Obgyno Wino Podcast Episode 87 - Cytomegalovirus, Parvovirus B19, Varicella Zoster, & Toxoplasmosis
"Nothing in this world can take the place of persistence. Talent will not: nothing is more common than unsuccessful men with talent. Genius will not; unrewarded genius is almost a proverb. Education will not: the world is full of educated derelicts. Persistence and determination alone are omnipotent." - Calvin Coolidge
PB #151 - Published June 2015 (Reaffirmed 2017)
1. Primary CMV infection in the first trimester carries the greatest risk to the fetus.
2. Parvo B19 exposure in pregnancy carries the risk of hydrops fetalis. Risk is higher earlier in gestation, but unlikely to develop if it hasn't developed by 8 weeks after maternal exposure.
3. Without treatment, there is a 10-15% risk of vertical transmission of toxoplasmosis in 1st trimester; as high as 60% in 3rd trimester, but the earlier the fetus is infected, the more severe the disease.
4. In pregnancies affected by parvo B19 infection, serial ultrasound should be recommended q1-2 weeks for 8-12 weeks after exposure to monitor for fetal ascites, placentomegaly, cardiomegaly, hydrops fetalis, and fetal growth restriction. Peak systolic velocity of the fetal middle cerebral arteries can also be monitored to predict fetal anemia.
5. Of these four infectious agents, varicella is the only one for which universal screening is recommended
Cytomegalovirus (CMV) basics
- double-stranded DNA virus in the herpes family
- spread through blood, urine, and saliva
- viremia can be detected 2-3 weeks after exposure in primary infection
- generally asymptomatic infection, but some people experience all of the normal flu-like symptoms
- lab values may show leukocytosis, lymphocytosis, abnormal liver function
- after primary infection, the virus can remain latent, emerging whenever it's feeling dandy (secondary infection)
- you can also be re-infected with a different strain
- incidence of primary infection is generally unknown, ranging from <0.4% to 4%
- secondary infection incidence is 14%
- vertical transmission can result from primary or secondary infection that passes across the placenta, exposure to contaminated genital tract secretions during birth, or breastfeeding
- congenital CMS is usually asymptomatic, though some may have jaundice, petechiae, thrombocytopenia, hepatosplenomegaly, and myocarditis
- CMV is the most common congenital infection (0.2 - 2.2% neonates)
- it's also very likely that you've been exposed in the past...
- transplacental transmission poses most significant risk of fetal infection: 30-40%
- greatest risk of transmission during 3rd trimester (up to 70%, compared to 30% in first trimester)
- however, first trimester transmission is more dangerous for the fetus
- of fetuses exposed in first trimester through primary infection of mom, 15% will have signs and symptoms at birth and up to 25% will develop sequelae
- 30% of severely infected infants will die, and 65-80% of survivors will be left with severe neurologic morbidity (e.g. hearing loss)
- risk of severe infection is far less with a secondary infection; vertical transmission risk is <2%
- really no great way to prevent infection, and there vaccine efforts are lacking phase III trials
How is maternal CMV diagnosed?
- PCR on saliva, urine, blood, cervical secretions, or breastmilk
- serologic testing is more common: anti-CMV IgG and IgM
- presence of IgM plus low-avidity IgG (produced before high-avidity IgG) is 92% sensitive for an infection that occurred within the past 2 months
- IgM is kinda tricky with CMV: only 10-20% of women with CMV IgM have a real primary infection (low specificity, high sensitivity)
- IgM titers can be elevated for many months after primary infection, may reflect reactivation or recurrent infection, or may be present in the absence of infection
- universal screening is not recommended (though can be considered in a patient with HIV or otherwise immunosuppressed)
Note: Yes. The practice bulletin states that CMV IgM may be elevated in the absence of infection. I looked through the original sources, and I can't make sense of that statement...I wrote to the editors, but I haven't heard back.
How is fetal CMV diagnosed?
- may be suspected in the first place in the context of a maternal infection
- ultrasound findings may be suggestive: abdominal and liver calcifications, hepatosplenomegaly, echogenic bowel or kidney, ascites, cerebral ventriculomegaly, intracranial calcifications, microcephaly, hydrops fetalis, and growth restriction
- each of these soft markers has poor positive predictive values in isolation
- PCR or culture of amniotic fluid (collected by amniocentesis) is diagnostic; PCR is more sensitive (80-90%) with upwards of 98% specificity; better sensitivity at <21 wga
There's no treatment of fetal or maternal CMV infection
- anti-viral therapies are approved by the FDA for patients with AIDS or history of organ transplant, but they aren't recommended in pregnancy
- CMV immune-globulin is currently under investigation as a means of preventing vertical transmission in primary CMV infection
- refer to MFM
Parvo B19 basics
- single-stranded DNA virus
- spread through respiratory secretions and hand-to-mouth
- an infected person is generally infectious for 5-10 days following exposure, prior to the onset of rash
- causes childhood xanthem erythema infectiosum (aka fifth disease)
- facial rash that looks like the kid was backhanded + fever, body rash, and arthralgias
- in adults, 20% of people are completely asymptomatic (but truncal rash and arthropathy are common)
- most infections are mild
- aplastic crisis is the most dreaded manifestation; generally transient; more common in patients with underlying hemoglobinopathies
- it's highly likely that you've already been exposed (50-65% of women of reproductive age are seropositive)
- if somebody in the household is exposed, 50% rate of seroconversion (20-50% risk of transmission if exposed in a child care setting or classroom)
- acute parvo B19 infection in pregnancy carries 15-30% risk of vertical transmission
- usually no risk to pregnancy, but there is an association with spontaneous abortion, hydrops fetalis, and stillbirth (esp if exposure occurs at <20 wga)
- 10-15% chance of pregnancy loss if infection occurs at <20 wga versus 5% at >20 wga
- up to 25% of nonimmune hydrops cases are associated with parvo B19 (the virus is cytotoxic to erythrocyte precursors)
- hydrops is unlikely to develop if it hasn't developed by 8 weeks after maternal exposure
- unclear long-term consequence of fetal exposure in the absence of disease including hydrops fetalis
- universal screening is not recommended
How is maternal parvo B19 diagnosed?
- if exposed, get serologies
- IgM negative w/ IgG positive --> prior exposure (immunity!)
- if IgM is positive (regardless of IgG status), you should recommend monitoring for fetal infection
- if IgM and IgG were negative both exposure is suspected, repeat serologies in 4 weeks
How is fetal parvo B19 diagnosed?
- PCR of amniotic fluid has a sensitivity of ~100%
- test if fetus shows signs of hydrops
How should pregnancies affected by parvo B19 by managed?
- serial ultrasound to monitor for fetal ascites, placentomegaly, cardiomegaly, hydrops fetalis, and fetal growth restriction (q1-2 weeks for 8-12 weeks after exposure)
- Doppler assessment of fetal middle cerebral arteries (peak systolic velocity) should be performed --> accurate predictor of fetal anemia
- fetal death can occur in absence of hydrops, but if still no sequelae 8-12 weeks after exposure, adverse outcomes are improbable
- if hydrops fetalis is present or severe fetal anemia is suspected based on Dopplers, you need to sample fetal hematocrit, as fetal blood transfusion will likely be required
- MFM should be helping you along the way
Varicella zoster virus (VZV) basics
- double-stranded DNA virus within the herpes family
- transmitted by respiratory droplets or close contact
- 60-90% infection rate if you are seronegative
- period of infectivity begins 48 hrs after vesicular rash appears (and persists until all vesicles have crusted over)
- other normal flu-like symptoms accompany the rash
Fun fact: Why did childhood varicella vaccination become so popular? Prior to the vaccine introduction in the U.S. in1995, 13,000 people would be hospitalized annually for varicella infection. 150 people died annually on average. After the vaccine became routine, annual deaths from VZV dropped to 14, predominantly adults >50 years.
- even before vaccination, risk of infection in pregnancy was low (<1-in-1000) because natural immunity levels were high
- infection is usually benign and self-limited, especially in children
- adults are more likely to suffer the serious consequences such as encephalitis and pneumonia
- 10-20% of pregnant who are exposed to VZV will develop pneumonia, which can carry a mortality rate of ~40%
- VZV can cross the placenta, resulting in congenital chickenpox
- 0.5-2% risk in 1st or 2nd trimester; 0% risk in 3rd
- congenital VZV can result in skin scarring, limb hypoplasia, chorioretinitis, and microcephaly
- neonatal VZV can be lethal to newborn if maternal disease developed w/in 5 days of birth or w/in 48 hrs postpartum (high viral load!)
- risk of transmission from contact with a person with active herpes zoster (shingles), but extremely unlikely compared to primary chickenpox
- universal screening is recommended early in pregnancy; if non-immune, vaccine is recommended immediately postpartum, with 2nd dose 4-8 weeks later
- pregnancy should be delayed for 1 month after the 2nd dose, as the vaccine is a live virus
How is maternal VZV diagnosed?
- clinical diagnosis, largely (kinda hard to miss that rash...)
- you can also perform PCR on sample from unroofed vesicle
- you can check serologies as well
How is fetal VZV diagnosed?
- monitor by ultrasound if acute maternal infection is diagnosed
- look for: hydrops, hyperechogenic foci in the liver and bowel, cardiac malformations, limb deformities, microcephaly, and fetal growth restrictions
Management of VZV infection in pregnancy
- oral acyclovir, if started within 24 hrs of the rash, can reduce the duration of symptoms/rash
- no additional benefit demonstrated with IV formulation
- anti-viral therapy doesn't ameliorate or prevent fetal effects
- if a non-immune patient is exposed, varicella zoster immune globulin (VZIG) should be administered within 4 days of exposure to reduce the risk of vertical transmission (evidence to support this practice is limited)
- VZIG should be given to newborns born to women who develop a varicella infection within 5 days of birth or 2 days after
- if infants show signs of varicella infection within 2 weeks of life, IV acyclovir is recommended
- caused by the intracellular parasite Toxoplasma gondii (T. gondii)
- review the life cycle
- oocytes and cysts are the latent forms
- tachyzoites ("trophozoites") are the invasive form
- transmission can occur through contact with cat poop or infected soils or consumption of undercooked meat or contaminated dairy from infected animals
- infection is usually asymptomatic, although nonspecific signs (e.g. non-tender cervical lymphadenopathy, fever, malaise, and hepatosplenomegaly) can appear in 10-20% of people after the 5-18 day incubation period
- without treatment, there is a 10-15% risk of vertical transmission in 1st trimester; as high as 60% in 3rd trimester, but the earlier the fetus is infected, the more severe the disease
- if infected in-utero, most newborns will have no signs of infection at birth (rash, hepatosplenomegaly, ascites, fever, periventricular calcifications, ventriculomegaly, or seizures), but 90% will develop sequelae with time (e.g. chorioretinitis, hearing loss, and severe developmental delay)
- universal screening is not recommended
How is maternal toxoplasmosis diagnosed?
- serum testing for T. gondii antibodies is the best we've got
- high false-positive and false-negative rates, though
- IgM can persist for many months or years after acute infection
- if IgM is negative and IgG is positive --> remote infection
- if IgM is negative, IgG is negative --> likely never exposed
- if IgM is positive, IgG is positive --> who the hell knows; you're looking either at a recent infection or a false-positive IgM
- you can repeat serologies in 2-3 weeks to look for an increase in IgG titers, which would suggest a recent infection
- low avidity IgG suggests infection was within the past 5 months
How is fetal toxoplasmosis diagnosed?
- if maternal infection is suspected, ultrasound can provide additional information
- look for: ventriculomegaly, intracranial calcifications, microcephaly, ascites, hepatosplenomegaly, and IUGR
- pretty darn suspicious? PCR of amniotic fluid is diagnostic; wait until >18 wga due decrease chance of false negative
How is toxoplasmosis in pregnancy managed?
- maternal treatment does not improve fetal outcomes
- nevertheless, the PB mentions that spiramycin can reduce placental transmission in the event of exposure
- if the fetus has been exposed, a combination of pyrimethamine, sulfadiazine, and foinic acid is recommended
- the same combination is recommended for neonates with toxoplasmosis infection for a duration of 1 year!