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

ABSTRACT: 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.

SUBMITTER: Coppola T

PROVIDER: S-EPMC6963523 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Coppola Tiziana T Mangold Jesse F JF Cantrell Sarah S Permar Sallie R SR

Vaccines 20190926 4

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 ...[more]

PMID: 31561584

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Project description:IntroductionMost infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated.MethodsTo confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used.ResultsA total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy.ConclusionWithout universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.

Project description:ImportanceCongenital cytomegalovirus (cCMV) has received far less clinical and public health attention as a teratogenic infection than the Zika virus epidemic. However, cCMV may be responsible for a large fraction of microcephaly cases in the United States.ObjectiveTo evaluate the association between cCMV and the prevalence at birth of microcephaly in the United States.Design, setting, and participantsThis population-based cohort study included pregnant women and their newborns identified in 2 insurance claims databases from the United States: Medicaid Analytic eXtract (January 1, 2000, to December 31, 2013) and IBM Research MarketScan, a database for employer-sponsored private health insurance (January 1, 2011, to September 30, 2015). All pregnancies that resulted in live births in women with full health benefits were included. Analysis began June 2016 and ended May 2020.ExposuresCongenital cytomegalovirus infection documented in inpatient or outpatient newborn claims records.Main outcomes and measuresThe primary outcome was microcephaly at birth documented in inpatient or outpatient newborn and/or maternal claims records. Cases with chromosomal abnormalities or neural tube defects were excluded. The association between cCMV and microcephaly was estimated in the pooled cohort using prevalence ratios (PRs) and 95% CIs.ResultsIn the pooled cohort of 2 338 580 pregnancies (2 075 410 pregnancies [88.7%] were among women younger than 35 years), 336 infants (0.014%) had a cCMV diagnosis. The prevalence of microcephaly among newborns with and without a cCMV diagnosis was 655 and 2.8 per 10 000 live births, respectively (PR, 232; 95% CI, 154-350). After restricting to CMV-tested newborns (572 [0.024%]) to correct for preferential testing of infants with microcephaly, the PR was 15 (95% CI, 5.2-41). However, this PR is biased if other cCMV-related outcomes (eg, hearing loss) trigger testing because cCMV prevalence in tested infants, with ([46%]) or without microcephaly (22 of 559 [3.9%]), would overestimate that in the source population. Therefore, the prevalence of cCMV in overall infants with microcephaly (22 of 669 [3.2%]) was compared with that from an external unbiased sample of US infants screened at birth (449 of 100 332 [0.45%]) to estimate a PR of 7.4 (95% CI, 4.8-11.5) as a conservative lower bound.Conclusions and relevanceCongenital cytomegalovirus infection increases the prevalence of microcephaly at birth by at least 7-fold. Prevention of CMV infection during pregnancy might substantially reduce the number of newborns with microcephaly and other cCMV-related outcomes in the United States.

Dataset Information

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

Publications

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

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