Serological screening of immunoglobulin M and immunoglobulin G during pregnancy for predicting congenital cytomegalovirus infection

Abstract

Background Cytomegalovirus (CMV) is one of the most frequent pathogens for congenital infections. Most cases of congenital CMV infection (cCMV) are asymptomatic at birth, but sensorineural hearing loss (SNHL) or neurodevelopmental delay can appear later in childhood. This prospective study examined the practicability of serological screening for anti-CMV immunoglobulin (Ig) G and anti-CMV IgM in pregnant women. Methods A total of 11,753 pregnant women were examined for CMV IgG and CMV IgM during the first or second trimester. When IgM was positive, IgG was reevaluated more than two weeks later. When IgG was negative, IgG was reevaluated in the second or third trimester. All neonates from mothers with positive/borderline IgM or IgG seroconversion underwent polymerase chain reaction assay for CMV using urine samples to diagnose cCMV. Levels of IgG and IgM were compared between mothers with and without cCMV. Receiver operating characteristic (ROC) curves for IgM titers were analyzed. Results Eight of 500 neonates (1.6%) born from mothers with positive IgG and positive IgM, and 3 of 13 neonates (23.1%) born from mothers with IgG seroconversion were diagnosed with cCMV. Neither IgM titers nor IgG titers differed significantly between cCMV and non-cCMV groups. The area under the ROC curve was 0.716 and the optimal cut-off for IgM was 7.28 index (sensitivity = 0.625, specificity = 0.965, positive predictive value = 0.238, negative predictive value = 0.993). Titers of IgG were not frequently elevated in pregnant women with positive IgM during the observation period, including in those with cCMV. All 11 cCMV cases were asymptomatic at birth and none had shown SNHL or developmental delay as of the last regular visit (mean age, 40 months). Conclusions Seroconversion of CMV IgG and high-titer IgM during early pregnancy are predictors of cCMV. High IgM titer (> 7.28 index) is a predictor despite relatively low sensitivity. Levels of IgG had already plateaued at first evaluation in mothers with cCMV. Maternal screening offered insufficient positive predictive value for diagnosing cCMV, but allowed identifying asymptomatic cCMV cases in an early stage.

Seroprevalence of CMV IgG and IgM in Korean women of childbearing age

“…A previous study performed in pregnant Korean women reported rates of CMV IgG+/IgM+1.3% and CMV IgG+/IgM grey zone 0.4% comparable to the present study 7 . A previous study performed in pregnant Japanese women reported IgG+/IgM+ (4.3%), IgG‐/IgM+ (0.2%) and IgG+/IgM grey zone (1.2%), rates about two times higher than those of the present study 14 …”

“…7 A previous study performed in pregnant Japanese women reported IgG+/IgM+ (4.3%), IgG-/IgM+ (0.2%) and IgG+/IgM grey zone (1.2%), rates about two times higher than those of the present study. 14 Although there was no significant difference between annual number of congenital CMV infection and CMV IgG or IgM results in this study, the number of congenital CMV infections was more than five to 10 times higher than that of congenital rubella infection, with fewer than 10 annual cases under nationwide disease control with an immunization programme. 6 However, the efficacy of a national health screening programme for CMV infection still needs to be investigated.…”

“…6 However, the efficacy of a national health screening programme for CMV infection still needs to be investigated. 4,14,15 Future studies regarding the efficacy of CMV screening in large populations are needed.…”

TORCH screening used appropriately in China?─three years results from a teaching hospital in northwest China

“…However, the negative to IgM antibody was observed in 15 CMV infections with dynamic increase for IgG level. The findings also demonstrate the opinion that the IgM result of a single serologic test is difficult and inconclusive to the diagnosis of TORCH infections [5, 21, 22].…”

The clinical significance, laboratory diagnostics possibilities of human cytomegalovirus infection

“…A humorális immunválasz vizsgálatára, szerológiai diagnózis felállítására alkalmas érzékeny módszer az enzimhez kötött immunadszorpciós vizsgálat (ELISA; enzyme-linked-immunosorbent assay), további lehetőségek még az indirekt immunfluoreszcencián alapuló eljárások, western-blot, line immonoassay. A szerológiai vizsgálatokhoz jelenleg a kereskedelmi forgalomból beszerezhető ELISA készletek specificitása és szenzitivitása igen változó (5,11). Recombináns antigének és CMV peptid-fragmentek használata javíthatja a specificitást.…”