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dr Firman Abdullah SpOG / OBGYN

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Tuesday, April 21, 2009

CMV infection in pregnancy

International Journal of Gynecology & Obstetrics
Volume 79, Issue 2, November 2002, Pages 111-116
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Intrauterine cytomegalovirus infection and glycoprotein...
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Background: Human cytomegalovirus (HCMV) clinical isolates display genetic polymorphisms, supposed to be related with strain-specific tissue-tropism and HCMV-induced immunopathogenesis. One recently discovered polymorphic gene is ORF UL73, encoding for the envelope glycoprotein gN. Among HCMV clinical strains, it shows four distinct genomic variants denoted as gN-1, gN-2, gN-3 and gN-4. Objectives: Aims of this study were to assess the prevalence of the different gN types in the populations examined and to investigate the possible relationship between genotypes and severity of congenital CMV disease. Study design: The gN genotyping was carried out by sequencing analysis of the HCMV ORF UL73. Comparisons were made by chi-square test and contingency tables. Results: All the four gN genotypes can cause congenital infections and the overall distribution was as follows: gN-1, 23.6%; gN-2, 1.1%; gN-3, 12.9%; gN-4, 62.4%. None of them seems to be preferentially associated with vertical transmission or with acute outcome of congenital infection. However, considering the chronic outcome and long-term sequelae, there was a statistically significant (P<0.05) difference between congenitally infected infants with or without adverse chronic outcome. Conclusions: HCMV congenital infections, which displayed a prevalence of the gN-1 variants, seem to be associated with favorable chronic outcome.
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Human cytomegalovirus is the most common cause of congenital and perinatal infections throughout the world. Primary infection with human cytomegalovirus usually follows a benign course, but the virus remains latent or persistent in the host cell thereafter. Understanding the epidemiology of human cytomegalovirus is a key element in the development of strategies for prevention of infection. Although the actual sites of latency or persistence of human cytomegalovirus infections are still controversial, peripheral blood mononuclear cells and endothelial cells appear to be major sites of infection. Persistent infections caused by human cytomegalovirus could be augmented by a decrease in major histocompatibility complex expression as well as by virus-mediated immune dysfunction. It is possible that specific cellular interactions as well as production of several cytokines are necessary for the reactivation of human cytomegalovirus. Breast-fed infants are susceptible to human cytomegalovirus infection from breast milk. Human cytomegalovirus was isolated more frequently from breast milk at more than 1 month after delivery than from colostrum or early breast milk. Human cytomegalovirus DNA was also not detected in colostrum, but was found in breast milk samples 1 month after delivery. To clarify the role of milk cells and whey in vertical infection by breast feeding, we separated breast milk into milk cells and whey and examined each fraction. Human cytomegalovirus was isolated more frequently from milk whey samples than from cell samples. Human cytomegalovirus particle shedding into whey may be more important in vertical infection by breast milk than cell-to-cell transmission. The supernatant of colostrum did not exert an inhibitory effect on human cytomegalovirus-infected cells. Serum levels of cell free soluble interleukin-2 receptor of mothers with DNA-positive milk at 1 month after delivery were significantly higher than those of mothers with DNA-negative milk. It is likely that levels of factors such as soluble interleukin-2 receptor in serum are related to the reactivation of human cytomegalovirus which occurs locally in the mammary gland of the lactating mother after delivery. This minireview focuses on recent advances in the study of human cytomegalovirus infection of breast milk.

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Maternal serum samples at 10 and 22 weeks of gestational age and cord blood samples were available from six cases of asymptomatic congenital human cytomegalovirus (HCMV) infection. Meaningful rises of serum IgG-antibody titers by ELISA occurred in three cases. Serum interferon (IFN)-γ activity was detected in all six cases. Serum cell free soluble interleukin-2 receptor (sIL-2R) activity rose above the normal range (145–519 U/ml) in one IgG and IgM antibody-positive and three IgG antibody-positive woman. Serum levels of sIL-2R and IFN-γ were not elevated in anti-HCMV antibody-negative healthy pregnant women. No HCMV IE DNA was detected by PCR in the serum of any of the pregnant women. HCMV DNA was detected in the serum of one of six infants with asymptomatic congenital HCMV infection. Assessment of the changes of serum cytokines such as sIL-2R and IFN-γ in HCMV antibody-positive pregnant women may be useful for the prenatal diagnosis of active HCMV infection during pregnancy.
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Human cytomegalovirus (HCMV) is the most common cause of congenital and perinatal infections throughout the world. Primary infection with HCMV usually follows a benign course, but the virus remains latent or persistent in the host cell thereafter. Under immunosuppressive conditions, latent or persistent infection can be reactivated to produce a wide variety of clinical manifestations. Understanding the epidemiology of HCMV infection is a key element in development of strategies for prevention of infection. Definition of sites and mechanisms involved in the maintenance of latent or persistent HCMV infection and reactivation is also essential for a thorough understanding of the pathogenesis of HCMV infection. This mini review focuses on recent advances in the study of persistent infection and reactivation of HCMV. Although the actual sites of latency or persistence of HCMV infections are still controversial, peripheral blood mononuclear cells (PBMC) and endothelial cells appear to be the principal site of infection. Persistent infections caused by HCMV could be augmented by a decrease in major histocompatibility complex (MHC) expression as well as by virus-mediated immune dysfunction. It is also likely that specific cellular interactions as well as production of several cytokines are necessary for the reactivation of HCMV.



doi:10.1016/S0020-7292(02)00239-4
Copyright © 2002 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd.
Article
Cytomegalovirus infection in pregnancy

L. Z. Wen, , a, W. Xinga, L. Q. Liub, L. M. Aoc, S. H. Chena and W. J. Zenga

a Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China b Virological Laboratory, Chinese Medical University, Shenyang, China c Pediatrics Institute, The Second Shanghai Medical University, Shanghai, China

Received 26 March 2002; revised 1 July 2002; accepted 3 July 2002. Available online 5 November 2002.




References and further reading may be available for this article. To view references and further reading you must purchase this article.


Abstract
Objectives: To investigate the effects of intrauterine human cytomegalovirus (HCMV) infection on pregnancy outcomes and infant development. Methods: The study group consisted of the HCMV-IgM-positive offspring of 75 pregnant women, and a control group of the non-infected offspring of 73 pregnant women. Chorionic villi, amnionic fluid, and umbilical blood were obtained to detect HCMV–late mRNA with a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The pregnancy outcomes were followed up. For all offspring, neurological development was evaluated with neurosonography, audiologic development with the brainstem auditory evoked potential (BAEP), and psychomotor development with the Beyley Scale of Infant Development (BSID). Results: In the study group the positive rate of late mRNA was 50% in the chorionic villi and 67.65% in the amnionic fluid and the umbilical blood; the incidence of abnormal pregnancy outcomes (abortion, preterm delivery, stillbirth, etc.) was much higher than in the control group (40% vs. 6.57%; χ2=24.06; P=0.001); the abnormal rate of neurosonography results at birth and 3 months after birth was higher in the study group than in the control group (P<0.05), as were BAEP values 4 months after birth (χ2=8.960; P=0.003). Scores for the Infant Mental Development Index (MDI) were apparently lower than in the control group. When congenitally infected children were tested at the age of 5.5–6.5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), their rate of mental retardation was still found to be approximately 20%. Conclusions: Intrauterine HCMV infection is closely related to abnormal pregnancy outcomes, infant neurological damage, mental retardation, and hearing loss.

Author Keywords: Human cytomegalovirus; Intrauterine infection; RT-PCR; Beyley Scale of Infant Development; Brainstem auditory evoked potential

International Journal of Gynecology & Obstetrics
Volume 79, Issue 2, November 2002, Pages 111-116
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