Congenital Cytomegalovirus Mortality in the United States, 1990–2006

Bristow, Benjamin; O’Keefe, Kaitlin; Shafir, Shira; Sorvillo, Frank

doi:10.1371/journal.pntd.0001140

Cited by 61 publications

(49 citation statements)

References 34 publications

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“…CMV is more common among socially disadvantaged groups and nonwhite minorities [2][3][4][5][6][7][8][9][10][11][12]. We have recently conducted geospatial analyses demonstrating that CMV seropositivity, including among pregnant women, significantly clusters in poor urban neighborhoods with large minority populations in North Carolina [11,12].…”

Section: Introductionmentioning

confidence: 99%

Neighborhood Disadvantage is Associated with High Cytomegalovirus Seroprevalence in Pregnancy

Lantos

Hoffman

Permar

et al. 2017

J. Racial and Ethnic Health Disparities

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Background Cytomegalovirus (CMV) is the most common infectious cause of fetal malformations and childhood hearing loss. CMV is more common among socially disadvantaged groups, and geographically clusters in poor communities. The Area Deprivation Index (ADI) is a neighborhood-level index derived from census data that reflects material disadvantage. Methods We performed a geospatial analysis to determine if ADI predicts the local odds of CMV seropositivity. We analyzed a dataset of 3527 women who had been tested for CMV antibodies during pregnancy. We used generalized additive models to analyze the spatial distribution of CMV seropositivity. Adjusted models included individual-level age and race and neighborhood-level ADI.Results Our dataset included 1955 CMV seropositive women, 1549 who were seronegative, and 23 with recent CMV infection based on low avidity CMV antibodies. High ADI percentiles, representing greater neighborhood poverty, were significantly associated with the nonwhite race (48 vs. 22, p < 0.001) and CMV seropositivity (39 vs. 28, p < 0.001). Our unadjusted spatial models identified clustering of high CMV odds in poor, urban neighborhoods and clustering of low CMV odds in more affluent suburbs (local odds ratio 0.41 to 1.90). Adjustment for both individual race and neighborhood ADI largely eliminated this spatial variability. ADI remained a significant predictor of local CMV seroprevalence even after adjusting for individual race. Conclusions Neighborhood-level poverty as measured by the ADI is a race-independent predictor of local CMV seroprevalence among pregnant women.

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Section: Introductionmentioning

confidence: 99%

Neighborhood Disadvantage is Associated with High Cytomegalovirus Seroprevalence in Pregnancy

Lantos

Hoffman

Permar

et al. 2017

J. Racial and Ethnic Health Disparities

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“…Each year, at least 40,000 babies are born with congenital infection, resulting in about 400 deaths and leaving 4,000 to 8,000 children with permanent neurological complications, such as hearing loss, visual impairment, and mental retardation (1,2). HCMV infection is also associated with stillbirth, preterm delivery, and intrauterine growth restriction (IUGR) (3)(4)(5)(6)(7)(8)(9), which are risk factors for perinatal and lifetime morbidity (10), including cardiovascular disease (11,12). There are more cases of permanent disability from congenital HCMV infection than from other, better known congenital conditions, such as Down syndrome, fetal alcohol syndrome, and neural tube defects (13,14).…”

mentioning

confidence: 99%

Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

Tabata

Petitt

Zydek

et al. 2015

J Virol

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Human cytomegalovirus (HCMV) is a major cause of birth defects that include severe neurological deficits, hearing and vision loss, and intrauterine growth restriction. Viral infection of the placenta leads to development of avascular villi, edema, and hypoxia associated with symptomatic congenital infection. Studies of primary cytotrophoblasts (CTBs) revealed that HCMV infection impedes terminal stages of differentiation and invasion by various molecular mechanisms. We recently discovered that HCMV arrests earlier stages involving development of human trophoblast progenitor cells (TBPCs), which give rise to the mature cell types of chorionic villi-syncytiotrophoblasts on the surfaces of floating villi and invasive CTBs that remodel the uterine vasculature. Here, we show that viral proteins are present in TBPCs of the chorion in cases of symptomatic congenital infection. In vitro studies revealed that HCMV replicates in continuously self-renewing TBPC lines derived from the chorion and alters expression and subcellular localization of proteins required for cell cycle progression, pluripotency, and early differentiation. In addition, treatment with a human monoclonal antibody to HCMV glycoprotein B rescues differentiation capacity, and thus, TBPCs have potential utility for evaluation of the efficacies of novel antiviral antibodies in protecting and restoring placental development. Our results suggest that HCMV replicates in TBPCs in the chorion in vivo, interfering with the earliest steps in the growth of new villi, contributing to virus transmission and impairing compensatory development. In cases of congenital infection, reduced responsiveness of the placenta to hypoxia limits the transport of substances from maternal blood and contributes to fetal growth restriction. IMPORTANCEHuman cytomegalovirus (HCMV) is a leading cause of birth defects in the United States. Congenital infection can result in permanent neurological defects, mental retardation, hearing loss, visual impairment, and pregnancy complications, including intrauterine growth restriction, preterm delivery, and stillbirth. Currently, there is neither a vaccine nor any approved treatment for congenital HCMV infection during gestation. The molecular mechanisms underlying structural deficiencies in the placenta that undermine fetal development are poorly understood. Here we report that HCMV replicates in trophoblast progenitor cells (TBPCs)-precursors of the mature placental cells, syncytiotrophoblasts and cytotrophoblasts, in chorionic villi-in clinical cases of congenital infection. Virus replication in TBPCs in vitro dysregulates key proteins required for self-renewal and differentiation and inhibits normal division and development into mature placental cells. Our findings provide insights into the underlying molecular mechanisms by which HCMV replication interferes with placental maturation and transport functions. H uman cytomegalovirus (HCMV) is the most common cause of congenital viral infection in the UnitedStates. Each year, at least 4...

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“…2,9,10 CMV is the most common cause of congenital infection in newborns with a reported incidence of 0.2 -2.5% 11 and is usually asymptomatic at birth but with cumulative effect on morbidity and mortality. 12 Symptomatic infants identifi ed at newborn screening generally have milder disorders than those referred for follow-up studies based on clinical abnormalities at birth. Prospective studies have shown that approximately half of the children born with symptomatic infection will develop sequelae.…”

Section: Resultsmentioning

confidence: 99%

The Role of Cytomegalovirus in Congenital and Early Postnatal Infections in Northeastern Bulgaria

2017

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Background: Human cytomegalovirus is a ubiquitous, large enveloped DNA β-herpesvirus that, like other herpesviruses, establishes lifelong latency following primary infection. It is the most frequent cause of congenital, neonatal and early postnatal infections with long lasting sequelae. Aim: The aim of the present study was to assess the prevalence of cytomegalovirus among a cohort of newborns and 1-3-month-old children with neurological symptoms, physical retardation, prolonged jaundice, thrombocytopenic purpura and other disabilities. Materials and methods:The study was a retrospective cross-sectional analysis of serological screening data for detection of specifi c anti-cytomegalovirus IgM and IgG in children from Northeastern Bulgaria. Results: Between 2003 and 2015, average prevalences of 18.8% (95% CI: 15.4 to 22.2) for anti-CMV IgM antibodies (suggesting acute infection) and 84.7% (95% CI: 81.6 to 87.8) for anti-CMV IgG antibodies were measured in a total number of 517 samples. The prevalence rate of anti-CMV IgM in 1-3-month-old children was 4-fold higher than that in newborns [25.8% (95% CI: 21.1 to 30.5) and 6.4% (95% CI: 2.9 to 9.9, respectively]. In contrast, no signifi cant diff erence was found for anti-CMV IgG positivity between newborns and 1-3-month-old infants (84% and 85%, respectively). Conclusions:The data obtained strongly encourage screening of pregnant women for anti-CMV IgG and IgM to avoid transmission of the infection and severe complications of congenital infection. BACKGROUND

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Congenital Cytomegalovirus Mortality in the United States, 1990–2006

Cited by 61 publications

References 34 publications

Neighborhood Disadvantage is Associated with High Cytomegalovirus Seroprevalence in Pregnancy

Neighborhood Disadvantage is Associated with High Cytomegalovirus Seroprevalence in Pregnancy

Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

The Role of Cytomegalovirus in Congenital and Early Postnatal Infections in Northeastern Bulgaria

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