Article | Published:

Retrospective review of neurodevelopmental outcomes in infants treated for neonatal abstinence syndrome

Journal of Perinatologyvolume 38pages587592 (2018) | Download Citation



Little is known about developmental outcomes in neonatal abstinence syndrome (NAS). We hypothesized that children treated for NAS would score lower than the normative sample on the Bayley Scales of Infant Development, 3rd edition.

Study design:

We performed a retrospective cohort study of 87 infants treated for NAS and evaluated at 2 years of age.


Children treated for NAS scored significantly lower than the norm (mean 100) on all 3 subscales (cognitive mean 96.5, language mean 93.8, motor mean 94.0, all p < 0.03). Children who lived with foster/adoptive families at follow up had higher cognitive scores (median 100 vs. 95, p = 0.03) than those who lived with biological relatives, and were less likely to have motor scores <85 (p = 0.02). Eight percent of children required treatment for strabismus.


Children treated for NAS are at risk for lower developmental scores and higher rates of strabismus at age 2 than the general population.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    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;372:2118–26.

  2. 2.

    Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-9. JAMA. 2012;307:1934-40.

  3. 3.

    Hamilton R, McGlone L, MacKinnon JR, Russell HC, Bradnam MS, Mactier H. Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy. Br J Ophthalmol. 2010;94:696–700.

  4. 4.

    McGlone L, Hamilton R, McCulloch DL, MacKinnon JR, Bradnam M, Mactier H. Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy. Br J Ophthalmol. 2014;98:238–45.

  5. 5.

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

  6. 6.

    Nygaard E, Moe V, Slinning K, Walhovd KB. Longitudinal cognitive development of children born to mothers with opioid and polysubstance use. Pediatr Res. 2015;78:330–5.

  7. 7.

    Ornoy A. The impact of intrauterine exposure versus postnatal environment in neurodevelopmental toxicity: long-term neurobehavioral studies in children at risk for developmental disorders. Toxicol Lett. 2003;140-1:171–81.

  8. 8.

    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.

  9. 9.

    Oei JL, Melhuish E, Uebel H, Azzam N, Breen C, Burns L, et al. Neonatal abstinence syndrome and high school performance. Pediatrics. 2017;139:e20162651.

  10. 10.

    Baldacchino A, Arbuckle K, Petrie DJ, McCowan C. Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis. BMC Psychiatry. 2014;14:104.

  11. 11.

    Hall ES, Isemann BT, Wexelblatt SL, Meinzen-Derr J, Wiles JR, Harvey S, et al. A cohort comparison of buprenorphine versus methadone treatment for neonatal abstinence syndrome. J Pediatr. 2016;170:39–44.e31.

  12. 12.

    Friedman DS, Repka MX, Katz J, Giordano L, Ibironke J, Hawse P, et al. Prevalence of amblyopia and strabismus in white and African American children aged 6 through 71 months the Baltimore Pediatric Eye Disease Study. Ophthalmology. 2009;116:2128–2134.e2121-2122.

  13. 13.

    Sundelin Wahlsten V, Sarman I. Neurobehavioural development of preschool-age children born to addicted mothers given opiate maintenance treatment with buprenorphine during pregnancy. Acta Paediatr. 2013;102:544–9.

  14. 14.

    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;56:1017–27.

  15. 15.

    Vestal-Laborde AA, Eschenroeder AC, Bigbee JW, Robinson SE, Sato-Bigbee C. The opioid system and brain development: effects of methadone on the oligodendrocyte lineage and the early stages of myelination. Dev Neurosci. 2014;36:409–21.

  16. 16.

    Robinson SE, Maher JR, Wallace MJ, Kunko PM. Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat. Neurotoxicol Teratol. 1997;19:295–303.

  17. 17.

    Robinson SE. Effect of prenatal opioid exposure on cholinergic development. J Biomed Sci. 2000;7:253–7.

  18. 18.

    Luine V, Gomez J, Beck K, Bowman R. Sex differences in chronic stress effects on cognition in rodents. Pharmacol Biochem Behav. 2017;152:13–9.

  19. 19.

    Samplin E, Ikuta T, Malhotra AK, Szeszko PR, Derosse P. Sex differences in resilience to childhood maltreatment: effects of trauma history on hippocampal volume, general cognition and subclinical psychosis in healthy adults. J Psychiatr Res. 2013;47:1174–9.

  20. 20.

    Bale TL, Epperson CN. Sex differences and stress across the lifespan. Nat Neurosci. 2015;18:1413–20.

  21. 21.

    Gupta M, Mulvihill AO, Lascaratos G, Fleck BW, George ND. Nystagmus and reduced visual acuity secondary to drug exposure in utero: long-term follow-up. J Pediatr Ophthalmol Strabismus. 2012;49:58–63.

  22. 22.

    Gill AC, Oei J, Lewis NL, Younan N, Kennedy I, Lui K. Strabismus in infants of opiate-dependent mothers. Acta Paediatr. 2003;92:379–85.

  23. 23.

    Song T, Li G, Liang Z, Tang Y, Yang Y, Xia J, et al. Chronic morphine exposure affects contrast response functions of V1 neurons in cats. Neuroscience. 2012;226:451–8.

  24. 24.

    Mei B, Niu L, Cao B, Huang D, Zhou Y. Prenatal morphine exposure alters the layer II/III pyramidal neurons morphology in lateral secondary visual cortex of juvenile rats. Synapse. 2009;63:1154–61.

Download references

Author information


  1. Perinatal Institute, Division of Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    • Stephanie L. Merhar
    • , Jennifer M. McAllister
    • , Kathryn E. Wedig-Stevie
    •  & Brenda B. Poindexter
  2. Division of Occupational and Physical Therapy, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    • Amy C. Klein
  3. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    • Jareen Meinzen-Derr


  1. Search for Stephanie L. Merhar in:

  2. Search for Jennifer M. McAllister in:

  3. Search for Kathryn E. Wedig-Stevie in:

  4. Search for Amy C. Klein in:

  5. Search for Jareen Meinzen-Derr in:

  6. Search for Brenda B. Poindexter in:


Source of funding: NIH UG1HD027853-27S1 (Poindexter/Merhar).

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Stephanie L. Merhar.

About this article

Publication history