Shabnam Peyvandi

Association of prenatal diagnosis of critical congenital heart disease with postnatal brain development and the risk of brain injury

IMPORTANCE The relationship of prenatal diagnosis of critical congenital heart disease (CHD) with brain injury and brain development is unknown. Given limited improvement of CHD outcomes with prenatal diagnosis, the effect of prenatal diagnosis on brain health may reveal additional benefits. OBJECTIVE To compare the prevalence of preoperative and postoperative brain injury and the trajectory of brain development in neonates with prenatal vs postnatal diagnosis of CHD. DESIGN, SETTING, AND PARTICIPANTS Cohort study of term newborns with critical CHD recruited consecutively from 2001 to 2013 at the University of California, San Francisco and the University of British Columbia. Term newborns with critical CHD were studied with brain magnetic resonance imaging preoperatively and postoperatively to determine brain injury severity and microstructural brain development with diffusion tensor imaging by measuring fractional anisotropy and the apparent diffusion coefficient. Comparisons of magnetic resonance imaging findings and clinical variables were made between prenatal and postnatal diagnosis of critical CHD. A total of 153 patients with transposition of the great arteries and single ventricle physiology were included in this analysis. MAIN OUTCOMES AND MEASURES The presence of brain injury on the preoperative brain magnetic resonance imaging and the trajectory of postnatal brain microstructural development. RESULTS Among 153 patients (67% male), 96 had transposition of the great arteries and 57 had single ventricle physiology. The presence of brain injury was significantly higher in patients with postnatal diagnosis of critical CHD (41 of 86 [48%]) than in those with prenatal diagnosis (16 of 67 [24%]) (P = .003). Patients with prenatal diagnosis demonstrated faster brain development in white matter fractional anisotropy (rate of increase, 2.2%; 95% CI, 0.1%-4.2%; P = .04) and gray matter apparent diffusion coefficient (rate of decrease, 0.6%; 95% CI, 0.1%-1.2%; P = .02). Patients with prenatal diagnosis had lower birth weight (mean, 3184.5 g; 95% CI, 3050.3-3318.6) than those with postnatal diagnosis (mean, 3397.6 g; 95% CI, 3277.6-3517.6) (P = .02). Those with prenatal diagnosis had an earlier estimated gestational age at delivery (mean, 38.6 weeks; 95% CI, 38.2-38.9) than those with postnatal diagnosis (mean, 39.1 weeks; 95% CI, 38.8-39.5) (P = .03). CONCLUSIONS AND RELEVANCE Newborns with prenatal diagnosis of single ventricle physiology and transposition of the great arteries demonstrate less preoperative brain injury and more robust microstructural brain development than those with postnatal diagnosis. These results are likely secondary to improved cardiovascular stability. The impact of these findings on neurodevelopmental outcomes warrants further study.

The many faces of hydrops

PURPOSE Fetal hydrops arises from multiple disease processes and can portend a grim prognosis. We reviewed our experience with hydropic fetuses to understand relevant antenatal anatomic and physiologic predictors of survival. METHODS We reviewed fetal ultrasounds and echocardiograms of hydropic fetuses evaluated from 1996 to 2013. RESULTS Overall neonatal survival in 167 fetuses was 44% (range, 0-75%) and was influenced by the underlying disease process. The anatomic distribution of fluid varied and was not significantly different between survivors and nonsurvivors. Univariate analysis indicated that resolution of hydrops and delivery at a later gestational age were predictive of survival (OR: 5.7 (95% CI: 2.5-13.2) and OR: 1.3 (95% CI: 1.1-1.4), respectively). Fetal intervention also improved survival in some diseases. Echocardiograms were reviewed to group fetuses with similar cardiac physiology and defined categories with high or low/normal cardiothoracic ratio (CTR). Among patients with a high CTR, the cardiovascular profile score was predictive of survival (p=0.009). CONCLUSION Survival in hydrops depends on the underlying disease, available fetal therapies to resolve hydrops, and the gestational age of delivery and not on the specific anatomic manifestations of hydrops. In hydropic fetuses with high CTRs, the cardiovascular profile score may be a useful prognostic indicator.

Risk of congenital heart disease in relatives of probands with conotruncal cardiac defects: An evaluation of 1,620 families

Current recurrence risk counseling for conotruncal cardiac defects (CTD) is based on empiric estimates from multiple studies. We examined the risk of congenital heart disease (CHD) in relatives of probands with CTDs to assist in counseling practices in the current era. One thousand six‐twenty probands with CTDs and no reported chromosomal or genetic abnormalities were recruited sequentially. A three‐generation pedigree was obtained for each proband by a genetic counselor detailing the presence and type of CHD in each family member. Risks and 95% confidence intervals (CI) were calculated for sub‐groups of relatives based on degree of relationship for all probands and by individual lesion of the proband. For pairs of affected relatives, concordance rates were calculated. Severity of CHD in the affected relative was assessed. The risk of CHD was higher in siblings (4.4%, 95% CI 3.4–5.4) than in parents (1.5%, 95% CI 1.1–1.9). Risk varied by the cardiac lesion of the proband with the highest risk in first‐degree relatives of probands with tetralogy of Fallot and the lowest in D‐transposition of the great arteries. 39% of affected parents and 69% of affected siblings had a concordant lesion (i.e., CTD). Most affected siblings of probands with severe CTDs had complex defects (58%), whereas very few affected parents had complex defects (20%). These data suggest that recurrence risk varies by lesion and relationship, with substantial concordance observed by cardiac lesion and complexity of disease, particularly among siblings. These findings contribute to risk counseling in the current era.

The association between cardiac physiology, acquired brain injury, and postnatal brain growth in critical congenital heart disease

Objective To assess the trajectory of perioperative brain growth in relationship to cardiac diagnosis and acquired brain injuries. Methods This was a cohort study of term neonates with hypoplastic left heart syndrome (HLHS) and d‐transposition of the great arteries (d‐TGA). Subjects underwent magnetic resonance imaging of the brain pre‐ and postoperatively to determine the severity of brain injury and total and regional brain volumes by the use of automated morphometry. Comparisons were made by cardiac lesion and injury status. Results A total of 79 subjects were included (49, d‐TGA; 30, HLHS). Subjects with HLHS had more postoperative brain injury (55.6% vs 30.4%, P = .03) and more severe brain injury (moderate‐to‐severe white matter [WM] injury, P = .01). Total and regional perioperative brain growth was not different by brain injury status (either pre‐ or postoperative). However, subjects with moderate‐to‐severe WM injury had a slower rate of brain growth in WM and gray matter compared with those with no injury. Subjects with HLHS had a slower rate of growth globally and in WM and deep gray matter as compared with d‐TGA (total brain volume: 12 cm3/wk vs 7 cm3; WM: 2.1 cm3/wk vs 0.6 cm3; deep gray matter: 1.5 cm3/wk vs 0.7 cm3; P < .001), after we adjusted for gestational age at scan and the presence of brain injury. This difference remained after excluding subjects with moderate‐to‐severe WM injury. Conclusions Neonates with HLHS have a slower rate of global and regional brain growth compared with d‐TGA, likely related to inherent physiologic differences postoperatively. These findings demonstrate the complex interplay between cardiac lesion, brain injury, and brain growth.

Gestational Age and Outcomes in Critical Congenital Heart Disease

Population-based cohort study to assess impact of GA on morbidity and mortality in preterm and term infants with CCHD. BACKGROUND AND OBJECTIVES: It is unknown how gestational age (GA) impacts neonatal morbidities in infants with critical congenital heart disease (CCHD). We aim to quantify GA-specific mortality and neonatal morbidity in infants with CCHD. METHODS: Cohort study using a database linking birth certificate, infant hospital discharge, readmission, and death records, including infants 22 to 42 weeks’ GA without chromosomal anomalies (2005–2012, 2 988 925 live births). The International Classification of Diseases, Ninth Revision diagnostic and procedure codes were used to define CCHD and neonatal morbidities (intraventricular hemorrhage, retinopathy, periventricular leukomalacia, chronic lung disease, necrotizing enterocolitis). Adjusted absolute risk differences (ARDs) with 95% confidence intervals (CIs) were calculated. RESULTS: We identified 6903 out of 2 968 566 (0.23%) infants with CCHD. The incidence of CCHD was highest at 29 to 31 weeks’ GA (0.9%) and lowest at 39 to 42 weeks (0.2%). Combined neonatal morbidity or mortality in infants with and without CCHD was 82.8% and 57.9% at <29 weeks and declined to 10.9% and 0.1% at 39 to 42 weeks’ GA. In infants with CCHD, being born at 34 to 36 weeks was associated with a higher risk of death or morbidity than being born at 37 to 38 weeks (adjusted ARD 9.1%, 95% CI 5.5% to 12.7%), and being born at 37 to 38 weeks was associated with a higher risk of death or morbidity than 39 to 42 weeks (adjusted ARD 3.2%, 95% CI 1.6% to 4.9%). CONCLUSIONS: Infants born with CCHD are at high risk of neonatal morbidity. Morbidity remains increased across all GA groups in comparison with infants born at 39 to 42 weeks. This substantial risk of neonatal morbidity is important to consider when caring for this patient population.

Epidemiology of Live Born Infants with Nonimmune Hydrops Fetalis—Insights from a Population-Based Dataset

OBJECTIVE To evaluate the incidence, etiology, and 1-year mortality of nonimmune hydrops fetalis (NIHF) and to identify risk factors for mortality in a contemporary population-based dataset. STUDY DESIGN The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharge, readmissions, and birth and death certificate date from 1 year before to 1 year after birth. We searched the database (2005-2012) for infants with NIHF (identified by the International Classification of Diseases, 9th Revision, Clinical Modification code). Hazard models were used to identify risk factors for mortality in infants with NIHF; results are presented as hazard ratios (HRs, 95% CI). RESULTS The incidence of NIHF was 2.5 out of 10 000 among live born infants. Neonatal mortality was 35.1% (364 out of 1037) and overall mortality was 43.2% (448 out of 1037) at 1 year of age. Gestational age (GA) was predictive of mortality with a HR of 2.4 (95% CI 1.9-3.2) for preterm compared with term infants. The GA-adjusted HR for mortality was 1.3 (95% CI 1.1-1.6) for polyhydramnios and 1.5 (95% CI 1.2-2.0) for large for gestational age infants compared with appropriate for GA infants. Aneuploid infants with critical congenital heart disease had an adjusted HR of 2.3 (95% CI 1.5-3.6) compared with euploid infants without a structural birth defect. CONCLUSIONS In this large, population-based study, prematurity, polyhydramnios, and large for gestational age were predictors of increased mortality. Mortality is highly variable among euploid and aneuploid infants with and without structural birth defects and critical congenital heart disease.

Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction.

Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls.

Revisiting the utility of technical performance scores following tetralogy of Fallot repair

Objective Although an important quality metric, current technical performance scores may not be generalizable and may omit operative factors that influence outcomes. We examined factors not included in current technical performance scores that may contribute to increased postoperative length of stay, major complications, and cost after primary repair of tetralogy of Fallot. Methods This is a retrospective single site study of patients younger than age 2 years with tetralogy of Fallot undergoing complete repair between 2007 and 2015. Medical record data and discharge echocardiograms were reviewed to ascertain component and composite technical performance scores. Primary outcomes included postoperative length of stay, major complications, and total hospital costs. Multivariable logistic and linear regression identified determinants of each outcome. Results Patient population (n = 115) had a median postoperative length of stay of 8 days (interquartile range, 6‐10 days), and a median total cost of

Twin-reversed arterial perfusion sequence associated with decreased fetal cerebral vascular impedance

71,147. Major complications occurred in 33 patients (29%) with 1 death. Technical performance scores assigned were optimum in 28 patients (25%), adequate in 59 patients (52%), and inadequate in 26 patients (23%). Neither technical performance score components nor composite scores were associated with increased postoperative length of stay. Optimum or adequate repairs versus inadequate had equal risk of a complication (P = .79), and equivalent mean total cost (

Preconceptual Folic Acid Use and Recurrence Risk Counseling for Congenital Heart Disease

100,000 vs