Abstract 1543

Poster Board I-566

Between 1992-1995, the National Heart, Lung, and Blood Institute sponsored a multi-center, double blind, randomized, placebo-controlled Phase III clinical trial of hydroxyurea (Multicenter Study of Hydroxyurea-MSH). This trial examined whether hydroxyurea, a myelosuppressive chemotherapeutic agent that also stimulates the production of fetal hemoglobin (HbF), would reduce pain episodes in adults with sickle cell anemia. The trial was stopped early because of significant benefits of pain reduction that was sustained in a nine-year follow-up. This also suggested that patients taking hydroxyurea had improved survival. Despite our best attempts to promote contraception among MSH patients, women had children and men fathered children.

One of the concerns about using hydroxyurea was that it might have teratogenic effects on offspring, particularly in the area of brain development and cognitive outcome. To address this question, all eligible adults in the MSH trial were contacted to provide consent to obtain developmental outcome data using telephone interview administration of the Vineland Adaptive Behavior Scales, 2nd Edition, Survey Form (VABS). The population mean for the VABS is 100 with a standard deviation of 15. Interviews were conducted by a trained psychologist using an interactive question and answer process, with probes to clarify any information that was unclear.

Consent was obtained for parents of 22 offspring meeting criteria for inclusion. A number of the parents had multiple offspring; eight of the study parents were male and three were female. The children ranged from 6-months to 17 years of age at the time of the VABS interview. Four of the parents could not be reached for the interview. Of the remaining 18, four were ineligible because the birth occurred before hydroxyurea was started. As a group, the offspring were functioning in the average range of development in all areas: Adaptive Behavior Composite (M=102.3), Communication Domain (M=98.5), Daily Living Domain (M=103.8), Socialization Domain (M=100.2), and Motor Domain (for children under age 5; M=108.3). One child was functioning below the average range; follow-up determined that this child was in a special education program but had a developmental disability that had occurred in other family members.

The number of children who met criteria for this study and whose parents could be contacted was very small, severely limiting any definitive conclusions about developmental risk for offspring. Studies of teratogenicity for prenatal substance abuse have used standardized observational tests of neurodevelopment; this study relied on parent report, which can be biased if not confirmed. When standardized tests have been used in studies of prenatal drug exposure (not hydroxyurea), subtle difficulties in executive function of offspring have been reported, sometimes years after the exposure. While our results are encouraging in that the offspring in this limited group are functioning in the average range, this observation is not conclusive and there is a need to study a larger sample of children who are offspring of adults treated with hydroxyurea according to community standards.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.