In a recent review published in the American Journal of Obstetrics and Gynecology, researchers described the impact, potential mechanisms, and management of maternal and fetal monkeypox virus (MPXV) infections.
Study: MONKEYPOX AND PREGNANCY: FORECASTING THE RISKS. Image Credit: nerudol/Shutterstock
Background
Studies have reported miscarriages, preterm births, congenital infections, and intrauterine demise associated with MPX. However, data on the risk factors, clinical presentation, potential placental transmission, mechanisms underlying potential placental transmission, pregnancy complications, and maternal-fetal health outcomes of MPX in pregnancy are scarce.
About the review
In the present review, researchers described the potential reasons and underlying mechanisms of maternal MPX infections and approaches to MPX management in pregnancy.
Reasons for and underlying mechanisms of maternal-fetal susceptibility to MPX virus
Pregnant women are highly prone to vertical MPX virus (MPXV) transmission due to immunological vulnerability, waning of anti-smallpox immunity among women of reproductive age (15 to 49 years), and since orthopoxviruses can overcome the syncytiotrophoblast placental barrier.
A gestational bias towards a helper T cell type 2 (Th2)-dominant environment (from a Th1-dominant environment) enhances maternal vulnerability to viral diseases. Th1 cytokines such as type 1 interferon (IFN) inhibit viral replication through direct antiviral and indirect immunoregulatory mechanisms. MPXV expresses IFNa/b-binding proteins (IFNa/bBP) that evade IFN-induced antiviral host immune responses.
Further, smallpox eradication and cessation of smallpox vaccinations created a niche for monkeypox (genetically similar to smallpox) due to waning natural immunity against smallpox. Reproductive age unimmunized women are prone to MPX due to lacking cross-protective antiviral immunity. Cross-border MPX transmission in populations lacking prior humoral immunity and in immunosuppressed persons could allow MPXV to evolve with mutations increasing MPXV virulence genetically.
Several mechanisms may be involved in the vertical transmission of MPXV since MPXV does not express cell-specific receptors that facilitate cellular tropism. MPXV may reach the fetus via the hematogenous spread arriving at the intervillous space from maternal uterine spiral arteries and binding to trophoblast cells, subsequently infecting cytotrophoblasts syncytiotrophoblasts, and cells of the fetal endothelium within the anchored or floating villi to eventually invade blood cells of the fetus.
MPXV could also directly ascend from the genital lesions via uterine and cervical tissue and colonize the decidua and chorionic membranes or could breach the placental barrier by fusing with trophoblasts facilitating internalization of viral DNA and viral replication in the host.
Approaches to MPX management in pregnancy
Clinicians must suspect MPX among pregnant females who present with (i) unexplained skin rash or genital ulcers or (ii) ≥1 clinical feature such as headache, fever, lymphadenopathy, asthenia, myalgia, asthenia, and (iii) within the previous three weeks had (a) traveled to nations with MPX cases, or (b) were in close contact with an MPX-infected individual or (iii) engaged in casual sex in travel.
Serial ultrasound (USG) surveillance for MPX features such as placental calcifications, ascites, hepatomegaly, fetal growth restrictions, and hydrops could benefit expecting females with real-time reverse transcription-polymerase chain reaction (RT-PCR) -confirmed and symptomatic MPX or those at high risk of MPX. RT-PCR with amniocentesis could establish fetal MPX.
MPXV shedding in the fluid of the amnion would probably occur after six to eight weeks of MPXV infection when the fetus produces adequate urine, or the fetus presents with skin lesions. MPX in the final trimester of pregnancy or when only four gestational weeks are remaining must not speed up delivery unless in case of clinical urgency or presence of relevant obstetric factors.
Studies characterizing acute humoral anti-MPX responses have indicated immunoglobulin M (IgM) and IgG seroconversion after four days of the clinical rash onset among unvaccinated persons. Therefore, postponing delivery by ≥7 days post-rash onset may permit maternal-fetal anti-MPXV IgG transfer. Cesarean section delivery with personal protective equipment (PPE) should be preferable for delivery by MPXV-infected women since anogenital MPXV exposure during vaginal delivery could increase the risk of neonatal sepsis, keratitis, necrotizing dermatological infections, and encephalitis.
Maternal MPX concerns include neuraxial anesthesia complications and intubation. For MPXV-infected women presenting with a widespread rash on the skin, extended-spectrum antibiotics with azithromycin and cefazolin must be administered before cutaneous incision to decrease the risk of surgical site infections (SSI) and post-cesarean endometritis.
For MPX-infected women with widespread mucocutaneous lesions, povidone-iodine must be used as a vaginal and skin antiseptic, and neonates highly prone to perinatally acquired MPX could be administered intravenous vaccinia immune globulin (VIGIV). MPXV may transmit via breast milk; therefore, breastfeeding may be delayed until the maternal rashes convert into scabs.
However, if breastfeeding is desired, the neonate must be swaddled fully to decrease cutaneous contact, and face masking must be performed by the infected mother to decrease droplet transmission. Infantile neurocognitive phenotype analysis may be performed to identify any developmental disorders due to potential in-utero MPXV transmission. Tecovirimat and VIGIV are considered most likely safe for MPX treatment. For pre-and post-exposure prophylaxis during pregnancy, the World Health Organization (WHO) has recommended MVA-BN vaccinations.
Conclusion
To conclude, based on the review findings, MPX could adversely impact maternal and fetal outcomes. Therefore, this category of individuals must be prioritized for MPX treatment and MPX research to develop management guidelines and improve preparedness against MPX.
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