- MeSH
- Child MeSH
- Hypoxia MeSH
- Brain Ischemia ultrasonography MeSH
- Humans MeSH
- Microcephaly MeSH
- Infant, Newborn MeSH
- Neonatal Abstinence Syndrome MeSH
- Psychomotor Disorders MeSH
- Heroin Dependence MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Publication type
- Case Reports MeSH
BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.
INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.
- MeSH
- Child MeSH
- Fetal Weight MeSH
- Cardiotocography MeSH
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Premature Birth * MeSH
- Randomized Controlled Trials as Topic MeSH
- Fetal Growth Retardation MeSH
- Heart Rate, Fetal physiology MeSH
- Pregnancy MeSH
- Ultrasonography, Prenatal * MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Clinical Trial Protocol MeSH
Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 18 months, 36 months, 6, 9, 12, 15 and 18 years of age. Oncological, obstetrical, neonatal and follow-up data of these children were collected. Parents were asked to complete questionnaires on their child's general health, school performances, social situation, behavioral development, executive functioning, and if their child receives supportive care. Non-Hodgkin lymphoma was diagnosed in 35.1%, Hodgkin lymphoma in 28.1%, acute myeloid leukemia in 15.8%, chronic myeloid leukemia in 12.3%, and acute lymphoblastic leukemia in 8.8%. Cognitive development at a median age of 10.7 years was within the normal range. In subgroup analyses of children in early childhood, the gestational age at birth was correlated with the cognitive outcome at a median age of 1.7 years. Scores for language development, intelligence, attention, memory and behavior, as well as clinical neurological and general pediatric examinations were within normal ranges. In subgroup analyses, the need for supportive care in the child was associated with the loss of the mother. Prenatal exposure to hematological maternal malignancies with or without treatment did not affect the neurodevelopment of the child in the long term. Yet, caution is indicated and surveillance of the emotional development of the child is needed, especially when the mother is deceased to cancer.
- MeSH
- Child MeSH
- Hematologic Neoplasms * complications MeSH
- Intelligence MeSH
- Infant MeSH
- Humans MeSH
- Mothers MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Antineoplastic Agents * MeSH
- Pregnancy MeSH
- Child Development MeSH
- Prenatal Exposure Delayed Effects * MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Systemic infection may negatively modulate the development of cerebral white matter and long-term outcome of neonates. We analyzed the growth of corpus callosum (using cranial ultrasonography) and neurodevelopment (Bayley Scales of Infant Development, Third Edition) in 101 very low-birth-weight newborns. We observed significantly reduced corpus callosum length at 3 months of corrected age (44.5 mm vs 47.7 mm, P = .004) and diminished corpus callosum growth (0.07 mm/d vs 0.08 mm/d, P = .028) in infants who experienced systemic infection. The subgroup exhibited inferior neurodevelopmental outcomes with predominant motor impairment. The results suggest that length and growth of corpus callosum might be affected by systemic inflammatory response in preterm newborns. The changes in corpus callosum can contribute to adverse neurodevelopment at 2 years of corrected age. Serial ultrasonographic measurements of the corpus callosum may be suitable to identify preterm infants with increased risk of neurodevelopmental impairment.
- MeSH
- Corpus Callosum diagnostic imaging growth & development MeSH
- Causality MeSH
- Cohort Studies MeSH
- Infant MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Neurodevelopmental Disorders epidemiology MeSH
- Infant, Premature MeSH
- Infant, Very Low Birth Weight MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Prospective Studies MeSH
- Sepsis epidemiology MeSH
- Ultrasonography methods MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
Systemic infection may negatively modulate the development of cerebral white matter and long-term outcome of neonates. We analyzed the growth of corpus callosum (using cranial ultrasonography) and neurodevelopment (Bayley Scales of Infant Development, Third Edition) in 101 very low-birth-weight newborns. We observed significantly reduced corpus callosum length at 3 months of corrected age (44.5 mm vs 47.7 mm, P = .004) and diminished corpus callosum growth (0.07 mm/d vs 0.08 mm/d, P = .028) in infants who experienced systemic infection. The subgroup exhibited inferior neurodevelopmental outcomes with predominant motor impairment. The results suggest that length and growth of corpus callosum might be affected by systemic inflammatory response in preterm newborns. The changes in corpus callosum can contribute to adverse neurodevelopment at 2 years of corrected age. Serial ultrasonographic measurements of the corpus callosum may be suitable to identify preterm infants with increased risk of neurodevelopmental impairment.
- MeSH
- Corpus Callosum diagnostic imaging growth & development MeSH
- Causality MeSH
- Cohort Studies MeSH
- Infant MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Neurodevelopmental Disorders epidemiology MeSH
- Infant, Premature MeSH
- Infant, Very Low Birth Weight MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Prospective Studies MeSH
- Sepsis epidemiology MeSH
- Ultrasonography methods MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
Spontaneous loss of a twin most often occurs in the first trimester. This phenomenon is called vanishing twin. Foetuses are especially vulnerable to various stress-related factors. As a result, twin loss in the uterus can produce deep and long-lasting consequences on mental health and may increase the risk of a variety of disease states in the surviving twin. In addition, twin loss may generate strong non-conscious stress that creates epigenetic alterations that impair the brain’s development endocrine and inflammatory substances produced by perturbed signalling pathways. These altered signalling pathways may generate lasting dysfunctions in various areas of the limbic system, predisposing the surviving twin to psychological and emotional problems later in life. We also hypothesise that specific cfDNA and other substances from the dead twin during its reabsorption may affect the surviving twin’s neurodevelopmental and emotional (e.g. resilience) development.
- Keywords
- Vanishing twin syndrom, cell-free fetal DNA,
- MeSH
- DNA analysis MeSH
- Twins MeSH
- Epigenesis, Genetic MeSH
- Humans MeSH
- Diseases in Twins MeSH
- Unconscious, Psychology MeSH
- Fetal Death MeSH
- Resilience, Psychological MeSH
- Stress, Psychological MeSH
- Abortion, Spontaneous genetics psychology MeSH
- Pregnancy, Twin MeSH
- Pregnancy Outcome MeSH
- Fetal Development MeSH
- Check Tag
- Humans MeSH
OBJECTIVE: To perform a systematic review of the literature available on the association between the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation and long-term neurodevelopmental outcomes of infants from pregnancies complicated by preterm prelabor rupture of membranes (PPROM). METHODS: A literature search, from their earliest entries to May 2020, was performed by employing three electronic databases (Web of Science, PubMed, and Scopus). The selection criteria were as follows: (1) singleton pregnancies with PPROM; (2) available information regarding MIAC and/or intra-amniotic inflammation; (3) long-term (at least one year of the corrected age) neurodevelopmental outcomes of respective infants. RESULTS: The initial search identified 10,953 articles, of which 8 were selected for full-text reading; however, none were included in the review owing to the following reasons: (i) spontaneous preterm labor with intact membranes and/or indicated (iatrogenic) preterm delivery were included in the studies without providing separate data for PPROM (n = 5); (ii) long-term, at least one year of the corrected age, neurodevelopmental outcomes of infants were not assessed (n = 1); (iii) the presence of both the abovementioned reasons (n = 1); (iv) amniotic fluid was not assessed, and a long-term neurodevelopmental outcome was not evaluated (n = 1). CONCLUSION: The literature search provides evidence of a knowledge gap in the association between the presence of MIAC and/or intra-amniotic inflammation and long-term neurodevelopmental outcomes in infants with PPROM.
- MeSH
- Chorioamnionitis * etiology MeSH
- Gestational Age MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Amniotic Fluid MeSH
- Fetal Membranes, Premature Rupture * MeSH
- Pregnancy MeSH
- Inflammation complications MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy and movement disorder. We evaluated a large cohort of patients (n = 25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor and ataxia. Later in the disease course, they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibres and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders.
- MeSH
- Alkyl and Aryl Transferases * MeSH
- Child MeSH
- Dolichols metabolism MeSH
- Humans MeSH
- Myoclonus * MeSH
- Neurodegenerative Diseases * genetics MeSH
- Retinitis Pigmentosa * genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVE: To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). METHODS: Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy - Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24 months. The timing and characteristics of the first ED-EEG were studied in relation to clinical outcome. Epilepsy-related outcomes were analyzed separately in a conventionally followed group (initiation of vigabatrin after seizure onset) and a preventive group (initiation of vigabatrin before seizures, but after appearance of interictal epileptiform discharges [IEDs]). RESULTS: Eighty-three infants with TSC were enrolled at a median age of 28 days (interquartile range [IQR] 14-54). Seventy-nine of 83 patients (95%) developed epileptiform discharges at a median age of 77 days (IQR 23-111). Patients with a pathogenic TSC2 variant were significantly younger (P-value .009) at first ED-EEG and more frequently had multifocal IED (P-value .042) than patients with a pathogenic TSC1 variant. A younger age at first ED-EEG was significantly associated with lower cognitive (P-value .010), language (P-value .001), and motor (P-value .013) developmental quotients at 24 months. In the conventional group, 48 of 60 developed seizures. In this group, the presence of focal slowing on the first ED-EEG was predictive of earlier seizure onset (P-value .030). Earlier recording of epileptiform discharges (P-value .019), especially when multifocal (P-value .026) was associated with higher risk of drug-resistant epilepsy. In the preventive group, timing, distribution of IED, or focal slowing, was not associated with the epilepsy outcomes. However, when multifocal IEDs were present on the first ED-EEG, preventive treatment delayed the onset of seizures significantly (P-value <.001). SIGNIFICANCE: Early EEG findings help to identify TSC infants at risk of severe epilepsy and neurodevelopmental delay and those who may benefit from preventive treatment with vigabatrin.
- MeSH
- Anticonvulsants therapeutic use MeSH
- Early Diagnosis * MeSH
- Electroencephalography MeSH
- Epilepsy diagnosis drug therapy etiology MeSH
- Tuberous Sclerosis Complex 1 Protein genetics MeSH
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Tuberous Sclerosis Complex 2 Protein genetics MeSH
- Tuberous Sclerosis complications diagnosis genetics MeSH
- Vigabatrin therapeutic use MeSH
- Developmental Disabilities epidemiology etiology MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
