Discordancy and fetal sex
Volume 162 Number 3
3. 4. 5.
6.
of fetal growth for the United States of--""merica. AM J OBSTET GVNECOL 1976; 126:555-64. Hoffman HJ, Stark CR, Lundin FE, AshbrookJD. Analysis of birth weight, gestational age, and fetal viability, U.S. births, 1968. Obstet Gynecol Surv 1974;29:651-81. Guttmacher AF, Kohl SG. The fetus of multiple gestations. Obstet GynecoI1958;12:528-41. Corney G, Thompson B, Campbell DM, MacGillivray I, Seedburgh D, Timlin D. The effect of zygosity on birth weight of twins in Aberdeen and Northeast Scotland. Acta Genet Med Gemellol (Roma) 1979;28:353-60. Corey LA, Nance WE, Kang KW, ChristianJC. Effects of type of placentation on birth weight and its variability in
7. 8. 9. 10.
monozygotic and dizygotic twins. Acta Genet Med Gemellol (Roma) 1979;28:41-50. Blickstein I, Shoham-Schwartz Z, Lancet M, Borenstein R. Characterization of the growth-discordant twin. Obstet Gynecol 1987;70: 11-5. Blickstein I, Lancet M. The growth discordant twin. Obstet Gynecol Surv 1988;43:509-15. Robertson EG, Neer KJ. Placental injection studies in twin gestation. AM J OBSTET GVNECOL 1983; 147: 170-3. Blickstein I, Lancet M. Second-breech presentation in twins-a possible adaptive measure to promote fetal growth. Obstet Gynecol 1989;73:700-2.
Fetal cytomegalovirus infection: A case report Richard L. Meisel, MD: Manuel Alvarez, MD," Lauren Lynch, MD," Usha Chitkara, MD: David J. Emanuel, MD,b and Richard L. Berkowitz, MD"
New York, New York Congenital cytomegalovirus infection is the most common perinatal infection. We describe a case of primary maternal cytomegalovirus infection during pregnancy and the prenatal diagnosis of fetal cytomegalovirus infection. Diagnosis was accomplished with percutaneous umbilical blood sampling. The fetal blood was evaluated with viral cultures. cytomegalovirus serologic testing, and nonspecific indicators of infection. Amniotic fluid was also cultured. All cultures were positive, which confirmed fetal infection. The pregnancy was terminated. Autopsy findings were consistent with fetal infection. The significance and utility of prenatal diagnosis are discussed. (AM J OBSTET GVNECOL 1990;162:663-4.)
Key words: Prenatal diagnosis. cytomegalovirus, pregnancy, fetal infection
Cytomegalovirus is the most common perinatal infection with the maJority of infected infants having a silent course without any obvious clinical problem at birth. However, 5% to 10% will have severe deficits, that include microcephaly and severe retardation. I U nfortunately, there is very little long-term follow-up information on the remaining infants, but some will develop adverse neurologic sequelae, including deafness and mild cognitive impairment. Thirty to fifty percent of women of childbearing age in the United States are susceptible to cytomegalovirus infection and approximately 1.4% to 2.2% will undergo seroconversion during pregnancy.2
From the D1VtllOn of Maternal-Fetal Medzcme, Department of Obstetncs, Gynecology and ReproductIVe SCience, Mount Smaz Medical Center," and the Department of PedUltncs, Memonal Sloan Kettenng Cancer Center. b RecelVedfor publlcatzan August 28, 1989; revzsed October 2,1989; accepted October II, 1989. Reprint requests: RIchard L. Mezsel, MD, Department of Obstetncs, Gynecology and ReproductIVe SCIence, Mount Smaz MedIcal Center, One Gustave L. Levy Place, New York, NY 10029.
611117368
Case report A 27-year-old, white woman, gravida 1, para 0, at 11 weeks' gestation was admitted to the hospital with a 3week history of fever, fatigue, and malaise. An expressive aphasia had developed during the day before admission. The physical examination showed an obese white woman with a temperature of 100.4 F, a mild expressive aphasia, and an II-week gestation. Her evaluation is summarized in Table I. The patient was discharged from the hospital 5 days after admission, after resolution of the symptoms, with the diagnosis of atypical migraine and primary cytomegalovirus infection. The patient was referred to our center for further evaluation (Table I). A diagnostic percutaneous umbilical blood sampling was offered, and the couple, planning to terminate the pregnancy if fetal infection was present, elected to proceed with the percutaneous umbilical blood sampling. The percutaneous umbilical blood sampling was performed uneventfully at 21 weeks' gestation and results were available within 5 days (Table I). Three days later, the pregnancy was terminated and an autopsy revealed a grossly normal male fetus with histologic evidence of nonspecific acute infection (white blood cell infiltrates in the lung and liver). There were rare inclusion cells, and immunofluores-
663
664 Meisel et al.
March 1990 Am J Obstet Gynecol
Table I. Clinical summary Test
Maternal evaluation White blood cell countt (No.lml) Lactate dehydrogenaset (lUlL) 'V-Glutamic pyruvic transaminase (IV IL) Serum glutamic oxaloacetic transaminaset (IV IL) Serum-glutamic pyruvic transaminaset (IV IL) Immunoglobulin M for cytomegalovirust Immunoglobulin G for cytomegalovirus Computerized tomographic scan Convalescent serologic testing Immunoglobulin M for cytomegalovirus Immunoglobulin G for cytomegalovirus Fetal evaluation Vltrasonogram Echocardiogram Fetal blood White blood cells (No./ml) Neutrophils (%) Lymphocytes* (%) Monocytes* (%) Eosinophils* (%) Platelets (No./ml) Red blood cells (No./ml) Hemoglobin (gml dl) Hematocrit (%) Lactate dehydrogenase (IV Iml) 'V-Glutamic pyruvic transaminase* (IVlml) Immunoglobulin M for cytomegalovirus (IV I ml) Fetal cytomegalovirus cultures Fetal bloodt Amniotic fiuidt
Result
13,500
Normal value*
4,000-10,000
280
94-172
240
8-69
117
12-45
172
7-40
Positive Negative Normal
Borderline Positive Normal Normal 3,500 2 60 15 5 258,000 3,180,00 13 40 202 60
4,200 5.5 81 1.5 1 254,000 2,890,00 12.2 37.8 261 24.4
Negative
Positive Positive
*Normal values for fetal blood (from Daffos F, Forestier F. Medicine et biologie du foetus humain. Paris: Maloine, 1988). t Abnormal result. *Varies >2 SD from normal. cence tissue studies were positive for cytomegalovirus in the fetal kidney, brain, liver, lung, adrenal, and placenta. Comment
In this case the fetal blood was both cultured and evaluated for nonspecific evidence of infection. The
latter assays were performed to look for other evidence of infection if the cultures were negative. These nonspecific indicators have been shown to be reliable predictors of fetal toxoplasmosis infection. Detection of specific fetal immunoglobulin M is unequivocal evidence of infection but may not have been seen because the immature fetal immune system has a variable response to infectious agents in the mid trimester. Positive cultures clearly documented fetal infection, and abnormalities in the differential cell count and 'V-glutamic pyruvic transaminase are consistent with fetal disease. The hallmark of this severe neonatal infection is cytomegalic inclusion disease. The autopsy result in this case was suggestive of early or mild cytomegalic inclusion disease. The findings of white blood cell infiltrates were consistent with acute infection. Immunoflorescent antibodies to viral proteins proved disseminated fetal infection, but it is unknown whether this would have evolved into the severe debilitating disease state. 1 Since a significant number of the infected neonates are born without clinical signs of cytomegalovirus infection, it is certainly possible that this fetus could have been born without obvious sequelae from its infection. The significance of documenting fetal infection in the presence of normal ultrasonograms is unclear. Advances in laboratory methods and technologies have improved the accuracy of cytomegalovirus diagnosis, and percutaneous umbilical blood sampling has provided a method for obtaining more specific information about the fetus in a timely fashion. Although this has allowed us to inform a patient that her fetus has been infected, in the absence of abnormalities detected on ultrasonography one is currently unable to predict whether the fetus will be adversely affected. In the absence of demonstrable evidence of infection, it may not be justified to assume that the fetus would be born uninfected since the virus could enter the fetal circulation after the fetus has been tested. Further work will delineate the prognostic significance and clinical utility of the prenatal detection of fetal cytomegalovirus infection. REFERENCES 1. Stern H, Tucker SM. Prospective study of cytomegalovirus infection in pregnancy. Br Med J 1973;2:268-70. 2. Stagno S, Pass RF, Dworsky ME, et al. Congenital cytomegalovirus infection: the relative importance of primary and recurrent maternal infection. N Engl J Med 1982; 306:945-9.
Volume 162 Number 3
3. 4. 5.
6.
of fetal growth for the United States of--""merica. AM J OBSTET GVNECOL 1976; 126:555-64. Hoffman HJ, Stark CR, Lundin FE, AshbrookJD. Analysis of birth weight, gestational age, and fetal viability, U.S. births, 1968. Obstet Gynecol Surv 1974;29:651-81. Guttmacher AF, Kohl SG. The fetus of multiple gestations. Obstet GynecoI1958;12:528-41. Corney G, Thompson B, Campbell DM, MacGillivray I, Seedburgh D, Timlin D. The effect of zygosity on birth weight of twins in Aberdeen and Northeast Scotland. Acta Genet Med Gemellol (Roma) 1979;28:353-60. Corey LA, Nance WE, Kang KW, ChristianJC. Effects of type of placentation on birth weight and its variability in
7. 8. 9. 10.
monozygotic and dizygotic twins. Acta Genet Med Gemellol (Roma) 1979;28:41-50. Blickstein I, Shoham-Schwartz Z, Lancet M, Borenstein R. Characterization of the growth-discordant twin. Obstet Gynecol 1987;70: 11-5. Blickstein I, Lancet M. The growth discordant twin. Obstet Gynecol Surv 1988;43:509-15. Robertson EG, Neer KJ. Placental injection studies in twin gestation. AM J OBSTET GVNECOL 1983; 147: 170-3. Blickstein I, Lancet M. Second-breech presentation in twins-a possible adaptive measure to promote fetal growth. Obstet Gynecol 1989;73:700-2.
Fetal cytomegalovirus infection: A case report Richard L. Meisel, MD: Manuel Alvarez, MD," Lauren Lynch, MD," Usha Chitkara, MD: David J. Emanuel, MD,b and Richard L. Berkowitz, MD"
New York, New York Congenital cytomegalovirus infection is the most common perinatal infection. We describe a case of primary maternal cytomegalovirus infection during pregnancy and the prenatal diagnosis of fetal cytomegalovirus infection. Diagnosis was accomplished with percutaneous umbilical blood sampling. The fetal blood was evaluated with viral cultures. cytomegalovirus serologic testing, and nonspecific indicators of infection. Amniotic fluid was also cultured. All cultures were positive, which confirmed fetal infection. The pregnancy was terminated. Autopsy findings were consistent with fetal infection. The significance and utility of prenatal diagnosis are discussed. (AM J OBSTET GVNECOL 1990;162:663-4.)
Key words: Prenatal diagnosis. cytomegalovirus, pregnancy, fetal infection
Cytomegalovirus is the most common perinatal infection with the maJority of infected infants having a silent course without any obvious clinical problem at birth. However, 5% to 10% will have severe deficits, that include microcephaly and severe retardation. I U nfortunately, there is very little long-term follow-up information on the remaining infants, but some will develop adverse neurologic sequelae, including deafness and mild cognitive impairment. Thirty to fifty percent of women of childbearing age in the United States are susceptible to cytomegalovirus infection and approximately 1.4% to 2.2% will undergo seroconversion during pregnancy.2
From the D1VtllOn of Maternal-Fetal Medzcme, Department of Obstetncs, Gynecology and ReproductIVe SCience, Mount Smaz Medical Center," and the Department of PedUltncs, Memonal Sloan Kettenng Cancer Center. b RecelVedfor publlcatzan August 28, 1989; revzsed October 2,1989; accepted October II, 1989. Reprint requests: RIchard L. Mezsel, MD, Department of Obstetncs, Gynecology and ReproductIVe SCIence, Mount Smaz MedIcal Center, One Gustave L. Levy Place, New York, NY 10029.
611117368
Case report A 27-year-old, white woman, gravida 1, para 0, at 11 weeks' gestation was admitted to the hospital with a 3week history of fever, fatigue, and malaise. An expressive aphasia had developed during the day before admission. The physical examination showed an obese white woman with a temperature of 100.4 F, a mild expressive aphasia, and an II-week gestation. Her evaluation is summarized in Table I. The patient was discharged from the hospital 5 days after admission, after resolution of the symptoms, with the diagnosis of atypical migraine and primary cytomegalovirus infection. The patient was referred to our center for further evaluation (Table I). A diagnostic percutaneous umbilical blood sampling was offered, and the couple, planning to terminate the pregnancy if fetal infection was present, elected to proceed with the percutaneous umbilical blood sampling. The percutaneous umbilical blood sampling was performed uneventfully at 21 weeks' gestation and results were available within 5 days (Table I). Three days later, the pregnancy was terminated and an autopsy revealed a grossly normal male fetus with histologic evidence of nonspecific acute infection (white blood cell infiltrates in the lung and liver). There were rare inclusion cells, and immunofluores-
663
664 Meisel et al.
March 1990 Am J Obstet Gynecol
Table I. Clinical summary Test
Maternal evaluation White blood cell countt (No.lml) Lactate dehydrogenaset (lUlL) 'V-Glutamic pyruvic transaminase (IV IL) Serum glutamic oxaloacetic transaminaset (IV IL) Serum-glutamic pyruvic transaminaset (IV IL) Immunoglobulin M for cytomegalovirust Immunoglobulin G for cytomegalovirus Computerized tomographic scan Convalescent serologic testing Immunoglobulin M for cytomegalovirus Immunoglobulin G for cytomegalovirus Fetal evaluation Vltrasonogram Echocardiogram Fetal blood White blood cells (No./ml) Neutrophils (%) Lymphocytes* (%) Monocytes* (%) Eosinophils* (%) Platelets (No./ml) Red blood cells (No./ml) Hemoglobin (gml dl) Hematocrit (%) Lactate dehydrogenase (IV Iml) 'V-Glutamic pyruvic transaminase* (IVlml) Immunoglobulin M for cytomegalovirus (IV I ml) Fetal cytomegalovirus cultures Fetal bloodt Amniotic fiuidt
Result
13,500
Normal value*
4,000-10,000
280
94-172
240
8-69
117
12-45
172
7-40
Positive Negative Normal
Borderline Positive Normal Normal 3,500 2 60 15 5 258,000 3,180,00 13 40 202 60
4,200 5.5 81 1.5 1 254,000 2,890,00 12.2 37.8 261 24.4
Negative
Positive Positive
*Normal values for fetal blood (from Daffos F, Forestier F. Medicine et biologie du foetus humain. Paris: Maloine, 1988). t Abnormal result. *Varies >2 SD from normal. cence tissue studies were positive for cytomegalovirus in the fetal kidney, brain, liver, lung, adrenal, and placenta. Comment
In this case the fetal blood was both cultured and evaluated for nonspecific evidence of infection. The
latter assays were performed to look for other evidence of infection if the cultures were negative. These nonspecific indicators have been shown to be reliable predictors of fetal toxoplasmosis infection. Detection of specific fetal immunoglobulin M is unequivocal evidence of infection but may not have been seen because the immature fetal immune system has a variable response to infectious agents in the mid trimester. Positive cultures clearly documented fetal infection, and abnormalities in the differential cell count and 'V-glutamic pyruvic transaminase are consistent with fetal disease. The hallmark of this severe neonatal infection is cytomegalic inclusion disease. The autopsy result in this case was suggestive of early or mild cytomegalic inclusion disease. The findings of white blood cell infiltrates were consistent with acute infection. Immunoflorescent antibodies to viral proteins proved disseminated fetal infection, but it is unknown whether this would have evolved into the severe debilitating disease state. 1 Since a significant number of the infected neonates are born without clinical signs of cytomegalovirus infection, it is certainly possible that this fetus could have been born without obvious sequelae from its infection. The significance of documenting fetal infection in the presence of normal ultrasonograms is unclear. Advances in laboratory methods and technologies have improved the accuracy of cytomegalovirus diagnosis, and percutaneous umbilical blood sampling has provided a method for obtaining more specific information about the fetus in a timely fashion. Although this has allowed us to inform a patient that her fetus has been infected, in the absence of abnormalities detected on ultrasonography one is currently unable to predict whether the fetus will be adversely affected. In the absence of demonstrable evidence of infection, it may not be justified to assume that the fetus would be born uninfected since the virus could enter the fetal circulation after the fetus has been tested. Further work will delineate the prognostic significance and clinical utility of the prenatal detection of fetal cytomegalovirus infection. REFERENCES 1. Stern H, Tucker SM. Prospective study of cytomegalovirus infection in pregnancy. Br Med J 1973;2:268-70. 2. Stagno S, Pass RF, Dworsky ME, et al. Congenital cytomegalovirus infection: the relative importance of primary and recurrent maternal infection. N Engl J Med 1982; 306:945-9.
