Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study

Kagan, Karl Oliver; Enders, Martin; Hoopmann, Markus; Geipel, A.; Simonini, Corinna; Berg, Christoph; Gottschalk, Ingo; Faschingbauer, Florian; Schneider, Michael; Ganzenmueller, Tina; Hamprecht, Klaus

doi:10.1002/uog.23596

Cited by 45 publications

(41 citation statements)

References 33 publications

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“…Revello et al conducted a randomized trial and found that this treatment did not significantly modify the course of primary CMV infection during pregnancy [ 23 ]. However, Kagan et al reported that HIG was effective for women with a recent primary infection in the first trimester or during the periconceptional period and when HIG was administered at a biweekly dose of 200 IU/kg [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Low Maternal Immunoglobulin G Avidity and Single Parity as Adverse Implications of Human Cytomegalovirus Vertical Transmission in Pregnant Women with Immunoglobulin M Positivity

Kaneko

Muraoka

Kusumoto

et al. 2021

Viruses

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Human cytomegalovirus (CMV) is the leading cause of neurological sequelae in infants. Understanding the risk factors of primary CMV infection is crucial in establishing preventive strategies. Thus, we conducted a retrospective cohort study to identify risk factors of vertical transmission among pregnant women with immunoglobulin (Ig) M positivity. The study included 456 pregnant women with IgM positivity. Information on age, parity, occupation, clinical signs, IgM levels, and IgG avidity index (AI) was collected. The women were divided into infected and non-infected groups. The two groups showed significant differences in IgM level, IgG AI, number of women with low IgG AI, clinical signs, and number of pregnant women with single parity. In the multiple logistic regression analysis, pregnant women with single parity and low IgG AI were independent predictors. Among 40 women who tested negative for IgG antibody in their previous pregnancy, 20 showed low IgG AI in their current pregnancy. Among the 20 women, 4 had vertical transmission. These results provide better understanding of the risk factors of vertical transmission in pregnant women with IgM positivity.

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Section: Discussionmentioning

confidence: 99%

Low Maternal Immunoglobulin G Avidity and Single Parity as Adverse Implications of Human Cytomegalovirus Vertical Transmission in Pregnant Women with Immunoglobulin M Positivity

Kaneko

Muraoka

Kusumoto

et al. 2021

Viruses

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“…In addition, whether using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection is beneficial still remains to be confirmed ( 29 ). In an observational study, hyperimmunoglobulin treatment at a biweekly dose of 200 IU/kg seemed to be potentially useful among women with a recent primary infection in the first trimester or during the periconception period ( 30 ). Thus, offering effective vaccination to susceptible women before conception may also be possible in the near future.…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence of Cytomegalovirus and Associated Factors Among Preconception Women: A Cross-Sectional Nationwide Study in China

Zhou

Wang

Shen

et al. 2021

Front. Public Health

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Background: Cytomegalovirus seroconversion during pregnancy is common and has a substantial risk of congenital infection with longterm sequale. Screening during pregnancy or vaccination have not been shown to be effective for eliminating congenital infections. Preconception screening policy has not been evaluated adequately in a large scale. This nationwide study aimed to investigate epidemiological features of cytomegalovirus seropositivity and its geographic variation among Chinese women planning a pregnancy to gather epidemiological evidence as an essential for developing novel prevention strategies.Method: This cross-sectional sero-epidemiological survey enrolled women intending to become pregnant within 6 months in mainland China during 2010–2012. The primary outcomes in this study were cytomegalovirus Immunoglobulin G and M seropositivity. Secondary outcomes were the associations between Immunoglobulin G and Immunoglobulin M, with socio-demographic characteristics, including age, occupation, education level, place of residence, and ethnicity. The overall seropositivity and regional disparity was analyzed on the individual and regional level, respectively.Results: This study included data from 1,564,649 women from 31 provinces in mainland China. Among participants, 38.6% (n = 603,511) were cytomegalovirus immunoglobulin G+, 0.4% (n = 6,747) were immunoglobulin M+, and 0.2% (n = 2,879) were immunoglobulin M+ and immunoglobulin G+. On individual level, participant's age, ethnicity, and residing region were significantly associated with IgG+, IgM+, and IgM+IgG+ (P < 0.001), while occupation, education level, and place of residence were not statistically significant (P > 0.05). On regional level, cytomegalovirus immunoglobulin G and immunoglobulin M seropositivity was highest in the eastern region (49.5 and 0.5%, respectively), and lowest in the western region (26.9 and 0.4%, respectively). This geographic variation was also noted at the provincial level, characterized by higher provincial immunoglobulin M+ and immunoglobulin G+ rates associated with higher immunoglobulin G seropositivity. In the subgroup analysis of immunoglobulin G seropositivity, areas of higher immunoglobulin G positivity had a higher rate of immunoglobulin M+, indicating an expected increased risk of reinfection and primary infection.Conclusions: A substantial proportion of women (>60%) were susceptible to cytomegalovirus in preconception period in China, and immunoglobulin G seropositivity was seen at a low-medium level with substantial geographic variation. Integration of cytomegalovirus antibody testing in preconception screening program based on regional immunoglobulin G seropositivity, should be considered to promote strategies directed toward preventing sero-conversion during pregnancy to reduce the risk of this congenital infection.

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“…Based on the new pharmacological study indicating that the half time of HIG is only about 10 days [ 112 , 113 ], a new investigation was recently undertaken in 149 pregnant women and 153 fetuses to study the efficacy of HIG in pregnant women with a very recent PI in the first trimester or during the periconceptional period with treatment starting at a median gestational age of 10.6 weeks and ending at 17.9 weeks. During this time, IV treatment with HIG was administered on the average only 4 times (every 2 weeks) until about 18 weeks of gestation at the HIG dosage of 200 IU/kg bodyweight [ 114 ]. Very recent PI in the first trimester of pregnancy along with timely initiation of treatment and an appropriate treatment dosage and interval were the parameters preventing maternal-fetal transmission.…”

Section: Preventionmentioning

confidence: 99%

“…This allows seronegative women at risk for PI to be identified and benefit from information about hygienic measures for primary prevention of PI [ 106 ]. In addition, PI can be diagnosed early and treatments for secondary prevention (i.e., prevention of virus transmission to the fetus and congenital disease [ 114 , 118 ]) can be proposed. Although serological screening during or before pregnancy is not universally recommended [ 15 ], we believe, on the basis of the results herein reported, that the approach here described allows a number of congenital infections as well as unnecessary pregnancy terminations to be prevented.…”

Section: Conclusion and Final Remarksmentioning

confidence: 99%

Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy

et al. 2021

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Congenital cytomegalovirus infection (cCMV) may affect about 1% of all newborns all over the world as a result of either a primary or recurrent human cytomegalovirus (HCMV) infection. While about 90% of infants affected by cCMV are asymptomatic at birth, the remaining 10% are symptomatic often with neurodevelopmental impairment and sensorineural hearing loss. In view of identifying the best approach to vaccine prevention of cCMV, this review will examine the most important steps made in the study of the immune response to, and diagnosis of, HCMV infection. The maternal immune response and immune correlates of protection are being partially identified with a partial contribution given by our laboratory. The diagnosis of primary infection is often difficult to achieve in the first three months of pregnancy, which is the time primarily involved in virus transmission to the fetus in association with the most severe symptoms and sequelae. Prevention of cCMV is anticipated by prevention of primary infection in early pregnancy by means of different measures, such as (i) behavioral-educational measures, (ii) immunoglobulin administration, (iii) antiviral treatment with valaciclovir. However, the most promising approach to cCMV prevention appears to be the development of a non-living vaccine, including at least three viral antigens: gB, pentamer complex gHgLpUL128L, and pp65, which have been shown to be able to stimulate both the humoral and the cellular arms of the maternal immune response. Primary HCMV infection may be managed in pregnancy by counseling of the couples involved by a team of specialists that includes virologists, obstetricians, infectivologists and neonatologists.

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Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study

Cited by 45 publications

References 33 publications

Low Maternal Immunoglobulin G Avidity and Single Parity as Adverse Implications of Human Cytomegalovirus Vertical Transmission in Pregnant Women with Immunoglobulin M Positivity

Low Maternal Immunoglobulin G Avidity and Single Parity as Adverse Implications of Human Cytomegalovirus Vertical Transmission in Pregnant Women with Immunoglobulin M Positivity

Seroprevalence of Cytomegalovirus and Associated Factors Among Preconception Women: A Cross-Sectional Nationwide Study in China

Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy

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