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Association of medication-assisted treatment and short acting opioids with newborn head circumference and birth weight

Journal of Perinatology volume 43, pages 277–282 (2023)Cite this article

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Abstract

Objective

We compared the association of methadone, buprenorphine, and short-acting opioid exposure with newborn head circumference (HC) and birth weight (BW), and evaluated gestational age (GA) as a mediator.

Study design

We included newborns born 2013–2018 identified by neonatal abstinence syndrome diagnosis code (N = 572) and birthday-matched unexposed controls (N = 571). Linear regressions of opioid exposure with HC and BW controlled for tobacco, marijuana, cocaine, gabapentin, cesarean section, Medicaid, and newborn sex, with mediation analysis by GA.

Result

Methadone was associated with 0.81 cm lower HC (95% CI = −1.22, −0.40) and 0.23 kg lower BW (95% CI = −0.35, −0.10) with approximately 24% and 41% mediated by GA, respectively. Buprenorphine and short acting opioids were not associated with HC or BW.

Conclusion

Methadone exposed newborns have smaller HC and lower BW not fully attributable to younger GA, suggesting a direct effect of methadone on intrauterine growth. Exploration of potential developmental consequences of this is urgently needed.

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Fig. 1: Head circumference by exposure.
Fig. 2: Birthweight by exposure.

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Data availability

Due to institutional guidelines on data sharing and resource barriers, we are not making our dataset public.

References

  1. 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 

  2. Minozzi S, Amato L, Jahanfar S, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev. 2020;11:CD006318.

    PubMed  Google Scholar 

  3. Jones HE, O’Grady KE, Malfi D, Tuten M. Methadone maintenance vs. methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict. 2008;17:372–86.

    Article  PubMed  Google Scholar 

  4. Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003;70:S87–101.

    Article  CAS  PubMed  Google Scholar 

  5. McQueen K, Murphy-Oikonen J. Neonatal Abstinence Syndrome. N Engl J Med. 2016;375:2468–79.

    Article  PubMed  Google Scholar 

  6. Jansson LM, Di Pietro JA, Elko A, Williams EL, Milio L, Velez M. Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: a comparison of fetal neurobehaviors and infant outcomes. Drug Alcohol Depend. 2012;122:213–9.

    Article  CAS  PubMed  Google Scholar 

  7. Coyle MG, Brogly SB, Ahmed MS, Patrick SW, Jones HE. Neonatal abstinence syndrome. Nat Rev Dis Prim. 2018;4:47.

    Article  PubMed  Google Scholar 

  8. Hirai AH, Ko JY, Owens PL, Stocks C, Patrick SW. Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses in the US, 2010-2017. JAMA. 2021;325:146–55.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sirnes E, Oltedal L, Bartsch H, Eide GE, Elgen IB, Aukland SM. Brain morphology in school-aged children with prenatal opioid exposure: A structural MRI study. Early Hum Dev. 2017;106-107:33–9.

    Article  CAS  PubMed  Google Scholar 

  10. Merhar SL, Kline JE, Braimah A, Kline-Fath BM, Tkach JA, Altaye M, et al. Prenatal opioid exposure is associated with smaller brain volumes in multiple regions. Pediatr Res. 2021;90:397–402.

    Article  PubMed  Google Scholar 

  11. Towers CV, Hyatt BW, Visconti KC, Chernicky L, Chattin K, Fortner KB. Neonatal Head Circumference in Newborns With Neonatal Abstinence Syndrome. Pediatrics. 2019;143. Epub 2018 Dec 10.

  12. Visconti KC, Hennessy KC, Towers CV, Howard BC. Chronic opiate use in pregnancy and newborn head circumference. Am J Perinatol. 2015;32:27–32.

    Article  PubMed  Google Scholar 

  13. Fill MA, Miller AM, Wilkinson RH, Warren MD, Dunn JR, Schaffner W, et al. Educational Disabilities Among Children Born With Neonatal Abstinence Syndrome. Pediatrics. 2018;142:e20180562.

  14. Patrick SW, Dudley J, Martin PR, Harrell FE, Warren MD, Hartmann KE, et al. Prescription Opioid Epidemic and Infant Outcomes. Pediatrics. 2015;135:842–50.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM. Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009. JAMA. 2012;307:1934–40.

    Article  CAS  PubMed  Google Scholar 

  16. Lindley AA, Benson JE, Grimes C, Cole TM 3rd, Herman AA. The relationship in neonates between clinically measured head circumference and brain volume estimated from head CT-scans. Early Hum Dev. 1999;56:17–29.

    Article  CAS  PubMed  Google Scholar 

  17. Aagaard K, Bach CC, Henriksen TB, Larsen RT, Matthiesen NB. Head circumference at birth and childhood developmental disorders in a nationwide cohort in Denmark. Paediatr Perinat Epidemiol. 2018;32:458–66.

    Article  PubMed  Google Scholar 

  18. Gampel SB, Nomura Y. Short and Long-Term Effects of Compromised Birth Weight, Head Circumference, and Apgar Scores on Neuropsychological Development. J Psychol Abnorm Child. 2014;3. Epub 2014 Aug 4.

  19. Piske M, Homayra F, Min JE, Zhou H, Marchand C, Mead A, et al. Opioid Use Disorder and Perinatal Outcomes. Pediatrics. 2021;148. Epub 2021 Sep 3.

  20. Brogly SB, Saia KA, Walley AY, Du HM, Sebastiani P. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis. Am J Epidemiol. 2014;180:673–86.

    Article  PubMed  Google Scholar 

  21. Corsi DJ, Hsu H, Fell DB, Wen SW, Walker M. Association of Maternal Opioid Use in Pregnancy With Adverse Perinatal Outcomes in Ontario, Canada, From 2012 to 2018. JAMA Netw Open 2020;3:e208256.

    Article  PubMed  Google Scholar 

  22. Miele MJ, Souza RT, Calderon IM, Feitosa FE, Leite DF, Rocha Filho EA, et al. Head circumference as an epigenetic risk factor for maternal nutrition. Front Nutr. 2022;9:867727.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Blair C, Raver CC. Poverty, Stress, and Brain Development: New Directions for Prevention and Intervention. Acad Pediatr. 2016;16:S30–6.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Schempf AH. Illicit Drug Use and Neonatal Outcomes: A Critical Review. Obstetrical Gynecol Surv. 2007;62:749–57.

    Article  Google Scholar 

  25. Maeda A, Bateman BT, Clancy CR, Creanga AA, Leffert LR. Opioid Abuse and Dependence during Pregnancy: Temporal Trends and Obstetrical Outcomes. Anesthesiology. 2014;121:1158–65.

    Article  PubMed  Google Scholar 

  26. Šimič Klarić A, Tomić Rajić M, Tesari Crnković H. Timing of Head Circumference Measurement in Newborns. Clin Pediatrics. 2014;53:456–9.

    Article  Google Scholar 

  27. Brogly SB, Hahn KA, Diaz SH, Werler M. Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy. J Addict Res Ther. 2015;6. Epub 2015 Dec 31.

  28. Ahrens KA, McBride CA, O’Connor A, Meyer MC. Medication for Addiction Treatment and Postpartum Health Care Utilization Among Pregnant Persons With Opioid Use Disorder. J Addict Med. 2022;16:56–64.

  29. de Castro A, Jones HE, Johnson RE, Gray TR, Shakleya DM, Huestis MA. Maternal methadone dose, placental methadone concentrations, and neonatal outcomes. Clin Chem. 2011;57:449–58.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jones HE, Heil SH, Tuten M, Chisolm MS, Foster JM, O’Grady KE, et al. Cigarette smoking in opioid-dependent pregnant women: neonatal and maternal outcomes. Drug Alcohol Depend. 2013;131:271–7.

    Article  PubMed  Google Scholar 

  31. Cleary BJ, Donnelly J, Strawbridge J, Gallagher PJ, Fahey T, Clarke M, et al. Methadone dose and neonatal abstinence syndrome-systematic review and meta-analysis. Addiction 2010;105:2071–84.

    Article  PubMed  Google Scholar 

  32. Crocetti MT, Amin DD, Jansson LM. Variability in the evaluation and management of opiate-exposed newborns in Maryland. Clin Pediatr (Philos). 2007;46:632–5.

    Article  Google Scholar 

  33. 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 

  34. Grossman MR, Lipshaw MJ, Osborn RR, Berkwitt AK. A Novel Approach to Assessing Infants With Neonatal Abstinence Syndrome. Hosp Pediatr. 2018;8:1–6.

    Article  PubMed  Google Scholar 

  35. 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;16:329–36.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wilcox AJ, Weinberg CR, Basso O. On the pitfalls of adjusting for gestational age at birth. Am J Epidemiol. 2011;174:1062–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 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;363:2320–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schmid M, Kuessel L, Klein K, Metz V, Fischer G, Krampl-Bettelheim E. First-trimester fetal heart rate in mothers with opioid addiction. Addiction 2010;105:1265–8.

    Article  PubMed  Google Scholar 

  39. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2004;3:CD002207.

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Acknowledgements

We acknowledge Kate Ahrens for her significant contribution to study design and Kaitlin Ostrander, Isabel Wolfe, Rebecca Bell and Lilly Watson for their contributions to data collection.

Funding

Funding for this study was received from the Barbara Bush Children’s Health Scholarship Academy for data abstraction.

Author information

Authors and Affiliations

  1. MaineHealth Institute for Research, Portland, ME, USA

    Anya J. Cutler

  2. Barbara Bush Children’s Hospital at Maine Medical Center, Department of Pediatrics, Portland, ME, USA

    David F. Cox & Sarah M. B. Gabrielson

  3. Barbara Bush Children’s Hospital at Maine Medical Center, Division of Neonatology, Portland, ME, USA

    Alan P. Picarillo

  4. Barbara Bush Children’s Hospital at Maine Medical Center, Division of Pediatric Neurology, Portland, ME, USA

    Alexa K. Craig

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Contributions

AJC carried out all analyses of the data and did the majority of the manuscript writing. AKC, SMBG, and DFC conceptualized and designed this study, coordinated and supervised data collection, provided clinical expertise for appropriate analytical modeling, and reviewed and revised the manuscript. APP provided critical clinical expertise in the review and revision of the manuscript.

Corresponding author

Correspondence to Anya J. Cutler.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study was approved as exempt research by the Maine Medical Center Institutional Review Board. This study was performed in accordance with the Declaration of Helsinki.

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Cutler, A.J., Cox, D.F., Gabrielson, S.M.B. et al. Association of medication-assisted treatment and short acting opioids with newborn head circumference and birth weight. J Perinatol 43, 277–282 (2023). https://doi.org/10.1038/s41372-022-01579-z

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