Risks of MMR vaccine in immunosuppressed and pregnant patients

May 28, 2019 The Tablet
pregnant woman

The contraindication to MMR vaccine in pregnancy is primarily a precautionary measure.

In the wake of Vancouver’s measles outbreak this past winter, pharmacist Raymond Li explores the need to review immunization status and immunize before pregnancy or immunosuppression when administering MMR vaccine  

By Raymond Li, BSC BC Drug and Poison Information Centre
Reviewed by C. Laird Birmingham, MD, MHSC, FRCPC

The recent measles outbreak has increased use of the measles, mumps, rubella (MMR) vaccine. This increases the possibility that patients with contraindications to the vaccine could inadvertently receive the vaccine, a vaccine that contains live attenuated viruses. The vaccine is contraindicated in patients who are immunosuppressed or pregnant, because of concerns of disseminated infection or risk to the fetus. This column will briefly discuss risks of the MMR vaccine in pregnancy and immunosuppression and steps to take if it is inadvertently administered.

Measles, mumps and rubella

Measles, mumps and rubella are independent diseases but are often thought of together because they cause some similar clinical symptoms (fever, upper respiratory symptoms, lymphadenopathy, maculopapular rash) and because the three vaccines were combined in 1971 to make immunization more efficient. In susceptible individuals, measles, mumps, and rubella are highly contagious diseases that are associated with a high rate of morbidity and mortality. The vaccines are highly effective in preventing infection and its associated morbidity and mortality. 

Infection in immuncompotent individuals is usually self-limited. However, serious complications including pneumonia and secondary infections can occur. Measles can cause diarrhea, otitis media, keratoconjunctivitis and encephalitis. The mortality rate from measles encephalitis is approximately 15%. Mumps complications include meningitis and rarely encephalitis (mortality rate of 1.5%), deafness, and pancreatitis. Rubella complications include arthritis, thrombocytopenia and rarely encephalitis.

In immunocompromised patients, measles can cause more severe disease with a prolonged course and a greater risk of death. The severity of mumps and rubella may not be increased in immunocompromised patients but there is a greater risk of mumps infection even in those with prior vaccination. 

In pregnancy, measles infection can cause severe disease in the mother and is associated with a higher risk of miscarriage and premature delivery. Mumps infection in pregnancy may cause an up to two-fold risk of spontaneous abortion in the first trimester, but disease severity is not increased in the mother. Neonatal parotitis and pneumonia may occur if maternal infection occurs late in pregnancy. Rubella infection is not more severe for the mother, but infection in the period  from just prior to conception up to 10 weeks of gestation can cause malformations in 90% of cases (congenital rubella syndrome =  CRS). Malformations are rare after the 16th gestational week but sensorineural hearing loss can occur as late as 20 weeks.

Estimates from the U.S. and the U.K. are that approximately 2.6% to 3.2% of adults have a major immunocompromising condition, not including HIV/AIDS and end-stage renal disease. 
Attenuating the vaccine viruses

Viruses can be attenuated by serial passage in cells from a species other than the normal host. With each passage in foreign host cells (e.g. chicken), the ability to infect the original host cells (i.e. human) is reduced. The measles and mumps vaccine viruses were attenuated by serial passage in embryonated chicken eggs and whole embryo or fibroblast cell cultures. The rubella vaccine virus was attenuated by passage in human lung fibroblast cell culture at colder temperatures (down to 30° C) which selected for a strain with lower virulence.

Disseminated infection from MMR vaccine viruses 

Immunocompromised patients A systematic review of the literature to 2016 reported the complication rate in 798 patients who received MMR live vaccine.  These patients had bone marrow transplant, or were receiving immunosuppressive therapy for inflammatory disease or solid organ transplant. One patient (juvenile idiopathic arthritis (JIA), on methotrexate) developed a fever and rash 20 days after vaccination, but the reaction was considered to have resulted from the underlying disease. Two other patients with solid organ transplant developed parotitis. In an international survey of rheumatologists and immunologists treating patients with interleukin blockers, one patient with systemic JIA (on canakinumab) received MMR vaccine and developed bacterial pneumonia and flare of her disease; these events were considered not to be vaccine-related. Thus the risk of disseminated disease from vaccine virus strains among immunocompromised patients appears to be low, though the authors of these papers state that the data are not sufficient to change current vaccination recommendations.


Pregnant patientsThe contraindication to MMR vaccine in pregnancy is primarily a precautionary measure. The greatest theoretical concern is with the rubella vaccine virus due to the teratogenic effects of natural infection. Fetal infection has occurred in roughly 3.5% of cases where rubella vaccine was given in pregnancy, but no features of CRS were observed in those cases. The theoretical risk of CRS is estimated to be 0.2 to 2.1%, but the observed risk remains zero as no cases have been reported from the vaccine in more than 3500 vaccinated mothers. The measles vaccine virus has not been shown to cross the placenta and infect the fetus. Although the mumps vaccine virus has been detected in the placenta, it has not been associated with fetal harm. 

Vaccine Strains

The Edmonston measles strain (and Schwartz and Moraten derivatives) used in North American vaccines was isolated from a schoolboy, David Edmonston. The mumps virus strains used are derived from the virus isolated by Merck researcher Maurice Hilleman from his daughter, Jeryl Lynn. The RA 27/3 rubella virus used in MMR vaccines was isolated by Stanley Plotkin et al. at the Wistar Institute in Philadelphia from a tissue sample from the 27th in a series of fetuses aborted during the 1964 rubella epidemic.

Management, monitoring and reporting

For all patients who receive MMR vaccine, adverse events (e.g., adenopathy/lymphadenopathy; parotitis; orchitis; rash; seizures; encephalopathy, encephalitis; meningitis) should be reported if they occur within 30 days following MMR vaccine administration. Refer patients who experience an adverse event to their physician for further assessment and diagnosis. An adverse event following immunization (AEFI) report must be submitted to the public health if the respective AEFI meets reporting criteria. Refer to the BC Immunization Manual, Part 5 – Adverse Events Following Immunization. 

For pregnant patients who inadvertently receive the MMR vaccine, termination of the pregnancy is not warranted. Inadvertent immunization during pregnancy is not considered a medical indication for therapeutic abortion and the pregnant woman should be reassured that teratogenicity from the vaccine has not been observed. An adverse reaction report (exposure during pregnancy) can be submitted to Health Canada’s MedEffect program even if there is no adverse outcome, though if fetal death or malformation occurs an AEFI report must be submitted to the public health unit. Note: Merck and GSK do not have North American pregnancy registries for their MMR vaccines.

For more information, see the BC Immunization Manual or contact your local public health unit. References available at bcpharmacy.ca.

This article is featured in The Tablet. The Tablet features pharmacy and industry news, profiles on B.C. pharmacists, information on research developments and new products.