To the Editor: In 2004, we reported central nervous system andlimb anomalies that followed exposure to statin drugs in thefirst trimester of pregnancy (April 8, 2004, issue).1 One case,in which there had been exposure to lovastatin, was describedas involving holoprosencephaly on the basis of three separatereports of a "cerebral/brain ventricular septal defect," withaccompanying cardiac malformations that had been submitted tothe Food and Drug Administration adverse-event database. Werecently learned that the manufacturer considered the structuralanomalies to be solely cardiac, and therefore we requested sourcedocumentation to clarify the conflicting reports. A detailedclinical report that was located among archival documents clearlydescribed an atrial septal defect, a ventricular septal defect,and aortic hypoplasia leading to cardiac failure, with secondarycentral nervous system dysfunction. It was apparent that a data-extractionerror had occurred, incorrectly categorizing the ventricularseptal defect as an intracranial anomaly. Correcting this misclassificationreduces our reported number of lovastatin-exposed fetuses withmidline central nervous system anomalies from three to two.We still believe that the preponderance of the evidence supportsthe hypothesis that early gestational exposure to statin drugsmay be teratogenic and that prospective studies should be initiated.
Robin J. Edison, M.D., M.P.H. Maximilian Muenke, M.D. National Institutes of Health Bethesda, MD 20892-3717 muenke{at}nih.gov
References
Edison RJ, Muenke M. Central nervous system and limb anomalies in case reports of first-trimester statin exposure. N Engl J Med 2004;350:1579-1582. [Free Full Text]
KOREN, G., INOUE, M.
(2009). Do Tumor Necrosis Factor Inhibitors Cause Malformations in Humans?. The Journal of Rheumatology
36: 465-466
[Full Text]
Belay, B., Belamarich, P. F., Tom-Revzon, C.
(2007). The Use of Statins in Pediatrics: Knowledge Base, Limitations, and Future Directions. Pediatrics
119: 370-380
[Abstract][Full Text]
Yi, P., Han, Z., Li, X., Olson, E. N.
(2006). The Mevalonate Pathway Controls Heart Formation in Drosophila by Isoprenylation of G{gamma}1. Science
313: 1301-1303
[Abstract][Full Text]
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