Deep Learning to Optimize Magnetic Resonance Imaging Prediction of Motor Outcomes After Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Magnetic resonance imaging (MRI) is the gold standard for outcome prediction after hypoxic-ischemic encephalopathy (HIE). Published scoring systems contain duplicative or conflicting elements. METHODS: Infants ≥36 weeks gestational age (GA) with moderate to severe HIE, therapeutic hypothermia treatment, and T1/T2/diffusion-weighted imaging were identified. Adverse motor outcome was defined as Bayley-III motor score <85 or Alberta Infant Motor Scale <10th centile at 12 to 24 months. MRIs were scored using a published scoring system. Logistic regression (LR) and gradient-boosted deep learning (DL) models quantified the importance of clinical and imaging features. The cohort underwent 80/20 train/test split with fivefold cross validation. Feature selection eliminated low-value features. RESULTS: A total of 117 infants were identified with mean GA = 38.6 weeks, median cord pH = 7.01, and median 10-minute Apgar = 5. Adverse motor outcome was noted in 23 of 117 (20%). Putamen/globus pallidus injury on T1, GA, and cord pH were the most informative features. Feature selection improved model accuracy from 79% (48-feature MRI model) to 85% (three-feature model). The three-feature DL model had superior performance to the best LR model (area under the receiver-operator curve 0.69 versus 0.75). CONCLUSIONS: The parsimonious DL model predicted adverse HIE motor outcomes with 85% accuracy using only three features (putamen/globus pallidus injury on T1, GA, and cord pH) and outperformed LR.

Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia.

OBJECTIVE: To review developmental outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). STUDY DESIGN: Neonates ≥35 weeks' gestation with mild HIE/TH (TH group, n = 30) were matched with healthy term-born infants (control group, n = 30) and reviewed for the presence and severity of magnetic resonance imaging (MRI)-detected neurological injury. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development (BSID). RESULTS: MRI injury was present in 13/30 (43.3%) neonates (11 mild, 1 moderate, and 1 severe injuries) in the TH group. The mean (standard deviation [SD]) corrected age at BSID III was 29.3 (3.9) months in the controls compared with 14.7 (3.9) months in the TH group (p < 0.01). The mean (SD) cognitive, language, and motor composite scores in neonates in the TH group (n = 16, 53.3%) and control groups (n = 30, 100%) were 99.4 (17.1) versus 93.0 (12.3), (p = 0.15), 89.5 (15.5) versus 100.2 (18.4), (p = 0.054), and 93.1 (15.4) versus 100.8 (16.3) (p = 0.13), respectively. CONCLUSION: Developmental outcomes of neonates with mild HIE/TH were similar to healthy, term-born neonates.

Re-examining the arterial cord blood gas pH screening criteria in neonatal encephalopathy.

OBJECTIVE: Screening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH ≤7.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate/severe encephalopathy. DESIGN, SETTING, PATIENTS: Infants born at a single centre between 2008 and 2015, who were ≥36 weeks, had no congenital anomalies and had a cABG pH ≤7.10 were identified for a retrospective cohort study. Maternal/perinatal and patient factors were collected. RESULTS: 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35/85 infants with pH <7.00 and 34/327 infants with pH between 7.00 and 7.10 had moderate/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5/35 and 13/34 infants in the two pH groups, respectively.A cABG pH threshold of ≤7.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods. CONCLUSION: Universal cord blood gas screening with a pH threshold ≤7.10 and mandatory encephalopathy examination results in greater detection of infants with moderate/severe encephalopathy and timely initiation of therapeutic hypothermia.

A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. OBJECTIVES: To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24 months. MATERIALS AND METHODS: MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24 months. Data were analyzed using univariate and multivariate linear and logistic regression. RESULTS: Fifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. CONCLUSION: A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18-24 months in neonates with HIE.

Safety and Short-Term Outcomes of Therapeutic Hypothermia in Preterm Neonates 34-35 Weeks Gestational Age with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To evaluate the safety and short-term outcomes of preterm neonates born at 34-35 weeks gestation with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. STUDY DESIGN: Medical records of preterm neonates born at 34-35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short-term safety outcomes and the presence, severity (mild, moderate, severe), and patterns of brain injury on magnetic resonance imaging were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. RESULTS: Thirty-one preterm and 32 term neonates were identified. Therapeutic hypothermia-associated complications were seen in 90% of preterm infants and 81.3% of term infants (P = .30). In the preterm infants, hyperglycemia (58.1% vs31.3%, P = .03) and rewarming before completion of therapeutic hypothermia (19.4% vs 0.0%, P = .009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs 0%, P = .04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (P = .07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs 25.0%, P = .001). CONCLUSIONS: Therapeutic hypothermia in infants born at 34-35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants.

A novel method for assessing cerebral autoregulation in preterm infants using transfer function analysis.

BACKGROUND: Autoregulatory dysfunction is an important contributor to brain injury in premature infants, particularly intraventricular hemorrhage (IVH). The autoregulatory system acts as a filter that dampens the systemic blood flow to follow a normal cerebral perfusion profile. METHODS: Simultaneous arterial blood pressure and cerebral near-infrared spectroscopy (NIRS) data were collected from infants born before 28 wk estimated gestational age. The resulting data were preprocessed and then divided into nonoverlapping 20-min epochs. The transfer function estimate was calculated to determine dampening ability. RESULTS: Sixty-two infants were prospectively recruited with a mean estimated gestational age of 25.4 ± 1.3 wk and birth weight of 832 ± 199 g. 67% were male, 24/62 had IVH, 17/62 received dopamine, 47/62 had antenatal steroid exposure, and 22/62 received fentanyl.Advancing estimated gestational age and birth weight z-score predicted stronger dampening while African-American race and IVH of any grade predicted weaker dampening. CONCLUSION: This preliminary report suggests an impairment in dampening ability associated with immaturity, decreased birth weight z-score, and African-American race. Decreased dampening is also associated with IVH, although these results cannot distinguish between decreased dampening as an antecedent or sequela of IVH. These observations should be studied in a larger sample.

Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial.

BACKGROUND: The impact of treating electrographic seizures in hypoxic ischemic encephalopathy (HIE) is unknown. METHODS: Neonates ≥36 weeks with moderate or severe HIE were randomly assigned to either treatment of electrographic seizures alone (ESG) or treatment of clinical seizures (CSG). Conventional EEG video was monitored in both groups for up to 96 hours. Cumulative electrographic seizure burden (SB) was calculated in seconds and converted to log units for analysis. MRI scans were scored for severity of brain injury. Infants underwent neurodevelopmental evaluation at 18 to 24 months. Statistical analyses were performed by using SAS 9.3 version (SAS Institute, Inc, Cary, NC). RESULTS: Thirty-five of 69 neonates (51%) who were randomly assigned and included in the study developed seizures (15 in ESG and 20 in CSG). Excluding infants with status epilepticus, median SB (interquartile range) in seconds in ESG (n = 10) was lower than in CSG (n = 16) (449 [113-2070] vs 2226 [760-7654]; P = .02). ESG had fewer seizures with shorter time to treatment (P = .04). Twenty-four of 30 (80%) surviving infants with seizures underwent neurodevelopmental evaluation at 18 to 24 months. Increasing SB in the combined cohort was significantly associated with higher brain injury scores (P < .03) and lower performance scores across all 3 domains on BSID III (P = .03). CONCLUSIONS: In neonates with HIE, EEG monitoring and treatment of electrographic seizures results in significant reduction in SB. SB is associated with more severe brain injury and significantly lower performance scores across all domains on BSID III.