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PEDIATRICS Vol. 112 No. 2 August 2003, pp. e153-e157

EXPERIENCE AND REASON

Congenital Cytomegalovirus Infection in Twin Pregnancies: Viral Load in the Amniotic Fluid and Pregnancy Outcome

Tiziana Lazzarotto, PhD^*, Liliana Gabrielli, MD^*, Maria Pia Foschini, MD^¶, Marcello Lanari, MD, Brunella Guerra, MD, Vincenzo Eusebi, MD^¶, Maria Paola Landini, MD^*

^* Section of Microbiology, Department of Clinical and Experimental Medicine
Department of Preventive Pediatrics and Neonatology, St Orsola Malpighi General Hospital, University of Bologna, Bologna, Italy
Department of Obstetrics and Gynecology, St Orsola Malpighi General Hospital, University of Bologna, Bologna, Italy
^¶ Section of Anatomic Pathology, Department of Oncology, Bellaria Hospital, University of Bologna, Bologna, Italy

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks’ gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 10³ genome equivalents (GE)/mL of females AF and 1.9 x 10⁵ GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 x 10⁴ GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.

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Key Words: cytomegalovirus • congenital infection • twin pregnancies • placenta • prenatal diagnosis • viral load

Abbreviations: CMV, cytomegalovirus • PCR, polymerase chain reaction • AF, amniotic fluid • Ig, immunoglobulin • GE, genome equivalents • qPCR, quantitative polymerase chain reaction • ABR, auditory brainstem-evoked response • PMNL, polymorphonuclear leukocyte • EIA, enzyme immunoassay

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Received for publication Sep 30, 2002; Accepted Apr 2, 2003.

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