SANTA CLARA, CA—“Neurodevelopmental disability is the most common and potentially disabling long-term outcome following infant heart surgery,” reported Daniel J. Licht, MD. In his talk at the 37th Annual Meeting of the Child Neurology Society, Dr. Licht reviewed neuroprotective studies that have been performed in this population, outlining the effects of temperature, blood flow, and gases in infant heart surgery and brain injury.
Congenital Heart Surgery and Brain Injury
Every year, 6,500 infants require surgery to repair a congenital defect in the first week of life, explained Dr. Licht, Assistant Professor of Neurology and Pediatrics and Director of the Neurovascular Imaging Lab at the Children’s Hospital of Philadelphia. Of these, nearly 3,000 have hypoplastic left heart syndrome or transposition of the great arteries, making these conditions among the three most common birth defects, along with cleft lip and palate and Down syndrome (trisomy 21).
Depending on the experience of the surgeon and hospital, infants with transposition of the great arteries have a 90% to 95% chance of survival, while those born with hypoplastic left heart syndrome have a 65% to 90% chance of survival. Treatment for the latter condition requires three surgeries during the first two years of life; thus, there is continued hypoxia (oxygen saturations average at about 85%) and higher central venous pressures, which can affect brain development. One in five of these children will have periventricular leukomalacia (PVL)—injury to the white matter of the brain, near the ventricles—before surgery. Postoperatively, this condition affects 50% of infants; stroke occurs in 8% to 9%. PVL is a condition that affects both infants with congenital heart defects and premature infants.
Citing results from his own study and another by Childs et al, Dr. Licht discussed a total maturation score (TMS) based on MRI characteristics of the brain, such as quantity of myelination, degree of cortical folding, the presence or absence of the germinal matrix, and the number of bands of migrating oligodendrocyte cells. Brain MRIs of infants with these severe forms of congenital heart defects demonstrate a TMS score consistent with the brain development of normal infants born at 35 weeks’ gestation.
“There is a time between 23 and 32 weeks’ gestation where premyelinating oligodendrocytes are vulnerable to hypoxia,” Dr. Licht indicated, quoting literature on PVL. He further speculated that populations of these vulnerable cells are still present in sufficient concentrations in the brains of infants with congenital heart defects at term when their brains are at a maturational stage equivalent to 35 weeks’ gestation. Abnormal oxygenation and low blood flow in utero, after birth, and around the time of surgery can lead to maturation-dependent vulnerability in a full-term infant with congenital heart defects. The result is PVL, which is amplified by hypoxia and low cardiac output associated with surgery.
Factors Affecting Long-Term Outcome
Although few studies have addressed the long-term cognitive outcomes of patients with congenital heart defects, the most comprehensive is the Boston Circulatory Arrest Study. A total of 170 participants who had a single heart defect and one operation were evaluated; of these, 155 were followed for up to eight years. Although the IQs of the children were normal, many had executive dysfunction and problems with planning and organizing. Thirty percent required remedial education.
The results mirror those of another study involving 109 families. The researchers found that 30% of the children had symptoms of ADHD, 50% needed remedial education, and 14% required a full-time special education classroom. “We have a population of survivors whose intelligence is relatively spared, but they have a high prevalence of behavioral problems that affect their ability to perform in school,” Dr. Licht emphasized.
Also as part of the Boston study, investigators studied the effects of using low-flow bypass or deep hypothermic circulatory arrest during surgery. Children were followed for one, four, and eight years. At four years, cardiac anatomy—especially ventricular septal defects—was associated with worse neurocognitive outcomes. At eight years, there was no difference between the groups in reading and math scores. However, children who had deep hypothermic circulatory arrest scored worse on manual dexterity, speech production, and phonologic awareness, whereas patients treated with low-flow bypass scored worse on behavioral measures, such as vigilance and impulsivity.
Dr. Licht also reviewed the results of the Blood Gas Management Study, which compared pH-stat strategy to the alpha-stat strategy. As blood cools, gas solubility increases. The partial pressure of carbon dioxide—a regulator of cerebral blood flow—decreases during cooling, leading to decreased cerebral blood flow. The pH-stat strategy artificially corrects this drop by adding carbon dioxide to the inhaled gas mixture, while the alpha-stat strategy allows for the natural drift to lower carbon dioxide pressures. In a study comparing the two blood gas management strategies, the authors of the study found no differences in cognitive outcomes at one, two, and four years. Babies with ventricular septal defects had worse outcomes.