Mild Delay Research Articles

Flow design and simulation of a gas compression system for hydrogen fusion energy production

An innovative gas compression system is proposed and computationally researched to achieve a short time response as needed in engineering applications such as hydrogen fusion energy reactors and high speed hammers. The system consists of a reservoir containing high pressure gas connected to a straight tube which in turn is connected to a spherical duct, where at the sphere’s centre plasma resides in the case of a fusion reactor. Diaphragm located inside the straight tube separates the reservoir’s high pressure gas from the rest of the plenum. Once the diaphragm is breached the high pressure gas enters the plenum to drive pistons located on the inner wall of the spherical duct that will eventually end compressing the plasma. Quasi-1D and axisymmetric flow formulations are used to design and analyse the flow dynamics. A spike is designed for the interface between the straight tube and the spherical duct to provide a smooth geometry transition for the flow. Flow simulations show high supersonic flow hitting the end of the spherical duct, generating a return shock wave propagating upstream and raising the pressure above the reservoir pressure as in the hammer wave problem, potentially giving temporary pressure boost to the pistons. Good agreement is revealed between the two flow formulations pointing to the usefulness of the quasi-1D formulation as a rapid solver. Nevertheless, a mild time delay in the axisymmetric flow simulation occurred due to moderate two-dimensionality effects. The compression system is settled down in a few milliseconds for a spherical duct of 0.8 m diameter using Helium gas and a uniform duct cross-section area. Various system geometries are analysed using instantaneous and time history flow plots.

Risk factors, prevalence and impact of comorbid autism in pediatric epilepsy: A population-based study

Objective: To determine the prevalence and risk factors for the development of autism in a population-based, retrospective cohort of children with new-onset epilepsy. Methods: Children with epilepsy, newly-diagnosed between 1980 and 2009, while resident in Olmsted County, MN, were identified through the Rochester Epidemiology Project database. Those followed beyond two years of age were included for study. Charts were reviewed to determine if subjects had been diagnosed with autism spectrum disorder (ASD), and also to collect seizure variables. Results: 459 children were identified (53% male). Mean age at seizure onset was 6.9 years (SD 5.0) and at follow-up was 17.2 years (SD 8.7). ASD was diagnosed in 34 (7.4%) cases, and preceded seizure onset in 15 children. Of those children for whom ASD was diagnosed after seizure onset, 58% had preceding established developmental delay. The most robust factor correlating with comorbid ASD was intellectual disability at seizure onset, with ASD being diagnosed in 4/295 (1.4%) of intellectually normal children, 19/101 (18.8%) with mild delay and 9/59 (15.3%) with moderate to severe delay (p<0.001). Other significant correlates were abnormal neurological examination (p<0.001), male sex (p=0.013), abnormal EEG background (p=0.023) and lack of a genetic etiology (p=0.012). Children with earlier onset of epilepsy did not have significantly higher rates of ASD. Comorbid ASD did not impact on epilepsy outcome, with similar rates of both seizure freedom at final follow-up (65% in those with ASD versus 69% in those without ASD, p=0.61) and medical intractability or need for epilepsy surgery (29% with ASD versus 18% without ASD, p=0.12). Conclusion: Comorbid ASD affects approximately 7.4% of children with epilepsy and coexisting intellectual disability is the most significant correlate. However, ASD does not appear to adversely impact epilepsy prognosis, as the majority of children still achieve seizure freedom long-term.

Prospective serial neuropsychological study in infants with Tuberous Sclerosis Complex (TSC): First analysis from the EPISTOP Project

Objective: The EPISTOP project is a multi-center prospective European study tracking epileptogenesis, epilepsy and neurodevelopment in infants with Tuberous TSC. Here we report the preliminary findings of serial neuropsychological evaluations in the first 24 months of life Methods: Between 2013 and 2016, 101 TSC infants younger than 5 months were enrolled; all were seizure-free and on no anti-epileptic drugs. Neuropsychological evaluations through Bayleys Scales of Infant Development (BSID) was performed for the first time at 6 months, while Autism Diagnostic Observation Schedule (ADOS) to screen autistic features was initiated at 12 months. All tests have been repeated every 6 months up to 24 months of age. At the time of the first data analysis (31/10/2016) BSID data have been collected at 6, 12, 18 and 24 months respectively for 32, 27, 17 and 15 patients; ADOS data have been collected at 12, 18 and 24 months for 12, 15 and 12 patients. Results: BSID revealed a normal cognitive developmental quotient (DQ) in 52%, 46% and 22% infants at the age respectively of 6, 12 and 24 months and a mild delay in 24%, 24%, and 45% children at the same age. A normal language DQ was observed in 38%, 24% and 11% children respectively at 6, 12 and 24 months and a normal motor DQ in 24%, 18% and 11% children respectively at 6, 12 and 24 months. ADOS revealed a high risk for autism in 8%, 23% and 29% children at 12, 18 and 24 months. Conclusion: Our findings showed that motor development was the first to be impaired with anomalies already detected at 6 months, and a clear deviation from the normal neurodevelopmental trajectory evident in all the domains from 12 months. Also an increase of the rate of children with high risk for autism over time have been observed.

The neuronal ceroidlipofuscinoses – The journey to the diagnostic

Objective: The neuronal ceroidlipofuscinoses (NCLs) are lysosomal-storage disorders, mostly autosomal recessive, comprising distinct entities historically classified as age of onset, neurological picture and progression. The diagnosis was confirmed on the clinical presentation and ultrastructural abnormalities on skin/conjunctive biopsy (accumulation of autofluorescent lipopigments). Through this presentation we wish to detail the diagnostic approach, the difficulties encountered in achieving it, emphasizing the importance of observing the clinical and neuroimaging clues which could contribute to an early etiologic diagnosis. Methods: We report 10 patients with normal development or mild language delay in the first 3 years of life, referred for refractory seizures, regression of motor abilities with ataxia, cognitive decline and visual impairment. The clinical phenotype led to the NCL suspicion. Extensive work-up was planned, aiming the differential diagnosis, necessary in the absence of genetic testing, unavailable. Results: In all cases EEG was performed, showing various abnormalities. Cerebral imaging (MRI, CT) showed marked atrophy mostly infratentorial. Biopsy of skin/conjunctiva confirmed the late infantile onset form in 5 patients. The genetic testing was possible in 5 children, showing mutations in CLN2 gene in 3 cases and CLN7 in 2. No biopsy or genetic testing were performed in 2 siblings, but clinical criteria and a rapid fatal evolution were arguments to include them. Conclusion: The journey to the NCL diagnostic started in all children from clinical and/or imaging clues, with different routes: long, with many investigations in the absence of the genetic tests, shorter in a few cases, referred to international centers, allowing intervention (CLN2 enzyme replacement therapy), an individualized management, so a better quality of life for the children and their families. We emphasize the importance of genetic testing availability in an era in which the treatment research is genetic targeted and we draw attention to the elements visible early that could raise the suspicion early.

TBR1 gene defects and their possible role for cortical malformations

Objective: Many forms of cortical malformation are supposed to be due to a genetic defect. However, except for the group of lissencephalies there is only little knowledge about causative genes for the wide group of cortical development disorders. We present a case with bifrontal pachygyria/polymicrogria who was referred to us because of an abnormal movement pattern and irritability and in whom whole exome sequencing (WES) revealed a mutation in the TBR1 gene. We discuss here its causal role. Methods and results: The initial clinical neurological examination showed an abnormal movement pattern with uncoordinated and uncontrolled movements and irritability. Follow-up until the age of 1 ½ years showed developmental progress with mild delay of motor and cognitive functions and amelioration of neurological signs. Cerebral MRI at 3 months displayed polymicrogyria/ pachygyria involving both frontal lobes. EEG on follow-up demonstrated bifrontal epileptic discharges without clear evidence for clinical seizures. Neither the analysis of the GPR56 gene known to be associated with bifronto-parietal polymicrogyria nor next generation sequencing analyzing a specific gene panel for brain development disorders found a causative mutation. WES finally revealed a de novo frameshift mutation in the TBR1 gene. Conclusion: In the mouse, the TBR1 gene, supposed to be a brain specific transcriptional regulator, is mainly expressed in the telencephalon (Bulfone et al. 1995) and knock out mice present with defects of cortical neuronal migration (Huang et al. 2014). Up to now, defects in the human have only been associated with autism spectrum disorders (Deriziotis et al. 2014). Our case for the first time indicates that its defects may be responsible for cortical maldevelopment in the human, supporting the hypothesis for a leading role of TBR1 in neuronal development based on findings in TBR1 deficient mice. We suggest the inclusion of TBR1 into the genetic analysis of the polymicrogyrias.

Parents’ Experiences Navigating Intervention Systems for Young Children With Mild Language Delays

The purpose of this study was to explore the experiences of parents of children with mild language delays who were referred to an Individuals With Disabilities Education Act (IDEA) birth-to-3 or preschool program, were determined not eligible for services, and were referred on to a community-based program for short-term speech-language therapy. Interviews were conducted in the parents’ preferred language (10 Spanish, 10 English). A grounded theory approach was applied to identify emergent themes. Results indicated that the process of recognizing a developmental delay, receiving assessment results, and enrolling in services presents challenges that require parents to demonstrate engagement and advocacy throughout. This study highlights parents’ motivations for seeking out early intervention services and underscores the importance of understanding parents’ experiences navigating developmental service systems. Program planners can partner with parents to address barriers and also capitalize on successes to facilitate timely response to developmental concerns, appropriate referrals, and effective interventions.

Copy Number Variations with Isolated Fetal Ventriculomegaly

Copy Number Variations (CNVs) are an important genetic cause of a number of neurodevelopmental disorders (NDs). However, the association between CNVs and the development and prognosis of fetal isolated mild ventriculomegaly (IMV) is unclear. To investigate possible associations between CNVs and the development of fetal IMV. This retrospective study recruited 154 subjects with ultrasound-confirmed fetal IMV and 190 subjects in a control cohort who underwent a high-risk prenatal serum screening program. The exclusion criteria included fetus G-banding chromosomal abnormality or positive fetus TORCH infection. DNA samples from all 344 fetuses were examined by an SNP-array. Developmental outcomes were assessed during postnatal follow-up. Fourteen pathogenic CNVs (pCNVs) were identified in 13 out of 154 IMV fetuses. Three pCNVs were found in 3 out of 190 subjects in the prenatal screening high-risk cohort, with a significant difference (P value=0.016, X2 test). Notably, the 14 pCNVs detected in the IMV cohort were all associated with neurodevelopmental disorders (NDs), including autism, intellectual disability. Among the 13 IMV fetuses carrying pCNVs, five subjects were found in the postnatal follow-up to manifest NDs, including two with autism and three with mild neurodevelopmental delay. The other 8 subjects consisted of three normal infants younger than 12-months old, two lost in the follow-up, and three with the termination of pregnancy. Out of 141 IMV subjects without detectable pCNVs, 123 subjects showed normal development, 16 were lost in the follow-up, 2 subjects terminated the pregnancy due to fetal hydrocephalus or congenital heart disease in the late fetus development. This study suggests an association between pCNVs and fetal IMV. pCNVs may be involved in the pathological process of fetal IMV and postnatal NDs. Identifying specific genomic alterations may provide an insight into pathogenetic mechanism and aid better diagnosis and prognosis of neurodevelopmental outcomes in fetal IMV.

Mad2 Overexpression Uncovers a Critical Role for TRIP13 in Mitotic Exit

The mitotic checkpoint ensures proper segregation of chromosomes by delaying anaphase until all kinetochores are bound to microtubules. This inhibitory signal is composed of a complex containing Mad2, which inhibits anaphase progression. The complex can be disassembled by p31comet and TRIP13; however, TRIP13 knockdown has been shown to cause only a mild mitotic delay. Overexpression of checkpoint genes, as well as TRIP13, is correlated with chromosomal instability (CIN) in cancer, but the initialeffects of Mad2 overexpression are prolongedmitosis and decreased proliferation. Here, we showthat TRIP13 overexpression significantly reduced, and TRIP13 reduction significantly exacerbated, the mitotic delay associated with Mad2 overexpression, but not that induced by microtubule depolymerization. The combination of Mad2 overexpression and TRIP13 loss reduced the ability of checkpoint complexes to disassemble and significantly inhibited the proliferation of cells in culture and tumor xenografts. These results identify an unexpected dependency on TRIP13 in cells overexpressing Mad2.

Characterizing the differential roles of striatal 5-HT1A auto- and hetero-receptors in the reduction of l-DOPA-induced dyskinesia

l-DOPA remains the benchmark treatment for Parkinson's disease (PD) motor symptoms, but chronic use leads to l-DOPA-induced dyskinesia (LID). The serotonin (5-HT) system has been established as a key modulator of LID and 5-HT1A receptors (5-HT1AR) stimulation has been shown to convey anti-dyskinetic effects. However, 5-HT1AR agonists often compromise clinical efficacy or display intrinsic side effects and their site(s) of actions remain debatable. Recently, highly selective G-protein biased 5-HT1AR agonists, F13714 and F15599, were shown to potently target 5-HT1A auto- or hetero-receptors, respectively. The current investigation sought to identify the signaling mechanisms and neuroanatomical substrates by which 5-HT1AR produce behavioral effects. In experiment 1, hemi-parkinsonian, l-DOPA-primed rats received systemic injections of vehicle, F13714 (0.01 or 0.02mg/kg), or F15599 (0.06 or 0.12mg/kg) 5min prior to l-DOPA (6mg/kg), after which LID, motor performance and 5-HT syndrome were rated. Both compounds significantly reduced LID, without affecting motor performance, however, acute administration of F13714 significantly induced 5-HT syndrome at anti-dyskinetic doses. In experiment 2, we elucidated the role of striatal 5-HT1AR in the effects of F13714 and F15599. Hemi-parkinsonian, l-DOPA-primed rats received bilateral intra-striatal microinjections of either F13714 (0, 2 or 10μg/side) or F15599 (0, 10 or 30μg/side) 5min prior to systemic l-DOPA (6mg/kg). Intra-striatal effects mimicked systemic effects, suggesting that striatal 5-HT1AR sub-populations play an important role in the anti-LID and pro-5-HT syndrome profiles of F13714 and F15599. Finally, in experiment 3, we examined the effects of F13714 and F15599 on D1 receptor (D1R) agonist-induced dyskinesia by administering either compound 5min prior to SKF 38393 (2mg/kg). While F13714 resulted in a mild delay in D1R-mediated dyskinesia, F15599 had no effect. Collectively these data suggest that the F-series compounds articulate their anti-LID effects through activation of a diverse set of striatal 5-HT1A hetero-receptor populations.

Clinical heterogeneity of glycine encephalopathy in three Palestinian siblings: A novel mutation in the glycine decarboxylase (GLDC) gene

IntroductionGlycine encephalopathy (GE), also known as non-ketotic hyperglycinemia (NKH), is a rare inborn error of glycine metabolism caused by a defect in glycine cleavage system, a multi-enzyme complex located in mitochondrial membrane. This defect results in elevated glycine concentration in plasma and cerebrospinal fluid (CSF). Clinical manifestations vary from severe lethargy, hypoactivity and apneic episodes in the neonatal form, mild or moderate psychomotor delay and seizures in the infantile form, and abnormal behaviors, ataxia and choreoathetoid movements in late onset form. More than 50 GLDC mutations were found, reflecting large heterogeneity of the gene. MethodsWe describe the clinical, biochemical and molecular characteristics of three Palestinian siblings who have distinct clinical phenotypes. Molecular study was performed utilizing standard Polymerase Chain Reaction (PCR) amplification then direct DNA sequencing for the affected family members. ResultsTheir phenotypes included severe symptoms in neonatal period, infantile onset of seizure and psychomotor delay and a mild late-onset form with speech delay at age 20months. All siblings were homozygous for a novel mutation Y164H in exon 4 of GLDC gene. The described novel homozygous variant in our study is predicted deleterious and pathogenic. ConclusionsThis article further expands the genetic spectrum of glycine encephalopathy and adds an evidence of the clinical heterogeneity of glycine encephalopathy even in siblings with identical mutation.

Serum glycomarkers of endoplasmic reticulum and lysosomal-endosomal system stress in human healthy aging and diseases.

To verify the idea that extracellular free oligosaccharides might be able to reflect the functional status of the endoplasmic reticulum (ER) and lysosomal-endosomal system, HPLC-profiles of serum-derived free oligosaccharides (FOS) in human healthy aging, acute myeloproliferative neoplasms, and cardiovascular pathologies were compared with intracellular glycans. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid, separated into the neutral and charged with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC). The charged FOS were digested with a sialidase and compared with free oligosaccharides from transferrin for structural decoding. HPLC-profiles of serum-derived FOS revealed mild delay of the dolichol phosphate cycle in ER, moderate intensification of ER-associated degradation (ERAD) and degradation in endosomal-lysosomal system with aging; an inhibition of the dolichol phosphate cycle, intensification of ERAD and increasing of lysosomal exocytosis in acute myeloproliferative neoplasms; intensification of ERAD and glycocojugate degradation with endosomal-lysosomal system in cardiovascular diseases. As serum free oligosaccharides are able to reflect specifically perturbations in ER and endosomal-lysosomal system under wide range of stressors they can serve as extracellular markers of functionality of these organelles.

Cognitive development in preterm infants: multifaceted deficits reflect vulnerability of rigorous neurodevelopmental pathways.

Prematurity remains the major cause of neonatal morbidity and mortality, with 15 million preterm births occurring worldwide in 2010. Infants born less than 37 weeks gestation are at high risk of abnormal neurodevelopmental outcomes, given that the central nervous system is extremely sensitive to an abnormal intra- and extra-uterine environment. Children born preterm have multiple neurodevelopmental sequelae involving dynamic and complex cognitive deficits. Former preterm infants have difficulty with each domain of cognition, including executive function, language, learning and memory, complex attention, perceptual-motor function and social cognition when compared to children born at term. Although deficits are not always severe, even mild delays can be impactful, resulting in a spectrum of outcomes from difficulties in school to an inability to lead an independent adult life. Here, we review current literature on the cognitive outcomes of infants born preterm with a focus on how specific disruption in crucial neurodevelopmental pathways render these children vulnerable to dynamic deficits in cognition as they mature. Further, we highlight promising therapies and intervention strategies aimed at mitigating these deficits, including the use of erythropoietin. With an increasing number of preterm infants surviving, understanding developmental deficits will allow therapies to be developed and optimized, in order to ensure the best outcome for this vulnerable patient population.

A case of Feingold type 2 syndrome associated with keratoconus refines keratoconus type 7 locus on chromosome 13q

We report on a 58-year old woman with microcephaly, mild dysmorphic features, bilateral keratoconus, digital abnormalities, short stature and mild cognitive delay. Except for keratoconus, the phenotype was suggestive for Feingold syndrome type 2 (FGLDS2, MIM 614326), a rare autosomal dominant disorder described in six patients worldwide, due to the haploinsufficiency of MIR17HG, a micro RNA encoding gene. Karyotype showed a de novo deletion on chromosome 13q, further defined by array-Comparative Genomic Hybridization (a-CGH) to a 17.2-Mb region. The deletion included MIR17HG, as expected by the FGLDS2 phenotype, and twelve genes from the keratoconus type 7 locus. Because our patient presented with keratoconus, we propose she further refines disease genes at this locus. Among previously suggested candidates, we exclude DOCK9 and STK24, and propose as best candidates IPO5, DNAJC3, MBNL2 and RAP2A.In conclusion, we report a novel phenotypic association of Feingold syndrome type 2 and keratoconus, a likely contiguous gene syndrome due to a large genomic deletion on 13q spanning MIR17HG and a still to be identified gene for keratoconus.

ALG13-CDG with Infantile Spasms in a Male Patient Due to a De Novo ALG13 Gene Mutation.

A boy presented at the age of 3.5 months with a developmental delay. He developed infantile spasms with hypsarrhytmia on EEG 1 month later. Additional symptoms were delayed visual development, asymmetrical hearing loss, hypotonia, and choreoathetoid movements. He also had some dysmorphic features and was vulnerable for infections. He was treated successively with vigabatrin, prednisolone, valproic acid, nitrazepam, and lamotrigine without a lasting clinical effect, but showed a treatment response to levetiracetam. Cerebral MRI showed hypoplasia of the corpus callosum and a mild delay in myelination. Further investigations including metabolic screening and glycosylation studies by transferrin isoelectric focusing were all considered to be normal. Whole-exome sequencing identified a de novo mutation in the ALG13 gene (c.320A>G, p.(Asn107Ser)). Mutations in this gene, which is located on the X-chromosome, are associated with congenital disorders of glycosylation type I (CDG-I). Mass spectrometric analysis of transferrin showed minor glycosylation abnormalities. The c.320A>G mutation in ALG13 has until now only been described in girls and was thought to be lethal for boys. All girls with this specific mutation presented with a similar phenotype of developmental delay and severe early onset epilepsy. In two girls glycosylation studies were performed which showed a normal glycosylation pattern. This is the first boy presenting with an epileptic encephalopathy caused by the c.320A>G mutation in the ALG13 gene. Since glycosylation studies are near-normal in patients with this mutation, the diagnosis of ALG13-CDG can be missed if genetic studies are not performed.

How Does the Narrowing of Eligibility Criteria Affect Enrollment in Part C Early Intervention?

In recent years, many states have narrowed their eligibility criteria for participation in the IDEA Part C early intervention (EI) program for infants and toddlers with or at risk for developmental delays. However, there is scant research on the effects of such a policy change on the population of children served or on the timing of children's access to EI services. Using data from an EI program serving a diverse, urban population in a large southeastern state, we compared characteristics of children who enrolled in EI the year before (n = 432) and the year after (n = 399), the state adopted more restrictive eligibility criteria for its EI program. Results indicated that following the policy change, children served in the program represented a smaller percentage of the resident birth-to-3 population; a smaller proportion of children enrolling in EI had mild delays; and children were 1.5 months older, on average, when they enrolled in services. The findings not only provide evidence that the narrowing of eligibility criteria achieved the intended effect of reducing EI enrollment but also raise concerns that the new policy may delay access to needed services for children with emergent developmental delays.

Psychological Assessment of Patients With Biotin-Thiamine-Responsive Basal Ganglia Disease.

Biotin-thiamine-responsive basal ganglia disease is a devastating autosomal recessive inherited neurological disorder. We conducted a retrospective chart review of all patients with biotin-thiamine-responsive basal ganglia disease who underwent a formal psychological assessment. Six females and 3 males were included. Five patients (56%) had an average IQ, two patients (22%) had mild delay, and two (22%) had severe delay. A normal outcome was directly related to the time of diagnosis and initiation of treatment. Early diagnosis and immediate commencement of treatment were associated with a favorable outcome and vice versa. The most affected domain was visual motor integration, while understanding and mathematical problem-solving were the least affected. In summary, this is the first study discussing the psychological assessment of patients with biotin-thiamine-responsive basal ganglia disease. The results of this study alert clinicians to consider prompt initiation of biotin and thiamine in any patient presenting with neuroregression and a basal ganglia lesion on a brain magnetic resonance imaging.

Does the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure change morbidity outcomes for high-risk congenital diaphragmatic hernia survivors?

PurposeIn high-risk congenital diaphragmatic hernia (CDH), significant barotrauma or death can occur before extracorporeal membrane oxygenation (ECMO) can be initiated. We previously examined ex utero intrapartum treatment (EXIT)-to-ECMO in our most severe CDH patients, but demonstrated no survival advantage. We now report morbidity outcomes in survivors of this high-risk cohort to determine whether EXIT-to-ECMO conferred any benefit. MethodsAll CDH survivors with <15% predicted lung volume (PPLV) from September 1999 to December 2010 were included. We recorded prenatal imaging, defect size, and pulmonary, nutritional, cardiac, and neurodevelopmental outcomes. ResultsSeventeen survivors (8 EXIT-to-ECMO, 9 non-EXIT) had an average PPLV of 11.7%. Eight of 9 non-EXIT received ECMO within 2days. There were no significant defect size differences between groups, mostly left-sided (13/17) and type D (12/17). Average follow-up was 6.7years (0–13years). There were no statistically significant differences in outcomes, including supplemental oxygen, diuretics, gastrostomy, weight-for-age Z scores, fundoplication, pulmonary hypertension, stroke or intracranial hemorrhage rate, CDH recurrence, and reoperation. No survivor in our cohort was neurologically devastated. All had mild motor and/or speech delay, which improved in most. ConclusionsIn this pilot series of severe CDH survivors, EXIT-to-ECMO confers neither significant survival nor long-term morbidity benefit. Level of evidenceLevel III treatment study.

Threatened preterm labor is a risk factor for impaired cognitive development in early childhood

Threatened preterm labor is a leading cause of hospital admission during pregnancy. Patients with an episode of threatened preterm labor who deliver at term are considered to have false preterm labor. However, threatened preterm labor has been proposed as a pathologic insult that is not always sufficient to induce irreversible spontaneous preterm birth but that could alter the normal course of pregnancy. The aim of this study was to evaluate threatened preterm labor during pregnancy as a risk factor of neurodevelopmental deficits of children at 2 years of age. Two-year-old children who were born late preterm (n=22) or at term after threatened preterm labor (n=23) were compared with at-term control children (n=42). Neurodevelopment was evaluated at a corrected age of 24-29 months with the use of the Merrill-Palmer-Revised Scales of Development. Children who were born at term after threatened preterm labor had lower scores than control children on global cognitive index (95.4 vs 104.2; P=.011), cognition (95.1 vs 103.1; P=.021), fine motor (95.2 vs 103.4; P=.003), gross motor (84.7 vs 99.8; P=.001), memory (92.9 vs 100.4; P=.015), receptive language (93.9 vs 102.9; P=.03), speed of processing (105.7 vs 113.3; P=.011), and visual motor coordination (98.8 vs 106.7; P=.003) subtests. Children born at term after threatened preterm labor had an increased risk of mild neurodevelopmental delay compared with control children (odds ratio for global cognitive index, 2.06; 95% confidence interval, 1.09-3.88; P=.033). There were no significant differences in any cognitive domain between children who were born late preterm and children who were born at term after threatened preterm labor. Threatened preterm labor is a risk factor for impairedcognitive development at 2 years of age, even if birth occurred atterm.

The neural retina in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP.

Determinants of developmental progress in pre-schoolers referred for neuro-developmental diagnosis.

To determine factors associated with change in developmental progress in pre-schoolers referred to a developmental clinic. Of 360 pre-schoolers referred to a Child Assessment clinic for neuro-developmental diagnosis before 3.6 years, 190 (53%) were reassessed prior to school entry and recruited to this study. They were assessed with the Bayley Scales of Infant and Toddler Development (3rd edn) before 3.5 years and the Griffiths Mental Development Scales before school entry. The influence of medical and environmental variables on improvement or deterioration in scores (±0.5 SD) was examined using logistic regression. Consistent scores were present in 51.6% of children, and associated with environmental variables. Children with stable scores were more likely to live in a suburb of social advantage (OR = 3.2; 95%CI = 1.37-7.64, P = 0.008) or to come from families dependent on welfare or public housing (OR=4.8; 95%CI = 2.19-10.49, P < 0.001). Improvement was seen in 18.1% of children; they were more likely to have commenced therapy after the first assessment (OR = 2.4; 95%CI = 1.05-5.58, P = 0.038). Deterioration of scores was seen in 30% of children. Children with a mild delay on initial assessment were less likely to deteriorate (OR = 2.9; 95%CI = 1.16-7.04, P = 0.022), while lower scores were more likely in children with neuro-motor disabilities (OR = 10.8; 95%CI = 2.64-44.58, P < 0.001), and chromosomal variations of both known and unknown significance (OR = 4.4; 95%CI = 1.54-12.76, P = 0.006). Socio-economic advantage and disadvantage are associated with stable scores, but introducing intervention is associated with improved scores. Deterioration is most likely in children with chromosomal variations or neuro-motor disabilities, and regular reassessment of these children is recommended.