Congenital cytomegalovirus infection in newborns suspected of congenital rubella syndrome in Iran: a cross-sectional study

Abstract

Background
Following rubella virus control, the most important cause of congenital infections is human cytomegalovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non-primary maternal infections. The present study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran.

Methods
Out of 1629 collected infants' serum samples suspected of CRS but negative for rubella IgM, 524 samples were selected regarding cCMV complications. These samples were divided into two age groups: 1- one month and younger, 2- older than 1 month up to one year. Anti-HCMV IgM detection was performed on these serums. Then HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results in IgM detection.

Results
Herein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM, 12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one month to one year was 14.5%. Identified genotypes in this study were gB-1(63.63%), gB2 (18.18%), and gB3 (18.18%), respectively.

Conclusions
This comprehensive study was performed on serum samples of symptomatic infants clinically suspected of cCMV from all over Iran. There was a good correlation between serology findings and PCR.

Full text

Mirsalehietal. BMC Pediatrics (2024) 24:31
https://doi.org/10.1186/s12887-023-04502-3
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BMC Pediatrics
Congenital cytomegalovirus infection
innewborns suspected ofcongenital rubella
syndrome inIran: across-sectional study
Negar Mirsalehi1, Jila Yavarian1, Nastaran Ghavami1, Maryam Naseri1, Farshad Khodakhah1,
Somayeh Shatizadeh Malekshahi2, Sevrin Zadheidar1, Talat Mokhtari‑Azad1 and
Nazanin‑Zahra Shafiei‑Jandaghi1,2*
Abstract
Background Following rubella virus control, the most important cause of congenital infections is human cytomeg‑
alovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non‑primary maternal infections. The pre‑
sent study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran.
Methods Out of 1629 collected infants’ serum samples suspected of CRS but negative for rubella IgM, 524 sam‑
ples were selected regarding cCMV complications. These samples were divided into two age groups: 1‑ one month
and younger, 2‑ older than 1 month up to one year. Anti‑HCMV IgM detection was performed on these serums. Then
HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results
in IgM detection.
Results Herein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM,
12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one
month to one year was 14.5%. Identified genotypes in this study were gB‑1(63.63%), gB2 (18.18%), and gB3 (18.18%),
respectively.
Conclusions This comprehensive study was performed on serum samples of symptomatic infants clinically sus‑
pected of cCMV from all over Iran. There was a good correlation between serology findings and PCR.
Keywords Human cytomegalovirus, Congenital rubella syndrome, Avidity assay, Genotype
Introduction
Human cytomegalovirus (HCMV) is a host-restricted
member in the β herpesvirinae subfamily of the Herpes-
viridae family [1]. Like other herpes viruses after primary
infection, the virus remains latent. e rate of seropreva-
lence in adults is around 45% to 100% worldwide. HCMV
can be transmitted both vertically and horizontally [2].
Transmission from the mother to the fetus or newborn
may occur during pregnancy, at birth time, and postna-
tal. Horizontal transmission happens through close con-
tact with contaminated saliva, urine, feces, blood, sexual
contact, and organ transplantation [3]. Postnatal HCMV
infection is acquired via interaction with cervical secre-
tions during birth, breast milk, blood transfusion, or
bodily fluids of infected persons. Approximately 9–88%
of seropositive women shed HCMV into their milk, and
*Correspondence:
Nazanin‑Zahra Shafiei‑Jandaghi
Nz‑shafiei@tums.ac.ir
1 Virology Department, School of Public Health, Tehran University
of Medical Sciences, Tehran, Iran
2 Department of Virology, Faculty of Medical Sciences, Tarbiat Modares
University, Tehran, Iran
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Mirsalehietal. BMC Pediatrics (2024) 24:31
roughly 50–60% of the newborns who have been fed
contaminated breast milk became infected [4]. During
pregnancy, HCMV is transmitted from the mother to
the fetus in approximately 35% of gestations with mater-
nal primary infection [5]. Intrauterine transmission of
HCMV may also happen in women with prior antibod-
ies to HCMV either by reactivation of previous maternal
infection (recurrent infection) or by the acquisition of a
different viral strain (re-infection). For these non-pri-
mary infections the proportion of vertical transmissions
is roughly 1.1 to 1.7% [6].
In newborns, postnatal HCMV infection is usually
asymptomatic [7]; however, prenatal infection may cause
devastating abnormalities [2]. In developed countries
following the control of rubella virus circulation, the
most important cause of congenital infections is HCMV
[1], with an estimated incidence rate of 0.5–2% in all live
births [8]. In developing countries, the rate of congenital
infection is around 2–4% [9] and 6–14% [10] in differ-
ent studies. e virus can replicate in the placenta, con-
taminate the fetus, and cause congenital CMV (cCMV)
and abnormalities in the fetus [11]. So, cCMV may hap-
pen both in primary and non-primary maternal infec-
tions but with different incidence rates [12]. Most of
the cCMV infections (CCI) [12] (75–90%) are asympto-
matic at birth. More or less than half of the symptomatic
infants are small for their gestational age, and one-third
are born prematurely. e most common observed clini-
cal findings are petechial rash, jaundice, hepatosple-
nomegaly and neurologic abnormalities [13]. Mental
retardation, seizures, speech delay, learning disabilities,
chorioretinitis, optic nerve atrophy, and defects in den-
tition are the other most common long-term complica-
tions in infants with cCMV [14, 15]. To diagnose cCMV
in suspected newborns up to roughly 3weeks after birth,
the standard technique is HCMV isolation from the
body fluids (such as urine, blood, saliva and cerebrospi-
nal fluid) using cell culture. However, virus isolation is
not generally used for cCMV diagnosis, as it is time con-
suming and expensive. e recommended and common
methods are the detection of HCMV-DNA and anti-
HCMV specific IgM [16, 17].
Nucleotide variability was determined for about 20
open reading frames (ORFs) of HCMV encoding, gly-
coproteins B (gB), gH, and gN, as well as tumor necro-
sis factor (TNF)-α receptor (UL144). In glycoprotein
B which is the major HCMV envelope protein com-
posed of 906 amino acids, the regions between 448 and
481 codons were defined as the highly polymorphic
site. Four main HCMV genotypes, gB1, gB2, gB3, and
gB4, and three rare non-prototypic variants, gB5, gB6,
and gB7, were defined based on this area [18]. HCMV
molecular genotyping can provide insights into HCMV
diversity within an individual host. Different strains of
HCMV may have varying levels of virulence, and geno-
typing can help identify which strains are more likely
to cause severe disease [19]. ere is no clear consen-
sus on whether there is an association between HCMV
genotype and specific clinical presentation. Some studies
have found no significant association between specific
genotypes and clinical features [20], while others have
found associations between certain genotypes and spe-
cific symptoms of cCMV infections [21, 22].
e present study aimed to screen cCMV using HCMV
specific IgM in newborns suspected of CRS in Iran. Our
secondary goal was to differentiate the primary and non-
primary maternal infections using IgG avidity assay in
newborns who were HCMV IgM positive. Furthermore,
probable congenital infections, perinatal and postna-
tal infections were also investigated for infants older
than 1 month of age, using the mentioned methods.
Finally, the genotypes of detected HCMV strains were
investigated.
Methods
Study design, patients andsamples
For congenital rubella surveillance, the Iran Ministry of
Health collects clinical samples of all suspected infants
younger than one-year-old from all over the country.
ese samples are sent to Measles and Rubella National
Laboratory in Virology Department, School of Public
Health, Tehran University of Medical Sciences. During
2016 and 2017, altogether 1629 serum samples of infants
suspected of CRS aged 3days up to one year were col-
lected. It should be noted that all of these samples were
negative for rubella specific IgM. Considering the simi-
larity and some difference between the symptoms of
CRS and cCMV, among these specimens, 524 serums of
symptomatic infants, who could be suspected of cCMV
based on the symptoms and complications, were selected
and assessed for HCMV infection. Based on the infants’
ages, their serum samples were divided into two groups.
In the first group, there were 244 serum samples of symp-
tomatic infants aged 1month and younger. In the second
group, there were 280 serum samples from infants aged
older than 1month up to one year.
Serology
Anti-HCMV IgM detection was performed on 524
serum samples using a commercial enzyme-linked
immunosorbent assay (Anti-CMV ELISA-IgM, Euro-
immunLubeck, Germany). e interpretation of IgM
results, according to the kit’s instruction was as follows:
Ratio < 0.8 was considered negative, ratio ≥ 0.8 to 1.1 was
considered borderline and ratio ≥ 1.1 was considered
positive.
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Mirsalehietal. BMC Pediatrics (2024) 24:31
en for both groups of infants HCMV IgG avidity
assay was carried out on all IgM positive and borderline
cases using a commercial kit (Anti-CMV ELISA-IgG
Avidity, Euroimmun Lubeck, Germany). Avidity results
were calculated and interpreted according to the kit man-
ual as follows: Avidity index (AI) > 40% was considered
as low avidity IgG indicating primary CMV infection. AI
40–60% was considered as moderate avidity (equivocal)
and AI > 60% was considered as high avidity antibody
indicating past CMV infection [23].
HCMV molecular detection andgenotyping
HCMV DNA detection was performed on all sam-
ples with positive and borderline results in IgM detec-
tion. At first, DNA was extracted using the High Pure
Viral Nucleic Acid Kit (Roche, Germany) according to
the manufacturer’s instructions. e extracted DNA
was stored at -20˚C before being used as a template to
detect CMV DNA. en, a semi-nested PCR reaction
was applied to detect CMV DNA by using specific prim-
ers for a part of the gB gene (UL55 region) from a pre-
vious study [24]. DNA amplification was performed in
50μl total reaction volume in the first and 50μl in the
second round. e first reaction contained: 5 μl PCR
Buffer, 2μl Mgcl2, 1.5μl dNTP, 1.5μl forward and1.5μl
reverse primers, 28μl deionized water, 0.5μl Taq DNA
polymerase and 10μl target DNA. In the second reaction
the volume of deionized water was 33μl and the target
DNA was 5μl (Table1). For virus type identification in
HCMV positive cases, the PCR products of the second
round were purified and subjected to Sanger sequencing
in forward and reverse directions. Sequencing reactions
were performed using the ABI Big Dye Terminator Cycle
Sequencing Kit and a 3130 Genetic Analyzer (Applied
Biosystems). For genotype identifications, a phylogenetic
tree with 1000 bootstrap was constructed using MEGA
10 software based on the maximum likelihood method
via the Tamura-Nei model.
Statistical analysis
Continuous and categorical variables were shown as
mean (SD) and n (%), respectively. To examine dif-
ferences between independent groups, the χ2 test, or
Fisher’s exact test is applied where appropriate. A two-
sided α of less than 0·05 was considered statistically sig-
nificant. Statistical analyses were performed using SPSS
version 22.
Result
HCMV serology andgenome detection results ininfants
aged 1month andyounger
Two hundred thirty-eight of these 244 infants had gender
information as follows: 124 (52.10%) were female and 114
(47.89%) were male (Table2). IgM detection, IgG avid-
ity evaluation and PCR were performed. e result of
HCMV IgM detection test on these 244 serum samples
showed that 5 (2.04%) cases were positive, 4 (1.63%) cases
were borderline and 235 (96.3%) cases were negative.
Totally, the rate of IgM detection which was considered
as CCI [12] in these infants was estimated 3.67%. IgG
avidity index (AI) was measured in positive and border-
line serums for HCMV IgM (8 out of 9, one sample was
excluded due to inadequate serum sample). e result
showed 7/8 (87.5%) had high AI and 1 (12.5%) had low AI
(Table3).
e evaluation of PCR results in these 8 samples
showed that HCMV-DNA was detected in 2 serums.
HCMV serology andgenome detection results ininfants
older thanone month toone year
Two hundred eighty serum specimens were collected
from infants aged older than 1month to 12months.
Of these 280 infants, 130 were female and 150 were
male (Table 4). Evaluation of IgM detection in these
infants showed: 19 (6.7%) serums were positive, 22 (7.8%)
were borderline and 239 (85.5%) cases were negative.
One IgM-positive sample was not evaluated for avidity
Table 1 PCR mix and condition for HCMV molecular detection and genotyping by Semi‑nested PCR
First round PCR mixture Second round PCR mixture Amplication Temperature Time
Component Volume Component Volume Pre-Denaturation 95◦C 5’
DDW 28 μl DDW 33 μl Denaturation 94◦C 1’
Buffer 5 μl Buffer 5 μl Annealing 55◦C 1’
Mgcl2 2 μl Mgcl2 2 μl Extension 72◦C 1’
dNTP 1.5 μl dNTP 1.5 μl Final extention 72◦C 8’
Forward Primer 1.5 μl Forward Primer 1.5 μl Hold 4◦C ‑
Reverse 1 Primer 1.5 μl Reverse 2 primer 1.5 μl
Taq DNA polymerase 0.5 μl Taq DNA polymerase 0.5 μl
Total 50 μl Total 50 μl
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Mirsalehietal. BMC Pediatrics (2024) 24:31
due to the insufficient amount of serum. Out of 40 posi-
tive and borderline IgM serums among mentioned
infants 8 (20%) had low AI, 16 (40%) had equivocal AI
and 16 (40%) had high AI (Table5). For all positive and
borderline IgM serums, PCR testing was done, in which 9
cases were positive.
Genotypes ofHCMV
Overall, 11 cases of HCMV detected genomes in this study
could be successfully genotyped. Herein, among four major
gB genotypes, gB-1, gB-2 and gB-3 were detected (Fig.1).
e most frequent genotype was gB-1(63.63%). en, gB2
(18.18%) and gB3 (18.18%) were found. Of the 2 identi-
fied strains in one month old and younger infants, one
belonged to the gB1 genotype, which was collected from
Khuzestan province and the other one belonged to gB3
genotype collected from Tehran province. In infants older
than one month to one year, out of 11 strains, 9 strains were
sequenced properly. e results showed, 6 cases (66.67%)
belonged to gB1 genotype from Tehran, Isfahan, Alborz,
and Mazandaran provinces, 2 (22.2%) was gB2 genotype
from Azerbaijan Sharghi and Khorasan and one (11.1%)
was gB3 genotype from Azerbaijan Sharghi province.
Discussion
The half-life of IgG antibodies is approximately 21
to 26days and maternal IgG generally disappears by
4months of life [25]. It should be noted that, low AI
among infants aged 1 month and younger indicates
a certain maternal HCMV primary infection. High
AI suggests a non-primary maternal infection but it
should be considered that some mothers may have
had primary infection in the first months of preg-
nancy. For older children, low AI indicates a current
HCMV infection, while high AI reveals a past HCMV
infection.
This study showed that in Iran during 2016–2017,
the incidence rate of CCI in symptomatic infants
aged 1month and younger was 3.67%. It is important
to note that congenital rubella was negative in these
infants.
In several studies conducted in Iran and other coun-
tries, the incidence rate of CCI in neonates and infants
was evaluated using different methods A cross-sec-
tional study in Birjand, Iran in 2018 showed that the
rate of CCI in randomly selected neonates (868 cases)
using PCR on saliva was 1.61% [26]. A study in Teh-
ran, Iran in 2017 tested 100 urine samples of sympto-
matic infants, under 3weeks of birth to diagnose CCI
using PCR and ELISA. HCMV-DNA was detected in
the urine of 58 infants and 20 serums were positive for
HCMV-IgM. The prevalence of cCMV was reported
58% [27].
In a prospective study in 2016 CCI was identified in 8
(0.49%) out of1617 urine specimens of symptomatic Ira-
nian neonates less than two weeks of age [28].
ese findings highlight the importance of early diag-
nosis and management of CCI in neonates and infants.
Table 2 Comparison of infants suspected of cCMV aged 1 month
and younger based on gender
Year Gender Total Chi-Square
Tests
P value:
Female Male
2016 42 (56.0%) 33 (44.0%) 75 (31.51%) 0.46
2017 82 (50.30%) 81 (49.69%) 163 (68.48%)
Total 124 (52.10%) 114 (47.89%) 238 (100%)
Table 3 IgG avidity in symptomatic infants suspected of cCMV
aged 1 month and younger
Year CMV IgM N IgG Avidity
Low AI
N (%) Equivocal AI
N (%) High AI
N (%)
2016 Positive 2 ‑‑‑‑ ‑‑‑‑ 2 (100%)
Borderline 1 1 (100%) ‑‑‑‑ ‑‑‑‑
2017 Positive 3 ‑‑‑‑ ‑‑‑‑ 3 (100%)
Borderline 2 ‑‑‑‑ ‑‑‑‑ 2 (100%)
Total Positive 5 ‑‑‑‑ ‑‑‑‑ 5 (100%)
Borderline 3 1 (33.33%) ‑‑‑‑ 2 (66.66%)
Positive and Borderline 1 (12.5%) ‑‑‑‑ 7 (87.5%)
Table 4 Comparison of infants suspected of cCMV older than 1
to 12 months of age based on gender
Year Gender Total
Female Male
2016 55 (42.3%) 75 (57.7%) 130 (46.42%)
2017 75 (50%) 75 (50%) 150 (53.57%)
Total 130 (46.42%) 150 (53.57%) 280 (100%)
Table 5 IgG avidity in symptomatic infants suspected of cCMV
older than 1 to 12 months of age
Year CMV IgM N IgG avidity
Low AI
N (%) Equivocal AI N
(%) High AI
N(%)
2016 Positive 7 2 (28.5%) 2 (28.5%) 3 (42.8%)
Borderline 8 2 (25%) 5 (62.5%) 1 (12.5%)
2017 Positive 11 2 (18.1%) 3 (27.7%) 6 (54.5%)
Borderline 14 2 (14.2%) 6 (42.8%) 6 (42.8%)
Total Positive 18 4 (22.2%) 5 (27.7%) 9 (50%)
Borderline 22 4 (18.1%) 11 (50%) 7 (31.8%)
Positive and Borderline 8 (20%) 16 (40%) 16 (40%)
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Further research is needed to better understand the epi-
demiology and clinical manifestations of HCMV infec-
tion in different populations.
e prevalence of CCI varies considerably in develop-
ing country, ranging from 6 to 14% [10], while in indus-
trialized countries such as Western Europe, the United
States, Canada, and Australia it affects around 0.5–0.7%
of all live births [29]. HCMV IgG avidity can be used to
distinguish primary from non-primary infection [23].
Like our study where maternal specimens are not availa-
ble, IgG avidity assay can be performed on infants’ serum
samples to determine whether their mothers had primary
infection during pregnancy. In infants 1 month of age
and younger, only 12.5% of CCI cases could be attributed
to the maternal primary HCMV infection, according to
the low AI results. On the other hand, 87.5% of neonates
with CCIhad high AI. is probably suggests that their
mothers had non-primary infections. However, there is
apossibility that some mothers had a primary infection
in the early months of pregnancy and the avidity had
matured by the end of pregnancy.
e nature of non-primary maternal HCMV infec-
tions could be re-infection with a different viral strain
of HCMV, or recurrent infection from reactivation of a
latent virus [30].
Studies have shown that the risk for long-term com-
plications was higher in infants born to mothers with
primary infection in the first half of pregnancy rather
than non-primary infections [1]. In developing countries
approximately 90% of women in childbearing age are
immune to HCMV therefore HCMV reactivations occur
more than primary infections [31].
In Iran, a cohort study found that 93% of child bear-
ing aged women were seropositive for HCMV [32], while
a prospective study in Iran showed that 84% of women
were HCMV seropositive and the rate of seropositivity
was higher in people with lower socioeconomic condi-
tions [33]. In another study, the seroprevalence of HCMV
among pregnant women in the east of Iran was 72.1%
[34]. In a systematic review conducted from 2008–2017
in Iran, the pooled prevalence rate of HCMV IgG among
women of reproductive age was estimated at 90%. e
highest prevalence rate of HCMV IgG was found in Teh-
ran, Rasht, Mashhad, and Yasuj, while the lowest preva-
lence was detected in Jahrom [35].
HCMV seropositivity in women of reproductive age
ranged from 45 to > 90%, globally. HCMV seropreva-
lence tends to be higher in developing countries (> 90%
in Brazil, 70–80% in Ghana, > 90% in India, 80–90% in
South Africa and > 90% in Turkey) and lower in devel-
oped countries (40–70% in Western Europe, 60–70% in
Australia, 60–70% in Canada and 50–60% in the United
States) [31].
Serum samples were used for cCMV detection by PCR
method although it is not the sample of choice [36].
Besides, the genotypes of detected HCMV were identi-
fied through nucleotide sequencing and phylogenetic
analysis.
Herein, the prevalence of HCMV infection among
infants older than one month to one year, was
Fig. 1 HCMV gB gene of strains from Iran compared with the HCMV reference sequences displayed in a phylogenetic tree determined
using the maximum likelihood method via Tamura‑Nei model with MEGA 10 software. Only bootstrap values greater than 70% are displayed
at the branch nodes. The genotypes of samples from Iran are indicated as solid circle. Sequences of Iran fell within gB1, gB2 and gB3 genotypes
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Mirsalehietal. BMC Pediatrics (2024) 24:31
14.5% which could be attributed to congenital, perina-
tal or postnatal infections. Astudy by Noor bakhsh etal.
evaluated the HCMV infection in infants suspected of
intrauterine infection and in controls. e study found
that 41.9% (31/74) of cases had HCMV IgM and 74%
(54/74) had HCMV IgG while in the control group, 6.2%
had HCMV IgM and 95.4% had HCMV IgG [37].
In a long-term study between 2003 and 2015, the
prevalence of HCMV IgM and IgG among 517 symp-
tomatic newborns and children aged 1–3 months old
was assessed. Among all of these cases, 97 (18.7%) were
HCMV IgM positive and 438 (84.7%) were HCMV IgG
positive. e rate of HCMV IgM positivity in 1–3months
old children (25.8%) was higher (fourfold) than that in
newborns (6.4%) [38, 39].
As mentioned, the results of IgG avidity assay in our
study showed that around 80% of symptomatic infants
older than one month to one year had high or moderate
avidity indicating IgG maturation in these infants due to
passing time.
For all positive and borderline IgM serum samples,
genome detection was performed by semi-nested PCR.
In infants aged one month old and younger, HCMV
genome was detected only in two cases, both of which
had high avidity IgG, which were caused by non-primary
maternal active infection. Of these 2 identified strains,
one case (50%) belonged to gB1 genotype and the other
case (50%) to gB3 genotype. Among the children of
the other group, HCMV genotype identification of 9
detected strains in this study showed, six cases (66.67%)
belonged to gB1 genotype, 2 (22.2%) cases to gB2 geno-
type and one (11.1%) case to gB3 genotype. e high
frequency of gB1 genotype was consistent with other
studies in Asia [40, 41].
HCMV genotyping is useful to examine potential dif-
ferences in the pathogenicity of strains and to show infec-
tions with a mixture of HCMV strains involved in HCMV
disease in adults and congenitally infected newborns
[42]. In a study conducted in the south of Iran, HCMV
genome detection was performed on 80 urine samples of
NICU hospitalized neonates in two age groups (younger
and older than 30 days) and only one newborn under
30days had HCMV-DNA. So the rate of CCI was esti-
mated 1.2% [43].
In the study conducted in Cuba on 361 newborns
with clinically suspected HCMV infection it was found
that 19.7% of infants had congenital infection. All of the
four major HCMV genotypes were detected among the
infants with the most frequent genotype being gB-2 [44].
e total frequency of cCMV infection was 18.4%
among 576 suspected Indian newborns (2 weeks after
Birth) with confirmed seropositive test. Between the
different gB genotypes, gB1 had the highest and gB4 had
the lowest frequencies [40].
is study had several limitations: e best samples
for CCI diagnosis are urine or saliva that were not avail-
able. Maternal serum samples were unavailable to assess
HCMV IgM and IgG.
Conclusion
is study was a comprehensive research conducted on
serum samples of symptomatic infants clinically sus-
pected of cCMV from all over Iran. Based on maternal
IgG avidity, in a few of the cases, this congenital infec-
tion was caused by a primary maternal infection while
in the majority of cases could be due to a non-primary
infection. In the latter group, the possibility that some
mothers had primary infection in the first months of
pregnancy and avidity matured at the end of pregnancy
should be considered. e incidence rate of HCMV
infection among infants older than one month to one
year, was evaluated which could be attributed to congeni-
tal, perinatal, or postnatal infections. e genotypes of
HCMV were identified, and gB-1 was the most frequent
genotype.
Acknowledgements
We express our thanks to our colleagues in the measles and rubella national
center, Virology Department, School of Public Health, Tehran University of
Medical Sciences.
Authors’ contributions
NM and NG contributed in tests performing, NM and SZ contributed in draft‑
ing the manuscript. SS and TM contributed in reviewing the paper critically. JY
and NZ‑SJ designed and supervised the study. All authors have approved the
final version of the article.
Funding
This work was funded and supported by Tehran University of Medical Sciences
(Grant No. 97–03‑27–38669).
Availability of data and materials
The data that support the findings of this study are available on request from
the corresponding author.
Declarations
Ethics approval and consent to participate
This study was approved in the Ethics Committee of Tehran University of
Medical Sciences with the approval code IR.TUMS.SPH.REC.1398.329. All
specimens used in this study were collected by Iran Ministry of Health for
national measles and rubella surveillance. No extra sample was collected
for this study. All methods were performed in accordance with the relevant
guidelines and regulations. We sought permission from Tehran University of
Medical Sciences (TUMS) review board for using the samples and informed
consent is exempted.
Consent for publication
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Page 7 of 7
Mirsalehietal. BMC Pediatrics (2024) 24:31
Received: 27 February 2023 Accepted: 20 December 2023
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