Three Cases of Vertical Transmission of Clade Ib Mpox Virus

Mpox (formerly known as monkeypox), which is caused by the virus MPXV, has been associated with adverse pregnancy outcomes, but evidence of vertical transmission remains limited.1-3 Concerns regarding transplacental transmission are heightened by the ongoing clade Ib mpox epidemic, which often affects persons of reproductive age.4 We report three cases of clade Ib MPXV infection in pregnant women in whom we assessed molecular and histopathological evidence of transplacental transmission across all trimesters. Details of the methods, clinical presentation, and histopathological testing are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.
The first case involved a woman at 6 weeks’ gestation who had fever, generalized rash, inguinal adenopathy, and painful genital discharge and edema. She tested positive for clade Ib MPXV. Despite supportive therapy, she had a spontaneous abortion. MPXV DNA was detected in placental and embryonic tissues, with cycle threshold (Ct) values of 20.1 and 13.4, respectively (Table 1). Histopathological testing of these tissues showed MPXV antigen colocalized with CD68-positive placental villous macrophages (Hofbauer cells) and alpha-fetoprotein–positive embryonic cells, a finding indicating transplacental transmission (Fig. S1A through S1K in the Supplementary Appendix).
The second case involved a woman with human immunodeficiency virus (HIV) infection who presented at 16 weeks’ gestation with widespread vesiculopustular lesions (most prominently in the genital area), fever, adenopathy, and dysphagia. Fifteen days after she tested positive for clade Ib MPXV, fetal movements ceased, and ultrasonography confirmed intrauterine fetal death. A cesarean delivery was performed after unsuccessful induction of labor. The fetus had several mpox-like lesions on the face, chest, abdomen, and upper limbs. MPXV DNA was detected in placental and fetal tissues, with Ct values of 19.3 and 18.3, respectively (Table 1).
The third case involved an HIV-positive woman at 34 weeks’ gestation who presented with fever, dysphagia, generalized mpox lesions, and genital ulcers and tested positive for clade Ib MPXV (Table 1). She was admitted to the hospital with hypotension but recovered and was discharged after 29 days. Thirteen days later, at 40 weeks’ gestation, she delivered a live infant who had multiple ulcerative skin lesions (Fig. S2). MPXV DNA was detected in a placental swab (Ct value, 23.7) and in an oropharyngeal swab obtained from the newborn (Ct value, 38.2). Histopathological testing showed MPXV antigen within the placental villi, colocalized with CD68-positive cells (Fig. S1L through S1P). Three months later, the mother reported the infant’s death, which was considered by the team of clinicians at Kamituga Hospital to have been probably unrelated to mpox.
These findings provide evidence that clade Ib MPXV can be vertically transmitted, resulting in pregnancy loss or congenital infection — data consistent with isolated previous reports regarding clade Ia MPXV.1,2 These findings support the importance of preventive interventions, including vaccination, in pregnant women. Prospective large-scale studies are necessary to better understand perinatal outcomes associated with mpox in pregnancy and to guide clinical management.