Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population: “The BraCHS Study”

Mussi-Pinhata, Marisa Márcia; Yamamoto, Aparecida Yulie; Aragon, Davi Casale; Duarte, Geraldo; Fowler, Karen B.; Boppana, Suresh B.; Britt, William J.

doi:10.1093/infdis/jiy321

Cited by 46 publications

(43 citation statements)

References 15 publications

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“…Our systematic review found similar birth prevalence, however, we were additionally able to report placental transmission rates for a study that distinguished chronic CMV infections from primary infections. The birth prevalence for this study demonstrated a lower cCMV birth prevalence in maternal chronic CMV infections compared with primary infections (0.5% vs. 2.8% respectively) [19]. The median birth prevalence for all three tiers of studies, including primary and chronic CMV infections, ranged from 1% to 2.1%.…”

Section: Discussionmentioning

confidence: 50%

“…Of those, 16 studies reported symptoms of affected infants. Overall, cCMV birth prevalence ranged from 0.4% to 6% [19,26,27,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Tier 1 studies, which differentiated primary versus chronic CMV maternal infections, had a median birth prevalence rate of 1%.…”

Section: Discussionmentioning

confidence: 99%

“…CMV serostatus was assessed in the first trimester, and the cCMV rates for both seronegative women and seropositive women, as well as the seronegative women with primary CMV acquisition during pregnancy were reported. Notably, there was a reduced cCMV birth prevalence among seropositive women (0.5%) versus preconception seronegative women (birth prevalence 2.8%) [19]. Moreover, there was a high rate of primary CMV acquisition during pregnancy in this population (14%, 5 of 36), demonstrating the frequent maternal CMV exposure in this population, and the observed placental transmission rate of 20% (1 in 5) is similar to what is expected in the setting of primary CMV acquisition.…”

Section: Tier 1 Studiesmentioning

confidence: 94%

“…All Tier 1 studies utilized infant saliva or urine PCR with or without urine culture for confirmation of cCMV infection and diagnosed a majority (>89%) of pregnant subjects with chronic CMV infections based on high avidity IgG binding. In Tier 1 studies, cCMV birth prevalence rates in highly seropositive populations ranged from 0.5% to 1.1% with a median rate of 1% [19,27,47] (Table 1, Figure 2). All studies included IgG avidity testing to confirm chronic maternal infection on at least a subset of the pregnant subjects.…”

Section: Tier 1 Studiesmentioning

confidence: 99%

“…In contrast, in areas of high CMV seroprevalence, seronegative mothers have high rates of CMV acquisition during pregnancy. For example, in a Brazilian cohort with a high CMV seroprevalence rate of 98.1%, the rate of CMV acquisition in seronegative mothers was reported to be 14%, 5/36 mothers [19]. Despite the high risk of maternal virus reactivation or reinfection, CMV placental transmission rates seem to be lower among mothers with non-primary infection compared to mothers with primary infection [6,20].…”

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confidence: 99%

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Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review

Coppola

Mangold²,

Cantrell

et al. 2019

Vaccines

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Congenital cytomegalovirus (cCMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL), and efforts are geared towards prevention through vaccine development. Transmission rates following primary maternal infection occur at rates of 30-40%, however reported placental rates upon non-primary maternal infection is reported to be less than <4%. There is significant debate about whether this reduction in transmission rate is due to pre-existing maternal immunity, which could identify possible immunologic targets for vaccines. To address this question, we performed a systemic review of the literature using Preferred Reporting Items for Systematic Review and Analysis (PRISMA) guidelines. We identified cohort studies in high CMV seroprevalent (>80%) areas or in developing regions that examined a cohort of at least 50 infants for congenital CMV acquisition. We identified 19 articles that met criteria and were further categorized based on pre-conception serology, maternal seroprevalence, or previously known seroprevalence. Birth prevalence rates ranged from 0.4% to 6% (median 1.1%), with the studies reporting on clinical outcome (16/19 studies) noting the majority of infected infants as asymptomatic. We also utilized a recent study that differentiated primary maternal infections from chronic infections in a highly seropositive population to calculate a placental transmission rate in women with pre-existing immunity compared to that of no pre-existing immunity. This work confirms a low cCMV birth prevalence in highly seropositive populations, indicates via a calculated placental transmission rate that the CMV placental transmission rate is lower in non-primary infection than that of primary infection, and reveals gaps in data for further research aiming to identify targets for vaccine development.Vaccines 2019, 7, 129 2 of 13 leading non-genetic cause of SNHL [9,11]. Furthermore, as many as 5% of infants without recognizable CMV-associated sequelae at birth may develop microcephaly or neurodevelopmental deficits within the first year of life [10].Placental transmission of CMV occurs in mothers with both prior natural immunity to CMV, termed 'non-primary CMV infection', and among seronegative mothers who contract CMV during pregnancy, termed 'primary infection' [2,5,12]. Congenital CMV infections occur in chronic CMV-infected women as a result from either reactivation of the virus from a previous infection or reinfection. The contribution of each of these potential routes of infection to non-primary cCMV incidence is not known. Recent studies show that seropositive mothers have high rates of reinfection with new virologic strains of CMV, ranging from 18-30% [13,14], suggesting that reinfection could be a major mode of non-primary cCMV infection. Birth prevalence of non-primary cCMV infection among infants born to all seropositive women is estimated to be 1%, yet placental transmission has been reported to be as high as 3.4% in women who have evidence of reinfection during pregnancy [8,15]. Seronegative mothe...

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Tier 1 Studiesmentioning

confidence: 94%

Section: Tier 1 Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

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Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review

Coppola

Mangold²,

Cantrell

et al. 2019

Vaccines

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Cytomegalovirus seroconversion in pregnant army personnel of the Israel Defense Forces: Trends and risk factors

Tov¹,

Walfisch

Schwartz

et al. 2021

Intl J Gynecology & Obste

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Objective Cytomegalovirus (CMV) seroconversion in pregnancy is a major health issue with potentially devastating fetal consequences. We opted to determine rates and trends of CMV seroconversion in pregnant army personnel and to isolate risk factors. Methods In this retrospective cohort study, all pregnancies of army personnel between 2009 and 2019 were evaluated (n = 10 409) and all pregnancies with CMV laboratory records were included. Seroconversion rate was calculated overall and per year. Demographic and obstetrical characteristics were compared between exposed and unexposed women. Independent predictors of seroconversion were further investigated using logistic regression models. Results Cytomegalovirus serology status was available in 7665 pregnancies. Seroconversion was evident in 66 women (4.15%) among the seronegative pregnancies. Women in the seroconversion group were significantly more likely to belong to a higher social class. In the regression models, adjusted for age, place of residence, and education, higher parity (adjusted odds ratio [aOR] 2, P < 0.001) and residing in a central district (aOR 2.67, P = 0.002) were significantly associated with seroconversion. Conclusion Higher social class appears to be a significant risk factor for CMV seroconversion during pregnancy. Residing in a central district and higher parity appear to be independently associated with an increased risk for seroconversion during pregnancy among army personnel.

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Impact of breast milk‐acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences?

Osterholm

Schleiss

2020

Reviews in Medical Virology

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Maternal-fetal transmission of cytomegalovirus (CMV) represents the most common infectious cause of long-term neurodevelopmental disability in children. Congenital CMV (cCMV) infection is associated with microcephaly, seizure disorders, cognitive disability, developmental delay, and sensorineural hearing loss (SNHL). Of these disabilities, SNHL is the most common, affecting approximately 10% of infants with cCMV. Although the sequelae of cCMV are well recognized, it is much less clear what long-term morbidities may occur in neonates that acquire post-natal CMV infection. Post-natal CMV (pCMV) infection is most commonly transmitted by breast-feeding, and in full-term infants is of little consequence. However, in preterm, very-low birthweight (VLBW) infants (<1500 g), pCMV can result in a severe sepsis-like syndrome, with wide-ranging end-organ disease manifestations. Although such shortterm complications are well recognized among clinicians caring for premature infants, the long-term risks with respect to adverse neurodevelopmental outcomes remain controversial. In this review, we provide an overview of the clinical manifestations of breast milk-acquired pCMV infection. In particular, we summarize studies that have examined-sometimes with conflicting conclusions-the risks of long-term adverse neurodevelopmental outcome in VLBW infants that acquire pCMV from breast milk. We highlight proposed preventive strategies and antiviral interventions, and offer recommendations for high-priority areas for future basic science and clinical research.

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Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population: “The BraCHS Study”

Cited by 46 publications

References 15 publications

Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review

Impact of Maternal Immunity on Congenital Cytomegalovirus Birth Prevalence and Infant Outcomes: A Systematic Review

Cytomegalovirus seroconversion in pregnant army personnel of the Israel Defense Forces: Trends and risk factors

Impact of breast milk‐acquired cytomegalovirus infection in premature infants: Pathogenesis, prevention, and clinical consequences?

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