TCD in Infants: A Report from the BABY HUG Trial.

Transcranial Doppler (TCD) is useful in children with sickle cell anemia (SCA) to detect increased risk of stroke. The use of TCD in infants less than 2 years of age is less well established, but has previously been shown to be feasible. As a secondary endpoint in the BABY HUG Trial, TCD is expected to provide useful information on the possible effects of hydroxyurea (HU) in babies with SCA. BABY HUG is an NHLBI-NICHD sponsored phase III clinical trial to compare hydroxyurea to placebo to ascertain effectiveness in preventing end organ damage of the spleen and kidney. Eligible subjects underwent a baseline TCD using the Nicolet Companion (EME) 2-MHz pulsed Doppler. All infants were 8–18 months of age at enrollment, had no history of stroke and were not receiving chronic blood transfusions. Blood flow velocities were recorded using the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol with the exception of reducing the standard sample volume to 4 mm. No sedation was used. The time averaged maximum mean was measured to determine the highest velocity on either side to categorize the study as normal (all recordings <170 cm/sec), conditional (170–199cm/sec) or abnormal (≥200 cm/sec). Recordings of the middle cerebral artery (MCA) and internal carotid artery (ICA) bifurcation defined an adequate TCD. TCD was not required for study entry but subjects with an abnormal exam were not eligible for randomization and treatment. TCD exams were read by blinded reviewers at the Medical College of Georgia. TCD results were transmitted to Clinical Trials & Surveys Corporation (C-TASC) for statistical analysis. As of June 24, 2005, 70 TCD exams had been attempted. Two exams were unsuccessful (no data) because of the children’s irritability and 1 was interpreted as inadequate. Of the remaining 67 TCD exams, 66 were normal and one baby had a high conditional TCD (190 cm/sec). No subjects were found ineligible for the study due to TCD results. The mean velocity of the left MCA was 117 cm/sec ±22.9 and that of the right MCA was 114 cm/sec ±24.9. Regression analyses were performed to examine the relationship of maximum flow velocity (VMAX) to age and total hemoglobin (Hb). VMAX was inversely correlated to Hb (left p=<0.0001, right=<0.0014) and directly associated with age (left p=<.0005, right p=<0.0022). When the mean MCA velocity was regressed against age and Hb, both age (p=0.0285) and Hb (p=.0024) were significant. Adequate baseline TCD evaluation was obtained on 67 out of 70 babies. As expected, baseline TCD velocities varied inversely with the degree of anemia and directly with age; all but one was normal by childhood sickle cell disease standards. These studies provide valuable normative data for infants with SCA, and for further assessment of the effect of HU on TCD in infants with SCA as the study progresses.