Impaired vision in children prenatally exposed to methadone: an observational cohort study

Abstract

Background/objectives: To examine prevalence of failed visual assessment at 8-10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure.

Subjects/methods: Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a 'fail'. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables.

Results: 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual 'fail' outcome, adjusted odds ratio 2.6, 95% CI 1.1-6.2; adjusted relative risk 1.8 (95% CI 1.1-3.4). Visual 'fail' outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference-11-27%).

Conclusions: Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure.

Trial registration: The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 .

Fig. 1. Euler diagram illustrating combinations of polydrug exposure and drug groups based on combined exposure data (see Table 1) for the 98 exposed children.

Opioid is methadone ± opiates; BDZ, benzodiazepines; stimulants are cocaine and/or amphetamines. Drug groups: 1) opioids alone (n = 17); 2) opioids + cannabinoid (n = 12); 3) opioids + benzodiazepine (n = 14); 4) opioids + benzodiazepine + cannabis (n = 30); 5) opioids + stimulants ± benzodiazepine or cannabis (n = 25). Opiates most likely illicit heroin. If infant or postnatal maternal urine was positive for opiates and opioid analgesia in labour was documented, in the absence of declared illicit maternal opiate or positive prenatal maternal urine, infant was not considered exposed.

Fig. 2. Dotplots showing visual detriment index (VDI) for 98 exposed children by drug group (left) and by treated neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS) status (right).

Left, by drug exposure group: 1) opioids alone (n = 17); 2) opioids + cannabinoid (n = 12); 3) opioids + benzodiazepine (n = 14); 4) opioids + benzodiazepine + cannabis (n = 30); 5) opioids + stimulants (cocaine and/or amphetamines) ± benzodiazepine or cannabis (n = 25). Right, by neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS) treatment category (n = 47 treated, n = 51 not treated).