Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease.

OBJECTIVE: Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. METHODS: From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. RESULTS: HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery. INTERPRETATION: Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157.

Diagnostic Yield of Cardiac Biomarker Testing in Predicting Cardiac Disease and Multisystem Inflammatory Syndrome in Children in the Pandemic Era.

OBJECTIVES: This study aimed to assess whether elevations in cardiac biomarkers are associated with pediatric cardiac diagnoses in the era of COVID-19 and multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: This single-center retrospective study analyzed children with a troponin drawn in the emergency department or inpatient unit between April 21 and December 31, 2020. The primary outcome was the presence of a cardiac diagnosis or MIS-C. Relationships among demographics, complaint, cardiac diagnostics, and cardiac biomarkers were analyzed. RESULTS: Four hundred eighty-six patients (mean ± SD; age 13.1 ± 7.8 years; 46.7% women) met inclusion criteria, for whom a cardiac diagnosis (excluding MIS-C) was made in 27 (5.6%) patients, with MIS-C diagnosed in 14 (2.9%) patients. The sensitivity and specificity of an elevated initial high-sensitivity troponin T (hsTropT) value (>14 ng/L) in predicting the composite outcome of a cardiac diagnosis or MIS-C were 54% and 89%, respectively. Four percent of patients with negative initial troponin values were found to have a cardiac diagnosis or MIS-C. Multivariable regression analysis demonstrated that elevated hsTropT (>14 ng/L; odds ratio [OR] [95% confidence interval]: 4.9 [1.70-14.0]) and elevated N-terminal pro B-type natriuretic peptide values (>500 pg/mL; 6.4 [2.01-20.1]) were associated with increased odds of a cardiac diagnosis or MIS-C. CONCLUSIONS: Children with elevated cardiac biomarkers have increased odds of a cardiac diagnosis or MIS-C and warrant workup regardless of indication for testing. Although a negative hsTropT may reassure providers, further investigation is critical in developing algorithms to reliably exclude cardiac disease.

Workup for Perinatal Stroke Does Not Predict Recurrence.

BACKGROUND AND PURPOSE: Perinatal stroke, including neonatal and presumed perinatal presentation, represents the age in childhood in which stroke occurs most frequently. The roles of thrombophilia, arteriopathy, and cardiac anomalies in perinatal ischemic stroke are currently unclear. We took a uniform approach to perinatal ischemic stroke evaluation to study these risk factors and their association with recurrent stroke. METHODS: We reviewed records of perinatal stroke patients evaluated from August 2008 to February 2016 at a single referral center. Demographics, echocardiography, arterial imaging, and thrombophilia testing were collected. Statistical analysis was performed using Fisher exact test. RESULTS: Across 215 cases, the median follow-up was 3.17 years (1.49, 6.46). Females comprised 42.8% of cases. Age of presentation was neonatal (110, 51.2%) or presumed perinatal (105, 48.8%). The median age at diagnosis was 2.9 days (interquartile range, 2.0-9.9) for neonatal stroke and 12.9 months (interquartile range, 8.7-32.8) for presumed perinatal stroke. Strokes were classified as arterial (149, 69.3%), venous (60, 27.9%), both (4, 1.9%), or uncertain (2, 0.9%) by consensus imaging review. Of the 215 cases, there were 6 (2.8%) recurrent ischemic cerebrovascular events. Abnormal thrombophilia testing was not associated with recurrent stroke, except for a single patient with combined antithrombin deficiency and protein C deficiency. After excluding venous events, 155 patients were evaluated for arteriopathy and cardioembolic risk factors; neither was associated with recurrent stroke. Positive family history of thrombosis was not predictive of abnormal thrombophilia testing. CONCLUSIONS: Thrombophilia, arteriopathy, or cardioembolic risk factors were not predictive of recurrent events after perinatal stroke. Thrombophilia evaluation in perinatal stroke should only rarely be considered.

Prevalence of Symptoms of Anxiety, Depression, and Post-traumatic Stress Disorder in Parents and Children Following Pediatric Stroke.

Post-traumatic stress disorder (PTSD), anxiety, and depression are seen in parents and children following critical illness. Whether this exists in parents and children following pediatric stroke has not been thoroughly studied. We examined emotional outcomes in 54 mothers, 27 fathers, and 17 children with stroke. Parents of children 0-18 years and children 7-18 years who were within 2 years of stroke occurrence were asked to complete questionnaires to determine their emotional outcomes. Of participating mothers, 28% reported PTSD, 26% depression, and 4% anxiety; in fathers, 15% reported PTSD, 24% depression, and none reported anxiety. Further, children reported significant emotional difficulty, with 24% having depression, 14% anxiety, and 6% PTSD by self-report ratings. Maternal PTSD, anxiety and depression, and paternal anxiety were all negatively associated with the child's functional outcome. Clinically significant anxiety (based on clinical thresholds) was not found in fathers; however, continuous scores were still analyzed for association between subclinical anxiety and functional outcome, which revealed a statistically significant association between more reported symptoms and higher Recovery and Recurrence Questionnaire scores. Prevalence of PTSD and depression are greater in parents compared to the general population in this preliminary study.

Indomethacin induced ductus arteriosus closure in midgestation fetus.

This article reports a rare but potentially serious complication of ductus arteriosus closure resulting from second-trimester indomethacin exposure. Serial echocardiograms are indicated to monitor for development of right heart dysfunction and to ensure delivery prior to the onset of right heart failure and hydrops fetalis.