Long-Term Visual and Neurodevelopmental Outcomes in Two Children with Congenital Nystagmus Secondary to Methadone Exposure In utero

Abstract

Methadone is used as a substitute for illicit opioids during pregnancy. However, the real effect of this molecule on visual and neurodevelopmental outcomes of the children exposed is not fully understood, since studies considered subjects born to polydrug-dependent mothers and followed for few months/years. We report the long-term outcomes of two infants with congenital nystagmus solely exposed to methadone in utero. Neurological and neurovisual evaluations were performed every year from the first year of life to 11 years of age. One child was diagnosed with developmental coordination disorder. Both cases presented with ophthalmologic (refractive errors), oculomotor (nystagmus and fixation, smooth pursuit, and saccades dysfunctions), and perceptive problems (reduced visual acuity and contrast sensitivity). While nystagmus and other oculomotor dysfunctions remained stable over time, visual acuity and contrast sensitivity improved; refractive errors worsened and required corrective lenses. Both children showed normal neurodevelopmental and cognitive profile. This report highlights the long-term visual and developmental outcomes of two children exclusively exposed to methadone underlining the possibility of a visual dysfunction and motor coordination disorder. These observations prompt the need to investigate prenatal drug exposure as a cause of congenital nystagmus.

Keywords

methadone - congenital nystagmus - pregnancy - neurovisual profile - children

Ethics Statement

Written informed consent to conduct laboratory and clinical testing, to participate in the study, and to publish the findings was obtained from parents.

Authors' Contribution

J.G. and E.F. designed the study. J.G., E.L., and L.P. collected data. J.G. and E.L. drafted the manuscript. J.G. and P.A. enrolled the patients. J.G. and A.F. performed the visual evaluation, and S.M. performed the cognitive evaluation. E.F. supervised the study. All authors read and approved the final manuscript.

Publication History

Received: 02 May 2023

Accepted: 19 June 2023

Article published online:
14 August 2023

• References

• 1 Monnelly VJ, Hamilton R, Chappell FM, Mactier H, Boardman JP. Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta-analysis. Dev Med Child Neurol 2019; 61 (07) 750-760
• 2 Farid WO, Dunlop SA, Tait RJ, Hulse GK. The effects of maternally administered methadone, buprenorphine and naltrexone on offspring: review of human and animal data. Curr Neuropharmacol 2008; 6 (02) 125-150
• 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 (06) 696-700
• 4 Spiteri Cornish K, Hrabovsky M, Scott NW, Myerscough E, Reddy AR. The short- and long-term effects on the visual system of children following exposure to maternal substance misuse in pregnancy. Am J Ophthalmol 2013; 156 (01) 190-194
• 5 McGlone L, Hamilton R, McCulloch DL. et al. Neonatal visual evoked potentials in infants born to mothers prescribed methadone. Pediatrics 2013; 131 (03) e857-e863
• 6 Hemmati Z, Conti AA, Baldacchino A. Ophthalmic outcomes in children exposed to opioid maintenance treatment in utero: a systematic review and meta-analysis. Neurosci Biobehav Rev 2022; 136: 104601
• 7 Galli J, Loi E, Molinaro A. et al; CP Collaborative Group. Age-related effects on the spectrum of cerebral visual impairment in children with cerebral palsy. Front Hum Neurosci 2022; 16: 750464
• 8 Barry JM, Birnbaum AK, Jasin LR, Sherwin CM. Maternal exposure and neonatal effects of drugs of abuse. J Clin Pharmacol 2021; 61 (Suppl. 02) S142-S155
• 9 Whitham JN, Spurrier NJ, Baghurst PA, Weston P, Sawyer MG. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: the results of a longitudinal study. Neurotoxicol Teratol 2015; 52 (Pt A): 17-24
• 10 Sakki HEA, Dale NJ, Sargent J, Perez-Roche T, Bowman R. Is there consensus in defining childhood cerebral visual impairment? A systematic review of terminology and definitions. Br J Ophthalmol 2018; 102 (04) 424-432
• 11 Chin EM, Kitase Y, Madurai NK, Robinson S, Jantzie LL. In utero methadone exposure permanently alters anatomical and functional connectivity: a preclinical evaluation. Front Pediatr 2023; 11: 1139378
• 12 Tinelli F, Gamucci A, Battini R, Cioni G. Congenital nystagmus in two infants born from mothers exposed to methadone during pregnancy. Ital J Pediatr 2013; 39: 40
• 13 Sprenger T, Berthele A, Platzer S, Boecker H, Tölle TR. What to learn from in vivo opioidergic brain imaging?. Eur J Pain 2005; 9 (02) 117-121
• 14 Monnelly VJ, Anblagan D, Quigley A. et al. Prenatal methadone exposure is associated with altered neonatal brain development. Neuroimage Clin 2017; 18: 9-14
• 15 Galli J, Ambrosi C, Micheletti S. et al. White matter changes associated with cognitive visual dysfunctions in children with cerebral palsy: a diffusion tensor imaging study. J Neurosci Res 2018; 96 (11) 1766-1774