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.

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.

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.

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.

Endotracheal intubation performance at a large obstetric hospital delivery room, Hanoi, Vietnam.

Introduction: Intrapartum-related events account for nearly 700,000 neonatal deaths globally yearly. Endotracheal intubation is a cornerstone in preventing many of these deaths, but it is a difficult skill to acquire. Previous studies have described intubation performances in high-income countries, but data from low- and middle-income countries are lacking. We aimed to assess the performance of delivery room intubation in a lower middle-income country. Methods: This prospective observational study was conducted at the Phu San Hanoi Hospital, Vietnam, from September 2020 to January 2021. Video cameras were positioned above the resuscitation tables and data were extracted using adopted software (NeoTapAS). All neonates requiring positive pressure ventilation were included. Our main variables of interest were time to first intubation attempt, first intubation attempt duration, and successful first intubation attempt. Results: 18,107 neonates were born during the five months. Of these, 75 (0.4%) received positive pressure ventilation, and 36 (0.2%) required endotracheal intubation of whom 24 were captured on video. The median time to the first intubation attempt was 252 seconds (range 91-771 seconds), the median first attempt duration was 49 seconds (range 10-105 seconds), and the first attempt success rate was 75%. Conclusion: Incidences of positive pressure ventilation and endotracheal intubation were low in comparison to global estimates. Three out of four intubations were successful at the first attempt and the procedural duration was often longer than recommended. Future studies should focus on how to achieve and maintain intubation skills and could include considering alternative devices for airway management at birth.

Incidence of Intrapartum-Related Events at the Largest Obstetric Hospital in Hanoi, Vietnam: A Retrospective Study.

Every year, 2.4 million neonates die during their first month of life and even more suffer permanent injury. The main causes are intrapartum-related events, prematurity, and infection, with sub-Saharan Africa and southern Asia being the worst affected regions. With a focus on intrapartum-related events, we aimed to assess the neonatal demographic characteristics, clinical management, and outcomes among neonates born at the largest obstetric hospital in Hanoi, Vietnam. This was a retrospective cross-sectional study that included all the inborn neonates in November 2019, which was selected as a representative month. A total of 4554 neonates were born during the study period. Of these, 1.0% (n = 44) were stillbirths, 0.15% (n = 7) died in hospital, 0.61% (n = 28) received positive pressure ventilation at birth, and 0.15% (n = 7) were diagnosed with hypoxic ischemic encephalopathy. A total of 581 (13%) neonates were admitted to the neonatal unit, among which the most common diagnoses were prematurity (37%, n = 217) and infection (15%, n = 89). Except for the intrapartum-related events, our findings are consistent with the previously documented data on neonatal morbidity. The intrapartum-related events, however, were surprisingly low in number even in comparison to high-income countries. Research on the current clinical practice at Phu San Hanoi Hospital may bring further clarity to identify the success factors.

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.

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.).

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 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.

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.

Neonatal resuscitation using a supraglottic airway device for improved mortality and morbidity outcomes in a low-income country: study protocol for a randomized trial.

BACKGROUND: Intrapartum-related death is the third leading cause of under-5 mortality. Effective ventilation during neonatal resuscitation has the potential to reduce 40% of these deaths. Face-mask ventilation performed by midwives is globally the most common method of resuscitating neonates. It requires considerable operator skills and continuous training because of its complexity. The i-gel® is a cuffless supraglottic airway which is easy to insert and provides an efficient seal that prevents air leakage; it has the potential to enhance performance in neonatal resuscitation. A pilot study in Uganda demonstrated that midwives could safely resuscitate newborns with the i-gel® after a short training session. The aim of the present trial is to investigate whether the use of a cuffless supraglottic airway device compared with face-mask ventilation during neonatal resuscitation can reduce mortality and morbidity in asphyxiated neonates. METHODS: A randomized phase III open-label superiority controlled clinical trial will be conducted at Mulago Hospital, Kampala, Uganda, in asphyxiated neonates in the delivery units. Prior to the intervention, health staff performing resuscitation will receive training in accordance with the Helping Babies Breathe curriculum with a special module for training on supraglottic airway insertion. A total of 1150 to 1240 babies (depending on cluster size) that need positive pressure ventilation and that have an expected gestational age of more than 34 weeks and an expected birth weight of more than 2000 g will be ventilated by daily unmasked randomization with a supraglottic airway device (i-gel®) (intervention group) or with a face mask (control group). The primary outcome will be a composite outcome of 7-day mortality and admission to neonatal intensive care unit (NICU) with neonatal encephalopathy. DISCUSSION: Although indications for the beneficial effect of a supraglottic airway device in the context of neonatal resuscitation exist, so far no large studies powered to assess mortality and morbidity have been carried out. We hypothesize that effective ventilation will be easier to achieve with a supraglottic airway device than with a face mask, decreasing early neonatal mortality and brain injury from neonatal encephalopathy. The findings of this trial will be important for low and middle-resource settings where the majority of intrapartum-related events occur. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT03133572 . Registered April 28, 2017.

Early prediction of unilateral cerebral palsy in infants with asymmetric perinatal brain injury - Model development and internal validation.

BACKGROUND: Early diagnosis of unilateral cerebral palsy is important after asymmetric perinatal brain injury (APBI). Our objective is to estimate the risk of unilateral cerebral palsy (UCP) in infants with APBI during the first months of life using neuroimaging and clinical assessment. PATIENTS AND METHODS: Prognostic multivariable prediction modeling study including 52 infants (27 males), median gestational age 39.3 weeks with APBI from Sweden (n = 33) and the Netherlands (n = 19). INCLUSION CRITERIA: (1) neonatal MRI within one month after term equivalent age (TEA), (2) Hand Assessment for Infants (HAI) between 3.5 and 4.5 months of (corrected) age. UCP was diagnosed ≥24 months of age. Firth regression with cross-validation was used to construct and internally validate the model to estimate the risk for UCP based on the predictors corticospinal tract (CST) and basal ganglia/thalamus (BGT) involvement, contralesional HAI Each hand sum score (EaHS), gestational age and sex. RESULTS: UCP was diagnosed in 18 infants (35%). Infants who developed UCP more often had involvement of the CST and BGT on neonatal MRI and had lower contralesional HAI EaHS compared to those who did not develop UCP. The final model showed excellent accuracy for UCP prediction between 3.5 and 4.5 months (area under the curve, AUC = 0.980; 95% CI 0.95-1.00). CONCLUSIONS: Combining neonatal MRI, the HAI, gestational age and sex accurately identify the prognostic risk of UCP at 3.5-4.5 months in infants with APBI.

A Novel Scoring System for Term-Equivalent-Age Cranial Ultrasound in Extremely Preterm Infants.

The role of term-equivalent-age (TEA) cranial ultrasound (cUS) in predicting outcome in preterm infants is increasingly being recognized. However, a detailed quantitative scoring system that allows comparison of groups and comparison with TEA magnetic resonance imaging (MRI) scoring systems is lacking. Eighty-four extremely preterm infants underwent cUS and MRI at TEA. Cranial US was evaluated using a novel detailed scoring system. Agreement between cUS and MRI scores was good (Spearman's ρ = 0.51, p < 0.001). Outcome at 30 mo corrected was assessed in 66 of 84 preterm and 85 term-born infants. Sensitivity was the same for cUS and MRI in prediction of cerebral palsy (75%) and severe cognitive delay (100%); the specificity was slightly higher for MRI (cerebral palsy: 97% vs. 90%, severe cognitive delay: 95% vs. 90%). The proposed novel cUS scoring system is a helpful tool in quantitative assessment of cUS at TEA and prediction of outcome at 30 mo.

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171.

MAGDALENA: study protocol of a randomised, placebo-controlled trial on cognitive development at 2 years of age in children exposed to SSRI in utero.

INTRODUCTION: Ten per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy. METHODS AND ANALYSIS: MAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9-21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups. ETHICS AND DISSEMINATION: This randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public. TRIAL REGISTRATION NUMBER: EudraCT2013-004444-31; Pre-results.