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 varicella virus (MPXV) infections.
Study: SMALLPOX AND PREGNANCY: FORECASTING THE RISKS. Image credit: nerudol/Shutterstock
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Studies have reported miscarriages, premature birth, congenital infections, and intrauterine death associated with MPX. However, data on risk factors, clinical presentation, potential placental transmission, mechanisms underlying potential placental transmission, pregnancy complications, and maternal-fetal health outcomes of MPX during 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 the management of MPX during pregnancy.
Reasons and underlying mechanisms of maternal-fetal susceptibility to MPX virus
Pregnant women are highly prone to vertical transmission of MPX virus (MPXV) due to immunological vulnerability, decreased immunity against smallpox among women of reproductive age (15 to 49 years), and since orthopoxviruses can overcome the syncytiotrophoblast placental barrier.
A gestational bias toward a dominant type 2 (Th2) T helper cell milieu (from a dominant Th1 milieu) enhances maternal vulnerability to viral disease. Th1 cytokines such as interferon type 1 (IFN) inhibit viral replication through direct antiviral and indirect immunoregulatory mechanisms. MPXV expresses IFNα/b binding proteins (IFNa/bBP) that prevent IFN-induced host antiviral immune responses.
Also, the eradication of smallpox and the cessation of smallpox vaccinations created a niche for smallpox (genetically similar to smallpox) due to the decline of natural immunity against smallpox. Unimmunized women of reproductive age are prone to MPX due to lack of cross-protective antiviral immunity. Cross-border transmission of MPX in populations lacking prior humoral immunity and in immunosuppressed individuals could allow MPXV to evolve with mutations that increase the virulence of MPXV genetically.
Several mechanisms may be involved in the vertical transmission of MPXV, since MPXV does not express cell-specific receptors that facilitate cell tropism. MPXV can reach the fetus through hematogenous spread that reaches the intervillous space from the maternal uterine spiral arteries and binds to trophoblast cells, subsequently infecting cytotrophoblasts, syncytiotrophoblasts, and cells of fetal endothelium within anchored or floating villi to invade fetal blood cells. .
MPXV could also ascend directly from genital lesions through uterine and cervical tissue and colonize the decidual 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 the management of MPX during pregnancy
Clinicians should suspect MPX among pregnant women who present with (i) unexplained skin rashes or genital ulcers or (ii) ≥ 1 clinical feature such as headache, fever, lymphadenopathy, asthenia, myalgia, asthenia, and (iii) during the previous three weeks. had (a) traveled to nations with cases of MPX, or (b) was in close contact with a person infected with MPX, or (iii) had casual sex during travel.
Serial ultrasonography (USG) surveillance for features of MPX such as placental calcifications, ascites, hepatomegaly, fetal growth restriction, and hydrops could benefit expectant women with reverse transcription polymerase chain reaction (RT- PCR) in real time, confirmed and symptomatic, or those at high risk of MPX. RT-PCR with amniocentesis could establish fetal MPX.
Clearance of MPXV in the amniotic fluid would likely occur after six to eight weeks of MPXV infection when the fetus produces adequate urine or the fetus has skin lesions. MPX in the last trimester of pregnancy or when there are only four weeks of gestation left should not accelerate labor unless there is a clinical emergency or the presence of relevant obstetric factors.
Studies characterizing acute anti-MPX humoral responses have indicated immunoglobulin M (IgM) and IgG seroconversion four days after the onset of clinical rash in unvaccinated individuals. Therefore, postponing delivery ≥7 days after rash onset may allow maternal-fetal anti-MPXV IgG transfer. Cesarean delivery with personal protective equipment (PPE) should be preferred for MPXV-infected women, as MPXV anogenital exposure during vaginal delivery could increase the risk of neonatal sepsis, keratitis, necrotizing dermatologic infections, and encephalitis.
Maternal MPX concerns include complications of neuraxial anesthesia and intubation. For MPXV-infected women with a generalized skin rash, extended-spectrum antibiotics with azithromycin and cefazolin should be administered before skin incision to reduce the risk of surgical site infections (SSI) and endometritis post – caesarean section
For MPX-infected women with generalized mucocutaneous lesions, povidone-iodine should be used as a vaginal and skin antiseptic, and neonates highly prone to perinatally acquired MPX could be given intravenous immune globulin from the vaccine (VIGIV ). MPXV can be transmitted through breast milk; therefore, breastfeeding can be delayed until the mother’s rashes become crusted.
However, if breastfeeding is desired, the newborn should be fully swaddled to decrease skin-to-skin contact, and the infected mother should wear a face mask to reduce droplet transmission. Infant neurocognitive phenotype analysis can be performed to identify any developmental disorders due to possible intrauterine transmission of MPXV. Tecovirimat and VIGIV are considered safer 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 results of the review, MPX could negatively affect maternal and fetal outcomes. Therefore, this category of individuals should be prioritized for MPX treatment and MPX research to develop management guidelines and improve preparedness against MPX.