Clinical Factors Associated with Cerebral Metabolism in Term Neonates with Congenital Heart Disease

Abstract

Objective: To determine associations between patient and clinical factors with postnatal brain metabolism in term neonates with congenital heart disease (CHD) via the use of quantitative magnetic resonance spectroscopy.

Study design: Neonates with CHD were enrolled prospectively to undergo pre- and postoperative 3T brain magnetic resonance imaging. Short-echo single-voxel magnetic resonance spectroscopy of parietal white matter was used to quantify metabolites related to brain maturation (n-acetyl aspartate, choline, myo- inositol), neurotransmitters (glutamate and gamma-aminobutyric acid), energy metabolism (glutamine, citrate, glucose, and phosphocreatine), and injury/apoptosis (lactate and lipids). Multivariable regression was performed to search for associations between (1) patient-specific/prenatal/preoperative factors with concurrent brain metabolism and (2) intraoperative and postoperative factors with postoperative brain metabolism.

Results: A total of 83 magnetic resonance images were obtained on 55 subjects. No patient-specific, prenatal, or preoperative factors associated with concurrent metabolic brain dysmaturation or elevated lactate could be identified. Chromosome 22q11 microdeletion and age at surgery were predictive of altered concurrent white matter phosphocreatine (P < .0055). The only significant intraoperative association found was increased deep hypothermic circulatory arrest time with reduced postoperative white matter glutamate and gamma-aminobutyric acid (P < .0072). Multiple postoperative factors, including increased number of extracorporeal membrane oxygenation days (P < .0067), intensive care unit, length of stay (P < .0047), seizures in the intensive care unit (P < .0009), and home antiepileptic use (P < .0002), were associated with reduced postoperative white matter n-acetyl aspartate.

Conclusion: Multiple postoperative factors were found to be associated with altered brain metabolism in term infants with CHD, but not patient-specific, preoperative, or intraoperative factors.

Keywords: brain dysmaturation; lactate; phosphocreatine; punctate white matter injury.

Figure 1

Enrollment during the study period. A majority of cases were enrolled prenatally. The number of cases excluded and reasons are depicted. Approximately one-half of the cases had both preoperative (Pre-op) and postoperative (Post-op) brain imaging time points obtained.

Figure 2

Quantitative MRS via the short-echo technique in a term neonate with CHD. Short-echo technique allows quantitation of additional metabolites (phosphocreatine [PCr], myo-inositol [mI], glutamine [Gln], and glutamate [Glu] and lipids/ macromolecules [Lip/MM], above and beyond long echo technique, which can measures NAA, choline [Cho], and creatine [Cr]). Three voxel locations were obtained in the order of frequency: top row, parietal white matter; middle row, parietal-occipital gray matter; and bottom row, thalamus.