Brain Volume and Metabolism in Fetuses With Congenital Heart Disease

Abstract

Background-Adverse neurodevelopmental outcome is an important source of morbidity in children with congenital heart disease (CHD). A significant proportion of newborns with complex CHD have abnormalities of brain size, structure, or function, which suggests that antenatal factors may contribute to childhood neurodevelopmental morbidity. Methods and Results-Brain volume and metabolism were compared prospectively between 55 fetuses with CHD and 50 normal fetuses with the use of 3-dimensinal volumetric magnetic resonance imaging and proton magnetic resonance spectroscopy. Fetal intracranial cavity volume, cerebrospinal fluid volume, and total brain volume were measured by manual segmentation. Proton magnetic resonance spectroscopy was used to measure the cerebral N-acetyl aspartate: choline ratio (NAA:choline) and identify cerebral lactate. Complete fetal echocardiograms were performed. Gestational age at magnetic resonance imaging ranged from 25 1 ⁄7 to 37 1 ⁄7 weeks (median, 30 weeks). During the third trimester, there were progressive and significant declines in gestational age-adjusted total brain volume and intracranial cavity volume in CHD fetuses relative to controls. NAA:choline increased progressively over the third trimester in normal fetuses, but the rate of rise was significantly slower (PϽ0.001) in CHD fetuses. On multivariable analysis adjusted for gestational age and weight percentile, cardiac diagnosis and percentage of combined ventricular output through the aortic valve were independently associated with total brain volume. Independent predictors of lower NAA:choline included diagnosis, absence of antegrade aortic arch flow, and evidence of cerebral lactate (PϽ0.001). Conclusions-Third-trimester fetuses with some forms of CHD have smaller gestational age-and weight-adjusted total brain volumes than normal fetuses and evidence of impaired neuroaxonal development and metabolism. Hemodynamic factors may play an important role in this abnormal development. (Circulation. 2010;121:26-33.)

Elucidating Metabolic Maturation in the Healthy Fetal Brain Using1H-MR Spectroscopy

“…Inclusion criteria were normal fetal sonography studies and the absence of any maternal medical conditions that might interfere with normal fetal growth and development (eg, chronic hypertension, preeclampsia, intrauterine growth restriction, placental abnormalities, gestational diabetes, and a known history of congenital heart disease). 16,17 Those with multiple gestations, evidence of congenital infection, documented prenatal chromosomal abnormalities, fetal sonography findings of dysmorphic features, dysgenetic brain lesions, or anomalies of other organ systems, and any maternal contraindication to MR (eg, mechanical heart valve, pacemaker, or any other ferromagnetic implants) were also excluded. No maternal or fetal sedation was used during the MR studies.…”

Prevalence and Spectrum of In Utero Structural Brain Abnormalities in Fetuses with Complex Congenital Heart Disease

“…As part of an ongoing prospective observational study that started in September 2007, pregnant women with a fetal CHD diagnosis confirmed by echocardiography at Boston Children's Hospital 7 and Children's National Medical Center were recruited as patients. A fetal echocardiography was performed by one of the center's experienced fetal echocardiographers on the day of the mother's appointment.…”

“…1,2 During the past decade, a growing body of evidence has demonstrated the high prevalence of preoperative brain imaging abnormalities in neonates with CHD, suggesting an antenatal origin in many cases. [3][4][5][6] More recently, our group has used quantitative MR imaging to demonstrate a progressive third-trimester deceleration in volumetric brain growth and metabolism in fetuses with CHD, 7 reduced volumes of gray (cortical and subcortical) and white matter, and significant delays in cortical gyrification and surface area in fetuses with hypoplastic left-heart syndrome (HLHS). 8 To date, there is only 1 published report of brain findings in fetuses with CHD by using conventional MR imaging.…”

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

“…Structural brain abnormalities beginning in utero and extending into the postoperative period have also been shown, including reduced brain volume and increased risk of white matter injury (Limperopoulos et al. 2010; Donofrio et al. 2011; Lynch et al.…”