A Randomized Trial of Laryngeal Mask Airway in Neonatal Resuscitation.

BACKGROUND: Face-mask ventilation is the most common resuscitation method for birth asphyxia. Ventilation with a cuffless laryngeal mask airway (LMA) has potential advantages over face-mask ventilation during neonatal resuscitation in low-income countries, but whether the use of an LMA reduces mortality and morbidity among neonates with asphyxia is unknown. METHODS: In this phase 3, open-label, superiority trial in Uganda, we randomly assigned neonates who required positive-pressure ventilation to be treated by a midwife with an LMA or with face-mask ventilation. All the neonates had an estimated gestational age of at least 34 weeks, an estimated birth weight of at least 2000 g, or both. The primary outcome was a composite of death within 7 days or admission to the neonatal intensive care unit (NICU) with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization. RESULTS: Complete follow-up data were available for 99.2% of the neonates. A primary outcome event occurred in 154 of 563 neonates (27.4%) in the LMA group and 144 of 591 (24.4%) in the face-mask group (adjusted relative risk, 1.16; 95% confidence interval [CI], 0.90 to 1.51; P = 0.26). Death within 7 days occurred in 21.7% of the neonates in the LMA group and 18.4% of those in the face-mask group (adjusted relative risk, 1.21; 95% CI, 0.90 to 1.63), and admission to the NICU with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization occurred in 11.2% and 10.1%, respectively (adjusted relative risk, 1.27; 95% CI, 0.84 to 1.93). Findings were materially unchanged in a sensitivity analysis in which neonates with missing data were counted as having had a primary outcome event in the LMA group and as not having had such an event in the face-mask group. The frequency of predefined intervention-related adverse events was similar in the two groups. CONCLUSIONS: In neonates with asphyxia, the LMA was safe in the hands of midwives but was not superior to face-mask ventilation with respect to early neonatal death and moderate-to-severe hypoxic-ischemic encephalopathy. (Funded by the Research Council of Norway and the Center for Intervention Science in Maternal and Child Health; NeoSupra ClinicalTrials.gov number, NCT03133572.).

Kidney outcomes in early adolescence following perinatal asphyxia and hypothermia-treated hypoxic-ischaemic encephalopathy.

BACKGROUND: Acute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007-2009 with a history of hypothermia-treated HIE. METHODS: At 10-12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI. RESULTS: Forty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI. CONCLUSION: Renal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Acute kidney injury in infants with hypothermia-treated hypoxic-ischaemic encephalopathy: An observational population-based study.

AIM: To describe incidence and outcome of acute kidney injury (AKI) in infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). METHODS: This observational population-based study included all term and near-term infants with hypothermia-treated HIE born between 2007 and 2009 in greater Stockholm. The KDIGO definition modified for neonatal patients was used to identify infants with AKI. We analysed association between AKI and neonatal morbidity/mortality. Furthermore, we calculated estimated glomerular filtration rate (eGFR) at the age of 10-12 years. RESULTS: Out of 83,939 live births in the Stockholm region, 66 infants underwent hypothermia treatment due to HIE. Out of 65 included infants, 45% suffered AKI. Degree of AKI correlated with HIE severity. One infant needed kidney replacement therapy; others were treated conservatively. AKI was associated with increased mortality and need for blood products (p < 0.05). eGFR at age 10-12 years was available for 72% of survivors. Nine children (21%) had subnormal eGFR, with no difference between those with and without a history of neonatal AKI. CONCLUSION: Despite therapeutic hypothermia, AKI remains a common complication in infants with HIE and is associated with increased neonatal mortality. Twenty-one per cent of children had subnormal eGFR at 10-12 years, highlighting the need for long-term follow-up of renal function.

Association of traction force and adverse neonatal outcome in vacuum-assisted vaginal delivery: A prospective cohort study.

INTRODUCTION: Traction force is a possible risk factor for adverse neonatal outcome in vacuum extraction delivery, but the knowledge is scarce and further investigation is needed. Our hypothesis was that high-level traction force increases the risk of admission to the neonatal intensive care unit. MATERIAL AND METHODS: The study was a hospital-based prospective cohort study on low- and mid-vacuum extractions at the labor and delivery ward, Karolinska University Hospital, Huddinge, Sweden. Traction forces were measured in 331 women. An electronical handle was used to measure and register traction force. The main exposure variable was high-level traction force (≥75th percentile) during the first three pulls and the primary outcome was admission to the neonatal intensive care unit. Logistic regression was used to estimate the adjusted risk. RESULTS: Among the exposed, 14/84 (16.7%) were admitted to neonatal intensive care, and among the unexposed 10/247 (4%). The crude odds ratio (OR) of admission to the neonatal intensive care unit when exposed to high-level traction force was 4.7, and the adjusted (birthweight, gestational length, cup detachment, number of pulls, duration, duration >15 minutes, mid-cavity fetal head station, failed extraction, indication and parity) OR was 2.85 (95% confidence interval [CI] 1.09-7.48). No significant effect was seen in Apgar scores <7 at 5 minutes or pH <7.1. CONCLUSIONS: High-level traction force may be a risk factor for neonatal complications. Although these results do not mandate any alterations in clinical guidelines, perioperative feedback on traction force may be useful to alert the obstetrician to a timely conversion to cesarean section. To study plausible traction force specific outcomes such as head traumas, a larger sample size is required.

Accuracy of pulse oximetry in preterm and term infants is insufficient to determine arterial oxygen saturation and tension.

AIM: Oxygen saturation is frequently monitored with pulse oximetry to assess vital signs in critically ill patients. Optimally, pulse oximetry closely tracks arterial oxygen tension (PaO2 ), which provides guidance in oxygen titration. We investigated whether monitoring peripheral oxygen saturation (SpO2 ) could accurately guide oxygen titration in newborn infants. METHODS: Twenty seven thousand two hundred thirty seven SpO2 readings were retrospectively paired with arterial oxygen saturation (SaO2 ) and PaO2 results from blood gas analyses performed in infants with arterial catheters in place. RESULTS: SpO2 overestimated SaO2 readings by 2.9 ± 5.8%. When pulse oximetry readings were within the defined oxygen saturation target range, 7809 (20.9%) SaO2 values were below and 2830 (7.6%) exceeded the target range. In 57% of patients, PaO2 levels < 6 kPa was diagnosed while SpO2 readings were > 90%. PaO2  > 11 kPa was recorded in 19% of cases, when SpO2 readings were < 95%. Infants treated with supplemental oxygen showed a threefold increased risk of hypoxaemia compared to infants breathing room air. Sensitivity and specificity for detecting upper and lower target range limits were fair to good. For SpO2 values below 91%, ISO quality criteria were no longer fulfilled. CONCLUSIONS: Based on arterial blood gas analyses as reference, pulse oximetry readings did not fulfil the performance requirements for titrating oxygen in neonatal patients.

Parental viewpoints and experiences of therapeutic hypothermia in a neonatal intensive care unit implemented with Family-Centred Care.

AIMS AND OBJECTIVES: To explore parental experiences of therapeutic hypothermia (TH) in their newborn infant suffering from hypoxic ischaemic encephalopathy following perinatal asphyxia. BACKGROUND: Since more than a decade, newborn infants are treated with TH following perinatal asphyxia to reduce mortality and disabilities and to improve neurological outcome. The infants' body temperature is lowered to 33.5°C for 72 hr, and the infant is usually cared for in an open incubator. The parents are not able to hold their infant skin to skin, which risks causing emotional reactions in parents and a loss of normal parent-infant bonding. DESIGN: A qualitative descriptive design using semi-structured interviews. METHODS: Up to 7 months after the event, interviews were conducted with 14 parents of seven infants who had received TH in a neonatal intensive care unit (NICU) in Sweden. The interviews were transcribed and analysed using framework approach. Findings were reported following the Standard for Reporting Qualitative Research (SRQR) checklist. RESULTS: From the interviews, an overall theme was found: Transition through a life-altering time, and three categories: (a) trepidation about prognosis, (b) transitioning into parenthood supported by the caring philosophy of family-centred care (FCC) and (c) rewarming as a milestone. CONCLUSIONS: Parental experiences of TH are based on the immediate emotions and stress of uncertainty of the infant's prognosis. The values of FCC in the NICU append a natural transitioning into parenthood by parental involvement in nursing care and decisions. The rewarming of the infant is seen as a restart to more or less normal circumstances from the critical period of delivery and TH. RELEVANCE FOR CLINICAL PRACTICE: The management of NICUs should update the awareness of and deepen knowledge about FCC. The emphasis ought to be on adequate information about TH and the values of FCC to parents in the NICU context.

A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia.

OBJECTIVE: To assess the predictive value of a novel magnetic resonance imaging (MRI) score, which includes diffusion-weighted imaging as well as assessment of the deep grey matter, white matter, and cerebellum, for neurodevelopmental outcome at 2 years and school age among term infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia. STUDY DESIGN: This retrospective cohort study (cohort 1, The Netherlands 2008-2014; cohort 2, Sweden 2007-2012) including infants born at >36 weeks of gestational age treated with therapeutic hypothermia who had an MRI in the first weeks of life. The MRI score consisted of 3 subscores: deep grey matter, white matter/cortex, and cerebellum. Primary adverse outcome was defined as death, cerebral palsy, Bayley Scales of Infant and Toddler Development, third edition, motor or cognitive composite scores at 2 years of <85, or IQ at school age of <85. RESULTS: In cohort 1 (n = 97) and cohort 2 (n = 76) the grey matter subscore was an independent predictor of adverse outcome at 2 years (cohort 1, OR, 1.6; 95% CI, 1.3-1.9; cohort 2, OR, 1.4; 95% CI, 1.2-1.6), and school age (cohort 1, OR, 1.3; 95% CI, 1.2-1.5; cohort 2, OR, 1.3; 95% CI, 1.1-1.6). The white matter and cerebellum subscore did not add to the predictive value. The positive predictive value, negative predictive value, and area under the curve for the grey matter subscore were all >0.83 in both cohorts, whereas the specificity was >0.91 with variable sensitivity. CONCLUSION: A novel MRI score, which includes diffusion-weighted imaging and assesses all brain areas of importance in infants with therapeutic hypothermia after perinatal asphyxia, has predictive value for outcome at 2 years of age and at school age, for which the grey matter subscore can be used independently.

Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis.

Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. CONCLUSION: This paper describes the Swedish consensus document produced by those meetings.

Brain Growth Gains and Losses in Extremely Preterm Infants at Term.

Premature exposure to the extrauterine environment negatively affects the brains' developmental trajectory. Our aim was to determine whether extremely preterm (EPT) infants, with no evidence of focal brain lesions, show morphological brain differences when compared with term-born infants. Additionally, we investigated associations between perinatal factors and neuroanatomical alterations. Conventional magnetic resonance imaging was acquired at term-equivalent age (TEA) from 47 EPT infants born before 27 weeks of gestation, and 15 healthy, term-born controls. Automatic segmentation and voxel-based morphometry-Diffeomorphic Anatomical Registration through Exponentiated Lie algebra (DARTEL) were used. Compared with controls, EPT infants displayed global reductions in cortical and subcortical gray matter, brainstem, and an increased cerebrospinal fluid volume. Regionally, they showed decreased volumes of all brain tissues, in particular cortical gray matter. Increased volumes of cortical gray and white matter were observed in regions involved in visual processing. Increasing prematurity, intraventricular hemorrhage grade I-II, and patent ductus arteriosus ligation were associated with decreased volumes and had a particular effect on the cerebellum. Concluding, EPT infants without focal brain lesions had an altered brain growth at TEA that particularly affected the gray matter, and varied when it came to the presence of perinatal risk factors. Brain growth gains in EPT infants may be related to a longer extrauterine experience.

Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia.

AIM: Postnatal hypoglycaemia increases the risk of adverse neurological outcomes in newborn infants, and adequate glucose control requires repetitive and painful blood sampling. This study evaluated a continuous glucose monitoring system (CGMS) that aims to improve glucose control and decrease the frequency of blood samples taken from neonates. METHODS: CGMS sensors, which measure glucose values every five minutes and require calibration twice a day, were placed on 20 infants at risk of hypoglycaemia. The infants also underwent blood glucose sampling, and the blood glucose values were compared with CGMS values six times during the first 30 minutes after sampling. RESULTS: We used 97/264 (37%) of the blood glucose values taken for the CGMS calibration. The highest accuracy, a mean of 0.22 (95% confidence interval 0.13-0.30 mmol/L), was found 15-19 minutes after sampling, due to the calibration process. No significant subcutaneous glucose time lag was detectable. CONCLUSION: The CGMS system was an accurate and feasible method for glucose control, provided earlier detection of hypoglycaemia in newborn infants and reduced their exposure to procedural pain. The delay in calibration in infants was a new finding and needs to be taken into account when comparing CGMS readings to blood glucose values.

Minimal enteral nutrition during neonatal hypothermia treatment for perinatal hypoxic-ischaemic encephalopathy is safe and feasible.

AIM: The safety and efficacy of enteral feeding during hypothermia treatment following hypoxic-ischaemic encephalopathy has not been studied before, resulting in variations in practice. Our study compared the benefits and safety of both early minimal and delayed enteral feeding during hypothermia treatment. METHODS: Our retrospective cohort study, from January 2009 to December 2011, compared a Swedish cohort, who received early enteral feeding during hypothermia, and a UK cohort, who received delayed enteral feeding. RESULTS: In Sweden (n = 51), enteral feeds were initiated at a median of 23.6 h and full oral feeding was achieved at 9 days (range 3-23). In the UK (n = 34), the equivalent figures were 100 h and 8 days (range 3-13) (p = 0.01). Both groups achieved enteral feeding at a median 6 days. The median length of hospital stay was 13 days in Sweden and 10 days in the UK (p = 0.04). More babies were fully breastfeeding or breastfed and bottle-fed at discharge in Sweden (85%) than the UK (67%) (p = 0.08). There were no significant differences between the two groups regarding adverse events. CONCLUSION: Early minimal enteral feeding during hypothermia proved feasible, with no significant complications. Delayed enteral feeding did not affect time to full enteral feeding.

Sex differences in outcome and associations with neonatal brain morphology in extremely preterm children.

OBJECTIVE: To investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology. STUDY DESIGN: A population-based cohort of infants born at <27 weeks gestation underwent magnetic resonance imaging (MRI) at term equivalent age (n = 107). Voxel-based morphometry (n = 27) and tract-based spatial statistics (n = 29) were performed in infants with normal MRI findings. Neurologic and developmental assessment (using the Bayley Scales of Infant and Toddler Development-Third Edition [BSITD-III]) was performed at 30 months corrected age (n = 91). RESULTS: EPT boys had lower mean cognitive composite scores (P = .03) and lower mean language composite scores (P = .04) compared with EPT girls. Rates of cerebral palsy were similar in the 2 sexes. No perinatal factor explained the variance in outcomes. Visual inspection of T1- and T2-weighted MRI images found that delayed myelination was found more frequently in boys, whereas cerebellar abnormalities were more common in girls. In the subgroup of children with normal MRI findings (n = 27), boys had poorer cognitive function (P = .015) and language function (P = .008), despite larger volumes of cerebellar tissue (P = .029). In boys, cerebellar volume was positively correlated with BSITD-III cognitive and motor scores (P = .04 for both). In girls, white matter volume (P = .02) and cortical gray matter volume (P = .03) were positively correlated with BSITD-III language score. At the regional level, significant correlations with outcomes were found only in girls. CONCLUSION: Cognitive and language outcomes at age 30 months were poorer in boys. Sex-related differences were observed on neonatal structural MRI, including differences in the patterns of correlations between brain volumes and developmental scores at both global and regional levels.

Early development of spatial patterns of power-law frequency scaling in FMRI resting-state and EEG data in the newborn brain.

Recent studies have revealed spatial and functional relations in the temporal dynamics of resting-state functional magnetic resonance imaging (rs-fMRI) or electroencephalography (EEG) signals recorded in the adult brain. By modeling the frequency power spectrum of resting-state brain signals with a power-law function 0(f)α1/fα, the power-law exponent α has been shown to relate to the connectivity patterns of spontaneous brain activity that forms so-called rs-fMRI networks in the human adult brain. Here, we present an analysis of the dynamic properties of rs-fMRI and EEG signals acquired both in the newborn and adult brain, and we demonstrate frequency scaling of a power-law kind for orders of magnitude in the hemodynamic (0.01-0.15 Hz) and the electrical (0.2-30 Hz) domain. We show that the spatial segregation of resting-state dynamics of intrinsic fMRI signals in terms of the power-law exponent α is closely related to previously delineated resting-state neuronal architecture that encompasses primary sensory cortices and associate cortex in newborns. Moreover, the spatial profiles of differences in temporal dynamics for rs-fMRI signals could also be observed in EEG measurements in the newborn brain, albeit at a coarser spatial scale, with larger power-law exponents in occipital and parietal cortices compared with signals from the frontal brain.

White matter microstructure is influenced by extremely preterm birth and neonatal respiratory factors.

AIM: The aim of this study was to investigate whether prematurity per se or perinatal risk factors explain altered brain structure after preterm birth, in extremely preterm (EPT) infants without focal brain lesions. METHODS: A population-based cohort of 58 EPT infants [gestational age (GA) <27 + 0 weeks] was examined with diffusion magnetic resonance imaging at term-equivalent age and compared with 14 term-born controls. Associations of diffusion measures with prematurity and neonatal risk factors were explored. Data were analysed with tract-based spatial statistics (TBSS) for whole-brain analysis and region-of-interest (ROI) analysis. RESULTS: Whole-brain analyses showed lower fractional anisotropy (FA) and higher mean diffusivity (MD) in several white matter (WM) tracts in the preterms, which was essentially confirmed by ROI analyses. Within the preterm GA range (23 + 0 to 26 + 6 weeks), GA at birth was not significantly associated with diffusion measures. Bronchopulmonary dysplasia predicted lower FA in the corpus callosum and right inferior longitudinal fasciculus; mechanical ventilation >2 days was predictive of higher MD in the right external capsule. CONCLUSION: White matter microstructure is influenced by preterm birth and by neonatal respiratory factors, whereas the degree of prematurity within the EPT range appears to be of less importance.

EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden.

AIM: The aim of this study was to investigate differences in mortality up to 1 year of age in extremely preterm infants (before 27 weeks) born in seven Swedish healthcare regions. METHODS: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated. RESULTS: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26 weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24 weeks. Among 707 infants born alive, regional differences were found both in mortality before 12 h and in the 365-day mortality rate for the subgroup (22-24 weeks) and for the total group (22-26 weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12 h or for infants born at 25 weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions. CONCLUSION: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

EEG response to a high volume (1.5 mL/kg) caudal block in infants less than 3 months.

INTRODUCTION: The substantial compression of the dural sac and the subsequent cranial shift of cerebrospinal fluid caused by a high-volume caudal block has been shown to significantly but transiently reduce cerebral blood flow. The aim of the present study was to determine whether this reduction in cerebral perfusion is significant enough to alter brain function, as assessed by electroencephalography (EEG). METHODS: Following ethics approval and parental informed consent, 11 infants (0-3 months) scheduled to undergo inguinal hernia repair were included in the study. EEG electrodes (using nine electrodes according to the 10-20 standard) were applied following anesthesia induction. Following a 5 min baseline period, a caudal block was performed (1.5 mL/kg), whereafter the EEG, hemodynamic, and cerebral near-infrared spectroscopy responses were followed during a 20 min observation period that was divided into four 5 min segments. Special attention was given to alterations in delta power activity since this may indicate cerebral ischemia. RESULTS: All 11 infants displayed transient EEG changes, mainly represented by increased relative delta power, during the initial 5-10 min postinjection. The observed changes had returned close to baseline values 15 min postinjection. Heart rate and blood pressure remained stable throughout the study. CONCLUSION: A high-volume caudal block appears to increase intracranial pressure, thereby reducing cerebral blood flow, to the extent that it transiently will affect cerebral function as assessed by EEG (increased delta power activity) in approximately 90% of small infants. TRIAL REGISTRATION NUMBER: ACTRN12620000420943.

Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.

IMPORTANCE: Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. OBJECTIVE: To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. MAIN OUTCOMES AND MEASURES: Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. RESULTS: At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). CONCLUSIONS AND RELEVANCE: Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.

Outcome at early school age and adolescence after hypothermia-treated hypoxic-ischaemic encephalopathy: an observational, population-based study.

OBJECTIVE: We aimed to describe long-term outcomes following hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). DESIGN: Prospective, population-based observational study. SETTING: Tertiary level neonatal intensive care units and neonatal outpatient clinic, Karolinska University Hospital, Stockholm, Sweden. PATIENTS: Sixty-six infants treated with TH due to HIE between 2007 and 2009. INTERVENTIONS: At 6-8 years and 10-12 years of age, children were assessed using a standardised neurological examination, the Movement Assessment Battery for Children, Second Edition (MABC-2) and the Wechsler Intelligence Scales for Children IV/V. Parents completed the Five-to-Fifteen (FTF) questionnaire. MAIN OUTCOME MEASURES: Adverse outcome among survivors was defined as cerebral palsy (CP), epilepsy, hearing or visual impairment, full-scale IQ (FSIQ) below 85, attention deficit disorder with/without hyperactivity, autism spectrum disorder or developmental coordination disorder. RESULTS: Mortality was 12%. Seventeen per cent of survivors developed CP. Mean FSIQ was normal in children without major neuromotor impairment. Assessment in early adolescence revealed emerging deficits in 26% of children with a previously favourable outcome. The proportion of children exhibiting executive difficulties increased from 7% to 19%. This was reflected also by a significantly increased proportion of children with an FTF score >90th percentile compared with norms in early adolescence. The proportion of children with an MABC-2 score ≤5th percentile was also significantly increased compared with norms. CONCLUSIONS: Survivors without major neuromotor impairment have normal intelligence. The incidence of executive difficulties appears to be increased in this patient population. More subtle difficulties may go undetected at early school-age.

Long-term motor development after hypothermia-treated hypoxic-ischaemic encephalopathy.

AIMS: To describe longitudinal motor development in children treated with therapeutic- hypothermia (TH) due to neonatal hypoxic-ischaemic encephalopathy (HIE) and to explore motor functioning in early adolescence. MATERIAL AND METHODS: Children treated with TH due to HIE during 2007-2009, in Stockholm, participated in a prospective follow-up study. Motor development was assessed on four occasions, reported as percentiles and at mean ages. Alberta Infant Motor Scale was used at 0.35 years of age, Bayley Scales of Infant and Toddler Development-III at 2.1 years and Movement Assessment Battery for Children (MABC-2) at 7.3 and 11.1 years of age. MABC-2 Checklist was completed by parents at 7.3 and 11.1 years of age. General cognition was assessed using Wechsler Intelligence Scales for Children Fifth Edition (WISC-V). RESULTS: Thirty-one percent (14/45) of the children had a motor score ≤ 15th percentile, indicating risk of motor difficulties at 11.1 years of age, and simultaneously the scores from parents of 52% (23/44), indicating risk of motor difficulties in the everyday context. These children had significantly lower motor percentile at 2.1 years of age, but within the normal range. Longitudinal motor development displayed a weak association with WISC-V Full Scale IQ (rs0.38, p = 0.013). CONCLUSION: Among survivors of hypothermia-treated HIE free of moderate/severe cerebral palsy, a third had MABC-2 scores indicating risk of motor difficulties at 11.1 years of age. As motor difficulties became more apparent over time, we suggest that children treated with TH due to neonatal HIE should be followed into at least middle school age.