Mpox (Monkeypox) in Pregnancy Updates

ABSTRACT

Background

Mpox is a zoonotic viral disease caused by the monkeypox virus, with potential for significant morbidity across all population groups, including pregnant individuals and neonates. Pregnancy represents an immunologically vulnerable state, rendering affected mothers more susceptible to severe disease progression.

Objective

To provide obstetricians and maternal‐fetal medicine specialists with an updated synthesis of the clinical presentation, adverse outcomes, and evidence‐based management strategies for Mpox infection during pregnancy.

Methods

A comprehensive literature search was conducted across multiple electronic databases‐Web of Science, PubMed, Scopus, ScienceDirect, ProQuest, Cochrane Library, SAGE, Springer, and Google Scholar‐for peer‐reviewed studies addressing Mpox infection in pregnancy. Additionally, international guidelines and consensus statements were reviewed, including those from the World Health Organization (WHO), Royal College of Obstetricians and Gynecologists (RCOG), Centers for Disease Control and Prevention (CDC), Society for Maternal‐Fetal Medicine (SMFM), and American College of Obstetricians and Gynecologists (ACOG).

Results

Mpox infection during pregnancy is associated with a spectrum of adverse maternal and perinatal outcomes. Pregnant individuals are at increased risk for disease exacerbation, necessitating hospitalization and intensive care. Documented perinatal complications include spontaneous miscarriage, preterm prelabour rupture of membranes (PPROM), preterm birth, intrauterine fetal demise, congenital Mpox infection, low birth weight, and neurodevelopmental delays.

Conclusion

Pregnant individuals diagnosed with Mpox should be prioritized for hospital admission, isolation, antiviral therapy, and continuous monitoring of maternal and fetal well‐being. Multidisciplinary coordination is essential to mitigate risks and optimize outcomes.

1. Introduction

Mpox is a zoonotic disease caused by the monkeypox virus (MPXV), an enveloped, double‐stranded DNA virus belonging to the Orthopoxvirus genus within the Poxviridae family [1].

The virus was first identified in 1958 in Denmark during research involving captive monkeys, and the first human case was documented in 1970 in the Democratic Republic of the Congo [2]. Since then, Mpox has exhibited sporadic outbreaks across various regions, culminating in a global surge that led the World Health Organization (WHO) to declare Mpox a Public Health Emergency of International Concern (PHEIC) on 23 July 2024 [3].

As of November 2024, a total of 115,101 laboratory‐confirmed Mpox cases have been reported across 126 countries, with 255 associated deaths (Figures 1 and 2) [4].

Figure 1.

Global distribution of confirmed cases of Mpox infection. Source: WHO, Mpox (monkeypox), Global trend [4].

Figure 2.

Global distribution of confirmed deaths from Mpox infection. Source: WHO, Mpox (monkeypox), Global trend [4].

Epidemiological data indicate that over 96% of infections occurred in males, while approximately 4% affected females. Among the infected female population, 60 cases were reported in pregnant individuals. Of these, 15 required hospitalizations, though none necessitated intensive care unit (ICU) admission, and no maternal deaths were recorded. Most infections were documented during the second and third trimesters of pregnancy [4].

Given the recent trajectory of transmission and the immunologically vulnerable state of pregnancy, Mpox poses a growing concern for maternal and perinatal health. This review synthesizes current evidence on the clinical presentation of Mpox in pregnancy and outlines recommended management strategies based on international guidelines.

1.1. Transmission of MPOX Infection

Although the MPXV was initially identified in monkeys, its natural reservoir remains unknown. Zoonotic transmission occurs through direct exposure to infected animals via bites, scratches, or contact during high‐risk activities such as hunting, skinning, trapping, cooking, handling carcasses, or consuming bushmeat [5].

MPXV can also be transmitted through direct contact with skin lesions, blood, or bodily fluids of infected animals or individuals. Human‐to‐human transmission is facilitated by respiratory droplets, close physical contact, and exposure to contaminated fomites such as bedding, clothing, or surfaces [6].

Emerging evidence suggests the possibility of vertical transmission [7]. MPXV DNA has been detected in placental tissue, umbilical cord blood, and fetal specimens, indicating transplacental passage. A documented case involved a preterm neonate born to an infected mother who exhibited clinical signs of Mpox and subsequently succumbed to the illness [8, ⁹].

As opposed to Mpox, the TORCH infection in pregnancy has a well‐established group of pathogens with known mechanisms of vertical transmission and significant fetal consequences [10].

Global surveillance data indicate that the predominant mode of transmission in recent outbreaks has been sexual contact, particularly among adult gay, bisexual, and other men who have sex with men [11].

Individuals with Mpox are considered infectious from the onset of symptoms until complete resolution of lesions, including the shedding of scabs. There is also concern regarding potential infectivity during the pre‐symptomatic phase, especially in cases involving mucosal lesions, although current evidence remains limited [12].

1.2. Clinical Presentation in Pregnancy

The clinical manifestations of Mpox infection are typically multisystemic and evolve in distinct phases. Most patients present with a prodrome characterized by fever, headache, myalgia, sore throat, pruritus, photophobia, nasal congestion, and cough. This is followed by the emergence of a characteristic rash, which progresses through macular, papular, vesicular, pustular, and scabbing stages [13, ¹⁴].

Physical examination findings commonly include; lymphadenopathy, involving cervical, submental, axillary, and inguinal nodes, conjunctivitis and ocular involvement, cutaneous lesions, including ulcers and hemorrhagic eruptions, genital ulcers, with occasional reports of scrotal edema in male patients, and hepatomegaly, observed in a minority of cases [15]. The rash distribution is typically centrifugal, with lesions more prominent on the face and extremities. However, involvement of the trunk, scalp, genitalia, oral mucosa, and ocular surfaces has also been documented [16].

The disease course generally follows three phases which include; incubation period (7–14 days) which is asymptomatic and non‐infectious phase; prodromal phase presents with fever, malaise, and upper respiratory symptoms; and eruptive phase presents with rash and mucocutaneous lesions, often accompanied by lymphadenopathy (Table 1) [14, 16].

Table 1.

Typical clinical presentation of Mpox infection in pregnancy [12].

2−21 days	1−5 days	2−3 weeks
Incubation period	Prodromal phase	Eruptive phase
(Exposure to Monkeypox virus to the development of symptoms)	Fever	Appearance of rash 1–3 days after fever subsides. (Rash presents in sequential stages: macule, papules, vesicles, pustules, umbilication, and crust formation)
	Headache
	Backache
	Lymphadenopathy
	Weakness

Appearance of rash 1–3 days after fever subsides. (Rash presents in sequential stages: macule, papules, vesicles, pustules, umbilication, and crust formation)

The clinical presentation of Mpox infection in pregnant individual mirrors that of the general population. However, due to the immunomodulatory changes of pregnancy, affected mothers may experience more severe disease manifestations. This includes heightened risk of systemic involvement, prolonged viral shedding, and increased susceptibility to complications. The immunocompromised state of pregnancy necessitates close monitoring and early intervention to mitigate maternal and fetal risks [17].

1.3. Complications During Pregnancy

Current evidence on the impact of Mpox infection during pregnancy, labor, and the postpartum period remains limited. However, emerging case reports and surveillance data suggest that maternal infection may be associated with adverse obstetric outcomes.

One notable study by Mbala et al. documented four cases of Mpox infection identified during the first and second trimesters of pregnancy. Among these, two pregnancies resulted in spontaneous miscarriage, one culminated in a live birth, and one ended in intrauterine fetal demise [7].

These findings, though based on a small sample size, underscore the potential for serious maternal and perinatal complications. The immunologically altered state of pregnancy may predispose affected individuals to more severe disease progression, with implications for fetal viability and development.

Given the paucity of robust data, there is an urgent need for systematic surveillance and prospective studies to better characterize the clinical course, vertical transmission risk, and outcomes associated with Mpox infection in pregnancy. Until more evidence becomes available, clinicians should maintain a high index of suspicion and prioritize early diagnosis, isolation, and multidisciplinary management for pregnant individuals presenting with suspected Mpox.

1.4. Diagnosis of MPOX in Pregnancy

Obstetricians should maintain a high index of suspicion for Mpox infection in any pregnant individual presenting with unexplained fever, generalized lymphadenopathy, vesiculopustular rash involving the face, trunk, extremities, genitalia, and perianal region [18]. This vigilance is warranted even in the absence of known epidemiological links, given the potential for atypical presentations and underreporting in endemic or resource‐limited settings.

Before considering Mpox, clinicians should first exclude common infectious aetiologies in pregnancy, such as, varicella‐zoster virus, herpes simplex virus, syphilis, cytomegalovirus, and toxoplasmosis [14, 19].

Diagnosis of Mpox relies on molecular detection of viral DNA. The preferred specimen for viral isolation is swab from skin lesions, mucosal surfaces, body fluids, or crusts. Conventional or real‐time polymerase chain reaction (RT‐PCR) is the diagnostic method of choice, and the positive PCR confirms Mpox infection.

In symptomatic patients without visible lesions, alternative sampling sites include, oropharyngeal swab, and rectal swab, especially in cases of suspected sexual transmission.

RT‐PCR on blood sample is not recommended by WHO due to low sensitivity and poor diagnostic yield. Serological (antibody) tests are not used for acute diagnosis. Serological tests may be employed for retrospective classification or epidemiological studies [12].

1.5. Treatment of MPOX Infection in Pregnant Mothers

1.5.1. Mild or Uncomplicated Disease

Pregnant individuals with mild or uncomplicated Mpox infection typically do not require hospitalization. Home isolation is appropriate if infection prevention and control (IPC) measures can be safely implemented in the household setting.

Recommended management includes, symptomatic care: antipyretics, analgesics, antiemetics, topical agents for pruritus and skin lesions, and nutritional support, mental health support: psychological counseling or telehealth‐based mental health services, and remote monitoring: regular follow‐up via telephone or telemedicine to assess for clinical deterioration. Home isolation should be discontinued only after complete resolution of symptoms and desquamation of all scabs [20].

1.5.2. Severe or Complicated Disease

Pregnant individuals with severe or complicated Mpox infection require hospital admission for intensive monitoring and clinical management. Isolation in a designated unit with resuscitative capabilities is recommended.

Clinical care should include; frequent monitoring of vital signs, neurological status, perfusion, nutritional intake, and rash progression; laboratory surveillance: complete blood count, renal and hepatic function tests; supportive therapy: pain control, hydration, nutritional supplementation, and management of systemic symptom; and antiviral therapy: initiation of antiviral agents early in the disease course is advised [21].

Tecovirimat and Brincidofovir are FDA‐approved for smallpox and are currently used under expanded access protocols for Mpox, including in pregnant and lactating individuals [12].

The STOMP Trial (Study of Tecovirimat for Mpox) is ongoing to evaluate the efficacy and safety of tecovirimat across diverse patient populations, including pregnant women. Final results will inform future treatment guidelines [22].

Vaccinia Immune Globulin Intravenous (VIGIV) may be considered in cases unresponsive to antiviral therapy or in conjunction with antivirals for severe disease manifestations. The use of VIGIV in pregnancy should be guided by clinical severity and multidisciplinary consultation [23].

1.6. Obstetric Management of MPOX Infection During Pregnancy

Mpox infection during pregnancy warrants heightened clinical vigilance due to potential maternal and fetal risks. While evidence remains limited, emerging data support a cautious and individualized approach to obstetric care.

Hospital admission should be prioritized for pregnant individuals diagnosed with Mpox to ensure close monitoring and timely intervention.

IPC measures must be rigorously implemented, mirroring protocols used for non‐pregnant patients, including appropriate use of personal protective equipment, isolation protocols, and staff training [24].

Enhanced fetal surveillance is recommended, including; serial ultrasound assessments for fetal growth and well‐being, Doppler study to evaluate placental and fetal circulation, and cardiotocography for real‐time fetal heart rate monitoring [13].

Congenital Mpox infection may be assessed via PCR testing of placental or amniotic fluid specimens, particularly in cases with suspected vertical transmission.

Preterm delivery is not advised in the absence of obstetric indications, as current evidence does not support improved outcomes with early delivery. Term delivery is considered acceptable, although the precise timing of vertical transmission remains unclear.

Cesarean delivery is not routinely recommended for Mpox infection. However, it may be indicated in the presence of active genital lesions to reduce the risk of neonatal transmission. The decision should be guided by shared decision‐making, acknowledging the limited data on perinatal outcomes [13].

Despite its known benefits, breastfeeding is contraindicated during active maternal infection due to the risk of severe neonatal disease. Expressed breastmilk should be discarded during isolation, and breastfeeding may resume once the mother is de‐isolated or confirmed negative for Mpox.

The obstetric care framework for Mpox in pregnancy remains dynamic. As further evidence emerges regarding vertical transmission, delivery timing, and lactation safety, clinical recommendations will require ongoing refinement [24, 25]. Figure 3 outlines the current care pathway, but clinicians should remain adaptable to new data and evolving consensus.

Figure 3.

shows an Obstetric care flow chart for Mpox infection during pregnancy. Source: Obstetric Care flow chart developed based on ACOG, RCOG, and sMFM recommendations [13, 24, 25].

1.7. Mpox Vaccines During Pregnancy and Lactation

Vaccination against Mpox is a critical preventive strategy, particularly for individuals at high risk of exposure. However, vaccine selection during pregnancy and lactation requires careful consideration of safety profiles and available evidence.

Several vaccines originally developed for smallpox are currently recommended for Mpox prevention (Table 2).

Table 2.

Types of vaccines available for Mpox infection for pregnant/lactating mother.

Vaccine types	Vaccine name	Replication status	Recommended in pregnancy/lactation
Non‐replicating	MVA‐BN (Modified Vaccinia Ankara‐Bavarian Nordic)	Non‐replicating	Recommended with caution
Replicating	LC16m8	Replicating	Not recommended
Replicating	ACAM2000	Replicating	Not recommended

1.8. Modified Vaccinia Ankara Bavarian Nordic (MVA‐BN) MVA‐BN

MVA‐BN is a third‐generation, non‐replicating vaccine derived from the Modified Vaccinia Ankara strain, with approximately 30 kilobases deleted from its viral genome to prevent replication in human cells. Although clinical data on its safety and efficacy in pregnant populations remain limited, WHO recommends its use in pregnant and lactating individuals when the anticipated benefits outweigh potential unknown risks. This recommendation is supported by preclinical studies in rats and rabbits, which have shown no evidence of teratogenicity [26].

The Centers for Disease Control and Prevention (CDC) also support the use of MVA‐BN in pregnancy and lactation, advising that it may be offered following a shared decision‐making process. This approach ensures that patients are informed of both the benefits and the limitations of current safety data [27].

1.9. Replicating Vaccines: LC16m8 and ACAM2000

Replicating vaccines such as LC16m8 and ACAM2000 are not recommended for use in pregnancy or during breastfeeding. Their safety and efficacy have not been adequately studied in these populations, and the potential for viral replication raises concerns regarding fetal exposure and adverse maternal outcomes.

Therefore, MVA‐BN is the only Mpox vaccine currently recommended for use in pregnancy and lactation, supported by WHO, CDC, European Medicines Agency, and Public Health Agency of Canada [26, 28].

WHO recommends mpox vaccination for healthcare workers who are at risk of exposure, particularly during outbreaks or in areas with community transmission. WHO does not recommend mass vaccination for the general population to optimize limited vaccine supply [29].

1.10. Implication of MPOX Infection

Mpox, initially endemic to several African countries, has emerged as a global public health concern due to its increasing geographic spread and potential for sustained human‐to‐human transmission. While the general population may experience a self‐limiting illness, Mpox infection during pregnancy poses heightened risks, with potential for severe maternal disease and adverse fetal outcomes.

Pregnancy presents unique clinical challenges in infectious disease management, particularly due to concerns around teratogenicity, spontaneous miscarriage, preterm birth, and stillbirth. Emerging evidence suggests that vertical transmission of Mpox is possible, and maternal infection may result in significant obstetric complications.

Given these risks, it is imperative that obstetricians and maternal health providers remain informed and vigilant regarding Mpox epidemiology, clinical presentation, and evidence‐based management strategies. Proactive dissemination of updated guidelines and integration of Mpox preparedness into maternal health protocols are essential to mitigate risks should future outbreaks or pandemics occur.

1.11. Evidence Gaps and Future Research Priorities for MPOX in Pregnancy

First human infection of Mpox was detected in 1970 in the Democratic Republic of the Congo, and followed by outbreaks reported from multiple countries, and by July 23, 2024 WHO had declared as Public Health Emergency of International Concern [13]. There were multiple discussion focusing on the Mpox infection, however, the knowledge among the sexual medicine experts, and the healthcare professionals were low, and also demonstrated a negative attitude towards Mpox infection [30, 31. There is a need for educating health professionals on the Mpox infection, and it is more crucial for the obstetricians to have adequate knowledge and stay updated with the latest available management guidelines on new uprising diseases.

Despite growing global attention to Mpox, the evidence base concerning its impact on pregnancy remains critically underdeveloped. The paucity of robust clinical data, coupled with limited inclusion of pregnant individuals in surveillance and research efforts, presents significant challenges to evidence‐based maternal care and public health preparedness.

The information on clinical outcomes and vertical transmission remain scare. The current literature offers only isolated case reports and retrospective analyses, primarily from endemic regions, with limited generalizability. The mechanisms and frequency of vertical transmission‐whether transplacental, intrapartum, or postpartum‐remain poorly understood. Documented cases of fetal demise and neonatal Mpox suggest potential for severe outcomes, yet systematic data are lacking [4].

Studies on placental pathology and fetal tissue to confirmed vertical transmission cases to elucidate mechanisms is required.

The MVA‐BN (JYNNEOS) vaccine, recommended for Mpox prevention, has not been adequately studied in pregnant populations. Safety profiles, immunogenicity, and passive antibody transfer to neonates are unknown, leaving clinicians without clear guidance on risk‐benefit assessments for vaccination during pregnancy [32]. Rigorous evaluation of MVA‐BN safety and immunogenicity in pregnancy, with long‐term follow‐up of exposed neonates is required.

Antiviral agents such as tecovirimat and brincidofovir are being used under expanded access protocols, but their safety, pharmacokinetics, and efficacy in pregnancy are unvalidated. There is an urgent need for pregnancy‐specific dosing guidelines and pharmacovigilance systems [27]. Monitoring of antiviral use in pregnancy, including maternal‐fetal drug transfer and adverse event reporting is necessary.

Obstetric management recommendations for delivery mode in Mpox‐positive pregnancies are largely extrapolated from other viral infections. While cesarean delivery is advised in the presence of genital lesions, there is no consensus for asymptomatic or recovering individuals. Comparative studies on transmission risk by delivery method are absent. A coordinated global research agenda like prospective cohort studies to track maternal, fetal, and neonatal outcomes across trimesters and geographic contexts longitudinally is essential.

Pregnant individuals are frequently excluded from outbreak surveillance, vaccine trials, and therapeutic studies. This exclusion perpetuates data gaps and undermines equitable healthcare responses. Ensuring representation of pregnant individuals in future vaccine and therapeutic trials, with appropriate ethical safeguards is necessary.

2. Conclusion

Mpox is an emerging infectious disease of global concern, with increasing incidence beyond its historically endemic regions. Pregnant individuals are considered a high‐risk population, as they may be more susceptible to severe disease progression and increased mortality. Early confirmation of diagnosis, assessment of disease severity, and prompt initiation of treatment are critical to improving maternal and fetal outcomes.

Although data on perinatal outcomes remain limited, reported complications include miscarriage, preterm birth, and stillbirth, suggesting potential vertical transmission and placental involvement. In light of these risks, a multidisciplinary approach to monitoring and management is recommended. A serial ultrasound examination to assess fetal growth and detect anomalies, evaluation for congenital infection, particularly in cases of confirmed maternal Mpox, delivery at term, when feasible, to optimize neonatal outcomes; testing of placental tissue and cord blood for Mpox virus at delivery, postnatal isolation of the neonate born to a mother with active Mpox infection, pending virologic assessment.

Given the paucity of evidence regarding Mpox in pregnancy and the postpartum period, clinical decisions should be made in close consultation with infectious disease specialists, ensuring individualized care that balances maternal and neonatal risks.

Author Contributions

Yeshey Dorjey: concept, literature review, manuscript writing, editing, and review, read and approved the final version of the manuscript. Deep Kiran Chhetri: concept, manuscript writing, editing, and reviewing, and approved the final version of the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Transparency Statement

The lead author Yeshey Dorjey affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.