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

Abstract

ObjectivesAntibiotics 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.DesignsA population-based drug utilisation study.SettingNorwegian primary care.Participants653 058 pregnancies derived from Medical Birth Registry of Norway linked to the Norwegian Prescription Database (2006–2016).Main outcome measureProportion of pregnancies exposed to antibiotics aggregated by week in pregnancy time windows.Statistical analysesWe 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.ResultsAntibiotics 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.ConclusionsITSA 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.

Antibiotic use during pregnancy in Sweden: A nationwide utilization study covering 2007–2019

“…12 Our findings were consistent with the earlier report from Sweden which found prenatal systemic antibiotic use to be highest during the second trimester, 4 although populationbased studies from Norway and Denmark reported the highest use in the third trimester. 9,12 Antibiotic use during the second trimester peaked between weeks 12 and 13, which corresponds to the timing after the second antenatal visit when infection screening for asymptomatic bacteriuria, UTIs and sexually transmitted infections among others takes place. 33 34,35 The immediate 6 weeks postpartum (puerperium) is especially prone to infections and this was evident in our results, with a proportionately high prevalence of systemic antibiotic use.…”

“…2006-2016]) 10,12 and our findings could therefore be attributed to relatively higher thresholds for antibiotic prescription in Sweden. 25 Sweden's long-standing national strategic program against antibiotic resistance has overseen sustained reductions in antibiotic use at population level 26 and has invariably been among the lowest in Europe.…”

“…However, in population-based studies from Norway and Denmark where increasing trends were reported prior to 2013, 9,12 more recent data indicated declining trends as reported in France and in our study. 12,13,23 Further, the overall prevalence of systemic antibiotic use during pregnancy was lower than reported in some other countries (UK [33.3%, 1992-2007 13 ), similar to the Netherlands (20.8%, 1994-2009) 11 but higher than in Germany (19.7%, 2000-2001). 10 Some differences could be explained by treatment guidelines which vary between countries and the heterogeneity in study methods,…”

“…given that the characteristics of antibiotic users were mostly similar to those from studies conducted elsewhere and represented groups with an underlying predisposition to infections and hence antibiotic use. 9,12,13 The baseline use before conception was also lower than in other countries (Germany [12.7%, 2000-2001]; Norway [10.9%,…”

Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study

“…Antibiotic exposure was high in this cohort, with 26% of mothers and 42% of children using out-patient antibiotics during pregnancy (including 3 months pre-conception) and first 2 years of life, respectively. However, these figures are comparable to antibiotic consumption in other Nordic countries [ 52 – 55 ]. Whereas this study cannot determine the underlying pathophysiological mechanisms or establish causality, these results underscore that potential short- and long-term consequences for the mother and child should be considered when prescribing antibiotics during pregnancy and early life.…”