Possible In Utero Transmission of SARS-CoV-2 and Severe Respiratory Disease in a Preterm Infant.

Severe acute respiratory syndrome coronavirus 2 infections are uncommon in newborn infants. This report describes possible in utero transmission of the B.1.1.7 (alpha) variant in a preterm infant born at 31 weeks' gestational age who presented with severe respiratory disease. The infant was treated with high-frequency oscillatory ventilation, antiviral medications, and corticosteroids and transitioned to noninvasive respiratory support on day 33. By day 63, she was off positive pressure support and breathing room air and she was discharged from the hospital on day 70. She demonstrated normal growth and development at a 6-month follow-up visit. Placental histopathology revealed placentitis characterized by loss of intervillous spaces resulting from fibrin deposition and inflammatory cell infiltration. Optimum management strategies for treating infants with severe acute respiratory syndrome coronavirus 2 infection have yet to be determined.

Neonatal Seizure Management: Is the Timing of Treatment Critical?

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden and describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks of gestation) requiring electroencephalographic (EEG) monitoring recruited to 2 multicenter European studies were included. Infants who received antiseizure medication exclusively after electrographic seizure onset were grouped based on the time to treatment of the first seizure: antiseizure medication within 1 hour, between 1 and 2 hours, and after 2 hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures, and antiseizure medication dose over the first 24 hours after seizure onset. RESULTS: Out of 472 newborns recruited, 154 (32.6%) had confirmed electrographic seizures. Sixty-nine infants received antiseizure medication exclusively after the onset of electrographic seizure, including 21 infants within 1 hour of seizure onset, 15 between 1 and 2 hours after seizure onset, and 33 at >2 hours after seizure onset. Significantly lower seizure burden and fewer seizures were noted in the infants treated with antiseizure medication within 1 hour of seizure onset (P = .029 and .035, respectively). Overall, 258 of 472 infants (54.7%) received antiseizure medication during the study period, of whom 40 without electrographic seizures received treatment exclusively during EEG monitoring and 11 with electrographic seizures received no treatment. CONCLUSIONS: Treatment of neonatal seizures may be time-critical, but more research is needed to confirm this. Improvements in neonatal seizure diagnosis and treatment are also needed.

A machine-learning algorithm for neonatal seizure recognition: a multicentre, randomised, controlled trial.

BACKGROUND: Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR). METHODS: This multicentre, randomised, two-arm, parallel, controlled trial was done in eight neonatal centres across Ireland, the Netherlands, Sweden, and the UK. Neonates with a corrected gestational age between 36 and 44 weeks with, or at significant risk of, seizures requiring EEG monitoring, received cEEG plus ANSeR linked to the EEG monitor displaying a seizure probability trend in real time (algorithm group) or cEEG monitoring alone (non-algorithm group). The primary outcome was diagnostic accuracy (sensitivity, specificity, and false detection rate) of health-care professionals to identify neonates with electrographic seizures and seizure hours with and without the support of the ANSeR algorithm. Neonates with data on the outcome of interest were included in the analysis. This study is registered with ClinicalTrials.gov, NCT02431780. FINDINGS: Between Feb 13, 2015, and Feb 7, 2017, 132 neonates were randomly assigned to the algorithm group and 132 to the non-algorithm group. Six neonates were excluded (four from the algorithm group and two from the non-algorithm group). Electrographic seizures were present in 32 (25·0%) of 128 neonates in the algorithm group and 38 (29·2%) of 130 neonates in the non-algorithm group. For recognition of neonates with electrographic seizures, sensitivity was 81·3% (95% CI 66·7-93·3) in the algorithm group and 89·5% (78·4-97·5) in the non-algorithm group; specificity was 84·4% (95% CI 76·9-91·0) in the algorithm group and 89·1% (82·5-94·7) in the non-algorithm group; and the false detection rate was 36·6% (95% CI 22·7-52·1) in the algorithm group and 22·7% (11·6-35·9) in the non-algorithm group. We identified 659 h in which seizures occurred (seizure hours): 268 h in the algorithm versus 391 h in the non-algorithm group. The percentage of seizure hours correctly identified was higher in the algorithm group than in the non-algorithm group (177 [66·0%; 95% CI 53·8-77·3] of 268 h vs 177 [45·3%; 34·5-58·3] of 391 h; difference 20·8% [3·6-37·1]). No significant differences were seen in the percentage of neonates with seizures given at least one inappropriate antiseizure medication (37·5% [95% CI 25·0 to 56·3] vs 31·6% [21·1 to 47·4]; difference 5·9% [-14·0 to 26·3]). INTERPRETATION: ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR. The benefit might be greater in less experienced centres, but further study is required. FUNDING: Wellcome Trust, Science Foundation Ireland, and Nihon Kohden.

Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia.

AIMS AND HYPOTHESIS: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was to show that it is feasible to study plasma neurofilament light (NfL) levels from newborns and to evaluate their temporal course. Hypothesis: Raised plasma NFL protein levels from newborns who undergo TH after HIE are associated with abnormal MRI outcomes. METHODS: Between February 2014 and January 2016, term newborns with HIE treated with TH for 72 h had plasma samples taken at three time points: (i) after the infant had reached target temperature, (ii) prior to commencing rewarming, and (iii) after completing rewarming. Infants with mild HIE who did not receive TH had a single specimen taken. NfL protein was analyzed using an enzyme-linked immunosorbent assay. RESULTS: Twenty-six newborns with moderate-severe HIE treated with TH were studied. Half of these had cerebral MRI predictive of an unfavorable outcome. Plasma NfL levels were significantly higher in the TH group with unfavorable outcome (median age 18 h) compared to levels from both the mild HIE group and TH group with favorable outcome (F = 25.83, p < 0.0001). Newborns who had MRIs predictive of unfavorable outcome had significantly higher NfL levels compared to those with favorable outcomes, at all three time points (mixed models, F = 27.63, p < 0.001). A cutoff NfL level >29 pg/mL at 24 h is predictive of an unfavorable outcome [sensitivity 77%, specificity 69%, positive predictive value (PPV) 67%, negative predictive value (NPV) 72%] with increasing predictive value until after rewarming (sensitivity 92%, specificity 92%, PPV 92%, NPV 86%). INTERPRETATION OF RESEARCH: Plasma NfL protein levels may be a useful biomarker of unfavorable MRI outcomes in newborns with moderate-severe HIE and may assist in selecting newborns for adjunctive neuroprotective interventions. Larger studies with NfL testing at earlier time points are required.

Automated electroencephalographic discontinuity in cooled newborns predicts cerebral MRI and neurodevelopmental outcome.

BACKGROUND AND HYPOTHESIS: Prolonged electroencephalographic (EEG) discontinuity has been associated with poor neurodevelopmental outcomes after perinatal asphyxia but its predictive value in the era of therapeutic hypothermia (TH) is unknown. In infants undergoing TH for hypoxic-ischaemic encephalopathy (HIE) prolonged EEG discontinuity is associated with cerebral tissue injury on MRI and adverse neurodevelopmental outcome. METHOD: Retrospective study of term neonates from three UK centres who received TH for perinatal asphyxia, had continuous two channel amplitude-integrated EEG with EEG for a minimum of 48 h, brain MRI within 6 weeks of birth and neurodevelopmental outcome data at a median age of 24 months. Mean discontinuity was calculated using a novel automated algorithm designed for analysis of the raw EEG signal. RESULTS: Of 49 eligible infants, 17 (35%) had MR images predictive of death or severe neurodisability (unfavourable outcome) and 29 (59%) infants had electrographic seizures. In multivariable logistic regression, mean discontinuity at 24 h and 48 h (both p=0.01), and high seizure burden (p=0.05) were associated with severe cerebral tissue injury on MRI. A mean discontinuity >30 s/min-long epoch, had a specificity and positive predictive value of 100%, sensitivity of 71% and a negative predictive value of 88% for unfavourable neurodevelopmental outcome at a 10 µV threshold. CONCLUSIONS: In addition to seizure burden, excessive EEG discontinuity is associated with increased cerebral tissue injury on MRI and is predictive of abnormal neurodevelopmental outcome in infants treated with TH. The high positive predictive value of EEG discontinuity at 24 h may be valuable in selecting newborns with HIE for adjunctive treatments.

A study of microRNAs from dried blood spots in newborns after perinatal asphyxia: a simple and feasible biosampling method.

BACKGROUND: The potential of microRNAs (miRNAs) as bedside biomarkers in selecting newborns with hypoxic-ischemic encephalopathy (HIE) for neuroprotection has yet to be explored. Commonly, blood-based biomarker tests use plasma or serum which don't allow evaluation of both intracellular and extracellular changes. METHODS: We describe a technique to extract and compare expression of miRNAs from a single small 6-mm-diameter dried blood spot (DBS) stored at room temperature with those from EDTA-blood, plasma, and urine. Three miRNAs (RNU6B, let7b, and miR-21) were quantified via extraction and quantitative RT-PCR performed from a DBS and compared with levels from EDTA-blood, plasma, and urine. Secondarily, candidate miRNAs let7b, miR-21, miR-29b, miR-124, and miR-155 in DBS were evaluated as potential biomarkers for HIE. RESULTS: Candidate miRNAs were extractable in all biosamples from newborns, with the highest expression in DBS. There was a good correlation between miRNAs' levels in DBS and EDTA-blood at -80 °C. No significant difference was observed in the miRNA levels between the favorable and unfavorable outcome groups for babies with HIE. CONCLUSION: DBS may be useful for studying the potential of miRNAs as biomarkers for brain injury.

Effects of hypothermia for perinatal asphyxia on childhood outcomes.

BACKGROUND: In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits. METHODS: We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher. RESULTS: A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children's health status and in results on 10 of 11 psychometric tests. CONCLUSIONS: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

Electrographic seizures are associated with brain injury in newborns undergoing therapeutic hypothermia.

OBJECTIVE: Seizures are common among newborns with hypoxic-ischaemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is associated with cerebral tissue injury independent of amplitude-integrated EEG (aEEG) background activity. STUDY DESIGN: Term neonates undergoing 72 h of TH at four centres were selected for study if they had continuous aEEG and MRI. The aEEG with corresponding 2-channel raw EEG (aEEG/EEG), was classified by severity of background and seizure burden; MR images were classified by the severity of tissue injury. RESULTS: Of 85 neonates, 52% had seizures on aEEG/EEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 h and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with severe injury on MRI were high seizure burden, poor aEEG background, 10 min Apgar and the need for more than one anticonvulsant. In multivariate logistic regression, high seizure burden was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to 17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant. CONCLUSIONS: Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.

Effect of caesarean section on brain maturation.

UNLABELLED: The rates of caesarean section (CS) are increasing worldwide. The short-term effects of CS in the newborn have been described and long-term reported risks of alterations of pathophysiology include altered microflora, increased risk of childhood asthma and childhood-onset type I diabetes mellitus. There has been emphasis on the respiratory morbidity related to the timing of elective CS. More recently, a population study demonstrated dose-dependent effect of each week of gestation on the need for special education. This highlights the importance of intrauterine brain development towards the end of pregnancy and hitherto largely unexplored possible effects on neurodevelopment if it is interrupted. CONCLUSION: The timing of CS is important not only because delivery before 39 weeks can increase respiratory morbidity, but also owing to the fact that ongoing intrauterine brain maturation could be significant for future neurodevelopment.

Blood sampling in infants (reducing pain and morbidity).

INTRODUCTION: Preterm or ill neonates may undergo 1 to 21 heel punctures or venepunctures a day. These punctures are likely to be painful. Heel punctures comprise 61% to 87% and venepunctures comprise 8% to 13% of the invasive procedures performed on ill infants. Analgesics are rarely given specifically for blood sampling procedures, but 5% to 19% of infants receive analgesia for other indications. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce pain-related distress and morbidity during venepuncture in preterm or term babies aged under 12 months in a neonatal unit? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: oral sweet solutions; pacifiers; and topical anaesthetics (lidocaine-prilocaine cream, tetracaine).

Moderate hypothermia to treat perinatal asphyxial encephalopathy.

BACKGROUND: Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain. METHODS: We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes. RESULTS: Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling. CONCLUSIONS: Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)

Blood sampling in infants (reducing pain and morbidity).

INTRODUCTION: Preterm or ill neonates may undergo 1-21 heel punctures or venepunctures per day. These punctures are likely to be painful. Heel punctures comprise 61-87% and venepunctures comprise 8-13% of the invasive procedures performed on ill infants. Analgesics are rarely given specifically for blood sampling procedures, but 5-19% of infants receive analgesia for other indications. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce pain-related distress and morbidity during venepuncture in preterm or term babies aged under 12 months in a neonatal unit? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: oral sweet solutions, pacifiers, and topical anaesthetics (lidocaine-prilocaine cream, tetracaine).

Severity of perinatal illness and cerebral cortical growth in preterm infants.

AIM: We have shown previously that the degree of prematurity affects cortical surface area growth. We now addressed the question whether cortical surface area growth after preterm birth is predicted by the severity of peri- and postnatal illness. METHODS: Cortical surface area was measured in 269 images from 111 infants born between 23 and 29 weeks and imaged at 23 to 48 weeks gestational age (GA). The severity of perinatal illness was assessed using the clinical risk index for babies score (CRIB I) and the severity of ongoing illness by the presence of chronic lung disease (CLD). The effects on cortical growth were modelled using generalized least-square regression for random effects with Bonferroni correction. To explore the results further we examined CRIB II, C-reactive protein (CRP) on the second day after birth, and time taken to achieve full enteral feeding. RESULTS: Cortical surface area grew by 12.4% per week. Reduced cortical growth was predicted by adverse CRIB I (-0.15% per week per unit) and development of CLD (-1.18% per week). Secondary analysis showed that growth was related to adverse CRIB II (-0.36% per week per unit) and increasing CRP (-0.03% per week per mMol), but not by the time taken to achieve full enteral feeding. CONCLUSION: After very premature birth illness severity predicts reduced cortical growth.

Relationship between white matter apparent diffusion coefficients in preterm infants at term-equivalent age and developmental outcome at 2 years.

OBJECTIVE: The aim of this study was to develop a simple reproducible method for the measurement of apparent diffusion coefficient values in the white matter of preterm infants using diffusion-weighted imaging to test the hypothesis that elevated mean apparent diffusion coefficient values are associated with lower developmental quotient scores at 2 years' corrected age. METHODS: We obtained diffusion-weighted imaging in 38 preterm infants at term-equivalent age who had no evidence of overt cerebral pathology on conventional MRI. Mean apparent diffusion coefficient values at the level of the centrum semiovale were determined. The children were assessed using a standardized neurologic examination, and the Griffiths Mental Development Scales were administered to obtain a developmental quotient at 2 years' corrected age. The relationship between mean apparent diffusion coefficient values and developmental quotient was examined. Clinical data relating to postnatal sepsis, antenatal steroid exposure, supplemental oxygen, gender, patent ductus arteriosus, and inotrope requirement were collected, and the mean apparent diffusion coefficient values for each group were compared. RESULTS: The mean (+/-SD) apparent diffusion coefficient value in the white matter was 1.385 +/- 0.07 x 10(-3) mm2/second, and the mean developmental quotient was 108.9 +/- 11.5. None of the children had a significant neurologic problem. There was a significant negative correlation between mean apparent diffusion coefficient and developmental quotient. CONCLUSION: These findings suggest that higher white matter apparent diffusion coefficient values at term-equivalent age in preterm infants without overt lesions are associated with poorer developmental performance in later childhood. Consequently, apparent diffusion coefficient values at term may be of prognostic value for neurodevelopmental outcome in infants who are born preterm and who have no other imaging indicators of abnormality.

Early growth in brain volume is preserved in the majority of preterm infants.

OBJECTIVE: Preterm infants have reduced cerebral tissue volumes in adolescence. This study addresses the question: Is reduced global brain growth in the neonatal period inevitable after premature birth, or is it associated with specific medical risk factors? METHODS: Eighty-nine preterm infants at term equivalent age without focal parenchymal brain lesions were studied with 20 full-term control infants. Using a deformation-based morphometric approach, we transformed images to a reference anatomic space, and we used the transformations to calculate whole-brain volume and ventricular volume for each subject. Patterns of volume difference were correlated with clinical data. RESULTS: Cerebral volume is not reduced compared with term born control infants (p = 0.765). Supplemental oxygen requirement at 28 postnatal days is associated with lower cerebral tissue volume at term (p < 0.001), but there were no significant differences in cerebral volumes attributable to perinatal sepsis (p = 0.515) and quantitatively defined diffuse white matter injury (p = 0.183). As expected, the ventricular system is significantly larger in preterm infants at term equivalent age compared with term control infants (p < 0.001). INTERPRETATION: Cerebral volume is not reduced during intensive care for the majority of preterm infants, but prolonged supplemental oxygen dependence is a risk factor for early attenuation of global brain growth. The reduced cerebral tissue volume seen in adolescents born preterm does not appear to be an inevitable association of prematurity, but rather caused by either specific disease during intensive care or factors operating beyond the neonatal period.

Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

BACKGROUND: We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. METHODS AND FINDINGS: We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. CONCLUSIONS: Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

Abnormal deep grey matter development following preterm birth detected using deformation-based morphometry.

Preterm birth is a leading risk factor for neurodevelopmental and cognitive impairment in childhood and adolescence. The most common known cerebral abnormality among preterm infants at term equivalent age is a diffuse white matter abnormality seen on magnetic resonance (MR) images. It occurs with a similar prevalence to subsequent impairment, but its effect on developing neural systems is unknown. MR images were obtained at term equivalent age from 62 infants born at 24-33 completed weeks gestation and 12 term born controls. Tissue damage was quantified using diffusion-weighted imaging, and deformation-based morphometry was used to make a non-subjective survey of the whole brain to identify significant cerebral morphological alterations associated with preterm birth and with diffuse white matter injury. Preterm infants at term equivalent age had reduced thalamic and lentiform volumes without evidence of acute injury in these regions (t = 5.81, P < 0.05), and these alterations were more marked with increasing prematurity (t = 7.13, P < 0.05 for infants born at less than 28 weeks) and in infants with diffuse white matter injury (t = 6.43, P < 0.05). The identification of deep grey matter growth failure in association with diffuse white matter injury suggests that white matter injury is not an isolated phenomenon, but rather, it is associated with the maldevelopment of remote structures. This could be mediated by a disturbance to corticothalamic connectivity during a critical period in cerebral development. Deformation-based morphometry is a powerful tool for modelling the developing brain in health and disease, and can be used to test putative aetiological factors for injury.

Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age.

OBJECTIVE: Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. METHODS: Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. RESULTS: Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. CONCLUSIONS: These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM.

Can clinical signs identify newborns with neuromuscular disorders?

OBJECTIVE: To evaluate retrospectively the prevalence of neuromuscular disorders in 83 newborns referred to a tertiary care center because of hypotonia and weakness and/or contractures, with a possible diagnosis of neuromuscular disorder. We also aimed to establish whether clinical signs could help to identify infants with neuromuscular disorders. STUDY DESIGN: Sixty-six of the 83 infants who fulfilled the inclusion criteria (79.5%) had an identifiable disorder, which was a neuromuscular disorder in 39 (46.9%). RESULTS: Absent or extremely reduced antigravity movements were mainly found in infants with neuromuscular disorders (sensitivity and specificity 97.4% and 75%), whereas partial range antigravity movements were more frequent in infants with other diagnosis. Contractures were mainly found in infants with peripheral nerve or muscle involvement but also were relatively frequent in infants with genetic or metabolic syndromes (sensitivity 69.2%, specificity 61.3%). Reduced fetal movements and abnormal liquor were frequent but not present consistently in infants with neuromuscular disorders (sensitivity 46.1% and 38.4%) and were found rarely in infants with other disorders (specificity 88.6% and 75.0%). CONCLUSIONS: Severe muscle weakness and contractures are the most reliable indicators of a neuromuscular disorder and should be carefully assessed in an infant with neonatal hypotonia.