Helen Mactier

Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources

Objectives  The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug‐misusing women.

Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know

Vitamin A is essential for optimal growth and development. In the developing world, vitamin A supplementation of the newborn infant reduces mortality. In the developed world, extremely preterm infants are born with low body stores of vitamin A and are at high risk of vitamin A deficiency. Optimal vitamin A supplementation for this population is not clearly defined, however, and, despite evidence of benefit, early vitamin A supplementation of extremely preterm infants is not uniformly practised in the United Kingdom. There is an urgent need for studies in preterm infants that include quantification of hepatic stores and functional assessment of vitamin A status as well as long term outcome.

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.

Reduced fetal growth in methadone-maintained pregnancies is not fully explained by smoking or socio-economic deprivation.

AIM To determine if reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is explained by cigarette smoking or socio-economic deprivation. DESIGN Retrospective cohort study. SETTING Inner-city maternity unit in Scotland. PARTICIPANTS A total of 366 singleton infants of methadone-prescribed opioid-dependent mothers compared with the Scottish birth population (n=103 366) as a whole. MEASUREMENTS Primary outcome measures were birth weight and head circumference. FINDINGS In infants of methadone-prescribed opioid-dependent mothers mean birth weight was 259 g [95% confidence interval (CI) 214-303 g; P<0.0001] less, and mean head circumference 1.01 cm (95% CI 0.87-1.15 cm; P<0.0001) less than in controls, allowing for gestation, cigarette smoking, area deprivation, infant sex and maternal age and parity. This represents an adjusted difference of -0.61 (95% CI -0.52--0.71; P<0.0001) Z-score in mean birth weight and -0.77 (95% CI -0.66--0.89; P<0.0001) Z-score in mean head circumference. CONCLUSIONS Reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is not fully explained by cigarette smoking, area deprivation, maternal age or parity.

Prevalence and Characteristics of Rib Fractures in Ex-preterm Infants

OBJECTIVES: This study aimed to identify the prevalence and characteristics of rib fractures in ex-preterm infants. METHODS: Infants born at <37 weeks’ gestation and admitted before 2011 to 3 regional neonatal units were identified from admission registers. For 2 centers, these data were available from 2000 onward and, for another center, from 2005. Electronic records were searched to identify chest radiographs performed up to age 1 year. Chest radiograph reports were then reviewed for evidence of rib fractures, and the case notes of all affected individuals were scrutinized. RESULTS: Of the 3318 eligible preterm infants, 1446 had a total of 9386 chest radiographs. Of these infants, 26 (1.8%) were identified as having a total of 62 rib fractures. Their median (range) gestation at birth was 26 weeks (23–34). The median chronological age of these infants at the time of the radiograph was 14 weeks (5 weeks to 8 months). The median corrected gestational age at the time of the radiograph was 39 weeks (34 weeks to 4 months). Of the 62 fractures, 27 (36%) were sited posteriorly, and 15 (53%) of the infants with posterior rib fractures were diagnosed with osteopathy of prematurity. Classic risk including conjugated hyperbilirubinemia and diuretics, were present in 23 of 26 (88%) infants. A full skeletal survey was performed in 8 of 26 (31%). Investigations for nonaccidental injury occurred in 4 of 26 (15%) cases. CONCLUSIONS: Evidence of rib fractures is present in ∼2% of ex-preterm infants. The evaluation of these fractures in infancy requires a detailed neonatal history irrespective of the site of rib fracture.

Maturation of Rod Function in Preterm Infants with and without Retinopathy of Prematurity

OBJECTIVES To establish normal development of rod electroretinograms in preterm infants and to assess the effects of retinopathy of prematurity (ROP). STUDY DESIGN We measured 88 Naka-Rushton functions from 41 preterm infants at maturities from 30 to 72 weeks postmenstrual age (PMA). Outcomes (log sigma, retinal sensitivity and V(max), retinal responsivity) were compared between control (no ROP), untreated ROP, and treated ROP. RESULTS In control infants, sensitivity increased by 1.5 log units from 30 to 40 weeks PMA and by a further 0.5 log units by 50 weeks PMA but was 0.5 log units less than in similarly-mature, healthy, term-born infants. Average retinal responsivity increased from 23 microV to 90 microV between 30 and 40 weeks PMA and was 35 muV greater at 40 weeks PMA than in similarly-mature term-born infants. At around 36 weeks PMA, (when onset of ROP peaks), infants with untreated ROP had average retinal sensitivity 0.2 log units lower than control infants; sensitivity was reduced further in infants treated for ROP. Retinal responsiveness did not differ between control subjects and untreated infants with ROP but was greatly reduced in infants treated for ROP. CONCLUSIONS Maturation of rod sensitivity appears to be slowed by preterm birth whereas maturation of rod responsivity is accelerated. ROP reduces retinal sensitivity, and treated ROP reduces both sensitivity and responsivity.