Laura McGlone

Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy

Background and aims There are growing concerns regarding visual outcome of infants exposed to opiates (including substitute methadone) and/or benzodiazepines in utero. We describe the combined ophthalmology and visual electrophysiology findings in 20 infants and children who had been exposed to substitute methadone and other drugs of misuse in utero. Methods This was a descriptive case series of 20 patients, all of whom had been referred to a paediatric visual electrophysiology service because of concerns regarding visual function, and all of whom had been exposed to methadone in utero. All children underwent a full ophthalmic and orthoptic examination as well as visual electrophysiology testing deemed appropriate on an individual basis. A review was undertaken of paediatric case notes and of maternal antenatal urine toxicology. Results Ophthalmic abnormalities included reduced acuity (95%), nystagmus (70%), delayed visual maturation (50%), strabismus (30%), refractive errors (30%), and cerebral visual impairment (25%). Visual electrophysiology was abnormal in 60%. A quarter of the children had associated neurodevelopmental abnormalities. The majority of children with nystagmus (79%) had been treated for neonatal abstinence syndrome (NAS). Conclusion Infants born to drug-misusing mothers prescribed methadone in pregnancy are at risk of a range of visual problems, the underlying causes of which are not clear. Those infants with NAS severe enough to receive pharmaceutical treatment may be at particular risk of developing nystagmus. The inclusion of visual electrophysiology in comprehensive visual assessment of children exposed to substance misuse in utero may help clarify the underlying causes by differentiating abnormalities of retinal and cortical origin.

Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy

Background Flash visual evoked potentials (VEPs) were abnormal in a cohort of 100 neonates exposed to maintenance methadone in utero. This prospective cohort study now describes clinical visual and electrophysiological outcomes at 6 months. Methods Visual assessment included modified Atkinson test battery; strabismus, nystagmus, reduced visual acuity, delayed visual maturation or refractive error (>3 dioptres) defined a fail. Pattern-onset VEPs were recorded to 120′, 60′ and 15′ checks. Results 81 drug-exposed and 26 comparison infants (79% and 52% of the original cohorts) were assessed at a median age of 27 weeks (range 26–30). 90% of drug-exposed infants had been additionally exposed to illicit drugs and 41% to excess alcohol in utero. 40% of the drug-exposed cohort failed clinical visual assessment: the relative risk of abnormal assessment was 5.1 (95% CI 1.3 to 20; p=0.02). Nystagmus was particularly common. VEP peak times were slower and amplitudes smaller in drug-exposed infants, of whom 70% had one or more abnormal VEP parameter. Abnormal visual outcome at 6 months was not associated with the pattern of additional drug exposure or a history of neonatal abstinence. Conclusions Abnormal visual electrophysiology in infants born to drug-misusing mothers prescribed maintenance methadone persists to 6 months of age, and is associated with abnormal clinical visual assessment.

Neonatal visual evoked potentials in infants born to mothers prescribed methadone.

OBJECTIVE: Drug misuse in pregnancy is associated with impaired infant visual development. Pilot data showed abnormal flash visual evoked potentials (VEPs) in neonates exposed to methadone in utero, but results were confounded by intrauterine growth restriction, gestation, and ongoing drug misuse. This large cohort study aimed to clarify the effects on neonatal flash VEPs of maternal drug misuse in pregnancy, including prescription of substitute methadone and subsequent development of neonatal abstinence syndrome. METHODS: This was a prospective cohort study. Flash VEPs were recorded within 3 days of birth from 100 healthy infants of drug-misusing mothers prescribed substitute methadone during pregnancy and 50 comparison infants matched for birth weight, gestation, and socioeconomic deprivation. VEP morphology was classified as mature, typical, or immature, and amplitudes and implicit times of the major waveform components measured. Drug exposure was determined by maternal history, maternal and infant urine, and meconium toxicology. RESULTS: VEPs from maternal drug-exposed infants were more likely to be of immature waveform (P < .001) and were smaller in overall amplitude (median 27 µV vs 39 µV, P < .001) compared with non–drug-exposed infants. Most infants were exposed to illicit drugs in addition to prescribed methadone; differences in VEP parameters were independently associated with maternal prescribed methadone and persisted after correcting for birth weight, cigarette smoking, and excess in utero alcohol exposure. CONCLUSIONS: In utero exposure to prescribed substitute methadone is associated with altered flash VEPs in the newborn period and these infants may warrant early clinical visual assessment.

Visual evoked potentials in infants exposed to methadone in utero

We investigated the effects of maternal drug misuse on neonatal visual evoked potentials (VEPs). Flash VEPs were recorded within 4 days of birth from 21 term infants of mothers misusing drugs and prescribed substitute methadone and 20 controls. Waveforms were classified as typical, atypical, immature or non-detectable, and amplitude and latencies were measured. VEPs from drug-exposed infants were less likely to be of typical waveform and more likely to be immature or non-detectable (p<0.01) than those of control infants. They were also smaller in amplitude (median 10.8 vs 24.4 μV, p<0.001). VEPs of drug-exposed infants had matured after 1 week but remained of lower amplitude than VEPs of newborn controls (p<0.01) and were non-detectable in 15%. Flash VEPs differ between maternal drug-exposed and non-drug-exposed newborns. Future research should address the specific effects of maternal methadone and/or other illicit drug misuse on infant VEPs, and associations between neonatal VEPs and subsequent visual development.

Infants of opioid-dependent mothers: neurodevelopment at six months.

OBJECTIVE The aim of this study is to describe infant neurodevelopment in 81 infants of methadone-prescribed opioid-dependent mothers. METHODS Griffith MD scores at six months. RESULTS Scores were lower in all domains compared to controls (p<0.001). Poly-drug exposed infants and those treated for neonatal abstinence syndrome performed significantly poorer (p=0.002 and p=0.008 respectively). CONCLUSIONS Infants of methadone-maintained opioid-dependent mothers show poorer neurodevelopment at six months of age than non-drug exposed comparison infants. Developmental difficulties are confounded by delayed visual development. PRACTICE IMPLICATIONS These highly vulnerable children merit close surveillance throughout infancy. SUMMARY Griffith MD scores at six months in 81 infants born to methadone-prescribed opioid-dependent mothers were lower in all domains compared to controls (p<0.001). Poly-drug exposed infants and those treated for neonatal abstinence syndrome performed significantly poorer (p=0.002 and p=0.008 respectively). Co-existing visual problems were common.

In utero drug and alcohol exposure in infants born to mothers prescribed maintenance methadone

Aims To describe the prevalence of in utero alcohol and illicit drug exposure in infants born to mothers prescribed methadone in pregnancy, and to compare the accuracy of maternal interview with infant toxicology. Methods Urine and meconium samples were collected from 56 infants born to mothers prescribed methadone during pregnancy and a confidential interview conducted soon after delivery. Samples were screened for drugs of misuse and meconium samples analysed for the presence of fatty acid ethyl esters (FAEEs) to detect prenatal alcohol exposure. Results 91% of infants had been exposed to illicit drugs in utero, including opiates (73%), benzodiazepines (70%) and cannabinoids (59%). 47% of infants had elevated FAEEs. Meconium was more sensitive at detecting in utero drug exposure than urine toxicology (p<0.01 for opiates, benzodiazepines, cannabinoids) or maternal interview (p=0.03 for opiates, p<0.01 for cannabinoids). Conclusions The majority of infants born to mothers prescribed methadone during pregnancy are exposed to polysubstance misuse, and almost one-half additionally exposed to excess alcohol.

Drug misuse in pregnancy: losing sight of the baby?

Maternal drug misuse can seriously affect the health of the fetus and newborn infant. The association of maternal drug misuse with prematurity, intrauterine growth restriction (IUGR) and neonatal abstinence syndrome (NAS) is well recognised, and there is growing concern about infant visual development and longer-term neurodevelopmental outcome. Drug misuse is associated with changes in the visual system as measured by the visual evoked potential (VEP) in adults and animal models. A recent study has shown abnormal VEPs in newborn infants exposed to methadone in utero, consistent with reports of delayed visual development in this population. Since visual abnormalities and neurodevelopmental abnormalities can be predicted by abnormal VEPs in infancy, it is postulated that the VEP may be a valuable tool in the detection of the adverse effects of maternal drug misuse upon the infant. This review summarises the impact of maternal drug misuse upon the health of the fetus and newborn infant, addresses the specific effects of maternal drug misuse upon the developing visual system and discusses the potential role of the VEP in the assessment of these infants.

Outcome in infants exposed to methadone in utero

We want to respond to Bell and Harvey-Dodds’ comments on the safety of methadone in pregnancy, specifically regarding postnatal development.1 Concerns are increasing about nystagmus and delayed visual development in infants born to drug misusing mothers,2 3 and we have shown alteration in visual evoked potentials in newborn infants exposed to methadone …

Neonatal abstinence syndrome can be a problem

Farrell and colleagues note that in pregnancy “methadone (substitution treatment) is safe and effective in terms of consistently better obstetric and perinatal outcomes.”1 They indicate that the only complication for the baby is a risk of neonatal abstinence syndrome and suggest that this “can be readily managed with withdrawal management and …

Abnormal visual evoked potentials in newborn infants of drug-misusing mothers: is prescription of substitute methadone to blame?

Background/aim Abnormal neonatal visual evoked potentials (VEPs) have been documented following in utero exposure to methadone and other illicit drugs: these pilot data were however confounded by intrauterine growth restriction, social deprivation and gestation.1 We now report a larger controlled study of the effects of maternal drug misuse upon neonatal VEPs. Methods Flash VEPs were recorded from 100 term infants of drug-misusing mothers prescribed substitute methadone, and 50 control infants matched for birthweight, gestation and socio-economic group. Drug exposure (including excess alcohol consumption) was determined by history, maternal and infant urine and meconium toxicology. VEPs were classified according to waveform, and amplitude and latencies measured. Results VEPs were recorded from all infants at a median age of 24 h (IQR 13–44). Gestation, birthweight and socio-economic group did not differ between groups. VEPs from drug-exposed infants were more likely to be of immature waveform (p<0.001) and were smaller in amplitude (median 27 μV vs 39.5 μV, p<0.001) compared to controls. Differences persisted after correcting for excess in utero alcohol exposure. The majority of infants were exposed to additional drugs of misuse: regression analysis indicated that differences in VEPs were due to methadone exposure and not to other illicit drugs. There was no association between VEP parameters and subsequent onset or severity of neonatal abstinence syndrome. Conclusion In utero exposure to prescribed substitute methadone and other illicit drugs is associated with alterations in neonatal visual electrophysiology. These changes appear to be due to methadone rather than alcohol or other associated drugs of misuse.