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Effects of chemotherapy during pregnancy on the placenta.

Abstract
Whereas the effects of chemotherapy during pregnancy for mother and fetus are well described, its effects on the placenta remain largely undetermined. We performed a retrospective clinicopathologic analysis of the placenta following chemotherapy. Charts were reviewed for type of malignancy, type and timing of chemotherapy, and fetal and pregnancy outcome. Placentas were studied by standard pathologic analysis as well as computer-assisted morphometry and fluorescence in situ hybridization (FISH) analysis. Patients (n = 13) underwent chemotherapy during pregnancy for carcinoma of breast (3), ovary (2), cervix (2), salivary gland (1), lymphoma/leukemia (4), or rhabdomyosarcoma (1). Eleven patients were treated with DNA-active cytotoxic agents during the 2nd and/or 3rd trimesters; their placentas showed nonspecific findings, including villous hypermaturity, distal villous hypoplasia, villous edema, and excessive extravillous trophoblast, and 4/11 (36%) were small-for-age. In one case (rhabdomyosarcoma), the mother was exposed to cytotoxic agents throughout the entire pregnancy. In this case, associated with severe congenital anomalies, the placenta showed striking nuclear pleomorphism of the extravillous trophoblast of the chorion laeve, associated with FISH-demonstrated hyperpolyploidy. One patient was treated with the targeted tyrosine kinase inhibitor, imatinib, in 2 consecutive pregnancies; these placentas showed no specific anomalies. Our findings suggest that chemotherapy during the 1st trimester induces excessive polyploidization of the chorion laeve trophoblast, likely representing an adaptive response to intraamniotic toxins. Second and 3rd trimester exposure to cytotoxic agents may predispose to placental underdevelopment. However, without appropriate controls (untreated patients with equivalent malignancies), the specific effects of chemotherapy in this group are difficult to assess.
AuthorsRosanna G Abellar, John R Pepperell, David Greco, Fusun Gundogan, Stefan Kostadinov, Joanna Schwartz, Umadevi Tantravahi, Monique E De Paepe
JournalPediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society (Pediatr Dev Pathol) 2009 Jan-Feb Vol. 12 Issue 1 Pg. 35-41 ISSN: 1093-5266 [Print] United States
PMID18462010 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
Topics
  • Abnormalities, Multiple (chemically induced)
  • Adolescent
  • Adult
  • Antineoplastic Agents (adverse effects)
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Placenta (drug effects, pathology)
  • Pregnancy
  • Pregnancy Complications, Neoplastic (drug therapy)
  • Pregnancy Trimester, First
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Retrospective Studies

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