The maternal and perinatal outcomes of pregnancies complicated by monkeypox infection

By Dr. Liji Thomas, MDReviewed by Danielle Ellis, B.Sc.Sep 13 2022

A new study reviews the available evidence on the impact of monkeypox infection during pregnancy.

Introduction

The monkeypox virus is an orthopoxvirus, just like smallpox and cowpox viruses. It has caused multiple outbreaks over the last couple of decades. More recently, a much larger outbreak occurred in developed countries in Europe and North America, none of which were known to be endemic to the disease.

The virus usually causes an initial prodromal phase characterized by fever, headache, enlarged lymph nodes, muscle aches, and severe weakness. The acute phase is then followed by the appearance of a rash spreading out from the point of initial contact with the virus, mostly on the face and limbs.

While most cases resolve spontaneously, pregnant and immunocompromised individuals develop more severe disease, and the mortality rate is somewhat higher compared to the overall mortality of 1%.

Smallpox in pregnancy is known to cause a much higher case fatality rate, especially in the third trimester. With this in mind, the authors of the current study, posted online in the American Journal of Obstetrics and Gynecology MFM, focused on the outcomes of monkeypox in pregnancy. They observed outcomes such as fetal loss, neonatal or perinatal death, fetal anomalies, preterm birth, maternal illness requiring hospitalization, maternal deaths, and vertical transmission.

What did the study show?

The researchers found only 4 studies dealing with 7 cases of monkeypox in pregnancy, two from Nigeria and one each from the Democratic Republic of Congo and Zaire. All the patients were infected during the first half of pregnancy, developed clinical illness, and all were hospitalized.

In this admitted microscopic study sample, none of the mothers died, but ~40% had miscarriages, and one in four babies died in the womb. One baby died at 6.5 weeks of age after birth, but apparently from poor feeding, though the clinical records showed the presence of a rash resembling congenital monkeypox.

Two-thirds of infected pregnancies were affected by fetal loss, in the first trimester, vs. 82% in the second trimester, clearly showing the deleterious effect of monkeypox infection in pregnancy irrespective of the stage of fetal development.

Less than a quarter of the pregnancies resulted in the birth of a live baby. Almost one in ten of the infected mothers had a preterm delivery.

The risk of vertical transmission was not properly assessed as the early second trimester fetal losses were not subject to viral detection tests, namely, polymerase chain reaction (PCR) testing. Despite this, almost two-thirds of infected mothers were found to have transmitted the virus to their progeny, the overall incidence being 62%.

What are the conclusions?

The findings from this systematic review, limited by the very small number of included cases, suggest a high rate of miscarriage and perinatal loss in people with monkeypox infection in pregnancy.”

The infection is associated with an increased risk of miscarriage, fetal death in utero, and vertical transmission. The very small sample size limits the generalizability of the findings, as do the clinical criteria for vertical transmission, which were based on both clinical suspicion as well as virus testing.

However, two fetuses did have signs of monkeypox infection, and severe disease was associated with adverse pregnancy outcomes. For this reason, “accurate fetal surveillance is warranted when maternal monkeypox infection is confirmed, especially when the infection is severe and requires hospitalization.”

Also, since almost all the mothers had to be admitted to hospital for severe illness, this could have confounded the rates of vertical transmission, as well as inflating the rates of adverse perinatal outcomes in pregnancy. Future research is required to establish the actual risk of transplacental transmission, weeding out unrelated causes of fetal death such as chromosomal anomalies and malformations.

Treatment avenues for monkeypox in high-risk patients include Tecovirimat and vaccinia immune globulin, though cidofovir and brincidofovir have shown evidence of teratogenicity in animal studies. A smallpox vaccine recently approved in the EU, Canada and the USA, with live non-replicating virus, is administered to pregnant women who have come into close contact with monkeypox patients. Such women should be given appropriate care depending on the clinical features and the potential effects of the therapy on the pregnancy and lactation.