The association of fetal cerebrovascular resistance with early neurodevelopment in single ventricle congenital heart disease

Abstract

Background Children with congenital heart disease are at risk for impaired neurodevelopment (ND). We investigated the association of fetal cerebrovascular resistance with ND in patients with single ventricle lesions. Methods In the Single Ventricle Reconstruction (SVR) and Infant Single Ventricle trials, 14-month ND was assessed using the Bayley Scales of Infant Development II. We investigated associations between ND scores and fetal middle cerebral artery pulsatility index (MCA-PI) z-scores, a Doppler-derived estimate of cerebrovascular resistance in a subset of those infants. Results Neurodevelopment assessments were performed at age 14.3 ± 1 months in 170 (74%) of 230 Infant Single Ventricle and 321 (58%) of 555 SVR subjects. Fetal echocardiographic data were available in 119 subjects, 72 (61%) of which had ND testing. Mean Psychomotor Development Index (PDI) (76 ± 20) and Mental Development Index (MDI) (89 ± 17) scores were lower than normative means (100 ± 15, P < .001). Mean MCA-PI z-score was −0.95 ± 1.52. Middle cerebral artery pulsatility index z-score correlated negatively with PDI (r = −0.27, P = .02) but was not associated with MDI. When MCA-PI z-score was added to a multivariable model controlling for factors identified in the SVR trial to predict PDI, the percentage of explained variation increased from 23% to 30%, and MCA-PI z-score remained an independent predictor (r = −3.864, P = .03). Middle cerebral artery pulsatility index z-score was not an independent predictor in a model adjusting for site. Conclusions Among fetuses with single ventricle anomalies, lower cerebrovascular resistance was associated with higher ND scores. This relationship is opposite to that observed with advanced intrauterine growth retardation and may represent a unique ability of these congenital heart disease fetuses to compensate for diminished cerebral oxygen delivery.

Congenital Heart Defects and Indices of Fetal Cerebral Growth in a Nationwide Cohort of 924 422 Liveborn Infants

“…No other subtypes were associated with disproportionately smaller head circumference, as previously suggested in other studies of TOF, HLHS, or aortic arch hypoplasia. 13,15,20,[41][42][43] We found disproportionately larger head circumferences relative to birth weight in major VSDs and other less severe subtypes of CHD. No previous studies have reported such associations.…”

“…Ultrasound studies have demonstrated brain sparing in fetuses with CHD, 13,16,17,19,42,43 and MRI studies have demonstrated decreased fetal cerebral volume before birth. 7,14 Recently, measures of fetal cerebral oxygenation were directly linked to prenatal brain volume.…”

Non-invasive assessment of cerebral oxygen metabolism following surgery of congenital heart disease

“…Recent studies show that CHD, resulting in abnormal cerebral blood flow and oxygen saturation, is frequently associated with impaired development of the fetal brain [2,3,16,17]. Postnatally abnormal cerebral perfusion and oxygen saturation persist in the preoperative and in the perioperative period and are linked to cerebral white matter injury [2,16,17,18,19].…”

“…Congenital heart disease (CHD) is associated with an increased risk of neurodevelopmental deficits [1]. Already in fetal life altered haemodynamics and reduced cerebral oxygenation due to the congenital heart defect may result in impaired brain growth and altered structural and cellular maturation particularly of the white matter [1][2][3]. Altered brain development increases cerebral vulnerability in the perioperative period [4,5].…”

Detección precoz de trastornos del neurodesarrollo en los primeros años de vida en niños con cardiopatías congénitas

“…Asimismo, Williams et al (2012a) defienden que los niños con CC tienen un alto riesgo de padecer problemas neurocognitivos, incluyendo dificultades de aprendizaje, problemas en la conducta y lentitud mental.…”