Clinical Infectious Diseases

MAJOR ARTICLE

Risk Factors for Congenital Cytomegalovirus Infection

Following Primary and Nonprimary Maternal Infection: A
Prospective Neonatal Screening Study Using Polymerase
Chain Reaction in Saliva
Marianne Leruez-Ville,1,2 Jean-François Magny,1,3 Sophie Couderc,4 Christine Pichon,5 Marine Parodi,6 Laurence Bussières,1,7
Tiffany Guilleminot,1,2 Idir Ghout,8,9 and Yves Ville1,5
1
EA 73-28, Université Paris Descartes, Sorbonne Paris Cité, 2Laboratoire de Microbiologie Clinique, Centre national de Réfèrence Cytomegalovirus-Laboratoire associé, and 3Réanimation
Néonatale, AP-HP, Hôpital Necker-E.M., Paris, 4Hôpital Intercommunal de Poissy-Saint Germain, Maternité, 5Maternité, 6Département d’Otologie, and 7Unité de Recherche Clinique, AP-HP, Hôpital
Necker-E.M., Paris, 8Unité de Recherche Clinique et Département de Santé Publique, AP-HP, Hôpital Ambroise Paré, Boulogne, and 9UMR-S 1168, Université Versailles St-Quentin-en-Yvelines,

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Montigny, France

Background.  The design of diagnostic and preventive strategies have been prevented by gaps in knowledge of the epidemiology
of congenital cytomegalovirus (cCMV) with the type of maternal infection as well as the lack of large-scale neonatal screening tools.
Methods.  In sum, 11 715 consecutive newborns were screened for cCMV by polymerase chain reaction (PCR) in saliva.
Prevalence, type of maternal infection, sociodemographic, obstetrical, and serological data were analyzed.
Results.  Positive predictive value of CMV PCR in saliva was 59%; false positive results were associated with lower viral loads
(P < .001). Maternal seroprevalence was 61%, birth prevalence was 0.37%, resulting from primary and nonprimary infections in 52%
and 47.7% of cases, respectively. The risk to deliver an infected baby after primary infection was increased in younger (OD = 7.9),
parous (OD = 4.1) women born in high resources countries (OD = 5.2) and from higher income groups (P = .019). The only 2 risk
factors to deliver an infected baby after nonprimary infection were to be young (OD = 4.6) and unemployed (OD = 5.8). The risk to
deliver an infected baby was 4-fold higher in women seronegative before their pregnancy (P = .021).
Conclusions.  A positive CMV PCR in newborns’ saliva should always be confirmed in a repeat-sample. Sociodemographic
characteristics of women giving birth to an infected baby after primary and nonprimary infection are different. Seronegative, parous
women represent the highest risk population for cCMV in countries with low to intermediate seroprevalence. Urgent action is
needed to stop the cCMV’s epidemic, particularly in this population easily identifiable by maternal serology and amenable to pre-
vention messages.
Clinical Trials Registration.  NCT01923636.
Keywords.  cytomegalovirus; congenital; screening; saliva; nonprimary infection.

Congenital CMV (cCMV) is the main cause of neurological
handicap of infectious origin with a birth prevalence of 0.65%
worldwide [1]. Although cCMV meets most criteria for screen-
ing programs, none have been implemented in any country.
This is explained by gaps in knowledge on several fronts. A bet-
ter understanding of the epidemiology of cCMV related to
both maternal primary and nonprimary infection is needed to
evaluate the impact of universal maternal serological screening.
A better knowledge of the performance of broad screening tools
is mandated before considering universal neonatal screening.
Received 27 January 2017; editorial decision 24 March 2017; accepted 10 April 2017;
published online April 17, 2017.
Correspondence: M.  Leruez-Ville, Laboratoire de Microbiologie Clinique, Hôpital Necker-
E.M., 149 rue de Sèvres, 75015 Paris, France (marianne.leruez@aphp.fr).
Clinical Infectious Diseases®  2017;65(3):398–404
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/cix337
Large scale screening studies have been published, but none
has reported birth prevalence in the light of sociodemograph-
ics, obstetrical and serological data within the same population
[2–7]. We undertook universal screening of cCMV infection in
live-born infants delivered in 2 French maternities located in the
Paris area between September 2013 and August 2015. Screening
was performed by CMV DNA detection and quantification by
real-time polymerase chain reaction (PCR) in saliva [5, 7]. All
positive screening tests were controlled in repeat samples allow-
ing calculation of the positive predictive value of the screening
test in saliva. For each infected newborn, the type of maternal
infection was characterized between primary or nonprimary.
Maternal demographics have rarely been considered and never
accordingly to the type of maternal infection within the same
study population [8–10]. We found that the type of maternal
infection is closely related to sociodemographic characteristics
with implications for prevention programs to be based upon.

398 • CID 2017:65 (1 August) •  Leruez-Ville et al

MATERIALS AND METHODS
Population
Consecutive newborns were swabbed for saliva in 2 materni-
ties in Paris (Necker and Poissy) between September 2013 and
August 2015. Data were collected prospectively: maternal age,
parity, gravidity, multiple pregnancies, employment status and
socio professional categories, geographic origin, and gestational
age at delivery.
Poissy-Saint Germain Hospital ethics committee approved
the study (2013-A00213-42). Written informed consent was
obtained before inclusion.
The study is registered in clinicaltrial.gov website under
NCT01923636.
METHODS
Cytomegalovirus DNA Detection and Quantification in Newborn Saliva
Samples
Saliva samples were collected at delivery with an open-celled
foam bud swab for optimum absorption and release, combined
with viral transport medium (Sigma-Virocult® M40 Compliant,
MWE Medical Wire, Witshire, UK). PCR were run daily from
Monday to Friday, samples were stored at +4°C before PCR
for at most 4  days. CMV DNA was extracted from 200  µL of
transport medium on the MagNaPure LC (Roche Diagnostic,
Meylan, France). CMV DNA in saliva was amplified with an
in-house assay [11]. To check for the quality of saliva sam-
ples, extraction and amplification, CMV PCR was duplexed
with an in-house glyceraldehyde 3-phosphate dehydrogenase
(GAPDH) PCR [12]. The 95% limit of detection of this assay
was calculated (Appendix 1). CMV DNA was quantified in
positive samples with CMV R-gene® kit (Argene, BioMérieux,
Marcy l’Etoile, France). The linearity of CMV DNA quantifica-
tion in saliva was tested (Appendix 2).
A second saliva sample and a blood sample were systemati-
cally collected 1–3 days later from all newborns with a first pos-
itive saliva sample.
Cytomegalovirus Serology in Pregnant Women
At Necker hospital, CMV serology testing is offered to all
pregnant women at 11–14 weeks. Immunoglobuin G (IgG)
and immunoglobulin (IgM) are tested on Liaison XL platform
(DiaSorin, Antony, France). In case of positive IgM, IgG avidity
is measured with the LIAISON® CMV IgG Avidity kit to exclude
or confirm primary infection in pregnancy as already described
[13]. Therefore, part of the mothers of screened newborns had
CMV serology testing prospectively. Alternatively, maternal
serology results for infected newborns were obtained retrospec-
tively on stored sera. In France, serum samples are collected at
first and third trimesters of pregnancy for serology testing and
women seronegative for toxoplasmosis are tested monthly; all
sera are stored for 1 year.
Definition of a Symptomatic/Asymptomatic Status at Birth
Symptomatic or asymptomatic status at birth relied on a com-
bination of clinical, laboratory, audiometric (automated audi-
tory brainstem response) and cerebral imaging assessments as
described [14] (Appendix 3).
Statistical Analysis
Prevalence of cCMV was defined as the proportion of infected
newborns among all live-born infants enrolled during the study
period. The positive predictive value (PPV) of CMV PCR on
saliva sample was defined as the proportion of patients with
positive subsequent saliva control sample among those who
were positive in the first saliva sample. Control samples were
obtained only in cases with a positive PCR in the first saliva
sample; the negative predictive value could therefore not be
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calculated.
Prevalence of cCMV and PVV of CMV PCR in saliva were
estimated along with their 2-sided 95% Clopper-Pearson exact
confidence intervals for binomial proportions. Descriptive
analyses were presented as frequency with percentage, median
with interquartile range, or mean with standard deviation.
Between-groups comparisons were conducted using χ2 test,
Fisher exact test, or Student test as appropriate. Multinomial
logistic regression was used to assess factors associated with
neonatal infection following maternal non-primary or primary
infection. Independent variables entered in the model showed
P values < .05 on univariate analysis. Newborns screened from
women referred with an already known CMV fetal infection
were excluded from the prevalence calculation but unclouded
to subsequent analysis. Risk ratio to deliver an infected baby
for women seronegative before pregnancy and 95% confidence
interval (CI) were estimated in a subgroup of women who had
CMV serology done in the first trimester in Necker. To check
for selection bias, sociodemographic and obstetrical data of
mothers who delivered in Necker were compared between
women who had a CMV serology done in the first trimester and
those who had not. Analyses were performed using the R 3.13
software, R Core Team (2014; R: A language and environment
for statistical computing, foundation for Statistical Computing,
Vienna, Austria. URL http://www.R-project.org/).
RESULTS
Polymerase Chain Reaction Performance
The 95% limit detection of the in-house CMV/GAPDH duplex
PCR assay was 869 (2.9 log10) copies/mL (Figure S1). The upper
limit of quantification of CMV R-gene® PCR in saliva samples
was 9.3 log10 copies/mL (Figure S2).
Prevalence of Cytomegalovirus Congenital Infection, Type of Maternal
Infection and Neonatal Status (Figure 1)
The study was proposed to mothers of 11 857 liveborn neo-
nates representing 84% of all births during the study period
Screening Congenital CMV in France  •  CID 2017:65 (1 August) • 399

Figure 1.  Flow chart of the study. Abbreviations: CMV, cytomegalovirus; PCR, polymerase chain reaction.
(88% [5328/6030] in Necker and 79% [6529/8145] in Poissy).
Members of staff were either too busy or forgot to propose the
study to 2318 (16%) mothers. In sum, 76 newborns were not
included because their mothers refused the study. And 41 saliva
samples were defective (not labeled, broken vial…). Among
the 11 740 newborns screened, 25 had a CMV PCR result not
interpretable because of a negative GAPDH PCR suggesting
improper sampling. In total, 11 715 neonates had an interpret-
able CMV PCR results, and 51 were screened and confirmed
infected. Seven of these 51 newborns were excluded from the
prevalence calculation because their mothers were referred with
a known CMV fetal infection.
The prevalence of cCMV was 0.37% (44/11 715) (95% CI:
0.246, 0.606) and was similar in Necker and Poissy: 0.39%
(21/5296) (95% CI: 0.246, 0.606) and 0.36% (23/6419) (95% CI:
0.227, 0.537), respectively (P = .848). And 23 (52% 95% CI: 36.7,
67.6) and 21 (48%, 95% CI: 32.5, 63.3) cases followed maternal
primary or nonprimary infection, respectively; similar propor-
tions were found in Necker 57% (12/21) vs. 43% (9/21) and in
Poissy 48% (11/23) vs. 52% (12/23) (P = .623).
Among the 44 infected neonates (51 minus 7 born from
mothers referred for CMV infection), 9 (21%) were sympto-
matic including: 4 (9%) with hearing loss, 4 (9%) with isolated
SGA (small for gestational age), and 1 with isolated thrombo-
cytopenia. The proportions of neonates with symptoms and
hearing loss were similar for both types of maternal infection in
Necker and Poissy with 21% vs. 19% and 8.6% vs. 9.5%, respec-
tively (P > .99). The 2 neonates infected after primary infection
400 • CID 2017:65 (1 August) •  Leruez-Ville et al
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had profound unilateral hearing loss with threshold of 100 db
in both cases. Whereas among the 2 neonates infected after
nonprimary infection, one had moderate unilateral hearing loss
(threshold 60 db), and the other had moderate to severe bilat-
eral hearing loss with respective threshold of 60 db in the best
ear and 70 db in the worst ear.
Positive Predictive Value of Congenital Cytomegalovirus (cCMV)
Screening With CMV Polymerase Chain Reaction in Saliva
CMV PCR was positive in the first saliva sample in 87 new-
borns. All 87 had subsequent saliva and blood control samples
with positive CMV PCR confirmed in only 51 following resa-
mpling. PPV of the screening test was 58.6% (95% CI = 47.5–
69.1). Median viral load in true positive samples was much
higher than in false positive samples (7.6 [inter quartile {IQ}
6.3, 8.4] vs 2.2 [IQ 1.8, 2.4] P < .001) (Figure 2).
Comparison of Socio-Demographic, Obstetrical and Serologic Maternal
Data Between Uninfected and Infected Newborns Following Maternal
Primary or Nonprimary Infection (Table 1)
The 48 mothers of the 51 infected neonates (44 plus the 7
infected newborns from referred mothers) were classified
depending on the type of maternal infection. Retrospective
CMV serology testing was performed in maternal stored sera
for these 51 infected neonates. This allowed classification into
primary and nonprimary group. Seroconversion during preg-
nancy was demonstrated in 16 women, the presence of positive
IgG, positive IgM, and low or intermediate IgG avidity was evi-
denced in 12 women; these 28 women composed the primary

Figure 2.  Comparison of CMV DNA loads in saliva between cases with a true
positive diagnosis of cCMV and those with a false positive diagnosis of cCMV.
Abbreviations: CMV, cytomegalovirus; cCMV, congenital cytomegalovirus.
infection group. Primary infection occurred in first, second, and
third trimesters in 17, 8, and 3 cases, respectively. Six women
had a known positive CMV serology before pregnancy, and 14
had a serology in the first trimester with the association of pos-
itive IgG, negative IgM, and high IgG avidity. These 20 women
composed the nonprimary infection group. Of note, none of the
48 women had a serological profile showing positive IgG, posi-
tive IgM, and high IgG avidity or with the association of positive
IgG, negative IgM, with low or intermediate IgG avidity.
All 3 groups were similar in age, gravidity, rate of multiple
pregnancies, or gestational age at delivery. Mothers of infected
newborns following primary infection were less often nulliparous
than mothers of uninfected newborns (P = .01), but this was not
true for mothers of newborns infected after nonprimary infection
(P = .846). Mothers of newborns infected after primary infection
were more often born in high-resource countries (P = .034). The
opposite was true of mothers of newborns infected after non-
primary infection for whom country of birth was more often of
low or intermediate resources (P = .03). There were more unem-
ployed among mothers of newborns infected after nonprimary
infection (P = .015), but this was not true of mothers of newborns
infected after primary infection (P = .501). Mothers from the lat-
ter group belonged more often to socio professional groups with
higher incomes than mothers of uninfected newborns (P = .019).
Maternal Risk Factors to Deliver an Infected Baby Following Maternal
Primary or Nonprimary Infection (Table 2)
To be parous and to be born in a high-resource country were
independent risk factors for delivering a baby infected after
primary infection (odds ratio [OR] = 4.178 [1.731, 10.083] and
5.2 [1.486, 18.199], respectively). Younger age <25 years was a
risk factor for congenital infection of both types (OR = 7.943
[2.647, 23.836] and 4.657 [1.484, 14.616] for primary and
nonprimary infections, respectively). Being unemployed was
the only other independent risk factor for delivering a new-
born infected after nonprimary infection (OR = 5.854 [2.157,
15.883]).
Risk of Delivering an Infected Newborn According to Maternal
Cytomegalovirus Serology in the 1st Trimester (Figure 3)
Overall, 2378 women had a serology performed at 11–14 weeks
in Necker laboratory and underwent neonatal screening, repre-
senting 45% of all women delivered in Necker. This subset was
similar to the whole population of Necker in age, parity, gravid-
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ity, country of birth, and employment status (Appendix 4, Table
S1). It was therefore considered to be a representative subset of
the population of women delivering in Necker.
Among these 2378 women, 1454 (61% 95% CI: 58, 62) were
classified as seropositive before pregnancy based on serologi-
cal profile in the first trimester (IgG positive/ IgM negative or
IgG positive/IgM positive with high IgG avidity), and 924 (39%)
were classified as seronegative before pregnancy (IgG negative/
IgM negative or IgG positive/IgM positive with low or inter-
mediate IgG avidity). The risk to deliver an infected baby was
significantly higher in seronegative women before pregnancy
than in women seropositive before pregnancy (0.86% vs 0.2%,
P = .021) (Figure 3).
DISCUSSION
We performed universal screening of all liveborn neonates in 2
maternities in France. The prevalence of cCMV was 0.37% in
this population of Paris and greater Paris area, therefore within
range of what was expected from the literature. Although
worldwide birth prevalence of cCMV infection has been esti-
mated to be 0.64% [15], prevalence varies accordingly to the
level of CMV immunity in pregnant women. Birth prevalence
is higher (>1%) in low-resource countries where maternal sero-
prevalence is high (>95%) including most African and Asian
countries [16]. These countries also have the lowest resources.
However, in countries with intermediate maternal seropreva-
lence (around 55–60%), such as France [17, 18] the birth preva-
lence is expected to be around 0.4% [1].
The proportions of congenital infections following pri-
mary and nonprimary maternal infections were 52% and 48%,
respectively, for a 61% maternal seroprevalence. A  search in
PubMed including: “cytomegalovirus,” “congenital,” and “risk
factors” did not retrieve a single previous prospective screen-
ing study linking maternal seroprevalence, birth prevalence of
infection, and the respective role of primary and nonprimary
infections within the same population. Because of this lack of
combined data, models have been developed to predict the
Screening Congenital CMV in France  •  CID 2017:65 (1 August) • 401
Table 1.  Comparison of Socio-Demographic, Obstetric, and Serologic Data Between Mothers of Infected and Uninfected Babies

Uninfected Newborns. Infected Newborns After Primary Infected Newborns After Nonprimary
Mothers N = 11 088 Infection. N = 28 P Infection. N = 20 P

Age 32.4 ± 5.4 31.3 ± 5.4 .293 30.6 ± 6.8 .272

Age < 25 y 818 (7.4%) 5 (17.2%) .052 5 (25%) .013
N N = 9927 N = 28 N = 20
Parous
 No 5904/9743 (45%) 9/28 (29%) .01 10/20 (50%) .846
 Yes 5326/9, 743 (55%) 20/28 (71%) 10/20 (50%)
Gravidity
 1 3839/9743 (40%) 9/28 (29%) .465 7/20 (35%) .862
 ≥2 5904/9743 (60%) 20/28 (71%) 13/20 (65%)
Multiple pregnancy
 No 10 531 (95%) 25/28 (89%) .165 18/20 (90%) .267
 Yes 557 (5%) 3/28 (11%) 2/20 (10%)
Country of birth

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  Europe, North America 3239/4682 (70%) 25/28 (89%) .034 9/20 (45%) .03
  Africa, Asia, Middle East, 1443/4682 (30%) 3/28 (11%) 11/20 (55%)
South America
Unemployed
 No 7150/9450 (76%) 23/28 (82%) .501 10/20 (50%) .015
 Yes 2300/9450 (24%) 5/28 (18%) 10/20 (50%)
Professional occupation
 1 146/6371 (2%) 1/20 (5%) .019 0/14 .208
 2 1658/6371 (26%) 8/20 (40%) 1 /14 (7%)
 3 1349/6371 (21%) 6/20 (30%) 1/14 (7%)
 4 872/6371 (14%) 0/20 3/14 (21%)
 5 16/6371 (0.3%) 0/20 0
 6 2300/6371 (36%) 4/20 (20%) 9/14 (64%)
 other 30/6371 (0.5%) 1/20 (5%) 0
Gestational age at delivery in wk 38.1 ± 6.2, N = 5048 38 ± 2.7, N = 27 .851 38 ± 2.3, N = 20 .924

Data are mean ±  standard deviation, n (%), or n/N (%) where data are missing.
Countries of birth of mothers from the first group: France (87%), other European Countries (12%), North American countries (1%).
Countries of birth of mothers from the second group: North African countries (39%), non-North African countries (26%), East Asian countries (19%), Middle East countries (6%), South
American countries (5%), others (5%).
Professional occupation: 1 =  independent retailers, entrepreneurs, 2 = executives, intellectual professions, 3 = intermediate professions, 4 = employees, 5 = workers, 6 = unemployed.

respective burden of cCMV arising from primary and non-
primary infections [19–21]. Applying these models to our
population bearing a 61% seroprevalence leads to an expected
proportion of congenital infections attributable to nonprimary
infections of over 70% and not under 50% as observed [21].
In light of our data, these models seem therefore to be over-
estimating the proportion of congenital infections following
nonprimary infections. Moreover, in our population, women
seronegative before pregnancy had a 4-fold higher individual
risk to deliver an infected baby than women seropositive before
pregnancy.
In our study, the proportion of symptomatic infected neo-
nates was higher than reported in a meta-analysis (20% vs 13%).
This may be at least partly due to the definition of a symptomatic
neonate that has evolved over time [15]. The proportion of neo-
nates with hearing loss at birth was 10%, and this was similar in
neonates infected after maternal primary or nonprimary infec-
tions. Neonatal hearing loss has long been thought to mainly

Table 2.  Risk Factors to Deliver an Infected Newborn After Maternal Primary Infection or After Maternal Nonprimary Infection

Risk to Deliver an Infected Neonate After Risk to Deliver an Infected Neonate After
Maternal Primary Infection Maternal Nonprimary Infection

OR [95% CI] P OR [95% CI] P

Age <25 y 7.943 [2.647, 23.836] <.001 4.657 [1.484, 14.616] .008

Parous 4.178 [1.731, 10.083] .001 1.23 [0.473, 3.199] .671
Born in a high-resource country 5.2 [1.486, 18.199] .01 0.648 [0.246, 1.703] .379
Unemployed 2.171 [0.747, 6.307] .154 5.854 [2.157, 15.883] <.001

Abbreviations: CI, confidence interal; OR, odds ratio.

402 • CID 2017:65 (1 August) •  Leruez-Ville et al


Figure  3.  Risk of delivering infected neonates according to CMV serology before pregnancy. Abbreviations: CMV, cytomegalovirus; IgG, immunoglobulin G; IgM,
immunoglobulin M. *Defective samples (not labeled, broken vial…) **Glyceraldehyde 3-phosphate dehydrogenase polymerase chain reaction negative indicating improper
sampling.
follow primary rather than nonprimary maternal infection [22].
However, our results together with other recent studies suggest
that hearing loss related to maternal nonprimary infection is as
severe as that related to maternal primary infection [4, 6, 23].
CMV detection in urine has been the gold standard for cCMV
diagnosis for years. However, a recent large prospective study of
cCMV screening showed that CMV PCR in saliva has excellent
sensitivity and specificity compared to standard saliva rapid cul-
ture; and that saliva could therefore be used for cCMV screen-
ing [5]. Similar performance was reported between urine and
saliva in 2 small studies [24, 25]. However, false positive cCMV
diagnoses in saliva could be an issue because CMV is frequently
present in breast milk [26] and in the birth canal [27], and
therefore contamination of the newborn’s saliva samples could
happen throughout the peripartum period. We systematically
controlled positive results in repeat saliva and blood samples.
Among the 11 715 samples tested, 51 were true-positive and 36
were false-positive giving a PPV for cCMV screening in saliva
samples of only 55%. CMV DNA quantification helped discrimi-
nate between false and true positive results since high viral loads
(>4.0 log copies/mL) were only found in true positive samples.
However, low viral loads were found both in true and false posi-
tive samples. Because the neonates were screened at birth in the
delivery room, false positive samples could result from contam-
ination by CMV DNA shed in vaginal secretions. These results
indicate that a positive CMV PCR in saliva obtained from a neo-
nate should be controlled in a subsequent sample particularly
when the amount of CMV DNA detected is low.
Studies conducted in the United States reported higher birth
prevalences of cCMV in African American women, younger
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than 25 years, with lower economic status, caring for preschool
children and living in a household with more than 3 people
[8–10]. Conversely, one study conducted in Australia reported
an association between higher socioeconomic status and cCMV
[28]. However, in these studies, sociodemographic character-
istics of the women were not studied accordingly to the type
of maternal infection. Our study provides a thorough analysis
of sociodemographic data associated with cCMV and demon-
strates that mothers of infected neonates belong to 2 markedly
different sociodemographic groups in the 2 types of maternal
infection. Although maternal age below 25 was a risk factor for
both types of infection, the risk to deliver an infected infant fol-
lowing primary infection was higher in parous women born in
high-resource country. Higher income was also associated with
the birth of an infected infant after primary infection. The risk
to deliver an infant infected following nonprimary infection
was higher in unemployed women, who also belonged to low
socioeconomical groups, whereas to be parous was not a risk
factor. Altogether, these results suggest that the source of con-
tamination for primary infection is mainly the mother’s older
child or children. However, women with lower socioeconomic
status have a higher likelihood of being exposed to individuals
shedding CMV in addition to their own children and therefore
have a higher risk of reinfection. Because this study showed that
seronegative, parous women represent the highest risk group
of congenital CMV infection, we advocate that these women
should be identified by CMV testing before pregnancy and tar-
geted by prevention messages. Indeed, educational and hygiene
measures aiming to avoid intimate contacts with young chil-
dren are efficient to prevent primary maternal infection [29].
Screening Congenital CMV in France  •  CID 2017:65 (1 August) • 403
 The strengths of our study are the large number of neonates
screened representing over 84% of all births together with the
concomitant availability of sociodemographic, obstetrical, and
serological data in pregnant women. Its limitations are that some
sociodemographic data were known for only 50% of the popu-
lation and that maternal serology in the first trimester was only
known in a subpopulation, though representative of the whole
population at the same center
In conclusion, our results convey 2 important messages:
professionals (pediatricians, pathologists…) should be aware
of the low PPV of CMV PCR in saliva samples, which man-
dates that positive screening tests should be repeated. The
burden of congenital infection is equally attributable to pri-
mary and nonprimary infections in a population with a 61%
seroprevalence. However, women seronegative before preg-
nancy have a 4-fold higher risk to deliver an infected baby.
Prevention strategies should aim at protecting all at-risk
women and at particularly targeting multiparous seronega-
tive women.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the authors to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the authors,
so questions or comments should be addressed to the corresponding author.
Notes
Acknowledgments.  We thank all women who participated in the trial,
and midwives and nurses from the delivery suite who obtained neonatal
samples. We also thank URC-CIC Paris Centre (Laurence Lecomte, Sophie
Pfister, Imane Mettouchi, Agnès Cimerman and Guillaume Masson) for the
implementation, monitoring, and data management of the study. Finally,
we thank Cindy Bard, the laboratory technician who performed part of the
PCR tests.
Financial support.  This study was funded by a research grant from the
French Ministry of Health (OM12196) and sponsored by the Département
de la Recherche Clinique et du Développement de l’Assistance Publique–
Hôpitaux de Paris.
Potential conflicts of interest.  M.  L. V.  declares having received fees
paid to her institution for expertise of diagnosis kits from BioMérieux, LFB
and for lectures from Siemens outside this work outside this work. J.  F.
M. declares receiving fees for expert testimony from Abbvie. Y. V. declares
receiving fees for lectures from General Electric outside this work. All
other authors report no potential conflicts. All authors have submitted the
ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that
the editors consider relevant to the content of the manuscript have been
disclosed.
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