Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Association between pharmacologic treatment and hospital utilization at birth among neonatal opioid withdrawal syndrome mother-infant dyads

Abstract

Objective

We linked mother-baby dyads to explore associations between maternal medication-assisted therapy (MAT) and infants’ pharmacologic treatment on birth hospital utilization for infants with NOWS.

Methods

We extracted singleton infant and maternal delivery discharges from PHIS hospitals with large volumes of deliveries for 2016–2019. We matched newborns with NOWS to maternal delivery discharges by hospital, day of birth, mode of delivery, and ZIP code. We examined the association between maternal MAT, infants’ pharmacologic treatment, and hospital utilization at birth.

Results

We included N = 146 mother-baby dyads from six hospitals (74% match rate). Among matched dyads, 51% received maternal MAT, 60% pharmacotherapy (37% both). Infants treated non-pharmacologically and born to mothers receiving MAT had the shortest stays vs. infants without pharmacotherapy or MAT (RR = 0.29; 95% CI: 0.25–0.35).

Conclusions

These findings underscore the importance of adequate perinatal treatment for opioid use disorder to improve outcomes for mothers and infants with opioid exposure.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Adjusted associations between maternal MAT and infants’ pharmacologic treatment.
Fig. 2: Adjusted associations between maternal MAT and infants’ pharmacologic treatment on utilization during birth hospitalization.

Similar content being viewed by others

Data availability

The datasets analyzed in this study are not publicly available as they were acquired through the Pediatric Health Information System which prohibits data sharing outside of its member hospitals.

References

  1. Bateman BT, Hernandez-Diaz S, Rathmell JP, Seeger JD, Doherty M, Fischer MA, et al. Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology. 2014;120:1216–24.

    Article  PubMed  Google Scholar 

  2. Brown JD, Doshi PA, Pauly NJ, Talbert JC. Rates of neonatal abstinence syndrome amid efforts to combat the opioid abuse epidemic. JAMA Pediatr. 2016;170:1110–2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012. J Perinatol. 2015;35:650–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pryor JR, Maalouf FI, Krans EE, Schumacher RE, Cooper WO, Patrick SW. The opioid epidemic and neonatal abstinence syndrome in the USA: a review of the continuum of care. Arch Dis Child Fetal Neonatal Ed. 2017;102:F183–F7.

    Article  PubMed  Google Scholar 

  5. Villapiano NL, Winkelman TN, Kozhimannil KB, Davis MM, Patrick SW. Rural and urban differences in neonatal abstinence syndrome and maternal opioid use, 2004 to 2013. JAMA Pediatr. 2017;171:194–6.

    Article  PubMed  Google Scholar 

  6. Wachman EM, Grossman M, Schiff DM, Philipp BL, Minear S, Hutton E, et al. Quality improvement initiative to improve inpatient outcomes for Neonatal Abstinence Syndrome. J Perinatol. 2018;38:1114–22.

    Article  PubMed  Google Scholar 

  7. Patrick SW, Kaplan HC, Passarella M, Davis MM, Lorch SA. Variation in treatment of neonatal abstinence syndrome in US children’s hospitals, 2004-2011. J Perinatol. 2014;34:867–72.

    Article  CAS  PubMed  Google Scholar 

  8. Abrahams RR, Kelly SA, Payne S, Thiessen PN, Mackintosh J, Janssen PA. Rooming-in compared with standard care for newborns of mothers using methadone or heroin. Can Fam Physician. 2007;53:1723–30.

    Google Scholar 

  9. Holmes AV, Atwood EC, Whalen B, Beliveau J, Jarvis JD, Matulis JC, et al. Rooming-in to treat neonatal abstinence syndrome: improved family-centered care at lower cost. Pediatrics. 2016;137:e20152929.

  10. Grossman MR, Berkwitt AK, Osborn RR, Xu Y, Esserman DA, Shapiro ED, et al. An initiative to improve the quality of care of infants with neonatal abstinence syndrome. Pediatrics. 2017;139:e20163360.

  11. Grossman MR, Osborn RR, Berkwitt AK. Neonatal abstinence syndrome: time for a reappraisal. Hosp Pediatr. 2017;7:115–6.

    Article  PubMed  Google Scholar 

  12. MacMillan KDL. Neonatal abstinence syndrome: review of epidemiology, care models, and current understanding of outcomes. Clin Perinatol. 2019;46:817–32.

    Article  PubMed  Google Scholar 

  13. Singh R, Houghton M, Melvin P, Wachman EM, Diop H, Iverson R, Jr., et al. Predictors of pharmacologic therapy for neonatal opioid withdrawal syndrome: a retrospective analysis of a statewide database. J Perinatol. 2021;41:1381–8.

  14. Patrick SW, Barfield WD, Poindexter BB, Committee On Fetus and Newborn, Committee on Substance Use and Prevention. Neonatal opioid withdrawal syndrome. Pediatrics. 2020;146:e2020029074.

  15. Howard MB, Schiff DM, Penwill N, Si W, Rai A, Wolfgang T, et al. Impact of parental presence at infants’ bedside on neonatal abstinence syndrome. Hosp Pediatr. 2017;7:63–9.

    Article  PubMed  Google Scholar 

  16. Wachman EM, Houghton M, Melvin P, Isley BC, Murzycki J, Singh R, et al. A quality improvement initiative to implement the eat, sleep, console neonatal opioid withdrawal syndrome care tool in Massachusetts’ PNQIN collaborative. J Perinatol. 2020;40:1560–9.

    Article  CAS  PubMed  Google Scholar 

  17. Grisham LM, Stephen MM, Coykendall MR, Kane MF, Maurer JA, Bader MY. Eat, sleep, console approach: a family-centered model for the treatment of neonatal abstinence syndrome. Adv Neonatal Care. 2019;19:138–44.

    Article  PubMed  Google Scholar 

  18. Blount T, Painter A, Freeman E, Grossman M, Sutton AG. Reduction in length of stay and morphine use for NAS With the “Eat, Sleep, Console” Method. Hosp Pediatr. 2019;9:615–23.

    Article  PubMed  Google Scholar 

  19. Milliren CE, Gupta M, Graham DA, Melvin P, Jorina M, Ozonoff A. Hospital variation in neonatal abstinence syndrome incidence, treatment modalities, resource use, and costs across pediatric hospitals in the United States, 2013 to 2016. Hosp Pediatr. 2018;8:15–20.

    Article  PubMed  Google Scholar 

  20. Bogen DL, Whalen BL, Kair LR, Vining M, King BA. Wide variation found in care of opioid-exposed newborns. Acad Pediatr. 2017;17:374–80.

    Article  PubMed  Google Scholar 

  21. Oesterle TS, Thusius NJ, Rummans TA, Gold MS. Medication-assisted treatment for opioid-use disorder. Mayo Clin Proc. 2019;94:2072–86.

    Article  PubMed  Google Scholar 

  22. Jones HE, Chisolm MS, Jansson LM, Terplan M. Naltrexone in the treatment of opioid-dependent pregnant women: the case for a considered and measured approach to research. Addiction. 2013;108:233–47.

    Article  PubMed  Google Scholar 

  23. American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130:e81–94.

    Article  Google Scholar 

  24. Substance Abuse and Mental Health Services Administration. Clinical Guidance for Treating Pregnant and Parenting Women with Opioid Use Disorder and Their Infants. Rockville, MD; 2018. Contract No.: HHS Publication No. (SMA) 18-5054.

  25. Wiegand SL, Stringer EM, Stuebe AM, Jones H, Seashore C, Thorp J. Buprenorphine and naloxone compared with methadone treatment in pregnancy. Obstet Gynecol. 2015;125:363–8.

    Article  CAS  PubMed  Google Scholar 

  26. Towers CV, Hyatt BW, Visconti KC, Chernicky L, Chattin K, Fortner KB. Neonatal head circumference in newborns with neonatal abstinence syndrome. Pediatrics. 2019;143:e20180541.

  27. Coulson CC, Lorencz E, Rittenhouse K, Ramage M, Lorenz K, Galvin SL. Association of maternal buprenorphine or methadone dose with fetal growth indices and neonatal abstinence syndrome. Am J Perinatol. 2021;38:28–36.

    Article  PubMed  Google Scholar 

  28. Ramage M, Ostrach B, Fagan B, Coulson CC. Stabilizing the mother-infant dyad for better outcomes from OB to FM: Caring for patients with perinatal opioid use disorder through the 4th trimester. North Carol Med J. 2018;79:164–5.

    Article  Google Scholar 

  29. Stover MW, Davis JM. Opioids in pregnancy and neonatal abstinence syndrome. Semin Perinatol. 2015;39:561–5.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Scott LF, Guilfoy V, Duwve JM, Rawl SM, Cleveland L. Factors associated with the need for pharmacological management of neonatal opioid withdrawal syndrome. Adv Neonatal Care. 2020;20:364–73.

    Article  PubMed  Google Scholar 

  31. Honein MA, Boyle C, Redfield RR. Public health surveillance of prenatal opioid exposure in mothers and infants. Pediatrics. 2019;143:e20183801.

  32. Hahn PD, Melvin P, Graham DA, Milliren CE. A methodology to create mother-baby dyads using data from the Pediatric Health Information System. Hosp Pediatr. 2022;12:884–92.

  33. Milliren CE, Melvin P, Ozonoff A. Pediatric hospital readmissions for infants with neonatal opioid withdrawal syndrome, 2016–2019. Hosp Pediatr. 2021;11:979–87.

    Article  PubMed  Google Scholar 

  34. Keren R, Luan X, Localio R, Hall M, McLeod L, Dai D, et al. Prioritization of comparative effectiveness research topics in hospital pediatrics. Arch Pediatr Adolesc Med. 2012;166:1155–64.

    Article  PubMed  Google Scholar 

  35. Jonas JA, Shah SS, Zaniletti I, Hall M, Colvin JD, Gottlieb LM, et al. Regional variation in standardized costs of care at children’s hospitals. J Hosp Med. 2017;12:818–25.

    Article  PubMed  Google Scholar 

  36. Congressional Budget Office. The Distribution of Household Income, 2016. 2019. https://www.cbo.gov/publication/55413.

  37. Ton TG, Bennett MV, Incerti D, Peneva D, Druzin M, Stevens W, et al. Maternal and infant adverse outcomes associated with mild and severe preeclampsia during the first year after delivery in the United States. Am J Perinatol. 2020;37:398–408.

    Article  PubMed  Google Scholar 

  38. Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K. Probabilistic linkage without personal information successfully linked national clinical datasets. J Clin Epidemiol. 2021;136:136–45.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Johnson KE, Beaton SJ, Andrade SE, Cheetham TC, Scott PE, Hammad TA, et al. Methods of linking mothers and infants using health plan data for studies of pregnancy outcomes. Pharmacoepidemiol Drug Saf. 2013;22:776–82.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Vigod SN, Gomes T, Wilton AS, Taylor VH, Ray JG. Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study. BMJ. 2015;350:h2298.

  41. Clark RRS, French R, Lorch S, O’Rourke K, Rosenbaum KEF, Lake ET. Within-hospital concordance of opioid exposure diagnosis coding in mothers and newborns. Hosp Pediatr. 2021;11:825–33.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Goyal S, Saunders KC, Moore CS, Fillo KT, Ko JY, Manning SE, et al. Identification of substance-exposed newborns and neonatal abstinence syndrome using ICD-10-CM—15 hospitals, Massachusetts, 2017. Morb Mortal Wkly Rep. 2020;69:951.

    Article  CAS  Google Scholar 

  43. Maalouf FI, Cooper WO, Stratton SM, Dudley JA, Ko J, Banerji A, et al. Positive predictive value of administrative data for neonatal abstinence syndrome. Pediatrics. 2019;143: e20174183.

  44. Peeler M, Gupta M, Melvin P, Bryant AS, Diop H, Iverson R, et al. Racial and ethnic disparities in maternal and infant outcomes among opioid-exposed mother-infant dyads in Massachusetts (2017–2019). Am J Public Health. 2020;110:1828–36.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Schiff DM, Nielsen T, Hoeppner BB, Terplan M, Hansen H, Bernson D, et al. Assessment of racial and ethnic disparities in the use of medication to treat opioid use disorder among pregnant women in Massachusetts. JAMA Netw Open. 2020;3:e205734.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Guerrero EG, Marsh JC, Duan L, Oh C, Perron B, Lee B. Disparities in completion of substance abuse treatment between and within racial and ethnic groups. Health Serv Res. 2013;48:1450–67.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Cook BL, Alegria M. Racial-ethnic disparities in substance abuse treatment: the role of criminal history and socioeconomic status. Psychiatr Serv. 2011;62:1273–81.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Pinedo M. A current re-examination of racial/ethnic disparities in the use of substance abuse treatment: Do disparities persist? Drug Alcohol Depend. 2019;202:162–7.

    Article  PubMed  Google Scholar 

  49. Elmore AL, Tanner JP, Lowry J, Lake-Burger H, Kirby RS, Hudak ML, et al. Diagnosis codes and case definitions for neonatal abstinence syndrome. Pediatrics. 2020;146:e20200567.

  50. Wen T, Batista N, Wright JD, D’Alton ME, Attenello FJ, Mack WJ, et al. Postpartum readmissions among women with opioid use disorder. Am J Obstet Gynecol MFM. 2019;1:89–98.

    Article  PubMed  Google Scholar 

  51. 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;5:513–9.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Shrestha S, Roberts MH, Maxwell JR, Leeman LM, Bakhireva LN. Post-discharge healthcare utilization in infants with neonatal opioid withdrawal syndrome. Neurotoxicol Teratol. 2021;86:106975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hwang SS, Liu CL, Yu Q, Cui X, Diop H. Risk factors for emergency room use and rehospitalization among opioid-exposed newborns in Massachusetts. Birth. 2021;48:26–35.

    Article  PubMed  Google Scholar 

  54. Lappen JR, Stark S, Bailit JL, Gibson KS. Delivery dose of methadone, but not buprenorphine, is associated with the risk and severity of neonatal opiate withdrawal syndrome. Am J Obstet Gynecol MFM. 2020;2:100075.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

CEM conceptualized and designed the study and planned the analyses with input from PDH, AO, PM, and DAG. With input from CEM, PDH acquired and analyzed the data. CEM, PDH, PM and DAG reviewed and interpreted statistical output. PDH and CEM drafted the initial manuscript. All authors reviewed and revised the manuscript. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Carly E. Milliren.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

The authors declare no competing interests.This study was performed in accordance with the Declaration of Helsinki. This study used de-identified administrative billing data and was considered not human subjects research by the Institutional Review Board at Boston Children’s Hospital.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hahn, P.D., Melvin, P., Graham, D.A. et al. Association between pharmacologic treatment and hospital utilization at birth among neonatal opioid withdrawal syndrome mother-infant dyads. J Perinatol 43, 283–292 (2023). https://doi.org/10.1038/s41372-023-01623-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-023-01623-6

Search

Quick links