A commentary on ACOG Practice Bulletin Number 151: Cytomegalovirus, Parvovirus B19, Varicella Zoster, and Toxoplasmosis in Pregnancy.
COMMITTEE ON PRACTICE BULLETINS-OBSTETRICS
ACOG Practice Bulletin Number 151: Cytomegalovirus, Parvovirus B19, Varicella Zoster, and Toxoplasmosis in Pregnancy. American College of Obstetricians and Gynecologists. Obstet Gynecol 2015;125:1510-25. Full text of ACOG Practice Bulletins is available to ACOG members at www.acog.org/Resources-And-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Obstetrics/Cytomegalovirus-Parvovirus-B19-Varicella-Zoster-and-Toxoplasmosis-in-Pregnancy
Cytomegalovirus, Parvovirus B19, Varicella Zoster, and Toxoplasmosis in Pregnancy
Among the many physiologic changes that occur during pregnancy, the maternal immune system is altered to dampen the maternal inflammatory response and allow for fetal antigen tolerance (1, 2). Although such immunologic changes diminish the chance of fetal rejection, they potentially increase maternal and fetal vulnerability to certain infectious diseases. Common infections that cause mild-to-moderate disease in healthy adults and children can cause serious maternal and fetal complications if acquired during pregnancy. A unique concern with maternal infection is the potential for mother-to-child transmission or congenital infection. Cytomegalovirus (CMV), parvovirus B19, varicella zoster virus (VAV) and toxoplasmosis are common infections associated with moderate-to-severe fetal and infant complications when acquired congenitally. The purpose of this document is to update the current understanding of these infections, including their clinical presentations; their modes and risks of perinatal transmission; and their maternal, fetal, and infant effects, and to offer guidelines for preventing and managing these infections during pregnancy.
Used with permission. Copyright the American College of Obstetricians and Gynecologists.
Key points about 4 perinatal infections
by Sarah J Kilpatrick, MD, PhD
Dr Kilpatrick is Helping Hand Endowed Chair, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.
This 2015 Practice Bulletin1 replaces one published in 2000. I will not review the basic facts about the 4 possible perinatal infections (type of virus or parasite, symptomatology, potential impact on the fetus, and methods of diagnosis in the mother and fetus); that information is in the full Practice Bulletin, which I recommend that you read. Listed here are what I consider the key diagnostic points about maternal and fetal infection, highlights of the few new findings, and information on the level A recommendations for each disease.
Risk of transmission to the fetus with maternal primary infection is approximately 30% to 40% and 0.15% to 2% with recurrent infection. If you are suspicious, check maternal immunoglobulin M (IgM) and immunoglobulin G (IgG) with avidity testing.
1. IgG avidity assay measures the maturity of the IgG antibody, which helps to identify a primary infection with greater accuracy than simple IgG and IgM titers. After an initial cytomegalovirus (CMV) infection, the IgG antibody produced has low avidity because it is not mature. After about 4 months, the antibodies mature, hence the high avidity. Therefore, if a woman has low-avidity IgG and positive IgM, she is likely to have a recent primary infection with CMV.
2. Use of polymerase chain reaction (PCR) on amniotic fluid is now recommended for diagnosis of fetal CMV infection. Fetal blood sampling is no onger recommended to make this diagnosis. PCR on amniotic fluid for CMV is more sensitive after 21 weeks’ gestation.
3. Remember that 75% of congenital CMV infections may be due to reactivation of old infection, or reinfection with a new strain of CMV, so evidence of old infection does not rule out the possibility of fetal CMV.
Exposure to an infected individual is associated with a 50% risk of maternal infection and 17% to 33% risk of fetal infection. If exposed, a pregnant woman should have IgG and IgM screening. If the anti-parvovirus IgM titer is positive, the woman is presumed to be infected and fetal infection is possible. The fetus of a woman with confirmed new parvovirus infection based on positive IgM should have be monitored for fetal anemia with serial ultrasounds to evaluate for presence of hydrops and placentamegaly, and Doppler interrogation of the middle cerebral artery (MCA) for peak systolic velocity. Elevated MCA Doppler is concerning for fetal anemia.2 MCA Doppler studies should be performed every 1 to 2 weeks for up to 12 weeks after maternal infection.
1. Fetuses who had hydrops due to maternal parvovirus infection and required in utero transfusion may have an increase in neurodevelopmental impairment.3
2. Routine screening of pregnant women for parvovirus IgM should not be performed.
Level A Recommendation
Pregnant women with acute parvovirus infection should be evaluated for fetal anemia with serial ultrasound studies, including Doppler assessment of peak systolic velocity of the fetal MCA.
Varicella is diagnosed based on typical symptoms. Serology is not generally used for diagnosis. Risk of fetal congenital infection is low (0.4%–2.0%) but neonatal infection when maternal disease occurs between 5 days before delivery until 2 days after delivery is associated with a high rate of neonatal death.
1. From 10% to 20% of pregnant women who contract a primary varicella infection will develop pneumonia and maternal risk of death from varicella is as high as 40%. Thus, these patients should be treated with oral acyclovir and varicella-zoster immune globulin (VZIG).
2. Varicella immunity status should be documented in early pregnancy by history of disease or history of vaccination. If a woman’s history is negative for either disease or vaccination, she can be tested for varicella IgG.
3. Congenitally infected fetuses with no varicella-associated anatomic abnormalities have normal neurodevelopment.4
4. Correction: Conception need be delayed by only 1 month after the varicella vaccine is received. The current practice bulletin says 3 months, but this will be corrected by ACOG in early 2016.
Level A recommendations
1. Oral acyclovir appears safe and should be considered in pregnant women with varicella lesions. The efficacy of intravenous (IV) acyclovir has not been established but it may reduce maternal morbidity and mortality associated with varicella pneumonia.
2. Pregnant women who are not immune to varicella and exposed to active varicella should receive VZIG within 96 hours of exposure to prevent or attenuate disease manifestations. (However, please note that it is very difficult to obtain VZIG and it must be gotten directly from the manufacturer [CDC 2013].5)
Congenital toxoplasmosis occurs in 25% to 50% cases, with higher rates in later gestation. Toxoplasmosis-specific IgM appears shortly after infection and once IgG titers appear, the patient is immune. However, the titers have high rates of false-positive and -negative results. If both IgG and IgM are positive, the infection may be acute and serologic testing should be repeated in 2 to 3 weeks. If IgG is increased, the infection is most likely acute. An experienced laboratory should be used for these assays.
1. Avidity testing can also be used for toxoplasmosis and low avidity is consistent with a primary infection within 5 months.
2. If fetal infection is suspected (eg, primary maternal infection plus fetal findings such as ventriculomegaly, intracranial calcifications, microcephaly, ascites, hepatosplenomegaly, and growth restriction), amniocentesis should be done after 18 weeks and PCR performed on amniotic fluid to test for toxoplasmosis DNA. The recommendation in 2000 was to proceed to fetal blood sampling for diagnosis.
3. Routine serologic testing for toxoplasmosis is not recommended in pregnancy.
Level A recommendations
1. Pregnant women acutely infected with toxoplasmosis should be treated with spiramycin to reduce transplacental transmission. (However, this drug is difficult to get and requires assistance from the FDA because it is not readily available in the United States [CDC 2015].6)
2. Fetal infection with toxoplasmosis should be treated with pyrimethamine, sulfadiazine, and folinic acid because this regimen better eradicates parasites in a fetus and placenta than does spiramycin alone and it can lessen the severity of fetal disease. ï¼
1. Raghupathy R. Th1-type immunity is incompatible with successful pregnancy. Immunol Today 1997;18:478–482. (Level III)
2. Robinson DP, Klein SL. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm Behav 2012;62:263–271. (Level III)
1. American College of Obstetricians and Gynecologists. Practice bulletin no. 151: Cytomegalovirus, parvovirus B19, varicella zoster, and toxoplasmosis in pregnancy. Obstet Gynecol. 2015;125:1510–1525.
2. Norton ME, Chauhan SP, Dashe JS. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol. 2015;212:127–139.
3. De Jong EP, Lindenburg IT, van Klink JM, et al. Intrauterine transfusion for parvovirus B19 infection: long-term neurodevelopmental outcome. Am J Obstet Gynecol. 2012;206:204 e1–5.
4. Mattson SN, Jones KL, Gramling LJ, et al. Neurodevelopmental follow-up of children of women infected with varicella during pregnancy: a prospective study. Pediatr Infect Dis J. 2003;22:819–823.
5. Centers for Disease Control and Prevention. Updated recommendations for use of VariZIG--United States, 2013. MMWR Morb Mortal Wkly Rep. 2013;62:574–576.
6. Centers for Disease Control and Prevention. Toxoplasmosis. DPDx - laboratory identification of parasitic diseases of public health concern. http://www.cdc.gov/dpdx/toxoplasmosis/dx.html. Accessed December 3, 2015.