SAN DIEGO — Brain development at birth is significantly delayed in full-term neonates with complex congenital heart defects, both on magnetic resonance imaging and by mean head circumference.
These observations “should stimulate discussion on the optimal timing of labor induction for those infants with prenatally diagnosed heart defects,” Dr. Daniel J. Licht said at the annual meeting of the American Association for Thoracic Surgery.
“Historically, the timing of delivery for neonates with prenatally diagnosed congenital heart disease was determined by lung maturity and surgical logistics. The current study suggests neonates with complex CHD should be delivered as close to term as possible,” said Dr. Licht, a child neurologist at Children's Hospital of Philadelphia.
Previous studies have shown that at birth, term infants with complex congenital heart defects have smaller head circumferences and, on MRI, have been shown to have structural simplicity of the brain as seen by open operculum. These infants “also have an unexpectedly high proportion of preoperative and postoperative white matter injury in the form of periventricular leukomalacia,” he said.
This finding has been corroborated by a report of biochemical immaturity of the white matter in infants with congenital heart defects as shown by MR spectroscopy (N. Engl. J. Med. 2007;357:1928–38).
Dr. Licht and his associates hypothesized that term infants with complex forms of congenital heart defects have structurally delayed brain development as measured by smaller head circumferences and a lower total maturation score (TMS), a validated MRI metric for assessing full brain maturity. The TMS is composed of four MRI characteristics: myelination, cortical folding, germinal matrix, and migrating bands of glial cells.
A 3-Tesla MRI was used to evaluate 29 full-term infants with hypoplastic left heart syndrome (HLHS) and 13 with transposition of the great arteries (TGA) just prior to heart surgery. Infants with evidence of perinatal distress, shock, or intrauterine growth retardation were excluded from the study “as these were felt to be independent risks for brain injury,” Dr. Licht said.
Clinical studies were reviewed by a single neuroradiologist who was blinded to the clinical data, and TMS was rated by two MRI readers who also were blinded to the data. Findings were compared with published normative data of similar gestational age. The mean gestational age of the 42 infants was 39 weeks and 64% were boys. Average birth weight was 3.4 kg.
The average head circumference for infants in the study was 34.5 cm, which is a full standard deviation below the expected normal of 35.5 cm. In addition, open operculum was seen on MRI in 36 of the infants (86%), and would be expected in less than 5%–10% of normal full-term infants
The average TMS for infants in the study was just over 10, which is significantly lower than reported normative TMS of 11.1 in noncardiac infants with a gestational age of 36–37 weeks.
“This average TMS … places our term infants with congenital heart defects at 35 weeks of gestational age, when white matter remains vulnerable and myelination is just beginning,” Dr. Licht said. “We conclude that this group of otherwise healthy term babies with congenital heart defects has immature brains as evidenced by the high prevalence of small head circumferences and open opercula and corroborated with the finding of reduced TMS scores, suggesting a delay in brain maturity of a full month.”
He noted that the relative immaturity of the central nervous system in these term neonates “may provide the substrate for the vulnerability to white matter injury in the pre-, intra-, and postoperative periods.”
The study was funded by the National Institute of Neurological Disorders and Stroke and by the Dana Foundation. Dr. Licht had no conflicts to disclose.
Open operculum, indicating structural simplicity of the brain, was seen in 86% of neonates with complex congenital heart defects on magnetic resonance imaging. Images courtesy Dr. Daniel J. Licht
