Two cases of MPXV infection during pregnancy in heterosexual cisgender women without classic cutaneous lesions, Northern California, 2022

Abstract

As part of an epidemiologic survey, we screened remnant samples collected for STI testing for mpox virus. We identified two cases of presumed MPXV infection in pregnant, heterosexual cisgender women. Here, we describe their pregnancy and birth outcomes. Both patients required induction of labor and experienced labor complicated by chorioamnionitis.

Highlights

• •We identified two pregnant women with presumed asymptomatic mpox infection.
• •One patient experienced intrahepatic cholestasis of pregnancy.
• •The other patient experienced oligohydramnios.
• •Both patients developed chorioamnionitis and required induction of labor.

Introduction

MPXV is an enveloped dsDNA virus in the Orthopoxvirus genus within the Poxvirus family. The 2022 outbreak of MPXV is unique in its size and scope, with more than 80,000 cases reported in over 100 non endemic countries [1]. This outbreak is further distinguished from previous ones in that it has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and that transmission is largely, though not exclusively, occurring through sexual networks with racial and ethnic minority groups disproportionately affected in the United States [2].

While the current MPXV outbreak is disproportionately impacting MSM, cisgender women have also been affected. The impact of monkeypox infection during pregnancy is poorly understood, with scant reporting in the literature [3], [4]. Previous studies of infection with smallpox, another member of the Orthopoxvirus genus, during pregnancy demonstrated a higher risk of both severe maternal and fetal disease outcomes including hemorrhagic smallpox, preterm delivery, stillbirth, and abortion [5]. While MPXV infection is generally less severe than that of smallpox, the small number of reports describing MPXV infection during pregnancy demonstrate potential risk of adverse fetal or maternal outcomes [4], [6], [7] Our case report details two subclinical cases of MPXV infection in cisgender pregnant women.

The authors conducted a cross sectional epidemiologic survey to estimate mpox prevalence in a cohort of individuals undergoing STI testing using remnant samples. This study was approved by the Stanford University Institutional Review Board (protocol #66786). Methods are described in detail elsewhere [8], [9]. Briefly, all available samples obtained for Chlamydia trachomatis (CT) and Neisseria gonorrhea (NG) were retrospectively screened for the presence of MPXV using qPCR targeting two viral sequences. The first qPCR targeted viral DNA polymerase which is widely conserved throughout nonvariola orthopoxviruses, including MPXV. The second targeted the viral tumor necrosis factor (TNF) receptor sequence, which is specific for MPXV clade II, the cause of the current outbreak. It is unknown how many of the samples screened were obtained from pregnant individuals. Pregnant patients in this healthcare system are typically screened twice for CT/NG, once in their first or second trimester and once at the end of their third trimester. Of the patients with positive MPXV testing from remnant samples, two were cisgender pregnant women.

Of note, MPXV testing in this study was approved as a part of a research protocol that prohibited disclosure of results to patients and care teams. The positive MPXV results were identified months after these samples were initially obtained and antiviral medications were no longer indicated.

Case 1

19-year-old G1P0 female presented at 24 weeks’ gestation for an initial prenatal exam (Table 1). The patient complained of vaginal itching and was treated with topical metronidazole. No rash or vesicular lesions were noted on exam. She reported one male sexual partner in the last year. CT/NG, human immunodeficiency virus, and syphilis laboratory testing obtained at this visit was negative. She had not been vaccinated against orthopoxviruses. Vaginal swabs collected for CT/NG during this visit were subsequently screened after storage at room temperature for eight weeks via qPCR for MPXV, which was positive with cycle thresholds of 30.7 (viral TNF receptor) and 35.8 (viral DNA polymerase).

Table 1.

Demographics, clinical course, and medications administered. Retrospective mpox testing performed after delivery on remnant vaginal swabs obtained for STI testing. STI: sexually transmitted infection; CT: Chlamydia trachomatis; NG: Neisseria gonorrhoeae; mU: milliunits; g: gram; mg: milligram; kg: kilogram.

	Clinical course	Medications
Case 1
Age: 19 years	•Presented with vaginal pruritus at 24 weeks and underwent STI testing •CT/NG testing negative and mpox test positive from vaginal swab •Labor induced at 36 weeks after developing intrahepatic cholestasis of pregnancy •Chorioamnionitis developed during labor	•Presumed vaginitis treated with topical metronidazole •Induction of labor with cook balloon, oxytocin infusion (2 mU/min) •Chorioamnionitis treated with 2 g IV ampicillin every 6 h for 24 h and 5 mg/kg gentamicin every 24 h for 48 h.
Gender: Female
Parity: 0
Case 2
Age: 22 years	•Screening CT/NG testing at 36 weeks negative •CT/NG testing was negative and mpox test positive from vaginal swab •At 38 weeks 4 days, labor was induced for oligohydramnios after 48 h of fluid leakage •Chorioamnionitis developed during labor	•Induction of labor with oxytocin infusion (2 mU/min) •Chorioamnionitis treated with 2 g IV ampicillin every 6 h for 24 h and 5 mg/kg gentamicin every 24 h for 48 h
Gender: Female
Parity: 0

At 36 weeks’ gestation, the patient presented with a two-week history of severe diffuse pruritus with elevated alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase and was diagnosed with intrahepatic cholestasis of pregnancy. Five days after her presentation for pruritus (and 12 weeks after the positive MPXV sample) she was admitted to the labor and delivery unit at 37 weeks and 3 days for induction of labor. During labor the patient developed a fever to 38.8 ℃. Fetal heart rate tracings showed a baseline rate of 145 bpm with moderate variability, accelerations, and intermittent decelerations (NICHD category II). Based upon these findings she was diagnosed with intrapartum chorioamnionitis and was treated with a 24-h course of ampicillin and gentamicin. Labor was otherwise uncomplicated, and the patient was afebrile postpartum. There were no adverse outcomes in the newborn.

The placenta was sent for pathology and was found to be meconium stained and have inflammation characteristic of amniotic fluid infection. There was a grade 2 (severe) stage 2 maternal response (intermediate), acute chorioamnionitis with an accompanying grade 1 (mild) stage 1 (early) fetal response umbilical cord with chorionic plate vasculitis. Further, there was evidence of chorangiosis and umbilical phlebitis. There was no evidence for viral infection. No samples were sent for culture.

Case 2

A 22-year-old G1P0 female presented at 36 weeks’ gestation for a routine prenatal visit (Table 1). On exam there was no bleeding from the os, membranes were found to be intact, and the fetal heart rate was baseline 150 and given a category I tracing. No rash or vesicular lesions were noted on exam. She reported one male sexual partner in the last year. Laboratory testing for CT/NG, human immunodeficiency virus, and syphilis obtained at this visit were all negative. She had not been vaccinated for orthopoxviruses. A vaginal swab collected for routine CT/NG screening subsequently underwent qPCR for MPXV, which was positive with cycle thresholds of 29.2 (viral TNF receptor) and 35.0 (viral DNA polymerase).

She was next seen at 38 weeks and 4 days gestation when she was admitted to labor and delivery for induction of labor after 48 h of amniotic fluid leakage with oligohydramnios (2.5 weeks after testing positive for MPXV). This patient’s labor was also complicated by chorioamnionitis. Maternal temperature peaked at 38.1 °C. Fetal heart rate peaked at 180 bpm with moderate variability, accelerations, and intermittent late decelerations (NICHD category II). The patient was treated with a 24-hour course of ampicillin and gentamicin after which she remained afebrile. Her postpartum course was uneventful and there were no complications with the patient or newborn. The placenta was not sent for pathology.

In this case series, we describe the clinical courses of two cisgender, heterosexual women with retrospectively identified MPXV test positivity during pregnancy. The perinatal courses of both individuals were complicated by chorioamnionitis, and one experienced intrahepatic cholestasis of pregnancy. Both neonates were delivered successfully, and there were no further maternal or neonatal complications. These two cases contribute to the small but growing body of literature describing MPXV infection during pregnancy (Table 2) [4], [10], [11].

Table 2.

Previously reported mpox cases in pregnant individuals with known gestational outcomes during the 2022–2023 outbreak.

Author/year	Manuscript type	Clinical course
Sampson et al., 2023 [10]	Case report (n = 1)	20-year-old female with genital ulcer positive for mpox virus and herpes simplex virus at 31 weeks’ gestation treated with tecovirimat (600 milligrams twice daily for 14 days). Underwent uncomplicated elective induction at 39 weeks 2 days with delivery of healthy neonate. Histopathologic examination of placenta was normal.
Oakley et al., 2023 [11]	Case series (n = 3)	3/23 patients with mpox during pregnancy in the case series had known gestational outcomes. One patient experienced spontaneous abortion at 11 weeks’ gestation and two patients had full-term uncomplicated deliveries. Further details are not reported.

The impact of MPXV infection during pregnancy on maternal and fetal outcomes remains poorly characterized. Studies from prior MPXV outbreaks have shown that MPXV infection during pregnancy is associated with increased risk for serious adverse outcomes including miscarriage, preterm delivery, and perinatal vertical transmission [4], [6]. From May to November 2022, 23 cases of confirmed MPXV infection in pregnant persons were reported to the CDC [7]. All 23 patients reported rashes at time of diagnosis and four required hospitalization for pain control and treatment of superimposed cellulitis. Of the three individuals for whom birthing outcomes were reported, two had successful and uncomplicated deliveries while one had a spontaneous abortion. There were two reported cases of vertical perinatal transmission, which were successfully treated with oral tecovirimat and vaccinia immune globulin [7].

Unlike prior reports of MPXV infection in pregnancy during the 2022 outbreak, neither of our patients presented with classic mucocutaneous lesions and presumed diagnosis was retroactively made from GC/CT swabs collected for routine testing. Collectively, these results suggest that MPXV infection during pregnancy can have a variable clinical course, ranging from subclinical presentations to severe maternal and fetal complications including fetal loss. It is possible that minimally symptomatic MPXV infections can have clinically significant maternal, fetal, and neonatal outcomes. Further research is needed to clarify if the timing, route of infection, or MPXV clade significantly impacts the clinical presentation of MPXV infection during pregnancy.

The limitations of our study include its small sample size and its retrospective, observational nature. Further, we were unable to assess whether transplacental or perinatal MPXV infection occurred in either neonate. Given the sharp increase of monkeypox incidence in 2022 and the risk for continued or intermittent sustained transmission, further investigation is needed to characterize the presentation, optimal management, and outcomes of MPXV infection in pregnant individuals.

Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

CRediT authorship contribution statement

ZTR: Conception and design of the study, acquisition of data, drafting and revision of manuscript. CAC: Conception and design of the study, acquisition and interpretation of data, creation of figures, revision of manuscript. JL: Conception and design of the study, acquisition of data, interpretation of data, revision of manuscript. DS: Acquisition and interpretation of data, revision of manuscript. CH: Acquisition and interpretation of data, revision of manuscript. MKS: Acquisition and interpretation of data, revision of manuscript. FY: Acquisition and interpretation of data, revision of manuscript. JM: Acquisition and interpretation of data, revision of manuscript. MSJ: Conception and design of study, acquisition and interpretation of data, revision of manuscript. JL: Conception and design of study, acquisition and interpretation of data, revision of manuscript. VL: Conception and design of study, acquisition and interpretation of data, revision of manuscript. BAP: Conception and design of study, acquisition and interpretation of data, revision of manuscript.

Conflicts of interest

None of the authors have conflicts of interest to disclose.

Data

Please submit data requests via email to the corresponding author at ztrenfro@stanford.edu.