Monkeypox in pregnancy: virology, clinical presentation, and obstetric management

Abstract

The 2022 monkeypox outbreak, caused by the zoonotic monkeypox virus, has spread across 6 World Health Organization regions (the Americas, Africa, Europe, Eastern Mediterranean, Western Pacific, and South-East Asia) and was declared a public health emergency of international concern on July 23, 2022. The global situation is especially concerning given the atypically high rate of person-to-person transmission, which suggests viral evolution to an established human pathogen. Pregnant women are at heightened risk of vertical transmission of the monkeypox virus because of immune vulnerability and natural depletion of population immunity to smallpox among reproductive-age women, and because orthopoxviral cell entry mechanisms can overcome the typically viral-resistant syncytiotrophoblast barrier within the placenta. Data on pregnancy outcomes following monkeypox infection are scarce but include reports of miscarriage, intrauterine demise, preterm birth, and congenital infection. This article forecasts the issues that maternity units might face and proposes guidelines to protect the health of pregnant women and fetuses exposed to the monkeypox virus. We review the pathophysiology and clinical features of monkeypox infection and discuss the obstetrical implications of the unusually high prevalence of anogenital lesions. We describe the use of real-time polymerase chain reaction tests from mucocutaneous and oropharyngeal sites to confirm infection, and share an algorithm for the antenatal management of pregnant women with monkeypox virus exposure. On the basis of the best available knowledge from prenatal orthopoxvirus infections, we discuss the sonographic features of congenital monkeypox and the role of invasive testing in establishing fetal infection. We suggest a protocol for cesarean delivery to avoid the horizontal transmission of the monkeypox virus at birth and address the controversy of mother-infant separation in the postpartum period. Obstetrical concerns related to antiviral therapy with tecovirimat and vaccinia immune globulin are highlighted, including the risks of heart rate-corrected QT-interval prolongation, inaccuracies in blood glucose monitoring, and the predisposition to iatrogenic venous thromboembolism. The possibility of monkeypox vaccine hesitancy during pregnancy is discussed, and strategies are offered to mitigate these risks. Finally, we conclude with a research proposal to address knowledge gaps related to the impact of monkeypox infection on maternal, fetal, and neonatal health.

Keywords: ACAM2000; COVID-19; MVA-BN; World Health Organization; antiviral; chickenpox; cidofovir; cowpox; emerging pathogen; miscarriage; monkeypox; obstetrical management; orthopoxvirus; outbreak; pregnancy; rash; sexual transmission; smallpox; tecovirimat; vaccine; vaccinia immune globulin; vaccinia virus; varicella-zoster; vertical transmission; zoonosis.

Figure 1

Monkeypox virus A, Monkeypox virus on transmission electron microscopy, negative staining (bar=200 nm). B, cutaway line drawing of the monkeypox virus. Tecovirimat targets the VP37 protein and inhibits formation of the viral envelope (E). Cidofovir targets DNA polymerase within the viral nucleosome (N) but is teratogenic, unlike tecovirimat. Image credit: Panel A – Andrea Männel 2001/ RKI Robert Koch Institute; Panel B – Authors’ original illustration using Biorender. CM, core membrane; E, envelope; LB, lateral body; N, nucleosome; OM, outer membrane; ST, surface tubules. Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.

Figure 2

Monkeypox rash A, Characteristic vesicular and B, pustular lesions in a person with polymerase chain reaction–confirmed human monkeypox infection. Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.

Figure 3

Management of monkeypox during pregnancy Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.

Figure 4

Possible barriers to monkeypox vaccination during pregnancy ACNM, American College of Nurse-Midwives; ACOG, American College of Obstetricians and Gynecologists; FIGO, International Federation of Gynecology and Obstetrics; HCP, healthcare provider; IRB, institutional review board; LMIC, low- and middle-income countries; RCOG, Royal College of Obstetricians and Gynaecologists. Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.

Supplemental Figure 1

Oral and perioral lesions in monkeypox A, Perioral umbilicated lesions. B, Perioral vesicular lesion on day 8, positive PCR test result. C, Ulcer on the left corner of the mouth on day 7, positive PCR test result. D, Tongue ulcer. E, Tongue lesion on day 5, positive PCR test result. F, G, and H, Pharyngeal lesions on days 0, 3, and 21, respectively, positive PCR test result on days 0 and 3 and negative PCR test result on day 21. Reproduced, with permission, from Thornhill et al. PCR, polymerase chain reaction. Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.

Supplemental Figure 2

Perianal, anal, and rectal lesions in monkeypox A, Anal and perianal lesions on day 6, positive PCR test result. B and C, Rectal and anal lesions in a single person, positive PCR test result. D, Perianal ulcers, positive PCR test result. E, Anal lesions. F, Umbilicated perianal lesion on day 3, positive PCR test result. G, Umbilicated perianal lesions on day 3, positive PCR test result. H, Perianal ulcer on day 2, positive PCR test result. In the context of pregnancy, these lesions might be confused with genital herpes, syphilis, or lymphogranuloma venereum. Reproduced, with permission, from Thornhill et al. PCR, polymerase chain reaction. Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.

Supplemental Figure 3

Maculopapular rash in monkeypox In the context of pregnancy, a maculopapular rash such as this might be confused with pruritic urticarial papules and plaques of pregnancy. Reproduced, with permission, from Thornhill et al. Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.