When does mother to child transmission of hepatitis C virus occur?
ABSTRACT To investigate when hepatitis C virus (HCV) infection from mother to child occurs, and evaluate possible associated factors.
Prospective cohort study.
Fifty four HCV infected children tested within three days of birth and their mothers.
HCV RNA polymerase chain reaction (PCR) results.
Seventeen of the children (31%, 95% confidence interval 19% to 46%) were positive in the first 3 days of life and could be assumed to have acquired infection in utero. Testing PCR positive was not associated with sex (53% v 49% boys; p=0.77) or mode of delivery (29% elective caesarean section in both groups; p=0.98). Children with evidence of intrauterine infection were significantly more likely to be of lower birth weight and infected with genotype 1 (58% v 12%, p=0.01). Although a higher proportion of infants born to HCV/HIV co-infected women were PCR positive in the first 3 days of life, this difference did not reach statistical significance; excluding infants born to co-infected women did not affect the results. Thirty seven of the children (68%) were negative in the first 3 days of life, 27 of whom were positive when tested again at 3 months, and nine were first PCR positive after 3 months (one child had no further tests).
These results suggest that at least one third and up to a half of infected children acquired infection in utero. Although postpartum transmission cannot be excluded, these data suggest that it is rare. The role of HCV genotypes in the timing and mechanism of infection should be explored further.
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ABSTRACT: The number of children affected by the hepatitis C virus (HCV) in the United States is estimated to be between 23000 to 46000. The projected medical cost for children with HCV in the United States is $199-366 million over the next decade. The implementation of routine screening of blood supply has virtually eliminated transmission via transfusion and vertical transmission is now the most common mode of infection in children. Infections acquired during infancy are more likely to spontaneously resolve and fibrosis of the liver tends to increase with age suggesting slow progressive histologic injury. Anti-viral treatment may be warranted in children with persistently elevated liver enzymes or with significant fibrosis on liver biopsy. Current standard of care includes weekly pegylated interferon and ribavirin twice daily. Predictors of high sustained viral response include genotype 2 and 3 and low viral load in children with genotype 1 (< 600000 IU/mL). Phase 1 and 2 trials with triple therapy (interferon, ribavirin, and a protease inhibitor) are ongoing. Triple therapy is associated with a significantly higher rate of sustained virologic response (> 90%). Only 34 pediatric patients were transplanted with hepatitis C between January 2008 and April 2013. The majority of pediatric patients were born prior to universal screening of blood products and, as of June 2013, there are only two pediatric patients awaiting liver transplantation for end-stage liver disease secondary to hepatitis C. Pediatric survival rates post-transplant are excellent but graft survivals are noticeably reduced compared to adults (73.73% for pediatric patients at one year compared to 87.69% in adult patients). New safe and effective antiviral therapies for recurrent HCV should help increase graft survival.World journal of gastroenterology : WJG. 08/2014; 20(32):11281-11286.
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ABSTRACT: Hepatitis C virus (HCV) affects about 3% of the world's population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.World journal of hepatology. 08/2014; 6(8):538-48.
When does mother to child transmission of hepatitis C virus
J Mok, L Pembrey, P-A Tovo, M-L Newell, for the European Paediatric Hepatitis C Virus Network
See end of article for
Professor Newell, Centre
Biostatistics, Institute of
Child Health (University
College London), 30
Guilford Street, London
WC1N 1EH, UK;
Arch Dis Child Fetal Neonatal Ed 2005;90:F156–F160. doi: 10.1136/adc.2004.059436
Objective: To investigate when hepatitis C virus (HCV) infection from mother to child occurs, and evaluate
possible associated factors.
Design: Prospective cohort study.
Patients: Fifty four HCV infected children tested within three days of birth and their mothers.
Main outcome measures: HCV RNA polymerase chain reaction (PCR) results.
Results: Seventeen of the children (31%, 95% confidence interval 19% to 46%) were positive in the first
3 days of life and could be assumed to have acquired infection in utero. Testing PCR positive was not
associated with sex (53% v 49% boys; p = 0.77) or mode of delivery (29% elective caesarean section in
both groups; p = 0.98). Children with evidence of intrauterine infection were significantly more likely to be
of lower birth weight and infected with genotype 1 (58% v 12%, p = 0.01). Although a higher proportion
of infants born to HCV/HIV co-infected women were PCR positive in the first 3 days of life, this difference
did not reach statistical significance; excluding infants born to co-infected women did not affect the results.
Thirty seven of the children (68%) were negative in the first 3 days of life, 27 of whom were positive when
tested again at 3 months, and nine were first PCR positive after 3 months (one child had no further tests).
Conclusions: These results suggest that at least one third and up to a half of infected children acquired
infection in utero. Although postpartum transmission cannot be excluded, these data suggest that it is rare.
The role of HCV genotypes in the timing and mechanism of infection should be explored further.
in HCV transmission,1 2 6 7and women with HCV viraemia are
more likely to transmit than non-viraemic women.8–11
Transmission through breast feeding is assumed to be rare
but cannot be excluded,7 12 13while the effect of mode of
delivery on risk of transmission remains uncertain.1 3 6 11
The exact time during pregnancy or delivery when HCV
transmission occurs is unclear. Both intrauterine4 14and
intrapartum6 11infection occur, but the relative contribution
by each route remain poorly quantified. Development of
successful strategies to prevent mother to child transmission
of HCV depends on understanding the timing of transmis-
sion, and associated factors.
The diagnosis of vertically acquired HCV infection is based
on detection of viraemia (HCV RNA by polymerase chain
reaction (PCR)) and/or the presence of specific non-maternal
antibody, with the timing of transmission inferred from
results of virus specific tests on samples drawn soon after
birth when a positive result implies intrauterine infection.15
Data available within the European Paediatric Hepatitis C
Network provided an opportunity to clarify when HCV
infection from mother to child occurs, and to evaluate factors
that may influence the timing of transmission.
he overall rate of mother to child transmission of hepa-
titis C virus (HCV) infection is 4–10%.1–7Maternal HIV co-
infectionhas beenassociatedwithuptoa fourfold increase
MATERIALS AND METHODS
The European Paediatric Hepatitis C Network, a prospective
study on mother to child transmission of HCV, was
established in 1998,7with prospectively collected information
also available for some infected children born in previous
years. Mother-child pairs were enrolled from 31 centres in
seven countries in Western Europe. Appropriate ethical
approval was obtained from each centre. Data on maternal
factors (HIV status, injecting drug use, HCV viraemia) were
collected at enrolment and during pregnancy, and mode of
delivery, birth weight, gestational age, and sex of the child
were recorded at delivery. Children were followed prospec-
tively from birth, with clinical assessments every three
months. Laboratory investigations were performed locally
and included serum HCV RNA, HCV antibody, and alanine
aminotransferase activity. The study protocol recommends
that a PCR test for HCV RNA is performed in the first three
days of life and then at 6 weeks, 3, 6, 9, 12, 18, and
24 months. Data were collected on study forms and sent to
the coordination centre at regular intervals.
HCV infection was diagnosed by qualitative HCV RNA PCR
and antibody tests. A child was considered to be vertically
infected with HCV if he/she tested positive for HCV RNA on
at least two separate occasions and/or was HCV antibody
positive at or beyond 18 months of age.
Intrauterine infection was assumed in infected children
who tested PCR positive for HCV RNA in the first 3 days of
life15(group 1). Group 2 consisted of infected children who
were PCR negative in the first 3 days. Late intrauterine infec-
tion (during the last month of pregnancy) or intrapartum
transmission (occurring during delivery) could be assumed in
infants who are PCR negative in the first 3 days of life but are
PCR positive by 4 weeks. Peripartum transmission included
late intrauterine and intrapartum infection.
Data processing and statistical analysis
Forms were checked and entered on to a Microsoft Access
database. Statistical analyses were carried out using Stata 7
(Stata Corporation, College Station, Texas, USA). Odds ratios
were calculated to estimate the effect of maternal, delivery,
and infant factors on being PCR positive in the first 3 days of
life, and x2tests were carried out where data were not
sufficient to calculate an odds ratio. Mantel-Haenszel odds
ratio estimates were obtained to allow for the effect of
potential confounding variables.
Abbreviations: HCV, hepatitis C virus; PCR, polymerase chain reaction
Overall, 290 vertically exposed children met the criteria for
HCV infection. Of these, 54 had a PCR test performed in the
first 3 days of life; 17 (31%, 95% confidence interval (CI) 19%
to 46%) were positive, and 37 (68%) were negative.
Factors associated with being PCR positive in first
3 days of life
between children who were PCR positive in the first 3 days
of life (group 1) and those who were PCR negative in the first
3 days of life (group 2) (table 1). A higher proportion of
infants born to HIV co-infected women were PCR positive in
the first 3 days of life than infants born to women with only
HCV infection, but this difference was not statistically signi-
ficant. Mode of delivery and sex were not associated with
being PCR positive in the first 3 days of life. Median gesta-
tional age was 39 weeks in each group and ranged from 33 to
41 weeks among infants in group 1 and from 34 to 41 weeks
among group 2 infants. Although mean birth weight was
significantly lower among the children with evidence of
intrauterine infection (2976 g (range 1820–3900) v 3327 g
(range 2520–4840)) in the group 2 children (t (two sided) =
22.09, p = 0.04), a significant difference was not observed
when low birthweight infants (,2500 g) were compared
with normal weight infants (table 1). Breast fed infants were
less likely to be PCR positive in the first 3 days of life than
formula fed infants, although this association was of border-
line significance because of the small numbers involved.
Infants infected with HCV genotype 1 were significantly more
likely to be PCR positive in the first 3 days of life than infants
infected with other HCV genotypes (2, 3, or 4).
Fourteen mothers had at least one HCV PCR test available
during pregnancy or around the time of delivery (median
time of testing four weeks before delivery, range 30 weeks
before delivery to 1.9 months postpartum). Four (40%) of
10 infants born to PCR positive women were themselves
PCR positive in the first 3 days of life compared with none of
four infants born to PCR negative women (table 1). The
difference was not significant because of the small numbers
involved, but suggests that women who are viraemic during
pregnancy may be more likely to transmit HCV before
Univariable odds ratios for the effect of sex, mode of
delivery, low birth weight, prematurity, infant feeding,
genotype, and maternal viraemia on being PCR positive in
the first 3 days were calculated separately for infants born to
women with only HCV infection and were similar to the
It was not appropriate to perform a multivariable analysis
with only 54 children, but bivariable odds ratios were
calculated (adjusting for one factor at a time) where possible.
None of the adjusted odds ratios for mode of delivery differed
substantially from the unadjusted estimate. Although the
odds ratio for the effect of maternal HIV infection increased
from 2.42 to 7.50 (95% CI 0.43 to 130.87, p = 0.10) when
allowing for genotype, it still did not reach significance and
the confidence interval was very wide.
The positive association between genotype 1 and being PCR
positive in the first 3 days of life remained significant when
adjusted for mode of delivery, sex, or maternal HIV infection,
but with wide confidence intervals (respective adjusted ORs
and p values: 6.90 and 0.02; 8.33 and 0.01; 14.00 and 0.008).
However, when maternal viraemia was allowed for, the odds
ratio for the effect of genotype decreased substantially and
was no longer significant (adjusted OR 1.33, 95% CI 0.05 to
32.96, p = 0.86), which reflects the fact that genotype was
only available for infants of viraemic women.
Factors associated with being polymerase chain reaction (PCR) positive in first 3 days of life
No of children PCR positive
in first 3 days Unadjusted odds ratio (95% CI)p Value
Mother HIV uninfected
Mother HIV co-infected
2.42 (0.64 to 9.16) 0.18
Mother PCR positive
Mother PCR negative
0.84 (0.26 to 2.69) 0.77
Vaginal & emergency CS
1.02 (0.27 to 3.79)0.98
Normal birth weight
Low birth weight (,2500 g)
Premature* (,37 weeks)
0.16 (0.02 to 1.52)0.07
Genotype 2, 3, 4
9.80 (1.10 to 86.98)0.01
*Excluding elective CS.
?Cannot calculate odds ratio because one cell is empty. Fisher’s exact p values given.
CS, Caesarean section.
Timing of mother to child transmission of hepatitis C virusF157
Infants PCR negative at birth (group 2)
One of the 37 infants who were negative in the first 3 days of
life had no subsequent PCR test results available but was
considered infected on the basis of positive antibody tests
beyond 18 months. Among the other 36 infants, the mean
age atfirstpositive PCR
3.0 months, range 12 days–15 months). After the initial
negative PCR result, 34 of 36 were tested again by 3 months
of age, and 27 were positive (fig 1). The remaining two had
their second PCR tests at 6 and 7 months. Of all 36 infants,
33 were PCR positive by 7 months of age. The remaining
three became PCR positive at 12.2, 13.4, and 15.0 months of
age. Of these three infants, one was breast fed until
12 weeks, and two were not breast fed.
Timing of infection was difficult to estimate for 12 group 2
infants who had late first positive PCR tests and were either
was 3.9 months (median
breast fed or had late last negative PCRs (table 2). Seven of 12
infants were breast fed, suggesting possible postnatal
transmission through breast milk. However, in five of these
seven, the last negative PCR was very early ((3 days). They
may have become PCR positive by 4 weeks (and intrapartum
transmission therefore possible), but were not tested again
until at least 3 months. Of the 24 group 2 infants who were
not breast fed, 19 were PCR positive when next tested
(between 26 days and 6.9 months). The remaining five tested
negative at least once again before testing positive at between
2.2 and 13.4 months and were negative after 4 weeks of age
(table 2). These five children had a similar pattern of PCR
results to the seven breastfed children, indicating that these
viraemia patterns may be due to features of HCV infection or
limitations of the assays used, rather than an indication of
timing of transmission and that some infants who are
6 PCR–, 1 indeterminate
54 infected infants with PCR test ≤ 3 days
34 tested again by 3 months
Further test by 7 months
Child 1 (BF), 6 (BF),
9 and 10 from table 2.
3 PCR+ at 12.2 months (child 11),
13.4 months (child 12) and 15.0
months (child 7, BF)
(17% peripartum transmission)
(50% peripartum transmission,
i.e. late intrauterine, intrapartum)
Includes child 2 (BF),
3 (BF), 4 (BF), 5 (BF)
and 8 from table 2.
1 no further PCR tests, Ab+>18 months
(31% in utero transmission)
2 tested again at 6 and 6.9 months
2 PCR+ (not BF)
tests in infected infants. Ab, antibody;
BF, breast fed; PCR, polymerase chain
Timing and results of PCR
(.4 weeks) and non-breastfed children with late first positive PCRs and late last negative
PCRs (.4 weeks)
Breastfed children with late first positive polymerase chain reactions (PCRs)
ChildBreast fedAge at last negative PCR
Age at first positive
Age breast feeding
1 Yes1 day (& an indeterminate
PCR result at 4 weeks)
For all these children, the first PCR test at ,3 days was negative.
F158Mok, Pembrey, Tovo, et al
infected intrapartum may not become PCR positive until after
4 weeks of age.
Estimates of timing of infection
Based on the timing of PCR tests, we can allocate the most
likely time of transmission for all 54 children. Seventeen were
PCR positive at (3 days, giving an estimate of intrauterine
transmission of 31% (95% CI 19% to 46%). Late intrauterine
or intrapartum (at delivery) transmission is most likely for 27
(50%, 95% CI 36% to 64%) who were PCR negative before
3 days but PCR positive when tested again by 3 months of
age. Timing of transmission was more difficult to allocate for
nine children (17%) who were PCR negative at (3 days and
first PCR positive after 3 months. For three of these nine
children, there was a long interval between the negative test
at (3 days and the next PCR test which was positive (child 1
in table 2 and two children who were not breast fed and first
tested positive at 6 and 6.9 months). The other six children
were PCR negative at (3 days, negative again after 4 weeks,
and not positive until after 3 months (children 6, 7, 9–12 in
table 2), but only two of these six were breast fed, suggesting
that peripartum transmission was most likely for all nine
children. (Child 8 in table 2 is included among the 27 infants
who were PCR positive by 3 months.) The remaining child
(2%) had no further PCR tests.
Our results suggest that at least one third (95% CI 19% to
46%) of infants acquire HCV infection during the intrauterine
period. Some children who tested PCR negative in the first
3 days of life may also have acquired infection in utero but
with levels of viraemia that were undetectable by PCR. If
transmission occurred late in pregnancy, viral replication
could have been insufficient in the first few days to result in a
positive PCR test, or HCV RNA production may have been
delayed. Low plasma volumes from newborns may also give
negative results in infants infected in utero. The 27 children
who were PCR positive when tested for the second time by
3 months of age may fit the picture of late intrauterine
transmission or intrapartum transmission, which would give
an estimate of peripartum (late intrauterine and intrapar-
tum) acquisition of infection of 36–64%. The lower mean
birth weight of children who were PCR positive in the first
3 days of life would be consistent with intrauterine transmis-
sion, although we lacked statistical power to detect a
significant difference in the proportion of low birthweight
infants between the two groups.
Resti et al4suggested that at least 46% (95% CI 19% to 75%)
of transmission occurred in utero, as six of 13 infected
children had HCV RNA detected immediately after birth, in
line with our findings. Gibb et al6proposed that substantial
intrapartum transmission of HCV occurred, but their results
are difficult to interpret as infection status was inferred for
many children. In over 1400 mother-child pairs from centres
of the European Paediatric HCV Network, mode of delivery
was not associated with risk of vertical transmission in
women with only HCV infection.7Several other smaller
studies have failed to find a significant protective effect of
elective caesarean section.3 4 8The lack of a protective effect of
elective caesarean section is consistent with a large propor-
tion of intrauterine transmission. However, difficulties in
interpreting early PCR results mean that conclusions reached
about timing of transmission are not always consistent with
evidence of the effect of mode of delivery. For example,
although elective caesarean section is known to substantially
reduce vertical transmission of HIV infection, time to first
positive HIV DNA PCR test in infected children does not
differ by mode of delivery.16
HCV has been detected in breast milk and colostrum,12 13
and in one study the transmission rate was higher in babies
exposed to HCV RNA positive breast milk.17However, in most
studies no association has been observed between transmis-
sion and mode of infant feeding.1 3 4Of the seven breastfed
children in our study with late first positive PCR tests, two
were last PCR negative after 4 weeks of age, suggesting
possible transmission through breast feeding.18However,
although we cannot exclude the possibility of postnatal
transmission, the occurrence of late last negative and late
first positive PCR tests in five of the non-breastfed children as
well as in these two breastfed children suggests that these
viraemia patterns may not necessarily indicate timing of
transmission. We would echo the need to be cautious in
inferring the timing of infection simply from early PCR
Intermittent viraemia has been observed in a large
proportion of children with vertically acquired HCV infec-
tion.20This may reflect fluctuations in viral load which is
undetectable at times, or low sensitivity of some PCR assays
resulting in a negative test at low virus levels. Poor sensitivity
of early assays may explain the late last negative PCR tests
observed in seven children, but three of these children were
born since 1999 when more sensitive assays were used.
Intrapartum transmission would therefore be most likely for
the nine children with first positive PCR tests after 3 months
of age, increasing our estimate of peripartum transmission to
67% (36/54, 95% CI 53% to 79%).
Although the assays used to detect HCV RNA vary between
centres, the results of qualitative assays are generally
consistent between laboratories.21Only about one fifth of
infected children enrolled in the European Paediatric HCV
Network had a PCR result in the first 3 days of life. Although
an early PCR test is recommended in the study protocol, there
are several reasons why this was sometimes not done,
including the high cost of PCR testing and the fact that some
women were identified as HCV infected from a blood test
taken at delivery with the result not available until four or
five days later. However, the mother-child pairs included in
this analysis were similar to the infected children who were
not tested in the first 3 days of life with respect to the main
variables of interest.
The limited number of children with early PCR results
hinders clarification of factors influencing timing of trans-
mission. Few studies have focused on the role of genotype as
a risk factor for vertical transmission. In a study of 37
women, HCV subtypes 1b and 3a were most commonly
transmitted.22Our results suggest that infants infected with
genotype 1 were significantly more likely to have evidence of
What is already known on this topic
The overall rate of mother to child transmission of hepatitis C
virus ranges from 4% to 10% and is known to be associated
with maternal HIV co-infection and HCV viraemia, but the
timing of transmission—during pregnancy, at delivery, or
postnatally—remains to be clarified.
What this study adds
Our results suggest that at least one third and up to a half of
infected children acquired infection in utero. Although
postpartum transmission through breast feeding cannot be
excluded, these data would confirm that it is rare. Our results
suggest that HCV genotype may influence the timing of
transmission and this should be explored further.
Timing of mother to child transmission of hepatitis C virusF159
intrauterine infection than those with other genotypes. The
reason for this is unclear, and further investigation is
Despite recent advances in our understanding of risk fac-
tors for mother to child transmission of HCV, the mechan-
isms and timing of transmission remain poorly understood.
We have shown that at least one third of HCV transmission
occurs in the intrauterine period, with around two thirds of
infections likely to occur in the peripartum period, but, with
the wide confidence intervals around our estimates, these
percentages could be 50% and 50%. Although the risk of
postpartum transmission through breast feeding cannot be
excluded, our results suggest that it is likely to be very low.
Maternal treatment to reduce the risk of vertical transmis-
sion, through lowering of viral load, is not currently possible,
as interferon a and ribavirin are contraindicated during
pregnancy. However, our results suggest that, if effective
treatment were to become available, it would need to be
initiated early in pregnancy, as at least one third of
transmission occurs in utero.
We wish to thank the laboratory colleagues of the European
Paediatric HCV Network collaborators and the women and children
who participated in the study.
J Mok, Paediatric HIV Service, Royal Hospital for Sick Children, 10
Chalmers Crescent, Edinburgh EH9 1TS, Scotland, UK
L Pembrey, M-L Newell, Centre for Paediatric Epidemiology and
Biostatistics, Institute of Child Health & Great Ormond Street Hospital for
Children NHS Trust, University College London, 30 Guilford Street,
London WC1N 1EH, UK
P-A Tovo, Dipartimento di Scienze Pediatriche e dell’Adolescenza,
Universita ` degli Studi di Torino, Piazza Polonia 94, 10126 Torino, Italy
The European Paediatric HCV Network is funded by a European
Commission concerted action grant–Quality of Life and Management of
Living Resources Programme, contract number: QLK2-CT-2001-01165.
L P is funded by a UK Medical Research Council Special Research
Training Fellowship in Health Services and Health of the Public Research.
Competing interests: none declared
Appropriate ethical approval was obtained from each centre.
European Paediatric HCV Network collaborators: A Amoroso
(Universita ` di Trieste, Trieste, Italy), F Asensi-Botet, A Pereda
(University Children’s Hospital La Fe `, Valencia, Spain), V Balossini, G
Bona, M Zaffaroni (Clinica Pediatrica, Universita ` del Piemonte
Orientale, Novara, Italy), A Bandelloni, A Coscia, C Fabris (Cattedra
di Neonatologia, Universita ` di Torino, Torino, Italy), C Belloni
(Neonatology and Neonatal Intensive Care Unit, IRCCS Policlinico San
Matteo, Pavia, Italy), G Bossi, B Salati (Department of Pediatrics, IRCCS
Policlinico San Matteo, Pavia, Italy), C Boucher (University Hospital
Utrecht, Utrecht, The Netherlands), W Buffolano (Dipartimento di
Pediatria, Universita ` Federico II, Napoli, Italy), K Butler (Our Lady
Hospital for Sick Children, Crumlin, Dublin, Ireland), L Cabero Roura,
JM Bertran Sanges (Hospital Universitari Materno-Infantil, Barcelona,
Spain), P Cigna (Centro di Neonatologia, Ospedale Infantile Regina
Margherita, Torino, Italy), LM Ciria, C Servera Ginard (Hospital Son
Dureta, Palma de Mallorca, Spain), G Claret Teruel, C Fortuny (Hospital
Sant Joan de De ´u, Barcelona, Spain), O Coll (Hospital Clinic, Barcelona,
Spain), A Corrias, R Ledda, S Floris (Servizio di Puericultura, Cagliari,
Italy), A De Maria (Dipartimento di Medicina Interna, Universita ` di
Genova, Genova, Italy), J Echeverria, G Cilla (Department of Paediatrics
and Department of Microbiology, Hospital Donostia, San Sebastian,
Spain), G Faldella, M Lanari, E Tridapalli, V Venturi, (Universita ` di
Bologna, Bologna, Italy), B Fischler, A-B Bohlin, S Lindgren, G Lindh
(Huddinge Hospital, Huddinge, Sweden), V Giacomet, L Schneider,
C Figini, L Caffarelli, A Vigano ` (Ospedale Sacco, Milano, Italy),
S Hannam, G Mieli-Vergani (King’s College Hospital, London, UK),
A Hatzakis (National Retrovirus Reference Centre, University of Athens,
Athens, Greece), C Inchley, HO Fjaerli (Akershus University Hospital,
Norway), A Maccabruni (Department of Infectious Diseases, Universita `
di Pavia, Pavia, Italy), M Marcellini, MR Sartorelli (Ospedale Bambino
Gesu `, Roma, Italy), P Martin Fontelos (Servicio de Pediatria, Instituto de
Salud Carlos III, Madrid, Spain), A Mazza (Ospedale Santa Chiara di
Trento, Trento, Italy), JYQ Mok (Royal Hospital for Sick Children,
Edinburgh), A Mu ˆr, M Vin ˜olas (Hospital del Mar, Universitat Autonoma
de Barcelona, Spain), DM Paternoster, P Grella (Istituto di Ginecologia e
Ostetricia, Padova, Italy), S Polywka (Institute for Medical Microbiology
and Immunology, University Hospital Eppendorf, Hamburg, Germany),
I Quinti, A M Casadei (Universita ` La Sapienza, Roma, Italy), A Rojahn,
A Berg (Ulleva ˚l University Hospital, Oslo, Norway), R Rosso, S Ferrando,
D Bassetti (Clinica Malattie Infettive, Universita ` di Genova, Genova,
Italy), J Ruiz Contreras, A Manzanares (Hospital 12 de Octubre, Madrid,
Spain), A Ruiz Extremera (Hospital Clinico San Cecilio `, Granada,
Spain), F Salvini, G V Zuccotti, (Ospedale San Paolo, Milano, Italy),
T Schmitz, I Grosch-Wo ¨rner, C Feiterna Sperling, T Piening (Charite ´
Virchow-Klinikum, Berlin, Germany), H Souayah, J Levy (Hospital St
Pierre, Brussels, Belgium), A Vegnente, R Iorio (Dipartimento di
Pediatria, Universita ` Federico II, Napoli, Italy), A Versace, S Garetto,
E Palomba, C Gabiano, L Balbo (Dipartimento di Pediatria, Universita ` di
Torino, Torino, Italy), R Wejstal, G Norkrans (Ostra Hospital, Goteborg,
Sweden), A Zanetti, E Tanzi (Universita ` di Milano, Milan, Italy)
1 Tovo PA, Palomba E, Ferraris G, et al. Increased risk of maternal-infant
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