Am J Perinatol 2021; 38(04): 383-391
DOI: 10.1055/s-0039-1697669
Original Article

Quantifying Medication Exposure in Very Low Birth Weight Neonates

1   Department of Pediatrics, Division of Neonatology, University of Maryland School of Medicine, Baltimore, Maryland
,
Temitope O. Akinmboni
1   Department of Pediatrics, Division of Neonatology, University of Maryland School of Medicine, Baltimore, Maryland
,
Sandra M. Mooney
2   Department of Nutrition, University of North Carolina Nutrition Research Institute, University of North Carolina Chapel Hill, Kannapolis, North Carolina
› Author Affiliations

Abstract

Objective Very low birth weight (VLBW) infants are exposed to medications with insufficient evidence describing pharmacokinetics and safety. Objective was to quantify and identify risk factors associated with the highest quartile of medication exposure.

Study Design Retrospective record review of VLBW infants admitted to a level-IV neonatal intensive care unit (NICU). We obtained baseline clinical and demographic characteristics, as well as data on all medications received during admission. Characteristics of patients within the upper quartile of medication use were compared with remaining patients.

Results Identified 106 infants, mean birth weight (BW) = 961 g, gestational age = 27.3 weeks. Infants received a median = 20 medications (range, 4–72). Those in the top quartile of medication use received ≥30 medications while in the NICU and had higher odds of being male sex, lower BW, longer length of hospital stay (LOHS), and bronchopulmonary dysplasia. Sepsis did not affect medication exposure. Antibiotics, opiates, and reflux medications were among the top prescribed.

Conclusion Infants are exposed to a large number of medications during NICU hospitalization, including potentially unnecessary antibiotics and reflux medications. Male sex, the presence of certain comorbidities such as necrotizing enterocolitis, and LOHS, are associated with higher exposure. Increased awareness of this issue may assist in decreasing medication exposure in VLBW populations.



Publication History

Received: 26 March 2019

Accepted: 16 August 2019

Article published online:
04 November 2019

© 2019. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 2006; 117 (06) 1979-1987
  • 2 Chauthankar SA, Marathe PA, Potey AV, Nanavati RN. Drug utilization in neonatal intensive care unit of a tertiary-care hospital in mumbai, india. Indian Pediatr 2017; 54 (11) 931-934
  • 3 de Souza Jr AS, Dos Santos DB, Rey LC, Medeiros MG, Vieira MG, Coelho HLL. Off-label use and harmful potential of drugs in a NICU in Brazil: A descriptive study. BMC Pediatr 2016; 16: 13
  • 4 Kieran EA, O'Callaghan N, O'Donnell CP. Unlicensed and off-label drug use in an Irish neonatal intensive care unit: a prospective cohort study. Acta Paediatr 2014; 103 (04) e139-e142
  • 5 Mazhar F, Akram S, Haider N, Hadi MA, Sultana J. Off-label and unlicensed drug use in hospitalized newborns in a Saudi tertiary care hospital: a cohort study. Int J Clin Pharm 2018; 40 (03) 700-703
  • 6 Krzyżaniak N, Pawłowska I, Bajorek B. Review of drug utilization patterns in NICUs worldwide. J Clin Pharm Ther 2016; 41 (06) 612-620
  • 7 Gulati R, Elabiad MT, Talati AJ, Dhanireddy R. Trends in medication use in very low-birth-weight infants in a level 3 NICU over 2 decades. Am J Perinatol 2016; 33 (04) 370-377
  • 8 Akinmboni TO, Davis NL, Falck AJ, Bearer CF, Mooney SM. Excipient exposure in very low birth weight preterm neonates. J Perinatol 2018; 38 (02) 169-174
  • 9 Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13: 59
  • 10 Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33 (01) 179-201
  • 11 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
  • 12 Dorling JS, Field DJ, Manktelow B. Neonatal disease severity scoring systems. Arch Dis Child Fetal Neonatal Ed 2005; 90 (01) F11-F16
  • 13 Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores. J Pediatr 2001; 138 (01) 92-100
  • 14 Warrier I, Du W, Natarajan G, Salari V, Aranda J. Patterns of drug utilization in a neonatal intensive care unit. J Clin Pharmacol 2006; 46 (04) 449-455
  • 15 Kumar P, Walker JK, Hurt KM, Bennett KM, Grosshans N, Fotis MA. Medication use in the neonatal intensive care unit: current patterns and off-label use of parenteral medications. J Pediatr 2008; 152 (03) 412-415
  • 16 Lass J, Käär R, Jõgi K, Varendi H, Metsvaht T, Lutsar I. Drug utilisation pattern and off-label use of medicines in Estonian neonatal units. Eur J Clin Pharmacol 2011; 67 (12) 1263-1271
  • 17 Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin Jr DK, Smith PB. Best Pharmaceuticals for Children Act—Pediatric Trials Network. Medication use in the neonatal intensive care unit. Am J Perinatol 2014; 31 (09) 811-821
  • 18 Shim SY, Cho SJ, Kong KA, Park EA. Gestational age-specific sex difference in mortality and morbidities of preterm infants: A nationwide study. Sci Rep 2017; 7 (01) 6161
  • 19 Binet ME, Bujold E, Lefebvre F, Tremblay Y, Piedboeuf B. Canadian Neonatal Network™. Role of gender in morbidity and mortality of extremely premature neonates. Am J Perinatol 2012; 29 (03) 159-166
  • 20 Lingappan K, Jiang W, Wang L, Moorthy B. Sex-specific differences in neonatal hyperoxic lung injury. Am J Physiol Lung Cell Mol Physiol 2016; 311 (02) L481-L493
  • 21 Semenas E, Nozari A, Sharma HS, Basu S, Rubertsson S, Wiklund L. Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs. Acta Anaesthesiol Scand 2010; 54 (03) 343-353
  • 22 Cotten CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin Jr DK. National Institute for Child Health and Human Development Neonatal Research Network. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics 2006; 118 (02) 717-722
  • 23 Cotten CM, Taylor S, Stoll B. et al; NICHD Neonatal Research Network. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123 (01) 58-66
  • 24 Tsai MH, Chu SM, Hsu JF. et al. Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU. Pediatrics 2014; 133 (02) e322-e329
  • 25 Kocek M, Wilcox R, Crank C, Patra K. Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2 years. Early Hum Dev 2016; 92: 29-32
  • 26 Zwicker JG, Miller SP, Grunau RE. et al. Smaller cerebellar growth and poorer neurodevelopmental outcomes in very preterm infants exposed to neonatal morphine. J Pediatr 2016; 172: 81-87
  • 27 Duerden EG, Guo T, Dodbiba L. et al. Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants. Ann Neurol 2016; 79 (04) 548-559
  • 28 Ho T, Dukhovny D, Zupancic JA, Goldmann DA, Horbar JD, Pursley DM. Choosing wisely in newborn medicine: five opportunities to increase value. Pediatrics 2015; 136 (02) e482-e489
  • 29 Guillet R, Stoll BJ, Cotten CM. et al; National Institute of Child Health and Human Development Neonatal Research Network. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2006; 117 (02) e137-e142
  • 30 More K, Athalye-Jape G, Rao S, Patole S. Association of inhibitors of gastric acid secretion and higher incidence of necrotizing enterocolitis in preterm very low-birth-weight infants. Am J Perinatol 2013; 30 (10) 849-856
  • 31 Terrin G, Passariello A, De Curtis M. et al. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics 2012; 129 (01) e40-e45