Prevention of maternal–fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration

Kagan, K. O.; Enders, Martin; Schampera, Matthias Stefan; Baeumel, E.; Hoopmann, Markus; Geipel, A.; Berg, Christoph; Goelz, Rangmar; Catte, Luc De; Wallwiener, D.; Brucker, Sara Y.; Adler, Stuart P.; Jahn, Gerhard; Hamprecht, Klaus

doi:10.1002/uog.19164

Cited by 112 publications

(82 citation statements)

References 26 publications

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“…Nigro et al 55 reported that CMV HIG therapy was associated with a significantly lower risk of congenital CMV infection, especially symptomatic infection. Recently, a prospective observational study reported that, after a primary maternal CMV infection in the first trimester, biweekly HIG administration at a dose of 200 IU/kg prevented maternal-fetal transmission up to 20 weeks' gestation 56 . Unfortunately, the potential efficacy of HIG was not borne out in a phase-II randomized, placebo-controlled, double-blind study 57 , which found no significant improvement in the risk of transmission, levels of virus-specific antibodies, T-cell mediated immune response, viral DNA in the blood or clinical outcome at birth.…”

Section: Recommendationsmentioning

confidence: 99%

ISUOG Practice Guidelines: role of ultrasound in congenital infection

Khalil

Sotiriadis

Chaoui³

et al. 2020

Ultrasound in Obstet & Gyne

130

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ISUOG Practice Guidelines: role of ultrasound in congenital infection Clinical Standards Committee The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care, because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (

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Section: Recommendationsmentioning

confidence: 99%

ISUOG Practice Guidelines: role of ultrasound in congenital infection

Khalil

Sotiriadis

Chaoui³

et al. 2020

Ultrasound in Obstet & Gyne

130

View full text Add to dashboard Cite

show abstract

“…Currently, treatment with immunoglobulins or antiviral therapy to prevent intrauterine transmission of CMV in pregnant women with primary CMV infection is not recommended as studies have not yet conclusively shown a benefit (63)(64)(65)(66). Data from a non-randomized study showed that biweekly administration of hyperimmunoglobulin until 20 weeks' gestation successfully prevented maternal-fetal transmission of primary infections (65). These data need to be confirmed by a randomized clinical trial (67); if the results are confirmed, two-weekly intervals for testing seronegative women would be necessary.…”

Section: What Are the Gaps In Our Understanding?mentioning

confidence: 99%

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts

et al. 2020

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Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in in utero transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education.

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“…IgG-antibodies against gB were shown to be highly neutralizing [18]. Scores of HCMV-specific-IgG reactivity were given on the y-axis, as described by Kagan et al [27] and the number of study participants is shown on the x-axis. A validation experiment was performed, using HIG-spiked whey.…”

Section: Hcmv-specific-igg Antibodiesmentioning

confidence: 99%

Human Cytomegalovirus Reactivation During Lactation: Impact of Antibody Kinetics and Neutralization in Blood and Breast Milk

Lazar¹,

Rabe²,

Goelz

et al. 2020

Nutrients

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Human cytomegalovirus (HCMV) is shed into breast milk in nearly every seropositive woman during lactation. This reactivation shows mostly a self-limited, unimodal course. The dynamics and functional role of HCMV-specific-IgG in breast milk and in plasma during reactivation are unknown. Milk whey viral loads were monitored with real-time PCR in 18 HCMV-seropositive mothers over two months postpartum. HCMV-antibody binding assays (ECLIA) and antigen-specific immunoblotting were performed from plasma and corresponding milk samples. Epithelial-cell-specific neutralization was used to analyze functional antibodies in plasma- and whey-pools. Viral loads in milk whey showed unimodal courses in 15 of 18 mothers with peak viral loads around one month postpartum. HCMV-specific-IgG-antibodies increased significantly in plasma and milk whey during reactivation. The mean levels of plasma IgG were about 275-fold higher than in whey. Only antibodies against tegument protein p150 were continuously expressed in both compartments. Anti-glycoprotein-B1 IgG-antibodies were variably expressed in whey, but continuously in plasma. Neutralization assays showed 40-fold higher NT-50 values in plasma compared to whey at two months postpartum. During reactivation, HCMV-specific-IgG reactivities and neutralizing capacities are much lower in whey than in plasma. Therefore, their specific role in the decrease and discontinuation of virus-shedding in milk remains unclear.

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Prevention of maternal–fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration

Abstract: After a primary maternal CMV infection in the first trimester, HIG administration prevents maternal-fetal transmission up to 20 weeks of gestation. This article is protected by copyright. All rights reserved.

Cited by 112 publications

References 26 publications

ISUOG Practice Guidelines: role of ultrasound in congenital infection

ISUOG Practice Guidelines: role of ultrasound in congenital infection

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts

Human Cytomegalovirus Reactivation During Lactation: Impact of Antibody Kinetics and Neutralization in Blood and Breast Milk

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