Increased Incidence of Villitis in Placentas Exposed to Chemotherapy During Pregnancy: Is There a Correlation?

Abstract

We have identified 9 pregnant patients who were diagnosed with malignancy and initiated chemotherapy during their second trimester (cervical cancer [n = 3], leukemia [n = 3], breast cancer [n = 2], and Hodgkin’s lymphoma [n = 1]). Five of the patients’ placentas were small for gestational age (SGA). Pathologic examination revealed inflammatory changes in 4 of the placentas: 2 from the SGA placentas and 2 from non-SGA placentas. Examination revealed 3 placentas with villitis of unknown etiology (VUE) and 1 with intervillositis; all were negative for bacterial and viral cultures and by immunohistochemical (IHC) stains. In the VUE cases, IHC stains showed positivity of CD25+/FOXP3+ with focal positivity and CD3 and CD4 IHC were focally to strongly positive. Literature suggests that the use of chemotherapy during pregnancy can be detrimental to both the mother and the fetus; however, there has been limited focus on the effects of chemotherapy on the placenta. We suggest that the inflammatory process noted in the placentas is due to chemotherapy-induced toxic effects.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination in Pregnancy

“…5 Some medications, when used in pregnancy, are associated with placental changes, including accelerated villous maturation with glucocorticoids, 6 abnormal placental shape with HIV protease inhibitors, 7 and chronic villitis or intervillositis after antineoplastic chemotherapy. 8 In addition, as described in the introduction of this manuscript, the novel mRNA vaccines induce an immune response via direct mRNA activation of TLR3, a process which has been associated in some mouse models with placental and fetal pathology.…”

“…2009 H1N1 influenza and antineoplastic chemotherapy are associated with estimated 3-fold increases in the risk of chronic villitis. 8,10 Therefore, we felt a 3 fold increased risk was an appropriate threshold for this preliminary analysis.…”