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Neonatal abstinence syndrome and early childhood morbidity and mortality in Washington state: a retrospective cohort study

Journal of Perinatology volume 37, pages 1124–1129 (2017)Cite this article

Subjects

Abstract

Objective:

The objective of the study was to evaluate the association between neonatal abstinence syndrome (NAS) and long-term childhood morbidity and infant mortality.

Study Design:

We conducted a cohort study of infants born in Washington State during 1990 to 2008 who were diagnosed with NAS (n=1900) or were unexposed (n=12,283, frequency matched by birth year). 5-year hospital readmissions and infant mortality were ascertained.

Results:

Children with history of NAS had increased risk of readmission during the first 5 years of life relative to unexposed children; this remained statistically significant after adjustment for maternal age, maternal education, gestational age and intrapartum smoking status (readmission rates: NAS=21.3%, unexposed=12.7%, adjusted relative risk (aRR) 1.54, 95% confidence interval (CI) 1.37 to 1.73). NAS was associated with increased unadjusted infant mortality risk, but this did not persist after adjustment (aRR 1.94, 95% CI 0.99 to 3.80).

Conclusion:

The observed increased risk for childhood hospital readmission following NAS diagnosis argues for development of early childhood interventions to prevent morbidity.

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References

  1. Kocherlakota P . Neonatal abstinence syndrome. Pediatrics 2014; 134: e547–e561.

    Article  Google Scholar 

  2. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB et al. Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl J Med 2015; 372: 2118–2126.

    Article  Google Scholar 

  3. Finnegan LP, Connaughton JF Jr, Kron RE, Emich JP . Neonatal abstinence syndrome: assessment and management. Addict Dis 1975; 2: 141–158.

    CAS  PubMed  Google Scholar 

  4. Hudak ML, Tan RC . Neonatal drug withdrawal. Pediatrics 2012; 129: e540–e560.

    Article  Google Scholar 

  5. Davies H, Gilbert R, Johnson K, Petersen I, Nazareth I, O'Donnell M et al. Neonatal drug withdrawal syndrome: cross-country comparison using hospital administrative data in England, the USA, Western Australia and Ontario, Canada. Arch Dis Child Fetal Neonatal 2016; 101: F26–F30.

    Article  Google Scholar 

  6. Patrick SW, Burke JF, Biel TJ, Auger KA, Goyal NK, Cooper WO . Risk of hospital readmission among infants with neonatal abstinence syndrome. Hosp Pediatr 2015; 5: 513–519.

    Article  Google Scholar 

  7. Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM . Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. J Am Med Assoc 2012; 307: 1934–1940.

    Article  CAS  Google Scholar 

  8. Patrick SW, Davis MM, Lehman CU, Cooper WO . Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012. J Perinatol 2015; 35: 667.

    Article  CAS  Google Scholar 

  9. Beckwith AM, Burke SA . Identification of early developmental deficits in infants with prenatal heroin, methadone, and other opioid exposure. Clin Pediatr 2015; 54: 328–335.

    Article  Google Scholar 

  10. Anand KJ, Campbell-Yeo M . Consequences of prenatal opioid use for newborns. Acta Paediatr 2015; 104: 1066–1069.

    Article  Google Scholar 

  11. Bandstra ES, Morrow CE, Mansoor E, Accornero VH . Prenatal drug exposure: infant and toddler outcomes. J Addict Dis 2010; 29: 245–258.

    Article  Google Scholar 

  12. Cleary BJ, Donnelly JM, Strawbridge JD, Gallagher PJ, Fahey T, White MJ et al. Methadone and perinatal outcomes: a retrospective cohort study. Am J Obstet Gynecol 2011; 204: 139.e1–139.e9.

    Article  Google Scholar 

  13. Hunt RW, Tzioumi D, Collins E, Jeffery HE . Adverse neurodevelopmental outcome of infants exposed to opiate in-utero. Early Hum Dev 2008; 84: 29–35.

    Article  CAS  Google Scholar 

  14. McGlone L, Mactier H . Infants of opioid-dependent mothers: neurodevelopment at six months. Early Hum Dev 2015; 91: 19–21.

    Article  CAS  Google Scholar 

  15. Norgaard M, Nielsson MS, Heide-Jorgensen U . Birth and neonatal outcomes following opioid use in pregnancy: a Danish population-based study. Subst Abuse 2015; 9: 5–11.

    PubMed  PubMed Central  Google Scholar 

  16. Ornoy A, Michailevskaya V, Lukashov I, Bar-Hamburger R, Harel S . The developmental outcome of children born to heroin-dependent mothers, raised at home or adopted. Child Abuse Negl 1996; 20: 385–396.

    Article  CAS  Google Scholar 

  17. Whiteman VE, Salemi JL, Mogos MF, Cain MA, Aliyu MH, Salihu HM . Maternal opioid drug use during pregnancy and its impact on perinatal morbidity, mortality, and the costs of medical care in the United States. J Pregnancy 2014; 2014: 906723.

    Article  Google Scholar 

  18. Hans SL . Developmental consequences of prenatal exposure to methadone. Ann NY Acad Sci 1989; 562: 195–207.

    Article  CAS  Google Scholar 

  19. Devarapalli M, Leonard M, Briyal S, Stefanov G, Puppala BL, Schweig L et al. Prenatal oxycodone exposure alters CNS endothelin receptor expression in neonatal rats. Drug Res 2016; 66: 246–250.

    CAS  Google Scholar 

  20. Hays SL, McPherson RJ, Juul SE, Wallace G, Schindler AG, Chavkin C et al. Long-term effects of neonatal stress on adult conditioned place preference (CPP) and hippocampal neurogenesis. Behav Brain Res 2012; 227: 7–11.

    Article  Google Scholar 

  21. Sanchez ES, Bigbee JW, Fobbs W, Robinson SE, Sato-Bigbee C . Opioid addiction and pregnancy: perinatal exposure to buprenorphine affects myelination in the developing brain. Glia 2008; 56: 1017–1027.

    Article  Google Scholar 

  22. Nygaard E, Slinning K, Moe V, Walhovd KB . Behavior and attention problems in eight-year-old children with prenatal opiate and poly-substance exposure: a longitudinal study. PLoS ONE 2016; 11: e0158054.

    Article  Google Scholar 

  23. Sutter MB, Leeman L, Hsi A . Neonatal opioid withdrawal syndrome. Obstet Gynecol Clin North Am 2014; 41: 317–334.

    Article  Google Scholar 

  24. Uebel H, Wright IM, Burns L, Hilder L, Bajuk B, Breen C et al. Reasons for rehospitalization in children who had neonatal abstinence syndrome. Pediatrics 2015; 136: e811–e820.

    Article  Google Scholar 

  25. Jones PD, Seoane L, Deichmann R, Kantrow C . Differences and similarities in the practice of medicine between Australia and the United States of America: challenges and opportunities for the University of Queensland and the Ochsner Clinical School. Ochsner J 2011; 11: 253–258.

    PubMed  PubMed Central  Google Scholar 

  26. O'Donnell M, Nassar N, Leonard H, Hagan R, Mathews R, Patterson Y et al. Increasing prevalence of neonatal withdrawal syndrome: population study of maternal factors and child protection involvement. Pediatrics 2009; 123: e614–e621.

    Article  Google Scholar 

  27. Wurst KE, Zedler BK, Joyce AR, Sasinowski M, Murrelle EL . A Swedish population-based study of adverse birth outcomes among pregnant women treated with buprenorphine or methadone: preliminary findings. Subst Abuse 2016; 10: 89–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Allocco E, Melker M, Rojas-Miguez F, Bradley C, Hahn KA, Wachman EM . Comparison of neonatal abstinence syndrome manifestations in preterm versus term opioid-exposed infants. Adv Neonatal Care 2016; 16: 329–336.

    Article  Google Scholar 

  29. Liu WF, Singh K, Faisal M, Li S . Maternal methadone treatment and neonatal abstinence syndrome. Am J Perinatol 2015; 32: 1078–1086.

    Article  Google Scholar 

  30. Nandakumar N, Sankar VS . What is the best evidence based management of neonatal abstinence syndrome? Arch Dis Child Fetal Neonatal Ed 2006; 91: F463.

    Article  CAS  Google Scholar 

  31. Osborn DA, Cole MJ, Jeffery HE . Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database Syst Rev 2002; (3): CD002059.

    Google Scholar 

  32. Velez M, Jansson LM . The opioid dependent mother and newborn dyad: non-pharmacologic care. J Addict Med 2008; 2: 113–120.

    Article  Google Scholar 

  33. Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med 2010; 363: 2320–2331.

    Article  CAS  Google Scholar 

  34. Burns L, Mattick RP . Using population data to examine the prevalence and correlates of neonatal abstinence syndrome. Drug Alcohol Rev 2007; 26: 487–492.

    Article  Google Scholar 

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Acknowledgements

We sincerely thank Seth Rowley for programming and data management; Alyson Littman for methodologic guidance; and the Washington State Department of Health for data access. Dr Witt receives funding support from the National Institute of Health, Institute of Child Health and Human Development (2T32HD057822-06); Principal Investigators: Dr Rivara and Dr Vavilala.

Author information

Authors and Affiliations

  1. Department of Epidemiology, University of Washington, Seattle, WA, USA

    C E Witt, K E Rudd, P Bhatraju, F P Rivara, S E Hawes & N S Weiss

  2. Harborview Injury Prevention and Research Center, Seattle, WA, USA

    C E Witt & F P Rivara

  3. Department of Surgery, University of Washington, Seattle, WA, USA

    C E Witt

  4. Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA

    K E Rudd & P Bhatraju

  5. Department of Pediatrics, University of Washington, Seattle, WA, USA

    F P Rivara

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  1. C E Witt
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Correspondence to C E Witt.

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The authors declare no conflict of interest.

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Witt, C., Rudd, K., Bhatraju, P. et al. Neonatal abstinence syndrome and early childhood morbidity and mortality in Washington state: a retrospective cohort study. J Perinatol 37, 1124–1129 (2017). https://doi.org/10.1038/jp.2017.106

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