Mpox (Monkeypox) Infection During Pregnancy

Abstract

BACKGROUND: 

An mpox (formerly “monkeypox”) outbreak began in 2022, leading to infection in special populations, including pregnant individuals.

CASE: 

We present a case of an individual who presented with a labial ulcer and subsequent papular rash at 31 weeks of gestation. She was diagnosed with mpox infection and was treated with tecovirimat. She had an uncomplicated induction of labor at 39 2/7 weeks of gestation and delivered a healthy neonate. The neonate had a positive immunoglobulin G test result for orthopoxvirus but did not have skin lesions or positive molecular test results suggestive of infection.

CONCLUSION: 

Transplacental transmission of mpox is possible, but, in this case, the neonate did not have clinical findings suggestive of active or antenatal mpox infection. Treatment with tecovirimat in gestational cases of mpox may be beneficial.

In Brief

Pregnant individuals are susceptible to maternal mpox (monkeypox) infection and are eligible for treatment. Although transplacental transmission of mpox is possible, this case did not result in fetal infection.

Teaching Points

1. Transplacental transmission of mpox (monkeypox) is known to occur; however, we present a case of third-trimester maternal mpox infection for which the patient was treated with tecovirimat, which resulted in a successful pregnancy without evidence of neonatal compromise or infection.
2. Treatment should be considered in all gestational mpox cases to reduce risk of maternal and neonatal complications.

Mpox (formerly “monkeypox”) is a zoonotic orthopoxvirus that was first diagnosed in humans in the 1970s.¹ Until the 2022 outbreak, mpox historically had been limited to endemic areas in Africa, and human-to-human transmission was considered a rare event.² To date, this recent outbreak has led to more than 85,000 cases globally, and transmission has been associated with close or intimate contact with an individual who has infection.³ Information about infection in special populations such as pregnant individuals and children is limited, hence the importance of this report. We describe the clinical presentation and successful treatment of a pregnant individual with mpox infection during the third trimester, resulting in the delivery of a healthy term neonate.

CASE

A 20-year-old woman at 31 weeks of gestation, with no chronic medical conditions, presented with 2 weeks of vaginal discharge, a new painful vaginal lesion, 1 day of vaginal bleeding, dysuria, and decreased fetal movement. She was admitted due to concerns for urinary tract infection and for fetal monitoring. Her prenatal course was significant for two episodes of gonorrhea infection, chlamydia infection, and a hospitalization at 26 weeks of gestation for pyelonephritis, treated with 7 days of ceftriaxone. Screening laboratory tests for human immunodeficiency virus (HIV) and syphilis were negative at her initial obstetrics appointment.

On admission, the patient was afebrile, normotensive, and tachycardic, with a heart rate of 134 beats per minute. Fetal heart rate monitoring was reassuring, and the patient’s examination did not demonstrate any bleeding or cervical dilation. Genital examination revealed an approximately 1-cm ulcer on the left labia majora, with heaped borders, along with labial swelling (Fig. 1), which was initially suspected to be a herpetic ulcer. Three additional papules with central umbilication were noted on the patient’s abdomen and one on her right lower extremity (Fig. 2). Physical examination revealed tender left inguinal lymphadenopathy. During her hospital course, the vaginal lesion increased in size, with surrounding erythema. The patient developed increasing numbers of erythematous, pruritic lesions on her trunk and extremities. On hospital day 6, she reported that her partner had tested positive for mpox 6 days before the patient's admission. On hospital day 7, a swab from the vaginal lesion tested positive for orthopoxvirus using polymerase chain reaction (PCR). Herpes simplex virus-1 PCR test results from the ulcer were also positive, which was thought to represent viral shedding rather than the etiology of the ulcer. Test results for varicella PCR and aerobic bacterial cultures from the lesion were negative.

Fig. 1.: Genital examination revealing ulcer with heaped borders.

Fig. 2.: Cutaneous examination showing umbilicated papule of the trunk.

The patient was counseled on complications that have been reported in known gestational infections, the potential benefits of reducing fetal complications with the use of tecovirimat, and the potential risks given that this drug has not been studied in pregnant individuals. She elected to proceed with treatment with oral tecovirimat 600 mg twice a day, which was started on hospital day 7. She also received a 7-day course of acyclovir for her concurrent herpes infection. Her obstetric monitoring remained stable, and she was no longer developing new skin lesions; therefore, she was discharged to complete a 14-day treatment course of tecovirimat. On outpatient evaluation, her lesions had fully resolved 10 days after starting tecovirimat. For the remaining antenatal period, weekly ultrasonograms were performed to assess the fetal biophysical profile and evaluate for fetal hydrops, which were reassuring.

Given the minimal information on antenatal risks of mpox infection and reassuring findings from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial,⁴ the patient was offered induction of labor and underwent a scheduled, uncomplicated vaginal delivery at 39 2/7 weeks of gestation. She delivered a viable male neonate weighing 3,209 g, with Apgar scores of 9 and 9. Her postpartum course was uncomplicated. The neonate was placed in an isolation room after delivery and received exclusive formula feedings pending evaluation by the pediatric infectious disease team, per institutional protocol. Examination of the neonate revealed a fluid-filled lesion at the top of the scalp, with some drainage of yellow, serous fluid. This lesion flattened within 2 hours of birth, with mild overlying erythema and yellow discoloration. The significant scalp molding and skin lesion were attributed to occiput posterior positioning during delivery. No fetal scalp electrodes were used during delivery, and no other fetal skin lesions were noted. The neonatal scalp lesion was tested for orthopoxvirus PCR, the result of which was negative. Once the negative test result was returned, isolation precautions were discontinued and the patient was offered the option of breastfeeding because her active lesions had resolved. The neonate's postnatal course was overall uncomplicated, and he was discharged on day of life 2.

Orthopoxvirus PCR test results from the cord blood, fetal serum, maternal vaginal fluid, and the exterior surface of the placenta were all negative. Histopathologic examination of the placenta did not reveal any evidence of chorioamnionitis, villitis, or funisitis. Orthopoxvirus immunoglobulin G (IgG) test results in the neonate were positive. He was seen for follow-up at 3 months of age and had normal growth and development, with no interval illnesses, rashes, or skin lesions.

DISCUSSION

We report a case of third-trimester maternal mpox infection treated with tecovirimat. There is little known on the potential for transplacental transmission of mpox from mother to fetus or the clinical outcomes of fetuses exposed to maternal mpox infection. The Centers for Disease Control and Prevention reported 23 cases of mpox infection during pregnancy in the Unites States between May 11, 2022, and November 7, 2022.⁵ Outcomes were reported for three of those cases: two patients had uncomplicated deliveries without transmission to the neonate, and one patient had spontaneous abortion at 11 weeks of gestation.⁵ This case was included in the Centers for Disease Control and Prevention's report; therefore, this is not an additional unreported case but provides further description of the clinical course and neonatal outcome. Before the 2022 outbreak, four cases of congenital infection had been reported from the Democratic Republic of Congo.⁶ One case occurred during the second trimester and resulted in the birth of a term neonate without evidence of congenital infection.⁶ Three cases resulted in fetal loss, two of which were spontaneous abortions and the third a preterm birth of a stillborn fetus.⁶ Examination of the fetal remains revealed maculopapular rash, hepatomegaly, peritoneal effusions, and hydrops fetalis.⁶ In the stillborn fetus, infection occurred at 18 weeks of gestation; there was cessation of fetal movement 3 weeks after the mother's clinical onset of infection. In addition, there was histologic evidence of fetal infection; however, no serologies were reported.⁶

Given the sparsity of reported cases, there is little guidance on fetal monitoring to detect complications such as those described in the stillborn fetus above. In this case, after maternal infection was confirmed, antenatal care was directed by both extrapolated data from smallpox and the prior reported maternal mpox infections.^6,7 A recently published review article recommends monthly growth ultrasonograms and umbilical artery Dopplers.⁸ Another, more conservative recommendation encourages fetal biometry, anatomic evaluation, measurement of the amniotic fluid volume, and fetal Doppler ultrasonography every 10–14 days.⁹ The American College of Obstetricians and Gynecologists also supports frequent fetal monitoring,¹⁰ but specific evidence-based recommendations are lacking. Our team ultimately initiated weekly antenatal ultrasonography to monitor for the development of fetal hydrops and to assess fetal well-being. In cases of gestational mpox infection, cesarean delivery is recommended unless lesions are resolved and vaginal and rectal PCR test results are negative.⁸ This patient had resolution of lesions at the time of delivery, but vaginal and rectal swabs were not obtained before delivery because this recommendation was released after she delivered.

This case resulted in an uncomplicated delivery and a reassuring physical examination that was not suggestive of fetal infection. The neonate had a positive orthopoxvirus IgG test result, which was collected on day 1 of life. Given the absence of any recognized symptoms, this likely represents placental transfer of IgG antibodies from the mother.

Tecovirimat is an inhibitor of the VP37 envelope wrapping protein of the orthopoxvirus; it is currently approved by the U.S. Food and Drug Administration for treatment of mpox through an expanded access for investigational new drug protocol.¹¹ The patient received tecovirimat, and neither the patient nor her infant have experienced any complications to date. If a pregnant individual becomes infected with mpox, treatment with tecovirimat should be considered to reduce risk of poor maternal and fetal outcomes. Pregnant individuals should avoid exposure to a partner who has tested positive for mpox or has suspicious lesions; however, if they have a high-risk exposure, vaccination with JYNNEOS should also be considered, because it is currently approved for the prevention of smallpox and mpox disease.^10,12