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

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

Differences in the pattern and regulation of mineral deposition in human cell lines of osteogenic and non-osteogenic origin

Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro in response to osteogenic medium (OM). It is unclear, however, whether this property is specific to cells of mesenchymal origin. We analysed the OM response in 3 non-osteogenic lines, HEK293, HeLa and NTera, compared to MSCs. Whereas HEK293 cells failed to respond to OM conditions, the 2 carcinoma-derived lines NTera and HeLa deposited a calcium phosphate mineral comparable to that present in MSC cultures. However, unlike MSCs, HeLa and NTera cultures did so in the absence of dexamethasone. This discrepancy was confirmed, as bone morphogenetic protein inhibition obliterated the OM response in MSCs but not in HeLa or NTera, indicating that these 2 models can deposit mineral through a mechanism independent of established dexamethasone or bone morphogenetic protein signalling

The luminance–response function of the human photopic electroretinogram: a mathematical model

The luminance–response function of the brief flash full-field photopic electroretinogram (ERG) rises to a peak before falling to a sub-maximal plateau – the 'photopic hill'. The combination of on- and off-responses inherent in the brief flash photopic ERG suggests that this luminance–response function could be modelled by the sum of a Gaussian function and a logistic growth function. Photopic ERGs to a luminance series of brief flashes against three different background luminances recorded from seven healthy adults showed the characteristic 'photopic hill' function for b-wave amplitudes which were satisfactorily fitted with the sum of a Gaussian curve and a logistic growth curve. As background luminance increased, both components shifted to the right on the luminance axis. The Gaussian component increased in amplitude while the logistic growth function component decreased in amplitude. The luminance–response function of a complete congenital stationary night blindness patient had almost no logistic growth component

Visual evoked potentials in children with developmental coordination disorder

Children who demonstrate problems with skilled movement in the absence of physical handicap are formally designated as suffering from developmental coordination disorder (DCD). Diagnosis of DCD was confirmed by the 'movement assessment battery for children'. Visually evoked potentials (VEPs) were recorded to evaluate the integrity of the visual pathway and to rule out the presence of any neurological lesions affecting visual input. Binocular, pattern onset VEPs were recorded in 14 children with DCD aged between five and seven years, and an age-matched control group using pattern onset, high contrast, grating stimuli. Implicit times to the first and second peaks and troughs were measured, and results between the two groups were compared. Inattention and movement artefact meant that VEPs were more difficult to record within the DCD group, resulting in smaller amplitudes of the waveform, but no significant differences in the implicit times were observed between the DCD group and controls. Further research is required to determine the specific source of the neurological deficits in DCD but a problem with the integrity of the afferent visual pathway does not appear to be a causal factor

Temporary Buydowns and Affordability

This paper is directed to a neglected aspect of the problem of home ownership affordability: the impact on affordability of temporary buy downs. A temporary buydown is an option offered to home buyers to reduce the mortgage payment in the early years of the loan. The borrower allocates cash up front to an escrow account from which funds are withdrawn monthly to supplement the borrower's mortgage payment.Temporary buydowns are underused partly because of the difficulty of determining whether, in any particular case, they will increase affordability. This paper develops a new instrument called the maximum affordable mortgage (MAX) which automatically allocates the buyer's available cash between buydown, down payment and other uses in a manner which maximizes affordability for the buyer, subject to whatever underwriting constraints the investor wishes to impose on payment graduation and/or the total size of the buydown.The lender originating the MAX must be able to solve a complex algorithm at the point of sale, but the complexity is all behind the scenes. Using a computer, a loan officer can quickly find the cash allocation that maximizes affordability. The power of the MAX in increasing affordability may be enhanced if it is combined with a buyup wherein the lender trades off lower points against a higher rate. Copyright American Real Estate and Urban Economics Association.

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.<p></p> 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.<p></p> 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.<p></p> 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.<p></p&gt

Idiopathic, isolated fovea plana with bilateral off-centre multifocal ERGs

<p>Background: The purpose of this paper is to report a case of idiopathic isolated fovea plana showing asymmetry in the multifocal electroretinogram (mfERG).</p> <p>Methods: We carried out optical coherence tomography (OCT) imaging, macular pigment density measurement, genetic testing and electrophysiological testing with visual evoked potentials and mfERGs on a young, highly myopic female of Pakistani origin, who had good visual acuity and no nystagmus.</p> <p>Results: OCT imaging revealed a complete absence of any foveal pit in either eye. Macular pigment density was normal and visual evoked potentials indicated normal chiasmal crossings, excluding albinism. Genetic testing revealed normal PAX6 coding data, excluding aniridia as a cause. mfERGs showed asymmetry consistent with off-centre fixation to the temporal side of the fovea in both eyes, but were otherwise normal.</p> <p>Conclusion: Lack of a foveal pit is a well-known finding in conditions such as oculocutaneous albinism and PAX6 gene-related aniridia. Isolated fovea plana is less common, and this case illustrates that the absence of a foveal pit does not necessarily result in a poor visual outcome. The finding of asymmetry in the mfERG in such a case is novel, and may indicate a functional adaptation to the structure of the fovea.</p&gt

A randomized trial of long-chain polyunsaturated fatty acid supplementation in infants with phenylketonuria

Forty-two infants (20 males, 22 females) with classical phenylketonuria (PKU) entered a prospective, double-blind, randomized study to investigate the effects on biochemical and physiological outcomes of a phenylalanine-free infant formula containing a fat blend supplemented with the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6 n-3), and arachidonic acid (AA, C20:4 n-6). Between entry and 20 weeks (entry and 1y) of age, median DHA levels in erythrocyte membrane phospholipids decreased by 15% (22%) in the LC-PUFA supplemented group (n=21) and by 61% (64%) in the control group (p<0.001; n=18). A dietary supply of LC-PUFA in infants with PKU prevents the decline in DHA levels associated with a diet supplying minimal sources of LC-PUFA. DHA status in turn, independent of diet, may influence the maturation of the visual system in infants with PKU