Monkeypox Clinical Care and Treatment During Pregnancy

Overview

Data are limited regarding monkeypox virus (MPXV) infection in pregnancy. It is unknown if pregnant women are more susceptible to MPXV or if infection is more severe in pregnancy. MPXV can be transmitted to the fetus during pregnancy or to the newborn by close contact during and after birth. Adverse pregnancy outcomes, including spontaneous pregnancy loss and stillbirth, have been reported in cases of confirmed monkeypox during pregnancy in endemic areas. Preterm delivery and neonatal monkeypox have also been reported. The frequency and risk factors for severity and adverse pregnancy outcomes are not known.

Signs and symptoms

The signs and symptoms of MPXV infection in pregnant women appear similar to those in other people with MPXV infection, including prodromal symptoms (e.g., fever, headache, lymphadenopathy, malaise, sore throat and cough) and rash.

The case-finding approach to a patient with suspected monkeypox is the same for pregnant women and others.

During pregnancy:

• The cause of fever may be difficult to differentiate from other infections, such as intra-amniotic infection (chorioamnionitis), until monkeypox lesions appear.
• Differentiate rash in a pregnant woman with risk factors for monkeypox from dermatoses of pregnancy, including polymorphic eruption of pregnancy (also known as pruritic urticarial papules and plaques of pregnancy).
• Carefully evaluate patients with rashes initially considered characteristic of more common infections (e.g., varicella zoster or sexually transmitted infections) for a characteristic monkeypox rash. Consider diagnostic testing especially if the patient has epidemiologic risk factors for MPXV infection.
• Co-infections of MPXV and sexually transmitted infections (STIs) and HIV have been reported, and the presence of an STI does not rule out monkeypox. CDC encourages a broad approach to testing.

Treatment

Although most adults with MPXV infection recover spontaneously, pregnant, recently pregnant, and breastfeeding women should be prioritized for medical treatment if needed. This is because of the probable increased risk of severe disease during pregnancy, risk of transmission to the fetus during pregnancy or to the newborn by close contact during and after birth, and risk of severe infection in newborns.

Offer treatment for monkeypox when indicated to pregnant, recently pregnant, or breastfeeding women. Discuss the risks and benefits of treatment with the patient using shared decision-making.

Closely monitor for severe disease and pregnancy complications. Individualize the decision to treat and monitor a pregnant woman as an outpatient or in the inpatient setting.'

Tecovirimat (also known as TPOXX or ST-246)

Following consultation with CDC, if treatment is indicated, tecovirimat should be considered the first-line antiviral for women who are pregnant, recently pregnant, or breastfeeding. Tecovirimat is an antiviral medication that is FDA-approved for the treatment of human smallpox disease caused by variola virus in adults and children. However, its use for other orthopoxvirus infections, including monkeypox, is not approved by the FDA. Therefore, CDC holds a non-research expanded access Investigational New Drug (EA-IND) protocol (sometimes called "compassionate use") that allows for the use of tecovirimat for primary or early empiric treatment of non-variola orthopoxvirus infections, including monkeypox, in adults and children of all ages.

Information about the impact of tecovirimat on reproductive development is limited to animal studies. No specific fetal effects were observed in these studies in which subject animals were administered oral tecovirimat at levels approximately 23 times higher than the recommended human dosage. It is not known if treatment with tecovirimat during pregnancy prevents congenital monkeypox.

There are no human data on the effect of tecovirimat on milk production, the presence of the drug in human milk, or the effects on breastfed children; information is limited to animal studies. Tecovirimat was present in breast milk in animal studies in which subject animals were administered oral tecovirimat at levels approximately 23 times higher than the recommended human dosage. It is not known if levels of tecovirimat expressed in breastmilk are sufficient for treatment of a breastfeeding child with monkeypox. If indicated, treat breastfeeding children with monkeypox independently.

Tecovirimat use allowed under the EA-IND protocol is intended to be used in concert with CDC guidance for treatment of monkeypox.

Cidofovir and Brincidofovir

Although cidofovir and brincidofovir have been considered as alternative antiviral therapies to treat monkeypox, animal studies showed evidence of teratogenicity. As such, do not use these medications to treat monkeypox in women who are in the first trimester of pregnancy. It is not known if cidofovir and brincidofovir are present in breast milk, so they should not be used in women who are breastfeeding due to the potential for serious adverse reactions in the breastfeeding infant.

Vaccinia Immune Globulin Intravenous (VIGIV)

Animal reproduction studies have not been conducted with vaccinia immune globulin intravenous (VIGIV); therefore, it is not known whether VIGIV can cause fetal harm when administered during pregnancy or whether it can affect future fertility. However, immune globulins have been widely used during pregnancy for many years without any apparent negative reproductive effects. Assess the risks and benefits of VIGIV administration for each individual patient. It is not known whether VIGIV is excreted in human milk, but because many drugs are excreted in human milk, use caution when VIGIV is administered to a breastfeeding woman.

Vaccines

JYNNEOS

JYNNEOS is a live, non-replicating viral vaccine approved by the Food and Drug Administration (FDA) for the prevention of both smallpox and monkeypox disease in individuals who are at high risk for smallpox or monkeypox.

Available human data on JYNNEOS administered to pregnant women are insufficient to determine if there are any vaccine-associated risks in pregnancy. Studies of JYNNEOS vaccine in animals have shown no evidence of harm to a developing fetus.

While there are no data for breastfeeding women, animal data do not show evidence of reproductive harm; breastfeeding is not a contraindication to receiving JYNNEOS. It is not known whether JYNNEOS is excreted in human milk. Data are not available to assess the impact of JYNNEOS on milk production or the safety of JYNNEOS in breastfed infants. However, because JYNNEOS vaccine is replication-deficient, it likely does not present a risk of transmission to breastfed infants.

JYNNEOS can be offered to pregnant or breastfeeding women who are otherwise eligible. The risks and benefits of JYNNEOS should be discussed with the patient using shared decision-making.

Vaccination prior to exposure and post-exposure prophylaxis

Vaccination prior to exposure or post-exposure prophylaxis should be offered when indicated to pregnant or breastfeeding women. The risks and benefits of vaccination should be discussed with the patient using shared decision-making.

Potential impacts for breastfeeding

Contact and breastfeeding

The benefits of skin-to-skin contact and rooming-in on breastfeeding and infant physiology are well known. However, given the risk of neonatal transmission of MPXV with close contact and potential for severe disease in newborns, direct contact between a mother in isolation for monkeypox and their newborn is not advised.

Separation (e.g., separate rooms) of a mother with monkeypox from their newborn is the best way to prevent transmission to the newborn. Full-time rooming in with a newborn is not recommended during a patient's infectious period.

The patient should be counseled about the risk of transmission and the potential for severe disease in newborns. If the mother chooses to have contact with the newborn during the infectious period, take strict precautions:

• No direct skin-to-skin contact.
• Fully clothe or swaddle during contact; after contact, remove and replace the clothing or blanket.
• The patient should wear gloves and a fresh gown at all times and cover all visible skin below the neck.
• Remove soiled linens from the area.
• The patient should wear a well-fitting source control (e.g., medical mask) during visit.

Continue these precautions until criteria for discontinuing isolation have been met (i.e., all lesions have resolved, the scabs have fallen off, and a fresh layer of intact skin has formed).

Discharge planning should take into account the duration of isolation, ability to strictly adhere to recommended isolation precautions, and availability of alternative caregivers.

Women in isolation for monkeypox may experience increased stress because of separation from their newborns, and postpartum depression symptoms may be worsened. Providers are encouraged to share resources with patients about coping with stress during this time.

Breastfeeding

Breast milk provides protection against many illnesses. However, given that MPXV is spread by close contact and neonatal monkeypox infection may be severe, breastfeeding should be delayed until criteria for discontinuing isolation have been met (i.e., all lesions have resolved, the scabs have fallen off, and a fresh layer of intact skin has formed).

Some women who are breastfeeding may need additional support from a lactation provider to initiate and maintain their milk production and avoid a breast infection while monkeypox lesions are healing.

It is unknown if MPXV is present in breast milk. Discard breast milk expressed from a patient who is symptomatic or isolated. To avoid inadvertently exposing an infant to MPXV, a healthy caregiver can feed pasteurized donor human milk or infant formula. Women who are breastfeeding should talk with their healthcare provider to determine if their lesions have healed so they can resume direct breastfeeding or feed expressed breast milk.

Restricting visitors

Limit visitors to pregnant or postpartum women with monkeypox to people essential for the patient's care and wellbeing. Encourage the use of alternative mechanisms for patient and visitor interactions, such as video-call applications for any additional support.

• Aisitors should have no direct contact with the patient. Inform visitors about appropriate use of personal protective equipment (PPE) according to facility visitor policy. Instruct visitors to only visit the patient room and not go to other locations within the facility, including the newborn nursery.

Infection control

Infection control practices for the care of patients with monkeypox who are pregnant are the same as those for patients who are not pregnant, including:

• Appropriately isolating patients with monkeypox
• Training for healthcare personnel on maternity and newborn care units on correct adherence to infection control practices and PPE use and handling
• Ensure sufficient and appropriate PPE supplies are positioned at all points of care.

Notify the pediatric team of the pregnant patient's monkeypox diagnosis to inform newborn evaluation.

Newborns born to women with monkeypox should be placed in isolation, and healthcare personnel caring for newborns born to women with monkeypox should also follow recommendations as specified in CDC's Monkeypox Infection Prevention and Control in Healthcare Settings.