Skip to main content
PLOS One logoLink to PLOS One
. 2020 May 21;15(5):e0233528. doi: 10.1371/journal.pone.0233528

Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission

Ángeles Ruiz-Extremera 1,2,3,4, María del Mar Díaz-Alcázar 1,3,*, José Antonio Muñoz-Gámez 1, Marta Cabrera-Lafuente 5, Estefanía Martín 6, Rosa Patricia Arias-Llorente 7, Pilar Carretero 1, José Luis Gallo-Vallejo 6, Francisca Romero-Narbona 8, M A Salmerón-Ruiz 5, Clara Alonso-Diaz 9,10, Rafael Maese-Heredia 8, Lucas Cerrillos 11, Ana María Fernández-Alonso 12, Carmen Camarena 5, Josefa Aguayo 11, Miguel Sánchez-Forte 12, Manuel Rodríguez-Maresca 12, Alfredo Pérez-Rivilla 9, Rosa Quiles-Pérez 1, Paloma Muñoz de Rueda 1,2,4, Manuela Expósito-Ruiz 4,13,14, Federico García 1,4,15, Fernando García 1,4,15, Javier Salmerón 1,2,3,4
Editor: Anna Kramvis16
PMCID: PMC7241747  PMID: 32437468

Abstract

Background & aim

Worldwide, measures are being implemented to eradicate hepatitis B (HBV) and C (HCV) viruses, which can be transmitted from the mother during childbirth. This study aims to determine the prevalence of HBV and HCV in pregnant women in Spain, focusing on country of origin, epidemiological factors and risk of vertical transmission (VT).

Methodology

Multicentre open-cohort study performed during 2015. HBV prevalence was determined in 21870 pregnant women and HCV prevalence in 7659 pregnant women. Epidemiological and risk factors for VT were analysed in positive women and differences between HBV and HCV cases were studied.

Results

HBV prevalence was 0.42% (91/21870) and HCV prevalence was 0.26% (20/7659). Of the women with HBV, 65.7% (44/67) were migrants. The HBV transmission route to the mother was unknown in 40.3% of cases (27/67) and VT in 31.3% (21/67). Among risk factors for VT, 67.7% (42/62) of the women had viraemia and 14.5% (9/62) tested HBeAg-positive. All of the neonates born to HBV-positive mothers received immunoprophylaxis, and none contracted infection by VT. In 80% (16/20) of the women with HCV, the transmission route was parenteral, and nine were intravenous drug users. Viraemia was present in 40% (8/20) of the women and 10% (2/20) were HIV-coinfected. No children were infected. Women with HCV were less likely than women with HBV to breastfeed their child (65% vs. 86%).

Conclusions

The prevalences obtained in our study of pregnant women are lower than those previously documented for the general population. Among the women with HBV, the majority were migrants and had a maternal family history of infection, while among those with HCV, the most common factor was intravenous drug use. Despite the risk factors observed for VT, none of the children were infected. Proper immunoprophylaxis is essential to prevent VT in children born to HBV-positive women.

Introduction

According to the World Health Organization (WHO) [1], chronic infection by hepatitis B virus (HBV) affects 257 million people. It is particularly prevalent in sub-Saharan Africa and in East Asia, affecting 5–10% of all adults, while in North America, less than 1% are infected. The estimated prevalence is less than 5% in eastern Europe, 1.5% in northern Europe, 2% in southern Europe and 1% in western Europe. However, these values are probably underestimates because, among other reasons, the data are obtained from blood donors [2]. Moreover, the situation in Europe may be adversely affected by changing patterns of migration [3,4]. According to a systematic review conducted by the European Centre for Disease Prevention and Control (ECDC) [5] based on articles published from 2005 to 2015, the prevalence in Spain was around 0.8% (0.6–1.1) and according to the latest report available [3] it was 0.66% (0.34–0.97).

The WHO has reported that 71 million people are infected with hepatitis C virus (HCV) [1] and that the most severely affected regions are Europe and the Eastern Mediterranean (2.3%). In Europe, the prevalence of HCV antibodies (anti-HCV) is estimated at 1.1% (95%CI 0.9–1.4) [5]. In Spain, the prevalence of antibodies is 1.7% and that of viraemia (HCV RNA positive) is 1.2% [6]. In the Ethon Cohort [7], the prevalence of anti-HCV positive (anti-HCV+ve) was 1.23% and only 0.32% had viraemia. However, this prevalence might be affected by changes in patterns of migration in Europe, especially in Spain [8].

In Spain, the prevalence of HBV infection (surface antigen positive) in pregnant women ranges from 0.1% to 4.4% [5,9,10]. The vertical transmission (VT) of HBV continues to be one of the main routes of infection worldwide [11], especially in areas where it is endemic [12]. High viral load (VL), which mainly affects HBeAg-positive (HBeAg+ve) women, is the most important risk factor, although women who are HBeAg-negative (HBeAg-ve) and who present high VL are also at risk of transmission [13]. In this population, 90% chronicity of infected newborns has been reported [14].

The prevalence of anti-HCV in pregnant women in Spain is estimated to be 0.5–1.4% [9,15,16], and the prevalence of viraemia 42–72%. The rate of VT among women with HCV is low, 1–8% in non-coinfected mothers and around 20% in those coinfected with HIV. However, 90% of infected children acquire the virus by VT. The factors related to the VT of HCV are VL and HIV coinfection [1719]. No other factors related to childbirth, epidemiology or breastfeeding have been associated with VT.

Screening for HBV in pregnancy is routinely recommended, as immunoprophylaxis against VT is feasible [12,20]. According to 2015 data, generalised immunoprophylaxis at birth has reduced the proportion of chronically-infected children aged under five years from 4.7% to 1.3% [1]. Nevertheless, up to 10% of newborns whose mothers present high VL become infected [14,21]. Accordingly, it is recommended that in HBV+ve women, VL should be assessed at 24 weeks of pregnancy and antiviral treatment administered if the VL is high. On the other hand, the determination of HCV in pregnancy is only recommended for at-risk populations such as intravenous drug users, women with high-risk sexual practices, women with HIV coinfection and women born in countries with high endemicity for HCV. In consequence, the prevalence reported in the literature may not correspond to reality. Prophylactic and therapeutic measures to eradicate HBV and HCV are currently being implemented. Children infected by VT should be included in this programme, but screening during pregnancy for HCV is not yet universal, and therefore some children who acquire the virus through VT will remain undiagnosed.

In view of these considerations, the main aim of this study is to determine the prevalence of HBV and HCV in pregnant women in Spain, taking into account their country of origin, epidemiological factors and the risk of VT.

Material and method

Patients

To determine the prevalence of HBV and HCV among a population of pregnant women, a multicentre prospective open-label cohort study was carried out from January to December 2015. The following hospitals took part: Hospital Universitario 12 de Octubre Madrid (HU12O), Hospital Universitario La Paz Madrid (HULP), Hospital Universitario San Cecilio Granada (HUSC), Hospital Universitario Virgen de las Nieves Granada (HUVN), Hospital Universitario Central de Asturias Oviedo (HUCA), Hospital Universitario Torrecárdenas Almería (HUT), Hospital Universitario Virgen del Rocío Sevilla (HUVR) and Hospital Universitario Virgen de la Victoria Málaga (HUVV).

The population analysed in the HBV prevalence study consisted of 21870 pregnant women, whose data were provided by the researchers at each hospital, from an anonymised database managed by its Microbiology Service, which compiles and manages these data as usual clinical practice in pregnancy. After the delivery, the mothers found to be HBV-positive (HBV+ve) were invited to participate in the study, by completing the epidemiological survey, stating their country of origin and providing details of the delivery. In every case, the mother’s informed consent was obtained. In addition, the donation of blood samples from each mother and child was requested, together with consent for medical follow-up of the neonate for 18 months. Fig 1 shows the flow chart for the recruitment of these participants.

Fig 1. Flow chart for selection of participants.

Fig 1

This figure shows the flow chart of pregnant women recruitment for prevalence, epidemiological and risk factors for vertical transmission studies.

In Spain, the determination of HCV does not form part of usual clinical practice, and so informed consent in this respect was requested and obtained in every case included in this study. Accordingly, tests for HCV were performed on 7659 women in week 12 of pregnancy, during the scheduled hospital visit for the detection of chromosomopathies. After the delivery, the mothers found to be HCV positive (HCV+ve) were invited to participate in the study, by completing the epidemiological survey, stating their country of origin and providing details of the delivery. In every case, informed consent in this respect was obtained. In addition, the donation of blood samples from the mother and child was requested, together with consent for medical follow-up of the neonate for 18 months. Fig 1 shows the flow chart for the recruitment of these participants.

The inclusion criteria were HBV surface antigen positive (HBsAg+ve) or anti-HCV+ve status confirmed by enzyme-linked immunosorbent assay (ELISA) and the provision of informed consent.

Epidemiological study

The study variables were participant’s age, country of origin and risk factors for infection. The risk factors considered were transfusion, intravenous drug abuse (IVDA), tattoos, piercing, surgery, dental treatment, infected partner, high-risk sexual practices, history of infection in the participant’s mother or siblings and HIV coinfection, categorised as yes, no or unknown. The survey also asked whether the woman knew about the infection prior to her pregnancy. The route of transmission of infection was categorised as vertical, parenteral, sexual or unknown.

Risk factors for vertical transmission

Antigen E (HBeAg) and antibody E (anti-HBe) were analysed for HBV, and VL was analysed for HBV and/or HCV.

The HBV+ve women were classified according to the EASL Clinical Practice Guidelines [22] as HBeAg-positive chronic infection (HBeAg+ve and DNA >107 IU/mL), HBeAg-positive chronic hepatitis (HBeAg+ve and DNA 104−107 IU/mL), HBeAg-negative chronic infection (HBeAg-ve and DNA <2000 IU/mL) and HBeAg-negative chronic hepatitis (HBeAg-ve and DNA >2000 IU/mL).

Other information compiled for the study included data on the pregnancy and delivery, including in vitro fertilisation, antiviral treatment for HBV during pregnancy, type of delivery, gestational age, time elapsed since the breaking of the waters, weight, Apgar score of the neonate at birth and the type of lactation.

The study protocol is the same as has been described in previous studies by this research group (17–19).

Analysis of the differences between HBV and HCV

The dependent variable was HBV+ve versus HCV+ve. The remaining variables were assumed to be independent.

Virologic assays

The serological determination of HBsAg, anti-HCV and anti-HIV was carried out by commercial ELISA, which is routinely used in the laboratories of each of the participating hospitals.

The VL of HBV and/or HCV was determined by COBAS TaqMan (cut-off <12 IU/mL, <15 IU/mL. Roche Diagnostics, respectively), distinguishing between not detected, below cut-off but not quantifiable and greater than cut-off and quantifiable. In the HBV+ve women, HBeAg and anti-HBe were also determined.

Statistical analysis

In our statistical analysis, the quantitative variables are described by the mean and the standard deviation, or in cases of non-normal distribution, by the median and the interquartile range. The qualitative variables are presented as absolute and relative frequencies. The corresponding prevalences and 95% confidence intervals were also calculated. The inter-group differences were determined by bivariate analysis, using Pearson’s chi-square test or Fisher’s exact test for the qualitative variables and Student’s t test or the Mann-Whitney U test for the continuous ones. The normality of the data distribution was examined by the Kolmogorov-Smirnov test. A p-value <0.05 was considered significant. All data analyses were performed using IBM SPSS 19 statistical software.

Ethical considerations

This study was carried out in accordance with the ethical guidelines of the Declaration of Helsinki of 1975, revised in 2013. All participants gave written and verbal informed consent. The study protocol was firstly approved by Comité Ético de Investigación Provincial de Granada (Ethics Committee of the Principal Investigator’s hospital) and later by the Ethics Committee at each participating hospital. The relevant provisions of Spanish data protection legislation were respected in all phases of the study.

Results

Prevalence of HBV and HCV in pregnancy

The prospective cohort for the HBV study consisted of 21870 pregnant women, of whom 91 were HBsAg+ve, with a prevalence of 0.42% (95% CI 0.33–0.50). Table 1 shows the distribution among the participating hospitals. The cohort for the HCV study contained 7659 women, of whom 20 were anti-HCV+ve, with a prevalence of 0.26% (95% CI 0.15–0.38). The prevalence of HBV differed significantly among the hospitals (p = 0.013), lowest at HUCA and highest at HULP, HUT and HUVR. On the other hand, the inter-hospital differences for anti-HCV prevalence were not significant (p = 0.52).

Table 1. Seroprevalence of HBV and HCV among pregnant women at each hospital.

HBV Positive cases Women (n) Prevalence (%) 95%CI
HU12Oa 18 4224 0.42 0.22–0.62
HULPb 17 2901 0.59 0.31–0.86
HUSCc –HUVNd 9 2262 0.39 0.14–0.66
HUCAe 1 2362 0.04 0.01–0.12
HUTf 13 2037 0.64 0.29–0.98
HUVRg 29 5903 0.49 0.32–0.67
HUVVh 4 2181 0.18 0.004–0.362
Total 91 21870 0.42 0.33–0.50
HCV Positive cases Women (n) Prevalence (%) 95%CI
HULPb 7 2901 0.24 0.06–0.42
HUSCc –HUVNd 2 903 0.22 0.01–0.53
HUCAe 5 1713 0.29 0.04–0.55
HUTf 3 1671 0.18 0.01–0.38
HUVVh 3 471 0.64 0.01–1.34
Total 20 7659 0.26 0.15–0.38

aHU12O: Hospital Universitario 12 de Octubre, Madrid.

bHULP: Hospital Universitario La Paz, Madrid.

cHUSC: Hospital Universitario San Cecilio, Granada.

dHUVN: Hospital Universitario Virgen de las Nieves, Granada.

eHUCA: Hospital Universitario Central de Asturias, Oviedo.

fHUT: Hospital Universitario Torrecárdenas, Almería.

gHUVR: Hospital Universitario Virgen del Rocío, Sevilla.

hHUVV: Hospital Universitario Virgen de la Victoria, Málaga.

Epidemiology and risk factors for vertical transmission in HBV-positive women

Of the 67 women included in the study, 31 (46.3%) were aware of the infection prior to pregnancy. None were coinfected with HCV, and there was one case (1.5%) of coinfection with HIV. By country of birth, 22 (32.8%) were Spanish, followed in frequency by those from China and Eastern Europe (Fig 2). The risk factors for infection in these pregnant women are shown in Table 2. The route of transmission was parenteral in 14 cases (20.9%), vertical in 21 (31.3%), sexual in 3 (4.5%) and unknown in 27 (40.3%). Of the women presenting VT, 13 (61.9%) were of foreign origin.

Fig 2. Geographic origin of pregnant women with HBV or HCV infection.

Fig 2

This figure shows the geographic origin of the pregnant women with HBV or HCV infection who participated in the epidemiological study, expressed in relative frequency.

Table 2. Epidemiology of pregnant women infected with HBV or HCV.

HBV n = 67 HCV n = 20 P
Median age of the mother [P25-P75] 33 [28–37] 34 [32.2–35.7] 0.106
Aware of infection 31 (46.3%) 13 (65%) 0.128
Co-infection with HIV 1 (1.5%) 2 (10%) 0.125
Country of origin
Spain 22 (32.8%) 11 (55%) 0.070
Other 44 (65.7%) 9 (45%)
Transfusion 1 (1.5%) 3 (15%) 0.043
IVDAa 0 (0%) 9 (45%) <0.001
Tattoo 6 (9%) 2 (10%) 1
Piercing 3 (4.5%) 1 (5%) 1
Surgery 13 (19.4%) 6 (30%) 0.383
Dental treatment 4 (6%) 1 (5%) 1
Infected partner 3 (4.5%) 3 (15%) 0.143
High-risk sexual practices 3 (4.5%) 3 (15%) 0.148
Family historyb 21 (31.3%) 0 (0%) 0.001
Unknown route of infection 27 (40.3%) 4 (20%) 0.066

aIVDA: Intravenous drug abuse.

bFamily history: previous infection in the mother or siblings.

Of the 62 HBsAg+ve women who provided samples, 42 (67.7%) had viraemia. Nine (14.5%) were HBeAg+ve and one (with a twin pregnancy) had chronic infection with a VL of 2070 IU/mL at the moment of delivery. Of the eight women who had HBeAg+ve chronic infection, six were treated during pregnancy: three achieved undetectable VL before delivery and in the other three the maximum VL was 1448 IU/mL. The two HBeAg+ve women who were not treated had a VL >108 IU/mL. Two of the HBeAg+ve women were Spanish, five were Chinese, one was from Central America and one was from sub-Saharan Africa. The ten neonates were monitored after birth, and none became infected. Of the 53 (85.5%) women who were HBeAg-ve, 40 had chronic infection and 13 had chronic hepatitis.

None of the pregnancies was achieved by in vitro fertilisation. The birth was spontaneous in 47 (72.3%) cases, by caesarean section in 13 (20%) (two of which were scheduled) and by instrumental delivery in five (7.7%). The data for the 69 neonates are summarised in Table 3. Only one of the low-weight children had a maternal history of antiviral treatment. Of the 30 neonates in whom the VL was analysed at birth, two were HBV+ve, although later tests were negative. All of the neonates born to HBsAg+ve women received immunoprophylaxis during the first twelve hours of life, for an average of 3.4 ± 3 hours. The ten children born to HBeAg+ve women received immunoprophylaxis in the first three hours of life. None of the 54 children who completed the follow-up became infected.

Table 3. Characteristics of the neonates born to HBV or HCV-positive mothers.

HBV n = 69 HCV n = 20 P
Prematurea 8 (11.6%) 4 (20%) 0.265
Weight (g) Mean ± standard deviation 3194.7 ± 681 2998.8 ± 582 0.248
Time elapsed since breaking of the waters (h) Mean ± standard deviation 7 ± 8 12 ± 17 0.212
Apgar score Median [P25-P75] 9 [5–10] 9 [6–10] 0.834
Breastfeeding 55 (86%) 13 (65%) 0.044

aPremature: gestational age <37 weeks.

Epidemiology and risk factors for vertical transmission in HCV-positive women

Thirteen women (65%) were previously aware of their HCV infection. None were coinfected with HBV and there were two cases (10%) of coinfection with HIV. By country of origin, the majority of women were from Spain (11 cases, 55%) and Eastern Europe (four cases, 20%) (Fig 2). The risk factors for infection are detailed in Table 2. The route of transmission was parenteral in 16 women (80%), of whom nine had a history of IVDA. The route of transmission was unknown in four cases (20%).

HCV RNA was positive (HCV-RNA+ve) in eight (40%) of the 20 women, with an average VL of 1.9x105 IU/mL (4.4x105–3.5x106 IU/mL). The distribution of genotypes was 1b (25%), 3 (25%), 4c (12.5%) and unknown (37.5%).

None of the pregnancies was achieved by in vitro fertilisation. Delivery was spontaneous in 12 cases (60%), by caesarean section in four (20%) and by instrumental delivery in four (20%). The data for the 20 neonates are summarised in Table 3. Five children of the eight women with viraemia completed the follow up and none became infected.

Analysis of the differences between HBV and HCV-positive pregnant women

As can be seen in Table 2, 65.7% (44/67) of the women with HBV were foreign born, versus only 45% (9/20) of the women with HCV. Nevertheless, the difference was not statistically significant (p = 0.07). A similar pattern was observed for the unknown route of maternal infection, which was more frequent among the women with HBV than those with HCV (40.3% vs. 20%; p = 0.066). VT as the mechanism of infection was more frequent for the HBV+ve women (31.3% vs. 0%; p = 0.001), while IVDA was more frequent in the HCV group (45% vs. 0%; p<0.001). Previous blood transfusion was also significantly higher in the HCV group (15% vs. 1.5%; p = 0.043).

There were no statistically significant differences among the neonates for any of the variables analysed, except that a significantly lower proportion of the women with HCV breastfed their children (65% vs. 86%; p = 0.044) (Table 3).

Discussion

In our study population, the prevalence of HBV was 0.42% (91/21870) and that of HCV was 0.26% (20/7659). The HBV+ve women were more likely to be foreign born than those with HCV. The most frequent route of transmission of HBV was of unknown origin, while among those of known origin, VT was most commonly observed. Regarding the risk factors for VT, 67.7% of the women presenting HBV had viraemia and 14.5% were HBeAg+ve. Immunoprophylaxis was administered correctly to all the neonates born to HBV+ve mothers. Among the HCV+ve mothers, the parenteral route of transmission was most common, mainly due to IVDA. In the HCV group, 40% had viraemia and 10% were co-infected with HIV. The HCV+ve women were less likely than HBV+ve to breastfeed their children.

In this study, the observed prevalence of HBsAg+ve was significantly different among the participant hospitals. The highest level was obtained for the HUT in Almeria (0.64%), a hospital that serves a large migrant population from North and sub-Saharan Africa. In contrast, the data for anti-HCV prevalence were fairly consistent among the participant hospitals, with the sole exception of the HUVV in Malaga, where the prevalence was higher, although in this case the sample size was very small.

In the general population in Spain, the prevalence of HBV is 0.66% (0.34–0.97) [3], which is higher than the prevalence we found in pregnant women. In a previous study conducted in 1986–89 [23] at the HUSC in Granada, based on a population of 4450 pregnant women, the prevalence of HBV was 1.53% (95% CI 1.14–1.92). Thirty years later, according to our findings, the prevalence in this city has fallen to 0.39%. For comparison, a 2009 study by Salleras et al. [24], with a population of pregnant women in Catalonia, and which has been taken as a benchmark for Spain by the ECDC [5], recorded a very low prevalence, of 0.1%.

Our findings show that 65.7% of the participants who were HBV+ve were foreign born, with a particularly strong presence of women from China and eastern Europe, which corroborates the pattern reported previously [25,26]. In a study conducted in Madrid [26], the highest rate of seropositivity was found among women from Romania and other Eastern European countries (23.7%), followed by those from China (20.3%) and sub-Saharan Africa (18.6%). In recent years, the prevalence of HBV in Spain has tended to decrease, and if the population considered excluded those of foreign origin, the prevalence would probably be even lower.

In most of the cases analysed in our study, the route of transmission of HBV infection was unknown, while the most common of the known routes was maternal family history of HBV infection (31.3%), although some women presented several risk factors for infection. A large majority of the women (67.7%) had viraemia and therefore were potential transmitters of infection. 14.5% were HBeAg+ve, which increased the risk of transmission still further. However, only six of these women received antiviral treatment during their pregnancy, which shows that not all hospitals follow clinical practice guidelines in this respect [22]. A previous study carried out in Granada with 4169 pregnant women [25] reported that HBV was present in 27, of whom only one (a woman of Asian origin) was HBeAg+ve.

All of the 69 neonates born to HBV+ve mothers received immunoprophylaxis during the first twelve hours of life, and the ten children born to HBeAg+ve women received immunoprophylaxis in the first three hours of life. None of the 54 neonates who completed the follow up became infected. This includes the two children of HBeAg+ve women with high VL who were untreated, which highlights the importance of correctly administering immunoprophylaxis to neonates at an early stage of life.

In our study, the prevalence of HCV was 0.26%, and only 40% of these cases were HCV-RNA+ve. On the other hand, previous studies in the general population have found a higher prevalence, of 1.7% (0.4–2.6), with HCV-RNA+ve in 68.6% of these cases [27]. Nevertheless, research has shown that the prevalence of HCV is lower among women than in the general population. In a study conducted in the United States [28], the prevalence in men was 1.56% versus 0.75% in women. In another study, also conducted in the USA [29], with 87924 pregnant women, the prevalence of HCV was 1.2%. In Navarre (Spain), a study of 7314 pre-surgical patients [30] revealed a prevalence of 0.94%, with higher values for men than for women (1.25% vs. 0.62%, p = 0.0049). Finally, a study carried out in 1993–95 with 3003 pregnant women at the HUSC in Granada [19] reported that only 19 were HCV+ve (0.63%) while 14 (74%) presented viraemia. Thus, the value of 0.26% obtained in the present study is much lower than these previous findings.

Among our study population, 55% of the women with HCV were Spanish, followed in frequency by those from Eastern Europe (20%), which is in line with previous findings [31]. According to earlier research [27], 80% of the cases recorded worldwide with positive viraemia are located in 31 countries, one of which is Spain, but over half of the infections correspond to just six countries: China, Pakistan, Nigeria, Egypt, India and Russia. Parenteral transmission is the most common route of infection, and most cases involve a history of IVDA, although in 20% of cases the origin of the infection is not known. This knowledge gap could justify the introduction of HCV screening in pregnancy. Similar findings have been reported in other studies [29,32,33]. Infection is significantly more frequent in people aged under 30 years, those who are of European descent, especially those from Eastern Europe, and those with a history of IVDA. The most frequent genotypes recorded in our study were 1b and 3, followed by 4, which is consistent with previous research findings [33]. Two women (10%) had co-infection by HIV, which increases the probability of HCV being transmitted to the child [17].

Among the children of women with HCV infection, 20% were premature, a value that is higher than in the general population. Moreover, only 65% initiated breastfeeding, which is well below the figure for children of HBV+ve mothers (86%) and the general population. These findings may be more influenced by the history of IVDA than by the HCV per se [34]. This may also be the reason why not all the children of mothers with viraemia completed the follow up.

Among the specific characteristics differentiating the HBV+ve women were the predominance of infection by VT and the larger proportion who breastfed their children. In addition, more were foreign born, compared to the women with HCV. In the HCV group, the main distinguishing features observed were blood transfusion and a history of IVDA.

The main limitation of this study concerned the determination of HCV in the pregnant women, since screening for this condition is not universal in Spain during pregnancy, and therefore signed informed consent was required. For this reason, the sample size for our analysis of HCV prevalence was lower than that for HBV. Furthermore, some of the Spanish hospitals that were invited declined to participate. Another limitation concerned the follow-up of the children of seropositive mothers; many of these children were adopted after birth and so their place of residence changed.

In summary, the prevalences of HBV and HCV that we report are lower than those documented previously. A significant number of the women with HBV were foreign born and/or had a maternal family history of infection. Among those with HCV, many had a history of IVDA, which probably influenced the fact that these women were less likely to complete follow up and less likely to breastfeed their children. Over half of the women with HBV had viraemia, and therefore were potential transmitters of the infection to the neonate. Therefore, the provision of appropriate immunoprophylaxis (including immunoglobulin therapy and vaccination) is important in neonates born to HBV+ve mothers. However, among the women with HCV, despite the presence of viraemia and coinfection with HIV, there was no transmission to the children.

Acknowledgments

We thank Pedro Lucas at FIBAO (Public Foundation for Biomedical Research in Eastern Andalusia) for designing the database used in this study.

This paper will be presented by Maria del Mar Diaz-Alcazar to obtain her Ph.D. within the doctoral programme ‘Clinical Medicine and Public Health’ at the University of Granada (Spain).

Data Availability

All relevant data are within the paper.

Funding Statement

This study received financial assistance from the following: Ciberehd, Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III. ISCIII, Proyecto del Plan Nacional I+D+i 2013-2016 (PI13/01925), Confinanciación Fondos FEDER. Gilead Fellowship Program (GLD14-00292 and GLD15-00307).

References

  • 1.World Health Organization. Global Hepatitis Report 2017. [Internet] Geneva: World Health Organization; 2017. Available from: http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/. [Google Scholar]
  • 2.Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L, et al. Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies. Journal of Hepatology 2018;69:718–35. 10.1016/j.jhep.2018.05.011 [DOI] [PubMed] [Google Scholar]
  • 3.Ahmad AA, Falla AM, Duffell E, Noori T, Bechini A, Reintjes R, et al. Estimating the scale of chronic hepatitis B virus infection among migrants in EU/EEA countries. BMC Infect Dis 2018;18(1):34–48. 10.1186/s12879-017-2921-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Ortiz E, Scanlon B, Mullens A, Durham J. Effectiveness of interventions for hepatitis B and C: a systematic review of vaccination, ccreening, health promotion and linkage to care within higher income countries. J Community Health 2019. [Epub ahead of print]. [DOI] [PubMed] [Google Scholar]
  • 5.Hofstraat SHI, Falla AM, Duffell EF, Hahné SJM, Amato-Gauci AJ, Veldhuijzen IK, et al. Current prevalence of chronic hepatitis B and C virus infection in the general population, blood donors and pregnant women in the EU/EEA: a systematic review. Epidemiol Infect 2017;145(14):2873–85. 10.1017/S0950268817001947 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Ministerio de Sanidad, Servicios Sociales e Igualdad. Plan estratégico para el abordaje de la hepatitis C en el Sistema Nacional de Salud. [Internet] Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad; 2015. Available from: https://www.mscbs.gob.es/ciudadanos/enfLesiones/enfTransmisibles/docs/plan_estrategico_hepatitis_C.pdf. [Google Scholar]
  • 7.Cuadrado A, Perello C, Llerena S, Escudero-García D, Gómez M, Estébanez A, et al. Design and cost effectiveness of a hepatitis C virus elimination strategy based on an updated epidemiological study (ETHON cohort). Poster presented at European Association for the Study of the Liver, The International Liver Congress, Paris. J Hepatol 2018;68 (Suppl 1):S164. [Google Scholar]
  • 8.Falla AM, Ahmad AA, Duffell E, Noori T, Veldhuijzen IK. Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a focus on migrants from anti-HCV endemic countries. BMC Infect Dis 2018;18(1):42–55. 10.1186/s12879-017-2908-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Ruiz-Extremera A, López-Garrido MA, Barranco E, Quintero MD, Ocete-Hita E, Muñoz de Rueda P, et al. Activity of hepatic enzymes from week sixteen of pregnancy. Am J Obstet Gynecol 2005;193(6):2010–6. 10.1016/j.ajog.2005.04.045 [DOI] [PubMed] [Google Scholar]
  • 10.Aristegui Fernández J, Diez-Domingo J, Mares Bermudez J, Martinon Torres F. Vacunación frente a la hepatitis B. Impacto de los programas de vacunación tras 20 años de su utilización en España. ¿Es tiempo de cambios? Enferm Infecc Microbiol Clin 2015;33(2):113–8. [DOI] [PubMed] [Google Scholar]
  • 11.Dionne-Odom J, Tita AT, Silverman NS. Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Society for Maternal-Fetal Medicine (SMFM). Am J Obstet Gynecol 2016;214:6–14. 10.1016/j.ajog.2015.09.100 [DOI] [PubMed] [Google Scholar]
  • 12.Wen WH, Lai MW, Chang MH. A review of strategies to prevent mother-to-infant transmission of hepatitis B virus infection. Expert Rev Gastroenterol Hepatol 2016;10(3):317–30. 10.1586/17474124.2016.1120667 [DOI] [PubMed] [Google Scholar]
  • 13.Bleich LM, Swenson ES. Prevention of neonatal hepatitis B virus transmission. J Clin Gastroenterol 2014;48(9):765–72. 10.1097/MCG.0000000000000115 [DOI] [PubMed] [Google Scholar]
  • 14.Jonas MM. Hepatitis B and pregnancy: an underestimated issue. Liver Int 2009;29(Suppl 1):133–9. [DOI] [PubMed] [Google Scholar]
  • 15.Muñoz-Almagro C, Juncosa T, Fortuny C, Guillén JJ, González-Cuevas A, Latorre C. Prevalence of hepatitis C virus in pregnant women and vertical transmission. Med Clin 2002;118(12):452–4. [DOI] [PubMed] [Google Scholar]
  • 16.Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis 2014;59(6):765–73. 10.1093/cid/ciu447 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Ruiz-Extremera A, Muñoz-Gámez JA, Salmerón-Ruiz MA, de Rueda PM, Quiles-Pérez R, Gila-Medina A, et al. Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children. Hepatology 2011;53(6):1830–8. 10.1002/hep.24298 [DOI] [PubMed] [Google Scholar]
  • 18.Ruiz-Extremera A, Salmerón J, Torres C, De Rueda PM, Giménez F, Robles C, et al. Follow-up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: the role of breast-feeding in transmission. Pediatr Infect Dis J 2000;19(6):511–6. 10.1097/00006454-200006000-00004 [DOI] [PubMed] [Google Scholar]
  • 19.Salmerón J, Giménez F, Torres C, Ros R, Palacios A, Quintero D, et al. Epidemiology and prevalence of seropositivity for hepatitis C virus in pregnant women in Granada. Rev Esp Enferm Dig 1998;90(12):841–50. [PubMed] [Google Scholar]
  • 20.Yi P, Chen R, Huang Y, Zhou RR, Fan XG. Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges. J Clin Virol 2016;77:32–9. 10.1016/j.jcv.2016.02.003 [DOI] [PubMed] [Google Scholar]
  • 21.Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, et al. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012;10(5):452–9. 10.1016/j.cgh.2011.10.041 [DOI] [PubMed] [Google Scholar]
  • 22.European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67(2):370–98. 10.1016/j.jhep.2017.03.021 [DOI] [PubMed] [Google Scholar]
  • 23.Del Castillo G, Ruiz-Extremera A, López F, Tomás J, Jiménez F, Salmerón FJ. Prevalencia del VHB en mujeres gestantes. Inmunoprofilaxis. Rev Soc Andal Pat Digest 1989;12:447–50. [Google Scholar]
  • 24.Salleras L, Domínguez A, Bruguera M, Plans P, Espuñes J, Costa J, et al. Seroepidemiology of hepatitis B virus infection in pregnant women in Catalonia (Spain). J Clin Virol 2009;44(4):329–32. 10.1016/j.jcv.2009.01.002 [DOI] [PubMed] [Google Scholar]
  • 25.Sampedro A, Mazuelas P, Rodríguez-Granger J, Torres E, Puertas A, Navarro JM. Marcadores serológicos en gestantes inmigrantes y autóctonas en Granada. Enferm Infecc Microbiol Clin 2010;28(10):694–97. 10.1016/j.eimc.2010.04.007 [DOI] [PubMed] [Google Scholar]
  • 26.López-Fabal F, Gómez-Garcés JL. Marcadores serológicos de gestantes españolas e inmigrantes en un área del sur de Madrid durante el periodo 2007–2010. Rev Esp Quimioter 2013;26(2):108–11. [PubMed] [Google Scholar]
  • 27.Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014;61(S):45–57. [DOI] [PubMed] [Google Scholar]
  • 28.Hall EW, Rosenberg ES, Sullivan PS. Estimates of state-level chronic hepatitis C virus infection, stratified by race and sex, United States, 2010. BMC Infect Dis 2018;18:224–38. 10.1186/s12879-018-3133-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Chappell C, Hillier SL, Crowe D, Meyn LA, Bogen DL, Krans EE. Hepatitis C virus screening among children exposed during pregnancy. Pediatrics 2018;141(6):1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Aguinaga A, Díaz González J, Pérez García A, Barrado L, Martínez Baz I, Casado I, et al. The prevalence of diagnosed and undiagnosed hepatitis C virus infection in Navarra, Spain, 2014–2016. Enferm Infecc Microbiol Clin 2018;36(6):325–31. 10.1016/j.eimc.2016.12.008 [DOI] [PubMed] [Google Scholar]
  • 31.Ramos JM, Masiá M, Padilla S, Escolano C, Bernal E, Gutiérrez F. Enfermedades importadas y no importadas en la población inmigrante. Una década de experiencia desde una unidad de enfermedades infecciosas. Enferm Infecc Microbiol Clin 2011;29(3):185–92. 10.1016/j.eimc.2010.11.011 [DOI] [PubMed] [Google Scholar]
  • 32.Alonso López S, Agudo Fernández S, García del Val A, Martínez Abad M, López Hermosa Seseña P, Izquierdo MJ, et al. Seroprevalencia de hepatitis C en población con factores de riesgo del suroeste de la Comunidad de Madrid. Gastroenterol Hepatol 2016;39(10):656–62. 10.1016/j.gastrohep.2016.05.002 [DOI] [PubMed] [Google Scholar]
  • 33.Acero Fernández D, Ferri Iglesias MJ, Buxó Pujolràs M, López Nuñez C, Serra Matamala I, Queralt Molé X. Changes in the epidemiology and distribution of the hepatitis C virus genotypes in North-Eastern Spain over the last 35 years. Gastroenterol Hepatol 2018;41(1):2–11. 10.1016/j.gastrohep.2017.09.004 [DOI] [PubMed] [Google Scholar]
  • 34.Pergam SA, Wang CC, Gardella CM, Sandison TG, Phipps WT, Hawes SE. Pregnancy complications associated with hepatitis C: data from a 2003–2005 Washington state birth cohort. Am J Obstet Gynecol 2008;199(Suppl 1):38–51. [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Anna Kramvis

7 Apr 2020

PONE-D-20-00132

Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission.

PLOS ONE

Dear Mrs Díaz Alcázar,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by May 22 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Anna Kramvis

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please note that according to our submission guidelines (http://journals.plos.org/plosone/s/submission-guidelines), outmoded terms and potentially stigmatizing labels should be changed to more current, acceptable terminology. For example: “Caucasian” should be changed to “white” or “of [Western] European descent” (as appropriate).

3. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. Moreover, please include more details on how the questionnaire was pre-tested, and whether it was validated.

Additional Editor Comments (if provided):

Please pay special attention to all the reviewers' comments and suggestions in particular paying special attention in improving the English language and grammar.

There are a number of errors even in the abstract: correct terminology for "E antigen" is HBeAg - please correct here and in the rest of the manuscript where it is referred to as "AgHBe". "VHB" should be HBV is assume, correct in the abstract and in all other sections of the manuscript. The comment of the prevalence being different to previous studies is not correct considering that here you only looked at prevalence in females. Please consider correcting this. The statement in the abstract "all neonates received immunoprophylaxis" I assume this is all neonates born to HBV+ve mothers! Thus please correct here and in the rest of the manuscript.

What is not clear is whether there is an overlap between the pregnant women tested for HBV and those for HCV. Please clarify!!

Where the ethical considerations the same for both HBV and HCV studies? Were separate protocols submitted to the institutional review boards?

Was the prevalence between the different hospitals significantly different? Could you explain why for example HUCA had 0.04% whereas HUT had 0.64% HBV prevalence? Were the population groups serviced different between the two hospitals? You do mention in your discussion that HUT had more pregnant women of foreign origin. Were they mainly from eastern Europe, China or sub-Saharan Africa? Another important analysis that would add value to your study, would be to compare the number of HBeAg-positivity between Spanish women, and the various immigrant populations, i.e. Chinese compared to European and African. It has important implications regarding the management of HBV infection. For example mother to child transmission is more frequent in Asian populations compared to Africans because of differences in the frequency of HBeAg-positivity in the two groups.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study by Ruiz-Extremera et al., entitled “Seroprevalence, epidemiology and clinical characteristics of hepatitis B and C viruses in pregnant women in Spain” aimed to study the prevalence of HBV/HCV in pregnant women, subsequent vertical transmission, and newborn immune prophylaxis etc. Additionally, the data was analyzed in view of human migration to identify other possible/associated risk factors.

The study is concise, addressing certain important issues like, the need for proper immune prophylaxis, probable nation wide vaccination program etc. Still further modifications are needed before deemed fit for acceptance. Some concerns that need to be addressed are as follows:

Some major points are:

1. The whole MS needs linguistic correction. For eg. In the abstract section: vide line no. 38-39 “HBV prevalence was analyzed in a population of 21,870 women and that of HCV, in one of 7,659 ”. In the line “that of HCV, in one of 7,659” does mean only one subject was positive out of 7659 subjects”.

I think a better way of representation is “HBV prevalence was analyzed in a population size of 21,870 women and for HCV, the study population size was 7,659 women”.

Another eg. Line no 83 , “chronification” should be “chronicity”.

2. For any data represented with percentages should accompany the numerical ration to ease things for understanding and more meaningful. Viz. line no. 43 “HBV prevalence was 0.42% and that of HCV, 0.26%” should be “HBV prevalence was 0.42% (91/21870) and that of HCV, 0.26% (20/7659)”. Also, it is better to mention the table number.

3. In the discussion section, vide line no. 298-299 “In the general population in Spain, the prevalence of HBV is 0.66% (0.34-0.97) (3), which is higher than was recorded in the present research”. As HBV chronicity display gander disparity, thus probably, this difference is expected. It will be better to comment on that.

4. This reviewer suggests including and discussing the importance of HBV vaccination in the conclusion section.

Reviewer #2: Line 38 Methodology. Multicentre open-cohort study performed during 2015. Which period of 2015?

The papers' english needs thorough grammar revision.

Examples ( Line 49. Viraemia was present in 40% and 10% were co-infected with HIV .

Line 75. only 0.32%. This prevalence could be modified by changes in patterns of migration

Line 76. towards the European Union in general and Spain, in particular (8).

Line 100. HIV coinfection or pregnant women from countries where HCV is endemic )

Figure 1 Diagram labelling is not very clear.

Figure 2 needs labelling

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 May 21;15(5):e0233528. doi: 10.1371/journal.pone.0233528.r003

Author response to Decision Letter 0


3 May 2020

We would like to thank you for the suggestions provided regarding the article entitled “Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission” by the authors Ángeles Ruiz-Extremera, María del Mar Díaz-Alcázar, José Antonio Muñoz-Gámez, et al. As requested, we provide more information in the rebuttal letter about the changes made to the manustript.

We very much appreciate the comments and suggestions made, which have been very helpful in improving the manuscript. We hope these changes are considered appropriate and that the manuscript is now suitable for publication. In any case, we will gladly consider any further comments you may have.

Attachment

Submitted filename: Response to Reviewers.doc

Decision Letter 1

Anna Kramvis

7 May 2020

Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission.

PONE-D-20-00132R1

Dear Dr. Díaz Alcázar,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Anna Kramvis

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Anna Kramvis

8 May 2020

PONE-D-20-00132R1

Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission.

Dear Dr. Díaz-Alcázar:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof. Anna Kramvis

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Rebuttal letter version 3.doc

    Attachment

    Submitted filename: Response to Reviewers.doc

    Data Availability Statement

    All relevant data are within the paper.


    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES