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.

Fetal and Infant Effects of Maternal Opioid Use during Pregnancy: A Literature Review including Clinical, Toxicological, Pharmacogenomic, and Epigenetic Aspects for Forensic Evaluation

“…The results of the literature search are summarized in Figure 1 . A total of 87 studies met the inclusion criteria and were included in the review [ 1 , 2 , 5 , 6 , 9 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , …”

“…In addition, children born to mothers treated with MTD or buprenorphine during pregnancy have significantly worse neurodevelopmental outcomes, including cognitive, psychomotor, and executive functioning; observed motor activity, behavior, and attention; and long-term visual outcomes, including congenital nystagmus, refractive errors, visual acuity, and contrast sensitivity, compared with children born to non-users [ 26 , 37 , 45 , 46 , 58 ]. A recent study suggests that buprenorphine use during pregnancy is associated with a lower risk of adverse outcomes than MTD use, particularly in relation to indices of behavioral, emotional, and cognitive regulation [ 43 ].…”

“… Studies organized by issue of interest. Foetus and infant clinical complications: Borrelli et al 2022 [ 20 ], O’Donnell et al2017 [ 22 ], Wolff et al 2014 [ 24 ], Maguire et al 2020 [ 26 ], Benck et al 2023 [ 27 ], Caritis et al 2019 [ 29 ], Conradt et al 2019 [ 31 ], Dryden et al 2022 [ 34 ], Duska et al 2022 [ 35 ], Epstein et al2013 [ 36 ], Galli et al 2023 [ 37 ], Garrison et al2016 [ 38 ], Irnes et al 2017 [ 39 ], Kushnir et al 2023 [ 42 ], McCarthy et al 2023 [ 43 ], McGlone et al 2014 [ 45 ], Monnelly et al 2019 [ 46 ], Newbury et al 2023 [ 49 ], Ramirez et al 2006 [ 54 ], Spowart et al 2023 [ 58 ], Towers et al2019 [ 60 ]. Foetus and infant cause of death: Kaltenbach et al 1998 [ 1 ], Sithisarn et al 2012 [ 2 ], Friguls et al 2012 [ 6 ], Lam et al 1992 [ 9 ], Fishman et al 2019 [ 11 ], Rausgaard et al 2023 [ 14 ], Bashore et al 1981 [ 16 ], Anbalagan et al 2023 [ 17 ], Ryan et al 2023 [ 18 ], Esposito et al 2022 [ 19 ], Little et al 1990 [ 21 ], Kandall et al 1976 [ 23 ], Athanasakis et al 2011 [ 25 ], Burns et al2010 [ 28 ], Cohen et al 2015 [ 30 ], Kandall et al 1991 [ 40 ], Kandall et al 1993 [ 41 ], Montanari et al 2018 [ 47 ], Montanari et al 2019 [ 48 ], Serra et al 2017 [ 57 ], Ward et al 1990 [ …”