Long-term Developmental Outcome Research Articles

Long-term predictors of developmental outcome and disease burden in SCN1A-positive Dravet syndrome.

Dravet syndrome is a severe infantile onset developmental and epileptic encephalopathy associated with mutations in the sodium channel alpha 1 subunit gene SCN1A. Prospective data on long-term developmental and clinical outcomes are limited; this study seeks to evaluate the clinical course of Dravet syndrome over a 10-year period and identify predictors of developmental outcome. SCN1A mutation-positive Dravet syndrome patients were prospectively followed up in the UK from 2010 to 2020. Caregivers completed structured questionnaires on clinical features and disease burden; the Epilepsy & Learning Disability Quality of Life Questionnaire, the Adaptive Behavioural Assessment System-3 and the Sleep Disturbance Scale for Children. Sixty-eight of 113 caregivers (60%) returned posted questionnaires. Developmental outcome worsened at follow-up (4.45 [SD 0.65], profound cognitive impairment) compared to baseline (2.9 [SD 1.1], moderate cognitive impairment, P < 0.001), whereas epilepsy severity appeared less severe at 10-year follow-up (P = 0.042). Comorbidities were more apparent at 10-year outcome including an increase in autistic features (77% [48/62] versus 30% [17/57], χ2 = 19.9, P < 0.001), behavioural problems (81% [46/57] versus 38% [23/60], χ2 = 14.1, P < 0.001) and motor/mobility problems (80% [51/64] versus 41% [24/59], χ2 = 16.9, P < 0.001). Subgroup analysis demonstrated a more significant rise in comorbidities in younger compared to older patients. Predictors of worse long-term developmental outcome included poorer baseline language ability (P < 0.001), more severe baseline epilepsy severity (P = 0.003) and a worse SCN1A genetic score (P = 0.027). Sudden unexpected death in epilepsy had not been discussed with a medical professional in 35% (24/68) of participants. Over 90% of caregivers reported a negative impact on their own health and career opportunities. Our study identifies important predictors and potential biomarkers of developmental outcome in Dravet syndrome and emphasizes the significant caregiver burden of illness. The negative impact of epilepsy severity at baseline on long-term developmental outcomes highlights the importance of implementing early and focused therapies whilst the potential impact of newer anti-seizure medications requires further study.

Hemispherotomy in Infants with Hemimegalencephaly: Long-Term Seizure and Developmental Outcome in Early Treated Patients.

Hemimegalencephaly (HME) is a rare brain congenital malformation, consisting in altered neuronal migration and proliferation within one hemisphere, which is responsible for early onset drug-resistant epilepsy. Hemispherotomy is an effective treatment option for patients with HME and drug-resistant epilepsy. Surgical outcome may be variable among different surgical series, and the long-term neuropsychological trajectory has been rarely defined using a standardized neurocognitive test. We report the epileptological and neuropsychological long-term outcomes of four consecutive HME patients, operated on before the age of three years. All patients were seizure-free and drug-free, and the minimum follow-up duration was of five years. Despite the excellent post-surgical seizure outcome, the long-term developmental outcome is quite variable between patients, ranging from mild to severe intellectual disabilities. Patients showed improvement mainly in communication skills, while visuo-perceptive and coordination abilities were more impaired. Epileptological outcome seems to be improved in early treated patients; however, neuropsychological outcome in HME patients may be highly variable despite early surgery.

Nutritional status of children with heart disease at the Komfo Anokye Teaching Hospital, Ghana

Background Undernutrition is associated with forty-five percent of all deaths in children under-five years. Irrespective of the type of heart disease (HD), malnutrition remains a constant phenomenon in children with both congenital and acquired HD. To minimize the long-term effect of malnutrition in a cohort of patient who have very limited chance of surgical treatment even when indicated, their nutritional statuses must be assessed periodically, and rehabilitation instituted early. The objective of this study was to assess the nutritional status of children attending the Pediatric Heart Disease clinic of the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana.&#x0D; MethodsA retrospective review of children up to fourteen years, enrolled into the Pediatric Heart Disease clinic with confirmed HD from November 2020 to June 2021 were systematically recruited. Their ages, weights, heights and mid-upper arm circumferences (MUAC) were measured by standardized methods to assess their nutritional status. Subsequently, their Weight-for-Height (WfH), Height-for-Age (HfA), Weight-for-Age (WfA), Body Mass Index-for-Age (BfA) and MUAC-for-Age (MfA) z-scores were determined based on the WHO Child Growth Standards (2006). Z-scores less than -2 standard deviations (SDs) or greater than +2SDs were considered abnormal. Data was collected and analyzed using Epidata and R statistical software respectively.&#x0D; ResultsA hundred and sixty-seven patient were recruited with 86 (51.5%) being females. The median age was 56 months (Range: 1 to 172). The mean z-score for the WfH was -1.21 (95%CI: -1.48 to -0.94), HfA -1.18 (95%CI: -1.44 to -0.93), WfA -1.81 (95%CI: -2.06 to -1.56), BfA -1.41 (95%CI: -1.61 to -1.21) and MfA -1.66 (95%CI: -1.87 to -1.46). None of the patients had a z-score greater than +2SD for all anthropometric methods determined. The percentage of children with z-scores less than -2SD for WfH was 20.5% (95%CI: 12.0 to 31.6), HfA 21.3% (95%CI: 14.4 to 29.6), WfA 41.5% (95%CI: 33.1 to 50.3), BfA 31.1% (95%CI: 23.1 to 40.2) and MfA 36.0% (95%CI: 28.6 to 44.0).&#x0D; ConclusionThere is a high prevalence of malnutrition, wasting and stunting among children attending the Pediatric Heart Disease clinic at KATH. Strategies should be put in place to improve their nutritional status, which in turn could improve surgical and long-term developmental outcome.

A nutty idea: Exploring a novel method using a hazelnut cocoa spread to temporarily increase maternal care behavior within a rat litter.

Maternal care plays a crucial role for infant development. In humans, skin-to-skin care is often used for preterm infants to reduce acute stress and improve long-term developmental outcome. Here we propose a new translational approach to study the effects of acute increases in maternal care on offspring development in rodents. First, pilot studies determined that dams spent more time licking pups covered in hazelnut cocoa spread (Nutella® )) than any other studied substance. For the main experiment, Sprague-Dawley rats were bred in-house, and Nutella® was applied four times a day to treatment pups (2 males/females per litter) of seven litters from PN2 to 5. Control pups (2 males/females per litter) were handled similarly without applying any substance. Maternal licking and grooming behavior was observed for 30min following each Nutella® application. Nutella® -covered pups received significantly more licking and grooming compared to control pups within each litter. There was no difference in body weight or basal serum corticosterone levels between Nutella® -covered and control pups on PN5, suggesting that the Nutella® application and subsequent increased maternal licking was not stressful for the pups. Future studies will investigate whether this increase in maternal care can protect pups from stress- or pain-induced rises in corticosterone.

KCNQ2 encephalopathy manifesting with Rett-like features: A follow-up into adulthood.

Kv7.2 (KCNQ2) channel dysfunctions cause a rare form of neonatal and infantile epileptic and developmental encephalopathy (MIM 613720).1 Unlike early clinical features and the epilepsy phenotype of KCNQ2 encephalopathy, data about the long-term developmental outcome are lacking. We followed up for over 3 decades a girl with this disease.

Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders

PurposeWe aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. MethodsWe retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. ResultsWe included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. ConclusionUCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

Dravet Syndrome -A case report from Aseer, Saudi Arabia

Dravet syndrome (DS) is an epileptic encephalopathy that presents with protracted seizures in infancy, associated with fever, and frequently categorized as febrile seizure at first presentation. In the second year, myoclonia, atypical absence and complex partial seizures develop. The correct diagnosis of DS and appropriate follow-up are delayed until after appearance of signs of developmental regression in the second year of life. Timely detection and diagnosis of DS followed by management with suitable anticonvulsants and treatment plan may reduce the seizure burden and improve long-term developmental outcome. We present a case of 2 years old female with recurrent attacks of generalized tonic colonic convulsion after 1st febrile convulsion diagnosed as Dravet syndrome. The diagnosis was based on history and gene study (SCN1A).&#x0D; Bangladesh Journal of Medical Science Vol.19(2) 2020 p.315-318

Does an elevated midline head position prevent periventricular-intraventricular haemorrhage in extremely low birth weight neonates?

Kochan M, Leonardi B, Firestine A, McPadden J, Cobb D, Shah TA, et al. Elevated midline head positioning of extremely low birth weight infants: effects on cardiopulmonary function and the incidence of periventricular-intraventricular hemorrhage. J Perinatol 2019, 39(1): 54-62. Germinal matrix-intraventricular haemorrhage (IVH) of the premature infant is the most common form of neonatal intracranial haemorrhage. A portion of infants with IVH suffer a related parenchymal injury called periventricular haemorrhagic infarction. Fluctuations in cerebral blood flow and increases in cerebral venous pressure have been implicated in the pathogenesis of these injuries 1. Head position can affect cerebral haemodynamics and has been evaluated for preventing IVH 2. A recent systematic review evaluated trials involving head positioning strategies to prevent IVH, reviewed two trials (n = 110), and found insufficient evidence to determine the effectiveness of a particular strategy 3. Both trials reviewed and examined the effect of head rotation. No trials were identified which investigated head elevation 3, 4. The current study aims to close this knowledge gap. This single-centre, prospective, randomized trial compared the use of an elevated midline head position to a flat head position for the prevention of intracranial haemorrhage in neonates <1000 g at birth. Baseline characteristics differed among the groups with more pre-eclampsia in the treatment group and more prolonged rupture in the control group. There was no difference in the primary outcome. However, there was improved survival and decreased grade IV (but not grade III) IVH in the treatment group. There was a trend towards escalating respiratory support in the treatment group. Of interest, none of the infants with grade IV IVH developed cystic PVL. A strength of the study included the early enrolment by four hours of life. Although enrolment at birth (with prenatal consent) would be preferred, this may be impractical as flat positioning may be required during initial stabilization procedures. There is a risk for bias with this study as it is unclear if allocation was concealed. Although the interpreting radiologists were blinded, blinding of all caretakers is not possible when evaluating this intervention. It is unclear if the effect of the intervention was due to the absence of periodic turning or the elevation, as infants in the two groups were treated differently in both regards. In fact, the control group may have been affected by compromised venous return due to turning the head only rather than head and body. A weakness of the study is the lack of long-term developmental follow-up. As demonstrated in the largest trial of prophylactic indomethacin, a decrease in severe IVH does not always produce an improvement in long-term developmental outcome 5. Another weakness is the lack of magnetic resonance imaging (MRI) to assess for periventricular leukomalacia (PVL). Mean blood pressures were slightly higher in the elevated group, but cerebral perfusion may have been affected by the elevation placing the infants at risk for PVL. These results suggest that an elevated head position may be beneficial over flat supine head positioning with periodic turning for improving survival and decreasing grade IV IVH. Further, the results suggest that the control and intervention conditions are both safe with no harm shown in either group. With the differences in baseline characteristics, lack of allocation concealment, lack of MRI to assess for PVL, and most importantly, lack of developmental follow-up, it is not possible to strongly suggest a practice change from the results of this trial. However, these results should inform the design of a large, multicentre trial of this simple intervention. https://ebneo.org/2019/06/head-position-intraventricular-hemorrhage/ None. None.

Follow-up study of extremely low birth weight preterm infants to preschool age in the light of perinatal complications

Owing to the rapid progress of the medical science and technology, the chances of survival of the extremely low birth weight (<1000 g) preterm babies have dramatically improved. Nevertheless, the research findings on their long-term developmental outcome are inconsistent. Our study has attempted to contribute to the understanding of the developmental mechanisms in the extremely low birth weight preterm infants and to the prediction of the developmental outcomes taking into account of the risk factors of development. 34 preterm children who were free of any major central nervous system injury were followed up from one to 5-6 years of age. The psychomotor development of the infants was assessed at 1 and 2 years of age and, at 5-6 years of age, intelligence tests were administered to the children. Perinatal and environmental factors were included in the data analysis. The extremely low birth weight preterm children as a group displayed no developmental delay at any of the measurement points. The mean developmental quotients were 98.6 and 106.6 at ages 1 and 2 years, respectively. At 5-6 years of age, the mean verbal IQ was 101.4, while the mean performance IQ was 92.9. Behind the group means there was a wide range of individual variations. The most powerful contributors to the developmental outcomes were birth weight, bronchopulmonary dysplasia, intra-uterine growth retardation, gender, and maternal education. The girls had a significant advantage over the boys in language development. Verbal intelligence was hampered by intracranial hemorrhage, while intrauterine growth restriction had a similar effect on the performance IQ. Our results suggest that even the extremely preterm infants may have rather good chances of satisfactory mental development. However, the individual developmental prospects are influenced by a great number of domain-specific risk- and protective factors. Although at a group-level, infant psychomotor development is a significant predictor of later intelligence quotient, the rate of development may change at any age. The phenomenon of "moving risk" underscores the importance of the long-term follow-up of preterm infants. Orv Hetil. 2018; 159(41): 1672-1679.

Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-year follow up of the ALLO-trial

ObjectiveTo evaluate the long-term neurodevelopmental and behavioral outcome of antenatal allopurinol treatment during suspected fetal hypoxia.Study designWe studied children born from women who participated in a randomized double-blind placebo controlled multicenter study (ALLO-trial). Labouring women in whom the fetus was suspected to have fetal hypoxia were randomly allocated to receive allopurinol or placebo. At 5 years of age, the children were assessed with 2 parent reported questionnaires, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL). A child was marked abnormal for ASQ if it scored below 2 standard deviation under the normative mean of a reference population in at least one domain. For CBCL, a score above the cut-off value (95th percentile for narrowband scale, 85th percentile for broadband scale) in at least one scale was marked as abnormal.ResultsWe obtained data from 138 out of the original 222 mildly asphyxiated children included in the ALLO-trial (response rate 62%, allopurinol n = 73, placebo n = 65). At 5 years of age, the number of children that scored abnormal on the ASQ were 11 (15.1%) in the allopurinol group versus 11 (9.2%) in the placebo group (relative risk (RR) 1.64, 95% confidence interval (CI): 0.64 to 4.17, p = 0.30). On CBCL 21 children (30.4%) scored abnormal in de allopurinol group versus 12 children (20.0%) in the placebo group (RR 1.52, 95% CI: 0.82 to 2.83, p = 0.18).ConclusionWe found no proof that allopurinol administered to labouring women with suspected fetal hypoxia improved long-term developmental and behavioral outcome. These findings are limited due to the fact that the study was potentially underpowered.Trial registrationNCT00189007 Dutch Trial Register NTR1383

Pessary for prevention of preterm birth in twin pregnancy with short cervix: 3-year follow-up study.

A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Mutational studies of the Aux/IAA proteins in Physcomitrella reveal novel insights into their function.

The plant hormone auxin regulates many aspects of plant growth and development. Auxin signaling involves hormone perception by the TRANSPORT INHIBITOR RESPONSE/AUXIN F-BOX (TIR1/AFB)-Aux/IAA co-receptor system, and the subsequent degradation of the Aux/IAA transcriptional repressors by the ubiquitin proteasome pathway. This leads to the activation of downstream gene expression and diverse physiological responses. Here, we investigate how the structural elements in the Aux/IAAs determine their function in Auxin perception and transcriptional repression. We took advantage of the facile genetics of the moss Physcomitrella patens to determine the activity of wild-type and mutant PpIAA1a proteins in a Δaux/iaa null background. In this way, Aux/IAA function was characterized at the molecular and physiological levels without the interference of genetic redundancy. We identified and characterized degron variants in Aux/IAAs that affect their stability and Auxin response. We also demonstrated that neither the Aux/IAA EAR motif nor Aux/IAA oligomerization is essential for the repressive function of Aux/IAA. Our study demonstrates how key elements within the Aux/IAA proteins fine tune stability and repressor activity, as well as the long-term developmental outcome.

Developmental Outcomes of Children Exposed to Maternal Sickle Cell Disease (SCD)

▪ BACKGROUNDPregnant women with SCD have an increased risk of both maternal and fetal complications, including preeclampsia, venous thromboembolism, and cardiomyopathy, as well as an increased risk of intrauterine growth restriction, preterm birth, low birth weight, and fetal demise. While in general children with a history of intrauterine growth restriction are at risk for abnormal neurodevelopment as well as later obesity and metabolic syndrome, the long-term developmental outcomes of children without SCD but exposed to maternal SCD are unknown. Better data about the long-term developmental outcome for children of mothers with SCD will provide guidance about the utility of disease modifying therapy during pregnancy. The objective of this study is to explore outcomes for children born to mothers with SCD using data from the Boston Birth Cohort (BBC). METHODSThe BBC is a prospective birth cohort established in 1998 at the Boston Medical Center (BMC) that recruits preterm cases (born at less than 37 weeks gestation) and full term controls. The BBC enrolls predominantly urban, low-income minority mothers and their children 24-72 hours after delivery at the BMC and follows the children from birth up to age 21 years. Data is collected on maternal preconception medical conditions, pregnancy complications, and pregnancy exposures through structured interviews at the time of enrollment and medical record extraction. Data on child development is collected from medical records and structured interviews performed by trained study staff at their scheduled pediatric appointments. Approximately 38% of study participants self-identify as black/African American, 22% as Hispanic, 19% as Haitian, and 8.5% as white. From maternal electronic medical record data capturing 147,827 emergency room and outpatient visits contributed by 5,972 subjects, we identified all women with ICD-9-CM codes for sickle cell disease (282.60-64, 282.68, 282.69, 282.41, 282.42) and probable (two or more 282.62 codes) sickle cell anemia. We then linked maternal and child data on the basis of a unique family-level study ID. Information on child development was obtained from electronic medical record data, based on the presence of relevant ICD-9-CM hospital diagnosis codes from pediatric outpatient, inpatient, and emergency room visits. RESULTSWe identified 93 women who had at least one of the ICD-9 codes for SCD. For this report we have included only those forty-one women who were coded at least twice with a 282.62 diagnosis (Hemoglobin SS disease with crisis). Six (15%) had poor fetal growth during their pregnancy, while eight (20%) were diagnosed with preeclampsia or antepartum hypertension. Among these mothers with available questionnaire and medical record extraction data (n = 38), 7 (18%) delivered their children before 37 weeks gestation, and 6 (16%) had children weighing less than 2500 grams at birth. Twenty mothers had children who received pediatric care at the Boston Medical Center, with ages ranging from 2 to 9 years of age; one was diagnosed with SCA, while 19 are unaffected carriers. Among the 19 children without SCD with available follow-up data, 5 (26%) carried a diagnosis code of overweight/obesity; their mothers were seen for an average of 73 medical visits (SD 50) during their pregnancy. Five children, without any overlap with the children diagnosed with obesity, were diagnosed with failure to thrive; while not statistically significantly different, their mothers had fewer medical encounters (mean 55, SD 37). Five children were diagnosed with delayed milestones, two of whom were late preterm (35 and 33 weeks gestation); two of these children were diagnosed with obesity and two with failure to thrive. DISCUSSIONThis exploratory, descriptive study represents the first data on long-term outcomes of children without SCD who were exposed to maternal SCD in utero . While we are limited by small sample size, finding that 26% of children born to mothers with SCD have developmental delay is a significant concern. This compares to the overall cohort where 12% of control children and 39% of preterm cases have been found to have developmental delay. Future studies will include medical record review of mothers to identify additional mothers with confirmed SCD in the cohort and exploration of additional predictors of these concerning outcomes. [Display omitted] DisclosuresLanzkron:Prolong: Research Funding; HRSA: Research Funding; Bayer: Research Funding; Global Blood Therapeutics: Research Funding; Pfizer: Research Funding; PCORI: Research Funding.

Clinical profile and treatment outcome of febrile infection-related epilepsy syndrome in South Indian children.

Purpose:To describe the clinical features and outcome of febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy, in a cohort of South Indian children.Materials and Methods:We performed a retrospective chart review of a cohort of children with previously normal development who presented with status epilepticus or encephalopathy with recurrent seizures following a nonspecific febrile illness during the period between January 2007 and January 2012. They were divided into two groups super refractory status epilepticus (SRSE) and refractory status epilepticus (RSE) depending on the duration and severity of the seizures.Key Findings:Fifteen children who met the inclusion criteria were included for the final analysis. The age of the children at presentation ranged 3-15 years (median 6.3 years). All the children presented with prolonged or recurrent seizures occurring 1-12 days (median 4 days) after the onset of fever. Eight children had SRSE while seven children had refractory seizures with encephalopathy. Cerebrospinal fluid (CSF) analysis was done in all the children in the acute phase, and the cell count ranged 0-12 cells/μL (median 2 cells/μL) with normal sugar and protein levels. Initial neuroimaging done in all children (MRI in 10 and CT in 5), and it was normal in 13 children. Treatment modalities included multiple antiepileptic drugs (AEDs) (4-9 drugs) (median 5 drugs). Midazolam (MDZ) infusion was administered in seven patients. Eight patients required barbiturate coma to suppress the seizure activity. The duration of the barbiturate coma ranged 2-90 days (median 3 days). Steroids were used in 14 children and intravenous immunoglobulin (2 g/kg) in 7 children. Three children died in the acute phase. All children were maintained on multiple AEDs till the last follow-up, the number of AEDs ranged 1-6 (median 5 AEDs). The patients with super refractory status in the acute phase were found to be more severely disabled at the follow-up; the median score of these patients on the Glasgow Outcome Scale (GOS) was 2 compared to 5 in the RSE group.Significance:This study reports one of the largest single center cohorts from India, with an adverse long-term developmental and seizure outcome. The duration and severity of seizures in the acute period correlated directly with the short-term and long-term clinical outcomes. There is an urgent need for developing new effective therapeutic strategies to treat this acute catastrophic epileptic syndrome.

Neonatal fatty acid status and neurodevelopmental outcome at 9 years

BackgroundLong-chain polyunsaturated fatty acids (LCPUFA) are important for prenatal brain development. Previous studies of others assessed outcome until 7years. The associations between neonatal LCPUFA status and long-term developmental outcome are debated. AimTo investigate the relationship between fatty acid status at birth and neurodevelopment at 9years. Age 9 is a unique age after a significant neurodevelopmental transition. Study designCorrelation study. Multivariable analyses were carried out to adjust for potential confounders. Subjects317 children who participated in a trial on effects of postnatal LCPUFA supplementation were eligible. 235 children (74%) were reassessed at age 9. Outcome measuresAt birth, docosahexaenoic acid (DHA) and arachidonic acid (AA) were determined in the wall of the umbilical vein. We primarily studied the correlation between DHA and AA with the complex form of minor neurological dysfunction (cMND). Secondary correlations that were studied were DHA and AA levels with cognitive development in terms of full IQ, and with behavioural development in terms of a total problem score. ResultsBoys with cMND showed lower DHA values in the umbilical vein than children with better neurological condition (p=0.033). A similar association was absent in girls. Neonatal AA values were not associated with neurological outcome. Neither neonatal DHA nor AA values were associated with cognition and behaviour at 9. ConclusionsHigher umbilical DHA levels in boys are associated with better neurological development at 9years. AA status at birth was not associated with neurodevelopment at 9years.

PO-0834 Long-term Developmental Outcome Of Children Prenatally Exposed To Antiepileptic Drugs

<h3>Background and aims</h3> The long-term effects of intra-uterine exposure antiepileptic drugs (AEDs) on cognitive functioning are limited and conflicting. The aim of the study was to assess the remote effects of fetal AEDs on cognitive outcomes in children. <h3>Methods</h3> Children, aged 2–4 years, with fetal exposure of carbamazepine (CBZ), lamotrigine (LTG) or valproate (VPA) monotherapy were recruited from the local registry of Epilepsy-Pregnancy. Neuropsychological assessment was performed in all cases with Learning Accomplishment Profile (LAP) for children of 1–6 years. All age groups were evaluated with Wide Range Assessment of Visual Motor Abilities (WRAVMA) tests. The results were compared to the results of the epidemiological study evaluating developmental achievements in general preschool children population. <h3>Results</h3> In total 39 children were assessed. Eleven (28%) were exposed to intra-uterine VPA, 22 (56%) to CBZ and six (15%) to LTG. From whole group poor performance in expressive speech was detected in nine persons (23%; 95% CI 12% - 44%) and there were no cases with fetal exposure to LTG. Out of children with fetal-VPA exposure (n = 11) the speech problems were observed in three cases (27%); from 22 children with CBZ intra-uterine exposure – in six (27%); no significant deficits were revealed in other developmental milestones. <h3>Conclusions</h3> The data of our study suggests that difficulties in verbal abilities are more often associated with fetal exposure to VPA and CBZ. For more conclusive results further profound neuropsychological evaluations are needed.

Are epigenetic changes in the intrauterine environment related to newborn neurobehavior?

Advances in the developmental origins of chronic diseases suggest that there are multiple environmental influences linked to normal variations in fetoplacental development [1]. The mechanism of this plasticity is thought to be through fetal programming involving epigenetic processes that alter gene expression and permanently set pathways linked to disease. A key question in the burgeoning field of human behavioral epigenetics is whether similar mechanisms can explain the development of behavioral ‘diseases’, in particular, mental health disorders [2]. However, the study of how variations in the intrauterine environment trigger epigenetic modifications that alter behavioral development is virtually uncharted territory. A good place to start is the neurobehavior of the newborn infant. It is well known that the postnatal environment has a substantial influence on child development [3,4]. By focusing on newborn neurobehavioral phenotypes, we have an opportunity to hone in on the role of the prenatal period before postnatal environmental factors come into play. In addition, newborn neurobehavior may predict long-term developmental outcome, allowing the identification of individual infants most likely to suffer mental illness and the pursuit of interventions to prevent or ameliorate later deficits. Focusing on the epigenetics of newborn neurobehavior could provide the molecular context for individual differences in neurobehavior as well as an understanding of children’s responses to the postnatal environment – that is, why some infants are more vulnerable or susceptible to poor developmental outcome than others. Newborn neurobehavior can be quantified with the NNNS (NICU Network Neurobehavioral Scale), a well-established evaluation that includes neurological and behavioral measures and indicators of stress [5] and has been shown to predict behavior problems, school readiness, and IQ through 4.5 years [6]. Here, we describe a series of studies relating epigenetic changes in placental genes and the NNNS in a sample of several hundred term, healthy infants who vary in physical growth, born to mothers with uncomplicated medical histories [7]. The placenta provides an ideal fetal record of the intrauterine environment and alterations to its function through epigenetic processes that could affect newborn neurobehavior [8]. The placenta modulates the fetal environment and has been described as a ‘third brain’ that links the developing fetal brain and the mature maternal brain, and is thus a sensitive functional tissue to understand the prenatal environment’s effects on neurobehavior [9]. The neuroendocrine system, in particular, programming of the HPA axis is a good model for the exploration of epigenetic effects on placental genes and newborn neurobehavior. This is a well-studied system that includes an extensive literature on cortisol reactivity and the development of mental health disorders [10] and is known to be an active system within placental tissue [11]. In the placenta, 11β-HSD-2 is responsible for the inactivation of maternal cortisol. Increased DNA methylation of 11β-HSD-2 Barry M Lester

Timing of cord clamping in very preterm infants: more evidence is needed

In December 2012, the American College of Obstetricians and Gynecologists published a Committee Opinion entitled "Timing of umbilical cord clamping after birth." It stated that "evidence exists to support delayed cord clamping in preterm infants, when feasible. The single most important benefit for preterm infants is the possibility for a nearly 50% reduction in IVH." However, the Committee Opinion added that the ideal timing of umbilical cord clamping has yet to be determined and recommended that large clinical trials be conducted in the most preterm infants. Published randomized controlled trials include <200 infants of <30 weeks' gestation, with assessments of neurodevelopmental outcome in less than one-half of the children. This is a major gap in the evidence. Without reliable data from randomized controlled trials that optimally include childhood follow-up evaluations, we will not know whether delayed cord clamping may do more overall harm than good. Ongoing trials of delayed cord clamping plan to report childhood outcomes in >2000 additional very preterm infants. Current recommendations may need to change when these results become available. Greater international collaboration could accelerate resolution of whether this promising intervention will improve disability-free survival in about 1 million infants who will be born very preterm globally each year.

PET in Infancy Predicts Long-Term Outcome during Adolescence in Cryptogenic West Syndrome

Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and developmental outcome in cryptogenic West syndrome. From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated. At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03). Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.

Evaluating the effectiveness of Parent Empowerment (COPE) program on participation of mothers of preterm infants hospitalized in NICUs of hospitals affiliated to Isfahan University of Medical Sciences and Health Services, 2009-2010

Abstract Background and aim: The birth of a preterm infant is a stressful event for parents. Because of special nature of the Neonatal Intensive Care Unit (NICU) environment, parents of infants admitted to a neonatal intensive care unit experience higher levels of tension, compared with parents of healthy infants the mother’s physical and psychological condition may negatively influence early and suitable mother–infant relationship, the mother’s participation in her infant care and the infant’s long-term developmental outcome. The purpose of this study was to evaluate the effectiveness of Creating Opportunities for Parent Empowerment (COPE) program on participation of mothers of preterm infants hospitalized in NICUs of hospitals affiliated to Isfahan University of Medical Sciences and Health Services. Method and material: A randomized clinical trial was conducted with 90 mothers of premature infants hospitalized in the neonatal intensive care units. COPE mothers received 2 intervention sessions of audiotaped and printed materials with workbook. This program consisted of information and behavioral activities about the appearance and behavioral characteristics of preterm infants and how best to parent them. Duration between sessions was 2 to 4 days. Data were collected by a questionnaire.The participation was evaluated just 2 to 4 days after second phase. Results: The mea score of mothers’ participation in experiment group was 9.14±0.84 and 9.43±1.06 for the first and second phase of post -test.Mothers in the Creating Opportunities for Parent Empowerment program reported significantly more participation in their infants care (p<0.001). Discussion and Conclusion: Creating Opportunities for Parent Empowerment program diminished mothers enhance the amount of mother’s participation. This study showed that early interventions during neonatal hospitalization and educational behavioral information in written form may have positive effect on maternal psychological condition and participation. Key words: nurse, parents’ empowerment , participation, preterm infant, randomized clinical trial