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Trends in Antibiotic Use by Birth Season and Birth Year

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Trends in Antibiotic Use by Birth Season and Birth Year Alan C. Kinlaw, PhD, a, b Til Stürmer, MD, PhD, a, b Jennifer L. Lund, PhD, b Lars Pedersen, PhD, c TrendsMichael D. Kappelman, inMD, MPH, Antibiotic d Julie L. Daniels, PhD, b Trine Fr Useøslev, MSc, c by b, e c, f BirthChristina D. Mack, Season PhD, Henrik Toft Sø rensen,and MD, DMSc, Birth PhD Year OBJECTIVES: abstract We examined 2 birth cohort effects on antibiotic prescribing during the first year of life (henceforth, infancy) in Denmark: (1) the birth season effect on timing and overall occurrence of antibiotic prescribing, and (2) the birth year effect amid emerging METHODS: N nationwide pneumococcal vaccination programs and changing prescribing guidelines. We linked data for all live births in Denmark from 2004 to 2012 ( = 561 729) across the National Health Service Prescription Database, Medical Birth Registry, and Civil Registration System. Across birth season and birth year cohorts, we estimated 1-year risk, rate, and burden of redeemed antibiotic prescriptions during infancy. We used interrupted time series methods to assess prescribing trends across birth year cohorts. Graphical RESULTS: displays of all birth cohort effect data are included. The 1-year risk of having at least 1 redeemed antibiotic prescription during infancy was 39.5% (99% confidence interval [CI]: 39.3% to 39.6%). The hazard of a first – prescription increased with age throughout infancy and varied by season; subsequently, Kaplan-Meier derived risk functions varied by birth season cohort. After rollout of a first vaccination program and new antibiotic prescribing guidelines, 1-year risk decreased by 4.4% over 14 months (99% CI: 3.4% to 5.5%); it decreased again after rollout of a second CONCLUSIONS: vaccination program by 6.9% over 3 years (99% CI: 4.4% to 9.3%). In Denmark, birth season and birth year cohort effects influenced timing and risk of antibiotic prescribing during infancy. Future studies of antibiotic stewardship, effectiveness, and safety in children should consider these cohort effects, which may render NIH some children inherently more susceptible than others to downstream antibiotic effects. WHAT’SW KNO N ON THIS SUBJECT: Widespread a b d Cecil G. Sheps Center for Health Services Research, Departments of Epidemiology and Pediatrics, University antibiotic use leads to bacterial resistance, and of North Carolina at Chapel Hill, Chapel Hill, North Carolina; cDepartment of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark; eQuintilesIMS, Durham, North Carolina; and fDivision of Epidemiology, unnecessary antibiotic use in early life may cause Department of Health Research and Policy, Stanford University, Stanford, California excess immune dysfunction in childhood. Antibiotic prescribing is influenced by seasonal and temporal Dr Kinlaw conceptualized and designed the study, conducted data analysis, interpreted factors, but data are limited regarding cohort data, drafted the initial manuscript, and reviewed and revised the manuscript; Dr St rmer ü effects on antibiotic use in children. conceptualized and designed the study, interpreted data, drafted the initial manuscript, and reviewed and revised the manuscript; Drs Lund, Kappelman, Daniels, Mack, and Sørensen WHAT THIS STUDY AddS: In this study, we conceptualized and designed the study, interpreted data, and reviewed and revised the characterize birth season and birth year cohort manuscript; Dr Pedersen and Ms Frøslev contributed to data analysis, interpreted data, effects on antibiotic prescribing during infancy, and reviewed and revised the manuscript; and all authors approved the final manuscript as which merit consideration in pediatric studies of submitted. antibiotic stewardship, effectiveness, and safety. DOI: https:// doi. org/ 10. 1542/ peds. 2017- 0441 We also provide new information on correlation Accepted for publication Jun 9, 2017 between risk, rate, and burden of antibiotic Address correspondence to Alan C. Kinlaw, PhD, Cecil G. Sheps Center for Health Services prescribing. Research, University of North Carolina at Chapel Hill, CB#7590, Chapel Hill, NC 27599. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). To cite: Kinlaw AC, Stürmer T, Lund JL, et al. Trends in Antibiotic Use by Birth Season and Birth Year. Pediatrics. 2017;140(3):e20170441 Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 140, number 3, September 2017:e20170441 ARTICLE Kinlaw et al https://doi.org/10.1542/peds.2017-0441 September 2017 Trends in Antibiotic Use by Birth Season and Birth Year 3 140 Pediatrics 2017 ROUGH GALLEY PROOF 24 30 During early life, children are often antibiotic prescribing guidelines. from 2004. We used Anatomical prescribed antibiotics for bacterial In 2007, the Danish childhood Therapeutic Chemical (ATC) J01 ’ infections. Approximately 20% vaccination program introduced codes to identify prescriptions for to 50% of children s antibiotic the 7-valent– PCV (PCV7), replacing systemic antibiotics redeemed from prescriptions are– used to treat it with the25 13-valent27 PCV (PCV13) January 1, 2004, to December 31, nonbacterial upper1 3 respiratory– in 2010. No studies have 2013, and classified antibiotics by tract infections, for 2,which 4 6 they evaluated the impact of these chemical substance (henceforth, are largely ineffective. In events on antibiotic prescribing in medication). Western industrialized countries Denmark during the first year of life Risk, Rate, and Burden of Antibiotic in particular, increasing advocacy (henceforth, infancy). Prescribing for rational antibiotic prescribing– Our objectives were to estimate has been associated with decreased 7 10 birth season cohort effects on population-level antibiotic use. antibiotic prescribing during infancy To examine differences by birth year In addition, pneumococcal conjugate in Denmark, and birth year cohort cohort in overall and medication- vaccination (PCV) programs have effects on antibiotic prescribing specific prescribing, we estimated 3 been associated with decreased potentially brought about by the IRF measures of antibiotic prescribing: risk of acute otitis media and lower 11 bulletin and PCV programs. (1) 1-year risk of at least 1 redeemed respiratory tract infections, 2 of – METHODS antibiotic prescription during infancy the most common indications for 4,12 16 by using Kaplan-Meier methods to antibiotics in children. Taken account for censoring at death or together, there is a need to better This cohort study included all live emigration; (2) incidence rate of characterize the changing patterns of births in Denmark from 2004 to redeemed antibiotic prescriptions, antibiotic prescribing in children. 2012, identified by using the Danish allowing for multiple redeemed Previous studies of trends in early life Medical Birth Registry (MBR), prescriptions per infant (henceforth, antibiotic prescribing have focused which has registered all live births – ’ 28 rate); and (3) 1-year burden of on rates in3, 8, cross-sectional9, 17 23 population in Denmark since 1973. We used antibiotic prescriptions, on the samples, counting multiple each child s unique 10-digit personal basis of the total days supplied for prescriptions per child and tending to registration number to link their – redeemed antibiotic prescriptions present results for coarse age groups individual-level data across multiple throughout infancy. For rate and ’ (eg, 0 4 years) or groups defined registries. After excluding children burden, we also computed each by the year or season when they with inconsistent identification medication s share of overall were observed (eg, during winter information (Supplemental prescribing, ie, the proportion of all 2010). In addition, studies of rates Information), we examined the antibiotic prescriptions (for the rate) implicitly estimate the frequency of remaining cohort from birth for 365 or all days supplied (for the burden). providers prescribing or dispensing days or until death or emigration. Birth Season Cohort Effect on antibiotics to groups of children; Time to First Redeemed Antibiotic To identify birth cohorts, we grouped Prescription however, studies of risk aggregate children by week, month, season individual-level data to clarify which (winter: December to February; well-defined cohorts of children spring: March to May; summer: June receive or redeem a given number to August; autumn: September to We assessed the impact of birth of prescriptions over a specific November), and year of birth. We season on age at first redeemed follow-up interval. Currently, data ascertained demographic information antibiotic prescription during are limited regarding cohort effects from the MBR and Civil Registration infancy by using Kaplan-Meier on the risk of overall and medication- 29 System and used the MBR to methods to account for censoring at specific antibiotic use during early identify clinical characteristics of the death or emigration. Infants were childhood. Datamother, on pregnancy,Antibiotics and birth event. stratified by birth season cohort In Denmark, recent policy and and assessed using age as the time guideline changes may have scale. We estimated the hazard (ie, induced changes in antibiotic The Danish National Health instantaneous risk) function for first ’ – prescribing. The Danish Health and Service Prescription Database redeemed antibiotic prescription Medicine Authority s Institute for contains nationwide records for and the Kaplan-Meier derived risk Rational Pharmacotherapy (IRF), all prescriptions
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