Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease.

BACKGROUND: Fetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. OBJECTIVES: This study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. METHODS: In this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. RESULTS: A total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). CONCLUSIONS: Among fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

Neurodevelopmental outcomes at 18 months of children diagnosed with CHD compared to children born very preterm.

OBJECTIVE: To compare neurodevelopmental outcomes and parent behaviour ratings of children born term with CHD to children born very preterm. METHODS: A clinical research sample of 181 children (CHD [n = 81]; very preterm [≤32 weeks; n = 100]) was assessed at 18 months. RESULTS: Children with CHD and born very preterm did not differ on Bayley-III cognitive, language, or motor composite scores, or on expressive or receptive language, or on fine motor scaled scores. Children with CHD had lower ross motor scaled scores compared to children born very preterm (p = 0.047). More children with CHD had impaired scores (<70 SS) on language composite (17%), expressive language (16%), and gross motor (14%) indices compared to children born very preterm (6%; 7%; 3%; ps < 0.05). No group differences were found on behaviours rated by parents on the Child Behaviour Checklist (1.5-5 years) or the proportion of children with scores above the clinical cutoff. English as a first language was associated with higher cognitive (p = 0.004) and language composite scores (p < 0.001). Lower median household income and English as a second language were associated with higher total behaviour problems (ps < 0.05). CONCLUSIONS: Children with CHD were more likely to display language and motor impairment compared to children born very preterm at 18 months. Outcomes were associated with language spoken in the home and household income.

Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. STUDY DESIGN: This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18 months of age. RESULTS: Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48 hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P < .001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P < .001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P < .001). CONCLUSION: The present study shows the complementary utility of cUS in the first 48 hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

The truth Hertz-synchronization of electroencephalogram signals with physiological waveforms recorded in an intensive care unit.

Objective.The ability to synchronize continuous electroencephalogram (cEEG) signals with physiological waveforms such as electrocardiogram (ECG), invasive pressures, photoplethysmography and other signals can provide meaningful insights regarding coupling between brain activity and other physiological subsystems. Aligning these datasets is a particularly challenging problem because device clocks handle time differently and synchronization protocols may be undocumented or proprietary.Approach.We used an ensemble-based model to detect the timestamps of heartbeat artefacts from ECG waveforms recorded from inpatient bedside monitors and from cEEG signals acquired using a different device. Vectors of inter-beat intervals were matched between both datasets and robust linear regression was applied to measure the relative time offset between the two datasets as a function of time.Main Results.The timing error between the two unsynchronized datasets ranged between -84 s and +33 s (mean 0.77 s, median 4.31 s, IQR25-4.79 s, IQR75 11.38s). Application of our method improved the relative alignment to within ± 5ms for more than 61% of the dataset. The mean clock drift between the two datasets was 418.3 parts per million (ppm) (median 414.6 ppm, IQR25 411.0 ppm, IQR75 425.6 ppm). A signal quality index was generated that described the quality of alignment for each cEEG study as a function of time.Significance.We developed and tested a method to retrospectively time-align two clinical waveform datasets acquired from different devices using a common signal. The method was applied to 33,911h of signals collected in a paediatric critical care unit over six years, demonstrating that the method can be applied to long-term recordings collected under clinical conditions. The method can account for unknown clock drift rates and the presence of discontinuities caused by clock resynchronization events.

Pearls & Oy-sters: Genetic Epilepsy: An Important Cause of Neonatal Seizures in Infants With Complex Congenital Heart Disease.

Genetic epilepsies, such as KCNQ2 gene variants, though uncommon, are potential causes of neonatal seizures in infants with complex congenital heart disease (CHD). KCNQ2-related seizures commonly present as tonic posturing with autonomic changes and a distinctive amplitude-integrated EEG (aEEG) pattern with increase in amplitude immediately followed by background suppression. Seizures are typically refractory to commonly used antiepileptics in this age group and respond best to sodium channel blockers such as carbamazepine and fosphenytoin. We report the cases of two neonates with complex CHD who presented with seizures secondary to KCNQ2 gene variation and how early recognition of clinical and EEG features led to early treatment and improved seizure burden. When investigating the etiology of neonatal seizures in the perioperative complex cardiac infant, genetic etiologies, such as KCNQ2 variants should be considered, particularly in the absence of clinical exam and neuroimaging features consistent with brain injury. These two cases highlight the importance of a precision medicine approach utilizing clinical examination and seizure semiology, bedside aEEG monitoring, genetic testing, and targeted treatments to improve patient care and outcomes.

The association between parent stress, coping and mental health, and neurodevelopmental outcomes of infants with congenital heart disease.

Caring for the complex needs of a child with congenital heart disease (CHD) can place significant burden on the family. Parent mental health and coping have important influences on resilience and neurodevelopmental outcomes in children with CHD. Objectives: To describe the uptake of a cardiac neurodevelopmental program (CNP), examine parent mental health and coping specific to parenting a child with CHD, and explore the relationship between parent mental health and child neurodevelopmental outcomes. Method: Implementation and uptake of the CNP was examined, and forty-four parents of children with CHD completed the DASS and RSQ-CHD. Results: The CNP showed significant uptake in follow-up and interventions offered including 100% completed brain MRIs of eligible patients, 35% increase in neonatal neurology consults, and 100% of families counselled on neurodevelopmental outcomes. A significant proportion of parents endorsed moderate/severe levels of anxiety (25%), depression (20%), and CHD-specific stress. Parents predominantly engaged in secondary control engagement coping (F(2,64)=75.04, p<.001, ηp2=.70). Secondary control engagement coping was associated with lower parent total stress (r=-.48, p=.006) and anxiety (r=-.47, p=.009). Higher parent stress was associated with higher anxiety (r=.45, p=.016), depression (r=.37, p=.05), more severe types of CHD (r=.35, p=.048), older child age (t(30)= -2.33, p=.03), and lower child cognitive scores (r=-.37, p=.045). More severe types of CHD were associated with lower language scores (F(3,35)=3.50, p=.03). Conclusions: This study highlights the relationship between parent mental health and early child cognitive outcomes in CHD and helps inform models of psychological care to reduce family burden and improve child outcomes.