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Medication utilization in children born preterm in the first two years of life

Journal of Perinatology volume 41, pages 1732–1738 (2021)Cite this article

Subjects

Abstract

Objective

To compare medications dispensed during the first 2 years in children born preterm and full-term.

Study design

Retrospective analysis of claims data from a commercial national managed care plan 2008–2019. 329,855 beneficiaries were enrolled from birth through 2 years, of which 25,408 (7.7%) were preterm (<37 weeks). Filled prescription claims and paid amount over 2 years were identified.

Results

In preterm children, the number of filled prescriptions was 1.4 times and cost was 3.8 times that of full-term children. Number and cost of medications were inversely related to gestational age. Differences peak at 4–9 months and resolve by 19 months after discharge. Palivizumab, ranitidine, albuterol, lansoprazole, budesonide, and prednisolone had the greatest differences in utilization.

Conclusion

Prescription medication utilization among preterm children under 2 years is driven by palivizumab, anti-reflux, and respiratory medications, despite little evidence regarding efficacy for many medications and concern for harm with certain classes.

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Fig. 1: Unique medications prescribed and costs by gestational since neonatal discharge.
Fig. 2: Duration of supply among medications with greatest difference in prescribing frequency.

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Data availability

Authors' data use agreement for the claims dataset does not permit public posting of this patient information.

Code availability

Code used to generate the results is available by request to the corresponding author; however, per terms of the health plan supplying the data, and because of the risk of reidentification, the underlying patient data are not able to be shared.

References

  1. Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: Final data for 2017. National Vital Statistics Reports; vol 67 no 8. Hyattsville, MD: National Center for Health Statistics; 2018.

  2. Smith VC, Zupancic JAF, McCormick MC, Croen LA, Greene J, Escobar GJ, et al. Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia. J Pediatr. 2004;144:799–803.

    PubMed  Google Scholar 

  3. Wade KC, Lorch SA, Bakewell-Sachs S, Medoff-Cooper B, Silber JH, Escobar GJ. Pediatric care for preterm infants after NICU discharge: high number of office visits and prescription medications. J Perinatol. 2008;28:696–701.

    Article  CAS  Google Scholar 

  4. Beam AL, Fried I, Palmer N, Agniel D, Brat G, Fox K, et al. Estimates of healthcare spending for preterm and low-birthweight infants in a commercially insured population: 2008–2016. J Perinatol. 2020. https://doi.org/10.1038/s41372-020-0635-z.

  5. Bamat NA, Kirpalani H, Feudtner C, Jensen EA, Laughon MM, Zhang H, et al. Medication use in infants with severe bronchopulmonary dysplasia admitted to United States children’s hospitals. J Perinatol. 2019;39:1291–9.

    Article  Google Scholar 

  6. D’Agostino JA, Passarella M, Martin AE, Lorch SA. Use of gastroesophageal reflux medications in premature infants after NICU discharge. Pediatrics. 2016;138. https://doi.org/10.1542/peds.2016-1977.

  7. Orenstein SR, Hassall E, Furmaga-Jablonska W, Atkinson S, Raanan M. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. J Pediatr. 2009;154:514–520.e4.

    Article  CAS  Google Scholar 

  8. Ho T, Dukhovny D, Zupancic JAF, Goldmann DA, Horbar JD, Pursley DM. Choosing wisely in newborn medicine: five opportunities to increase value. Pediatrics. 2015;136:e482–9.

    Article  Google Scholar 

  9. Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117:e817–20.

    Article  Google Scholar 

  10. Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatr. 2018;172:e180315.

    Article  Google Scholar 

  11. Wagner KL, Wagner SC, Susi A, Gorman G, Hisle-Gorman E. Prematurity and early childhood fracture risk. Pediatrics. 2018;141:757.

    Google Scholar 

  12. FDA. FDA requests removal of all ranitidine products (Zantac) from the Market. FDA; 2020. https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market. Accessed 22 Jun 2020.

  13. Amneal Pharmaceuticals, LLC. Issues voluntary nationwide recall of nizatidine oral solution, 15 mg/mL, due to potential levels of n-nitrosodimethylamine (NDMA) impurity amounts above the levels established by FDA. US Food Drug Adm; 2020. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/amneal-pharmaceuticals-llc-issues-voluntary-nationwide-recall-nizatidine-oral-solution-15-mgml-due. Accessed 22 Jun 2020.

  14. Landry JS, Croitoru D, Jin Y, Schwartzman K, Benedetti A, Menzies D. Health care utilization by preterm infants with respiratory complications in Quebec. Can Respir J. 2012;19:255–60.

    Article  Google Scholar 

  15. Damgaard AL, Hansen BM, Mathiasen R, Buchvald F, Lange T, Greisen G. Prematurity and prescription asthma medication from childhood to young adulthood: a Danish national cohort study. PLoS ONE. 2015;10:e0117253.

    Article  Google Scholar 

  16. Damgaard AL, de B, Gregersen R, Lange T, Buchvald F, Hansen BM, et al. The increased purchase of asthma medication for individuals born preterm seems to wane with age: a register-based longitudinal national cohort study. PLoS ONE. 2018;13:e0199884.

    Article  Google Scholar 

  17. Ryan RM, Keller RL, Poindexter BB, D’Angio CT, Shaw PA, Bellamy SL, et al. Respiratory medications in infants <29 weeks during the first year postdischarge: the Prematurity and Respiratory Outcomes Program (PROP) Consortium. J Pediatr. 2019;208:148–155.e3.

    Article  CAS  Google Scholar 

  18. Duijts L, Meel ER van, Moschino L, Baraldi E, Barnhoorn M, Bramer WM, et al. European Respiratory Society guideline on long term management of children with bronchopulmonary dysplasia. Eur Respir J. 2019. https://doi.org/10.1183/13993003.00788-2019.

  19. Lakhani CM, Tierney BT, Manrai AK, Yang J, Visscher PM, Patel CJ. Repurposing large health insurance claims data to estimate genetic and environmental contributions in 560 phenotypes. Nat Genet. 2019;51:327–34.

    Article  CAS  Google Scholar 

  20. Fried I, Beam AL, Kohane IS, Palmer NP. Utilization, cost, and outcome of branded vs compounded 17-alpha hydroxyprogesterone caproate in prevention of preterm birth. JAMA Intern Med. 2017;177:1689–90.

    Article  Google Scholar 

  21. Geva A, Gronsbell JL, Cai T, Cai T, Murphy SN, Lyons JC, et al. A computable phenotype improves cohort ascertainment in a pediatric pulmonary hypertension registry. J Pediatr. 2017;188:224–231.e5.

    Article  Google Scholar 

  22. Natarajan G, Shankaran S. Short- and long-term outcomes of moderate and late preterm infants. Am J Perinatol. 2016;33:305–17.

    Article  Google Scholar 

  23. Fawke J, Lum S, Kirkby J, Hennessy E, Marlow N, Rowell V, et al. Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study. Am J Respir Crit Care Med. 2010;182:237–45.

    Article  Google Scholar 

  24. Thunqvist P, Tufvesson E, Bjermer L, Winberg A, Fellman V, Domellöf M, et al. Lung function after extremely preterm birth—a population-based cohort study (EXPRESS). Pediatr Pulmonol. 2018;53:64–72.

    Article  Google Scholar 

  25. Ambalavanan N, Carlo WA, McDonald SA, Yao Q, Das A, Higgins RD, et al. Identification of extremely premature infants at high risk of rehospitalization. Pediatrics. 2011;128:e1216–1225.

    Article  Google Scholar 

  26. Keller RL, Feng R, DeMauro SB, Ferkol T, Hardie W, Rogers EE, et al. Bronchopulmonary dysplasia and perinatal characteristics predict 1-year respiratory outcomes in newborns born at extremely low gestational age: a prospective cohort study. J Pediatr. 2017;187:89–97.e3.

    Article  Google Scholar 

  27. Mourani PM, Kinsella JP, Clermont G, Kong L, Perkins AM, Weissfeld L, et al. Intensive care unit readmission during childhood after preterm birth with respiratory failure. J Pediatr. 2014;164:749–755.e3.

    Article  Google Scholar 

  28. Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK, Smith PB. Medication use in the neonatal intensive care unit. Am J Perinatol. 2014;31:811–22.

    Article  Google Scholar 

  29. Schmiedl S, Fischer R, Ibáñez L, Fortuny J, Klungel OH, Reynolds R, et al. Utilisation and off-label prescriptions of respiratory drugs in children. PLoS ONE. 2014;9. https://doi.org/10.1371/journal.pone.0105110.

  30. Eichenwald EC, Committee on Fetus and Newborn. Diagnosis and management of gastroesophageal reflux in preterm infants. Pediatrics. 2018;142. https://doi.org/10.1542/peds.2018-1061.

  31. Collaco JM, Kole AJ, Riekert KA, Eakin MN, Okelo SO, McGrath-Morrow SA. Respiratory medication adherence in chronic lung disease of prematurity. Pediatr Pulmonol. 2012;47:283–91.

    Article  Google Scholar 

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Funding

This research was supported by the following funding sources: NHLBI U01HL121518 (KDM) and T15LM007092 (PI: Nils Gehlenborg).

Author information

Authors and Affiliations

  1. Computational Health Informatics Program, Boston Children’s Hospital, Boston, MA, USA

    Jonathan C. Levin & Kenneth D. Mandl

  2. Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA

    Jonathan C. Levin

  3. Division of Pulmonary Medicine, Boston Children’s Hospital, Boston, MA, USA

    Jonathan C. Levin

  4. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Jonathan C. Levin & Kenneth D. Mandl

  5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Andrew L. Beam

  6. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

    Kathe P. Fox & Kenneth D. Mandl

Authors
  1. Jonathan C. Levin
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  4. Kenneth D. Mandl
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Contributions

JCL designed and conducted the analysis and drafted the initial manuscript. ALB designed initial code to identify the cohort, assisted with statistical analysis, and reviewed the manuscript. KPF assisted with design of the analysis and reviewed the manuscript. KDM provided supervision for the design and analysis and provided multiple manuscript revisions.

Corresponding author

Correspondence to Jonathan C. Levin.

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The authors declare that they have no conflict of interest.

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Levin, J.C., Beam, A.L., Fox, K.P. et al. Medication utilization in children born preterm in the first two years of life. J Perinatol 41, 1732–1738 (2021). https://doi.org/10.1038/s41372-021-00930-0

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