Transient dilated cardiomyopathy in a newborn exposed to idarubicin and all-trans-retinoic acid (ATRA) early in the second trimester of pregnancy

Abstract

Acute promyelocytic leukemia was diagnosed in a 28-year-old pregnant woman at 13 gestational weeks. She was immediately started on idarubicin and all-trans-retinoic acid (ATRA) and achieved remission after her fourth cycle of treatment. Serial fetal ultrasonograms throughout pregnancy did not reveal any intrauterine growth retardation or other obvious malformations. The mother delivered a term (36.7 gestational weeks), 2720-gram female neonate. The infant was admitted to the intermediate care nursery for observation due to transient mild respiratory distress during the peripartum period. Because of right ventricular hypertrophy on an electrocardiogram, an echocardiogram was performed on the first day of life which showed moderate dilation of the right atrium and right ventricle with mildly depressed function, two small secundum atrial septal defects, and a small patent ductus arteriosus. The neonate remained hemodynamically stable and no arrhythmias were detected. The remainder of the hospital course was uneventful. When reassessed 1-1/2 months later, she was doing well and did not show any signs of congestive heart failure. A repeat echocardiogram at that time demonstrated complete resolution of the right heart enlargement and closure of the ductus arteriosus with persistence of the small and hemodynamically insignificant secundum atrial septal defects.

Differential response of human fetal smooth muscle cells from arterial duct to retinoid acid

“…Retinoid exposure during gestation can induce developmental defects if administered before neurulation; however, if given after neurulation, it is not so teratogenic [22] . Exposure to idarubicin and RA early in the second trimester of pregnancy causes transient dilated cardiomyopathy in a term newborn [23] . However, some published studies have sug- gested that vitamin A is important in the development of the fetal ductus arteriosus [24,25] .…”

Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

“…Although the experience is quite limited, there were no fetal malformations reported suggestive of retinoic acid embryopathy. 111 However, because some cases of reversible fetal arrhythmias and other cardiac complications at birth have been reported, 114,115 stringent fetal monitoring, with particular emphasis on cardiac function, is recommended for patients receiving ATRA alone or combined with chemotherapy during pregnancy.…”

How I treat leukemia during pregnancy

“…As ATRA therapy in pregnancy has been associated with fetal cardiac toxicity including reversible arrhythmias, the importance of cardiac monitoring should be highlighted. 3,13,37 In consultation with obstetric colleagues, elective delivery can be scheduled according to fetal maturity and a gestational age of 32 weeks or more is usually acceptable. Antenatal corticosteroids before preterm delivery are recommended to alleviate the complications of respiratory distress syndrome.…”