURE: Proportion of pregnancies exposed to antibiotics aggregated by week in pregnancy time windows. STATISTICAL ANALYSES: We descriptively analysed antibiotic prescription fills patterns and components in pregnant women. The changes in antibiotic fills in pregnancy time windows were assessed using ITSA. Interruptions points at week 4 to week 7 into pregnancy and delivery were used. Factors associated with antibiotic fills during pregnancy were identified using generalised estimating equations for Poisson regression. Recurrent antibiotic use was estimated using proportion of women who filled antibiotic prescription in a subsequent pregnancy. RESULTS: Antibiotics were filled in 27.6% pregnancies. The ITSA detected an immediate decrease of 0.07 percentage points (95% CI −0.13 to –0.01) in the proportion of exposed pregnancies at 4 weeks after conception, mainly among women taking folic acid before pregnancy. This proportion increased shortly after delivery (immediate change=1.61 percentage points (95% CI 0.31 to 2.91)) then decreased gradually afterwards (change in slope=−0.19 percentage points, 95% CI −0.34 to –0.05)). The strongest factor associated with antibiotic fills during pregnancy was having recurrent urinary tract infections (adjusted OR=2.65, 95% CI 2.59 to 2.72). Women who had filled antibiotics during a pregnancy were up to three times more likely to fill antibiotics in the subsequent pregnancies. CONCLUSIONS: ITSA highlighted important impact of pregnancy and delivery on antibiotic fillings. Having antibiotic fills in a pregnancy was associated with recurrent antibiotic fills in subsequent ones.