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Olfactory function in congenital cytomegalovirus infection: a prospective study.

ABSTRACT: Congenital cytomegalovirus (CMV) infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. Here, we have assessed in a prospective study conducted on children in two French hospitals from 2016 to 2019, infection severity and olfactory performance after congenital CMV infection. Children with congenital CMV infection aged 3 to 10 years and healthy controls (CTL) matched for age and sex to CMV children symptomatic at birth (sCMV) were enrolled. Olfactory discrimination was assessed using mono-odorants and binary mixtures. Data were analyzed for 54 children with PCR-confirmed congenital CMV infection, including 34 sCMV (median [IQR] age, 6 [5-8] years; 19 [55.9%] male), and 20 CMV asymptomatic at birth (aCMV, median [IQR] age, 4 [3-6] years; 12 [60.0%] male). sCMV were compared to 34 CTL children. Olfactory scores in CMV-infected children were independent from vestibular deficit and hearing loss. The olfactory score was efficient to discriminate between CTL and sCMV for children > 6 years (area under the receiver-operating characteristic curve (AUC, 0.85; P = 0.0006), but not for children < 7 years. For children > 6 years, the proportion of children with total olfactory score < 4 differed between sCMV and CTL groups (91.2% and 18.7%, P < 0.001), but not between aCMV and age-matched healthy control groups. Conclusion: Congenital CMV infection is associated with reduced olfactory performance in children with infection symptoms at birth. Clinical trial registration: NCT02782988 (registration date: May 26, 2016). What is Known: •Congenital cytomegalovirus infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. •Depending on neonatal clinical presentation, children are either categorized as having a symptomatic or asymptomatic infection at birth. What is New: •Congenital cytomegalovirus infection is associated with reduced olfactory performance in children with infection symptoms at birth.

SUBMITTER: Lazarini F

PROVIDER: S-EPMC8758467 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:BackgroundAn understanding of the correlation between maternal immunity and congenital cytomegalovirus (CMV) infection is critical for informing the design and evaluation of an effective maternal vaccine. This study aimed to quantitatively measure the protective effect of pre-existing maternal immunity against congenital CMV (cCMV) infection.MethodsA mother-child cohort study was conducted in three maternal and child health hospitals in China from 2015 to 2018. Pregnant women were consecutively enrolled, and anti-CMV pp150 IgG concentration at early, middle and late gestational ages were evaluated. Their newborns were screened for cCMV infection by CMV-DNA testing of saliva and urine.FindingsIn total, 6729 pregnant women were enrolled, and 6602 of them (98·11%) were positive for CMV IgG at their early gestational age visit (median time: 13 gestational weeks (GW); time range: 6-25 GW). In total, 6228 live newborns were born to seropositive mothers, and 48 (0·77%) of these infants were diagnosed with cCMV infection. The geometric mean concentration (GMC) of CMV IgG at an early gestational age in the women who delivered cCMV-positive newborns (i.e., the transmitters) was 8·54 IU/mL; this was significantly lower than the GMC in the non-transmitters (11·01 IU/mL; P=0·04). In early gestation, the risk of cCMV infection decreased as maternal IgG antibody levels increased (P=0·020); however, the same was not true in middle or late gestation (P>0·05). Using receiver operating characteristic analysis, a CMV IgG concentration of 12·83 IU/mL was established as the optimal diagnostic threshold. Compared to lower levels of CMV IgG (<12·83 IU/mL) in seropositive pregnant women, higher maternal CMV IgG levels (≥12·83 IU/mL) were associated with a 50% reduction in cCMV infection risk in infants (relative risk=0·50; 95% confidence interval: 0·27-0·93; P=0·028).InterpretationFor seropositive women, a higher level of CMV IgG at an early gestational age is associated with a lower risk of cCMV infection in their newborns.FundingNational Natural Science Foundation of China; Science and Technology Key Project in Fujian Province; Merck Sharp & Dohme Corp., Kenilworth, NJ, USA; Fieldwork Funds for graduate students of Xiamen University.

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Olfactory function in congenital cytomegalovirus infection: a prospective study.

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