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The cytomegalovirus (CMV) is the most common maternal-fetal transmission infectious disease. The diagnosis of this infection is rarely made on antenatal sonographic signs. Pathological examination could, in this case, make etiologic diagnosis. We report the case of a terminated pregnancy, at the term of 19 weeks of gestation, occurring in a 31-year-old woman. The sonography found a terminated pregnancy with anamnios. Histological examination of samples of fetal internal organs showed intranuclear inclusions, compatible with CMV infection. The main objective of our work is to emphasize the value of histological examination in the diagnosis of fetal death etiology. Moreover, we will discuss the benefit of antenatal screening of CMV maternal infection., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the role of viral infections in causing fetal and infant death., Study Design: We assessed a well-validated population database of fetal (≥20 weeks gestation) and infant death for infective deaths and deaths from viruses over a 21-year period (1988-2008). We analyzed by specific viral cause, timing (late fetal loss [20-23 weeks], stillbirth [≥24 weeks], neonatal death [0-27 days], and post-neonatal infant death [28-364 days]) and across time., Results: Of the 989 total infective deaths, 108 were attributable to viral causes (6.5% of late fetal losses, 14.5% of stillbirths, 6.5% of neonatal deaths, and 19.4% of postneonatal infant deaths). Global loss (combined fetal and infant losses per 100,000 registerable births) was 139.6 (95% CI, 130.9-148.3) for any infective cause and 15.2 (95% CI, 12.3-18.1) for viral infections. More than one-third (37%) of viral-attributed deaths were before live birth, from parvovirus (63%) or cytomegalovirus (33%). Parvovirus accounted for 26% (28 of 108) of all viral deaths. Cytomegalovirus was associated with a global loss rate of 3.1 (95% CI, 1.8-4.4) and an infant mortality rate of 1.3 (95% CI, 0.4-2.1) per 100,000 live births; 91% of cases were congenital infections. Herpes simplex virus caused death only after live births (infant mortality rate, 1.4; 95% CI, 0.5-2.3). No changes in rates were seen over time., Conclusion: We have identified a substantial contribution of viral infections to global fetal and infant losses. More than one-third of these losses occurred before live births. Considering our methodology, our estimates represent the minimum contribution of viral illness. Strategies to reduce this burden are needed., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To describe the characteristics of pregnant women who accept the influenza vaccine and evaluate the relationship between vaccination and adverse pregnancy outcomes., Methods: Retrospective cohort study of women receiving prenatal care during the 2009-2011 influenza seasons. Vaccination status was ascertained through our perinatal record system and clinic vaccination logs. Pregnancy outcomes included a primary composite of miscarriage, fetal demise, preterm birth (PTB) <37 weeks and neonatal demise. Stratification and logistic regression were used to adjust for potential confounders., Results: Of 3104 eligible pregnant women, 1094 (35%) received the influenza vaccine. Women vaccinated were more likely to be older, obese, primiparae, and have medical complications or a prior PTB. In univariable analyses, flu vaccination was associated with increased adverse composite outcome and PTB. After multivariable adjustments, vaccination was no longer associated with adverse outcomes in women with medical complications but remained associated with adverse outcomes among those without known co-morbidity., Conclusions: Vaccination was associated with an increased adverse composite outcome in pregnant women without identified co-morbidity but not those with co-morbidities. This association is likely due to selection bias, which should be considered in planning of observational studies of the impact of vaccination on pregnancy outcomes.

This study assessed the effect of whole-herd porcine reproductive and respiratory syndrome (PRRS) modified-live virus (MLV) vaccination on herd-level reproductive performance, PRRS virus (PRRSV) viremia, and antibody in a subset of females in a 1,200-sow commercial herd in Thailand. Following a PRRSV outbreak, the entire herd was vaccinated with PRRS MLV twice at 3-week intervals and at 3-month intervals, thereafter. Reproductive performance data over a 3-year period were available for analysis. Serum samples were collected before and after vaccination and tested by PRRSV ELISA and reverse transcription-polymerase chain reaction. Vaccination was statistically associated with a lower abortion rate (1.4 vs. 1.6 %), farrowing rate (83.8 vs. 90.0 %), total born (10.6 vs. 11.4 piglets/litter), liveborn (10.0 vs. 10.3 piglets/litter), stillbirths (4.6 vs. 7.0 %), mummies (0.7 vs. 1.6 %), and a higher return rate (11.3 vs. 5.9 %) when compared with the period before the PRRSV outbreak. Pregnant females vaccinated during early gestation farrowed fewer liveborn and more mummies than the comparison group, whereas females vaccinated during late gestation had a lower farrowing rate. In this herd, PRRS whole-herd vaccination had neutral, positive, and negative effects on reproductive performance. Thus, the decision to implement whole-herd vaccination should be balanced between the benefits derived from reproductive performance improvements, e.g., fewer abortions, stillborn piglets, and mummified fetuses, and the effect of vaccination on pregnant females.

The aims of this study were to determine (1) the pathogenesis of experimental infection with a Korean type 1 porcine reproductive and respiratory syndrome virus (PRRSV) by defining the viral distribution and the sites of viral replication and (2) the relationship between viral replication and apoptosis in stillborn fetuses and live born piglets from infected pregnant gilts. At 3 weeks ante partum, four pregnant gilts were inoculated intranasally with Korean type 1 PRRSV. Stillborn fetuses from the infected gilts were of crown-to-rump length 25.8-27.1 cm consistent with fetal death between 106 and 110 days of gestation. Type 1 PRRSV was isolated from the fetal tissues and these isolates were shown to be identical to the challenge virus by sequence analysis. Type 1 PRRSV RNA was detected in the lung, lymph node, heart, tonsil, thymus, liver, adrenal gland and spleen of live born piglets and stillborn fetuses from the infected gilts. The mean number of apoptotic cells per unit area of lung (P = 0.003), heart (P = 0.011), thymus (P = 0.003), liver (P = 0.011) and spleen (P = 0.002) was significantly higher in stillborn fetuses than in live born piglets. Dual labelling showed that the majority of cells either contained type 1 PRRSV or were apoptotic, but not both. Apoptotic cells were more numerous than PRRSV(+) cells. The results of the study demonstrated that type 1 PRRSV induces reproductive failure in pregnant gilts. Apoptosis induced by type 1 PRRSV may be associated with the incidence of stillborn fetuses in PRRSV-infected pregnant gilts., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Because parvovirus B19 infection during pregnancy has been associated with increased risk of fetal loss in small or selected study populations, the authors evaluated the risk in a population-based study. A nested case-control study was conducted by using a population-based screening for syphilis in 3 regions in Denmark from 1992 to 1994. Cases of women with fetal loss were identified in the National Patient Register (n = 2,918), and control women with live-born children were identified in the Medical Birth Register (n = 8,429) by matching on age and sampling week. First-trimester serum samples were tested for parvovirus B19 immunoglobulin M positivity. Parvovirus B19 immunoglobulin M positivity was associated with a 71% increased risk of fetal loss (odds ratio = 1.71, 95% confidence interval: 1.02, 2.86). Adjustment for number of children or stratifying for gestational age at loss did not change the risk estimate. Assuming causality, only 0.1% of fetal losses were attributable to parvovirus B19 positivity, a proportion which could increase to approximately 1% during epidemic periods. In conclusion, acute parvovirus B19 infection during the first trimester of pregnancy was associated with an increased risk of fetal loss. However, the impact on the overall burden of fetal losses appeared small even during epidemics.

Fetal varicella syndrome (FVS) is due to transplacental infection by the Varicella zoster virus following maternal infection. The risks for the fetus and neonate depend on the timing. When varicella occurs around delivery, it often leads to disseminated neonatal varicella. When varicella occurs during pregnancy, transmission can occur, but is usually asymptomatic; some infants develop zoster postnatally and a few have FVS. Before 20 weeks' gestation, FVS can occur, with an incidence of about 1%. The lesions can affect the skin, limbs, central and autonomous nervous systems, eyes, cause calcifications, and growth retardation; mortality is high. Lesions typically follow one or several nerve territories, suggesting that damage results from in utero zoster following primary fetal infection. There has been little study of prenatal diagnosis of FVS. Serial ultrasound examination can detect various anomalies, magnetic resonance imaging can be of use to investigate for microphthamia and cerebral lesions, and amniocentesis can diagnose viral transmission. Prevention strategies include vaccination and post-exposure prophylaxis with immune globulin and/or antivirals. Perspectives for treating infected fetuses in utero require further research., (© 2012 John Wiley & Sons, Ltd.)

Background: Human cytomegalovirus (CMV) is the most common congenital infection in developed countries and is a known cause of intrauterine fetal death. We examined CMV infection in stillbirths and the relationship with histopathological findings at autopsy., Methods: We collected liver, kidney, and placenta specimens from 130 stillbirths. CMV DNA and protein were detected using polymerase chain reaction and immunohistochemistry, along with routine autopsy of stillborn infants., Results: Overall, CMV DNA was detected in 15% of singleton, >20-week stillborn infants. CMV DNA was detected in kidney (9%), liver (11%), and placenta (5%) specimens, with 75% of infections confirmed by immunohistochemistry. Fetal thrombotic vasculopathy was the only histopathological abnormality associated with CMV infection (in 60% CMV-infected vs 28% uninfected stillbirths P = .010)., Conclusions: Stillbirth has multiple etiologies. However, the detection of CMV DNA in 15% of fetal tissues or placentae suggests a strong association between CMV infection in pregnancy and stillbirth. Molecular testing during postmortem investigation has an important role to determine the contribution of CMV infection.

This study was undertaken to investigate the occurrence of viral infection in fetal death by examining tissues for the presence of DNA of several viral agents. Tissue specimens including heart, kidney, liver, lung, and placenta of 73 cases of fetal death were examined with 27 cases of elective termination of pregnancy as a control group. DNA extracted from these samples was tested for the presence of HSV, CMV, EBV, VZV, HHV-6, HHV-7, and PVB19. Viral DNA was found in one or more tissue samples from 25/73 cases (34%): CMV in 20, HSV in 5, parvovirus B19 in 5, HHV-7 in 3, and HHV-6 in 2. The presence of HHV-6 in fetal tissue has been reported rarely. No study so far has reported the detection of HHV-7 in fetal tissues with normal or adverse outcomes. Viral DNA was not found in any of the termination of pregnancy samples. Among the positive cases, eight had dual infection. One further case was positive for three viruses: HSV, CMV, and HHV-7. HHV-6 was the sole infectious agent in two cases, HHV-7 in one case, PVB19 in three, and CMV in ten cases. The finding of multiple viral DNA in 12% of the cases suggests the involvement of complex risk factors in cases of fetal loss. Although the cause of fetal death often includes other factors (e.g., chromosomal abnormalities) these data suggest the incidence of viral infective etiology may be higher than considered previously. However, larger studies are required to establish this link., (Copyright © 2011 Wiley-Liss, Inc.)

The objective of this study was to determine the seroprevalence of cytomegalovirus (CMV) infections through antenatal screening data and the association of this virus with obstetric complications. Serum samples from 125 apparently healthy pregnant women sent for antenatal screening from various hospitals in Malaysia between January 2007 and December 2008, were examined for CMV specific IgM and IgG antibodies using an enzyme-linked immunosorbent assay method. Of the 125 pregnant women tested, anti-CMV IgG antibody was found in 105 (84%) of the cases and anti-CMV IgM in 9 cases (7.2%). Both CMV IgM and IgG were also found in another 37 women whose serum samples were sent for investigation of various obstetric complications: 17 cases of spontaneous abortions, 15 cases of fetal anomalies detected during ultrasound examination, 1 case of incomplete abortion, 3 cases with premature delivery of infant with congenital anomalies and 1 case of infertility. Our preliminary data which only represented a small study group has shown the prevalence of CMV infection among the local population and the association of CMV in obstetric complications.

Reproductive performance of gilts and sows in a swine commercial herd following an outbreak of porcine epidemic diarrhea virus (PEDV) were investigated. A PEDV outbreak was observed in March 2008 in a swine herd in Thailand. The disease was diagnosed by clinical symptoms, gross and histopathology and viral detection using reverse transcriptase-polymerase chain reaction assay. The intestines of the infected piglets were collected, minced and fed to all of the gilts and sows within 2 weeks after the onset of the PEDV outbreak. Reproductive data were collected during a period from January 2007 to July 2008 and were retrospectively evaluated. The farrowing rate (FR), return rate (RR), abortion rate (AR), number of total piglets born per litter (TB), number of piglets born alive per litter (BA), percentage of stillbirth piglets per litter (SB), percentage of mummified fetus per litter (MM) and piglet's birth weight (BW), before and after the PEDV outbreak were compared. It was found that the impact of PEDV infection on the reproductive performance of gilts and sows depended on the period of pregnancy when the females were exposed to the pathogen, and parity number. The pregnant females infected with PEDV during the first 30 days of pregnancy had a 12.6 percentage point decrease of FR (91.1% vs. 78.5%, P=0.003), a 5.7 percentage point increase of RR (3.5% vs. 9.2%, P=0.01), a 1.3 percentage point increase of AR (2.1% vs. 3.4%, P=0.01) and a 2.0 percentage point increase of MM (3.5% vs. 5.6%, P<0.001). SB increased in the pregnant females that were infected with PEDV during 91-120 days of pregnancy (1.8 percentage points, 4.5% vs. 6.2%, P=0.01). The impacts of PEDV infection on subsequent reproductive performance were more severe in the pregnant gilts than the pregnant sows. PEDV infection during the first 30 days of pregnancy resulted in a decrease of TB by 1.4 (11.7 vs. 10.3 piglets/litter, P<0.001) and a decrease of BA by 2.2 (10.7 vs. 8.5 piglets/litter, P<0.001) in the gilts' litters, while the influence of PEDV infection on TB and BA was not significant in sows (P>0.05). It was concluded that natural infection of PEDV in the pregnant gilts and sows caused a reduction of subsequent reproductive performance., (Copyright © 2010 Elsevier B.V. All rights reserved.)

During a 2-month period a newly repopulated Danish pig herd experienced an increase in numbers of stillborn and mummies, caused by porcine circovirus type 2 (PCV2) associated reproductive failure. Based on recordings of data over time, the progression of the clinical outbreak was studied and the diagnostic value of different techniques was evaluated. Foetal hearts (38 cases and 13 controls) were examined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) for the detection of PCV2; and total immunoglobulin G (IgG) was measured in pleura cavity fluid. PCV2 IHC was positive in 14/38 of the case foetuses, which were delivered during a 9 days period early in the outbreak. On the basis of the results obtained by IHC and PCR, the foetuses were divided into 3 categories: PCV2 negative; moderately positive (10(4) to 10(7) copies per 500 ng DNA); and massively positive for PCV2 (>10(7) copies per 500 ng DNA). All control- and IHC positive foetuses were included in the negative and massively positive groups, respectively. Ten case foetuses had elevated IgG levels, which did not correlate with the IHC or PCR results. Based on the clustering of the IHC positive foetuses, it is suggested that IHC only is suited for diagnosing acute stages of reproductive failure, whereas quantitative PCR can be used as a sensitive diagnostic method within a wider time span. It seems that IgG measurements are unpredictable as indication of intrauterine infection with PCV2., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Introduction: In most cases of stillbirth, the cause is still unknown., Aim: The impact of parvovirus B19/erythrovirus infection and chromosomal abnormalities in stillborns and neonatal deaths., Material and Methods: 57 consecutive cases, 23 second-trimester abortions (from gestational weeks 16 to 22), 27 intrauterine fetal deaths (from gestational week 22 onwards) and 7 early neonatal deaths were examined for intrauterine parvovirus B19 infection with PCR, dot blot, Southern blot, in situ hybridization, specific IgM and IgG antibodies in maternal serum, fetal serum, placenta and fetal liver tissue. Chromosomal analysis and extensive histopathology were performed on all fetuses., Results: A sensitive PCR was developed and enabled detection of 9 (15.8%) parvovirus B19-infected fetuses. Parvovirus B19 IgM and IgG antibody tests were in good concordance with PCR findings. 5 of 9 infected fetuses had a concurrent abnormality that could have contributed to fetal death, 4 of which (44%) were trisomy karyotypes, compared to 0/48 in the non-B19-infected group (p = 0.0004)., Conclusion: Combination of PCR and specific parvovirus B19 IgG/IgM tests enabled high detection rates of parvovirus B19 infection in this series of 57 consecutive pregnancies with adverse outcomes. The high mortality rate in the B19-infected fetuses was partly explained by a high occurrence of fetal trisomy, compared to non-B19-infected fetuses, suggesting a higher vulnerability of the former. After correction for this concomitant karyotype abnormality, the percentage of presumably lethal infection due to parvovirus B19 was 8.8%., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: To assess the association between maternal parvovirus B19 infection and fetal death, birthweight and length of gestation., Design: Case-control study., Setting: Population based., Population: Cases were all 281 women with fetal death within a cohort of 35 940 pregnant woxmen in Norway. The control group consisted of a random sample of 957 women with a live born child., Method: Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. First trimester serum samples were tested for antibodies against parvovirus B19 (IgM and IgG). In seronegative women, further serum was analysed to detect seroconversion during pregnancy., Main Outcome Measures: Fetal death, length of gestation and birthweight., Results: Two of 281 (0.7%) of the women who experienced fetal death and nine of 957 (0.9%) of the controls had presence of IgM antibodies, crude odds ratio 0.8; 95% CI (0.2-3.5). In initially, seronegative women, 3.1% (2/65) with fetal death and 2.6% (8/307) with a live birth seroconverted, crude odds ratio 1.2; 95% CI (0.2-5.7). Presence of maternal parvovirus-specific IgG or IgM antibodies in the first trimester, or seroconversion during pregnancy were not associated with lower birthweight or reduced length of gestation in live born children, but was associated with low birthweight in stillborn offspring., Conclusion: Maternal parvovirus B19 infection was not associated with fetal death in our study. Very few cases of fetal death may be attributed to maternal parvovirus B19 infection.

Infection may cause stillbirth by several mechanisms, including direct infection, placental damage, and severe maternal illness. Various organisms have been associated with stillbirth, including many bacteria, viruses, and protozoa. In developed countries, between 10% and 25% of stillbirths may be caused by an infection, whereas in developing countries, which have much higher stillbirth rates, the contribution of infection is much greater. In developed countries, ascending bacterial infection, both before and after membrane rupture, with organisms such as Escherichia coli, group B streptococci, and Ureaplasma urealyticum is usually the most common infectious cause of stillbirth. However, in areas where syphilis is prevalent, up to half of all stillbirths may be caused by this infection alone. Malaria may be an important cause of stillbirth in women infected for the first time in pregnancy. The two most important viral causes of stillbirth are parvovirus and Coxsackie virus, although a number of other viral infections appear to be causal. Toxoplasma gondii, Listeria monocytogenes, and the organisms that cause leptospirosis, Q fever, and Lyme disease have all been implicated as etiologic for stillbirth. In certain developing countries, the stillbirth rate is high and the infection-related component so great that achieving a substantial reduction in stillbirth should be possible by reducing maternal infections. However, because infection-related stillbirth is uncommon in developed countries, and because those that do occur are caused by a wide variety of organisms, reducing this etiologic component of stillbirth much further will be difficult.

To establish a real-time polymerase chain reaction with SYBR Green for detection and quantification of porcine parvovirus (PPV) in porcine tissues, two primers specific for the non-structural protein 1 gene were designed. The detection limit of this assay was 3-23 gene copies/reaction, equivalent to 0.001 TCID(50)/ml. The assay was linear over a 10(6) dilution range of template concentrations. Other porcine pathogens involved in reproductive disorders (porcine circovirus 2, porcine reproductive and respiratory virus, pseudorabies virus, classical swine fever virus) were negative by this assay. This assay could detect PPV titres at least 10(5) smaller than the hemagglutination assay. To better understand the pathogenesis of PPV, the levels of viral DNA in various tissues of artificially challenged sows and their fetuses were quantified with this method. The virus was found mainly in the heart, lung, spleen, kidney, and endometrium of sows, and mainly in the heart, spleen, lung, and testis of fetuses. This study provides a new tool for the study of PPV infection and distribution in sows and their fetuses.

Background: The Ljungan virus (LV) has been shown to cause central nervous system malformations in laboratory mouse models. The LV has also been associated with intrauterine fetal death in humans. We investigated the presence of LV in a series of human hydrocephaly and anencephaly cases from elective abortions., Methods: A series of elective abortions owing to hydrocephaly, anencephaly, and similarly aged trisomy 21 elective abortions as controls were examined for LV by immunohistochemistry and real time RT-PCR. A second experiment involved newborn mice exposed to LV., Results: LV was diagnosed in 9 of 10 cases with hydrocephalus and in 1 of 18 trisomy 21 controls by immunohistochemistry. Five of nine cases with anencephaly had a positive PCR result, whereas none of the 12 trisomy 21 available for PCR testing had a positive result. The 47 newborn mice exposed to LV all developed encephalitis, with eight having hydrocephalus. None of the 52 control animals had encephalitis or hydrocephalus., Conclusion: The association between LV and both hydrocephaly and anencephaly suggests that LV may be playing an important role in central nervous system malformations in humans.

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus and may lead to nonimmune fetal hydrops and fetal demise. Twin pregnancies complicated by infection due to parvovirus B19 are very rare clinical events. We present a dichorionic, diamniotic, dizygotic twin pregnancy after in vitro fertilization with parvovirus B19 infection and viral transmission to both twins, but different outcomes. At 19 weeks gestation, hydrops fetalis was diagnosed for male twin A, female twin B did not show any abnormalities. At 22 weeks gestation an acute parvovirus B19 infection was detected and twin A was diagnosed with intrauterine fetal death (IUFD) by ultrasound at 23 weeks gestation. Viral DNA was detected in maternal blood as well as in placenta and liver tissue of this twin. Twin B was born at 35 weeks gestation asymptomatically and no signs of hydrops or other congenital anomalies but viral DNA was detected by PCR in serum. At the age of 2 years, both IgG titres against B19 and parvovirus DNA amplification copies were still positive in plasma of the surviving twin, but no clinical signs were detectable. It is remarkable that both twins were infected with parvovirus B19 early in pregnancy but showed a discordant clinical outcome. Our case report describes the rare occurrence of an intrauterine fetal death (IUFD) of one twin and the asymptomatic infection of the other in a twin pregnancy.

Objectives: Following up on prior evidence from animal and human studies of Ljungan virus (LV) in intrauterine fetal death (IUFD), we examine additional cases of IUFD using two standard assays of viral detection: immunohistochemistry (IHC) and real time RT-PCR., Materials and Methods: Frozen and formalin-fixed specimens from IUFD cases were tested for the presence of LV using real time RT-PCR and IHC, respectively. Formalin-fixed organs from terminated pregnancies diagnosed as trisomy 21 were used as controls in the IHC assay., Results: Presence of LV was demonstrated in all five IUFD cases by IHC and further confirmed in three of these cases by real time RT-PCR. Only one of 18 trisomy 21 controls was LV positive by IHC., Conclusion: The presence of LV in IUFD patients has been confirmed by two different assays., ((c) 2009 Wiley-Liss, Inc.)

Bovine viral diarrhea virus (BVDV) infection in goats can result in severe reproductive losses, with abortion rates reaching 80%. Infection with BVDV in aborted goat fetuses and stillborn kids can result in placentitis, encephalitis, myocarditis, and thymic depletion. This study investigates the distribution of viral antigen within the organ systems of aborted goat fetuses, stillborn kids, and nonviable kids infected with BVDV at various stages of gestation using immunohistochemistry (IHC). Virus antigen was detected within the placenta (8/13), thymus (4/9), heart (4/11), and brain (4/15) of affected goats. Uncommonly, BVDV antigen was detected within the skin (1/14), liver (1/13), kidney (1/12), lung (1/11), and trachea (1/3). BVDV antigen was not detected within the spleen (0/9), nasal turbinate (0/2), or thyroid (0/3). The results of this study indicate that placenta, heart, thymus, and brain are the most reliable tissues for BVDV antigen detection using IHC in aborted goat fetuses.

There are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV-1/2) cause fetal infections, which may lead to fetal death. In a prospective case-control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV-1/2 genomes. Formalin-fixed, paraffin-embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty-four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV-1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR-positive and PCR-negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death.

Disease outbreaks characterized by reproductive failure and/or neurologic disorders, which are commonly referred as "Porcine Reproductive and Neurologic Syndrome (PRNS)", were observed in many swine farms in Iowa and other states. Although an infectious cause was suspected to account for the disease, no conclusive diagnosis had been reached with respect to conventional infectious agents. Extensive laboratory diagnostic investigation on suspect cases repeatedly resulted in the isolation of a cytopathic enveloped virus of 50-60nm in size from nervous and second lymphoid tissues and sera and, to reflect its unknown identity, named "Virus X". The presence of virus particle with morphological characteristics similar to Virus X in tissues from affected animals was also observed on thin-section positive-staining electron microscopy. Isolates of Virus X were not readily recognized by antibodies raised against any known viruses pathogenic to swine but by antisera collected from animals surviving clinical episode, indicating that Virus X is likely a previously unrecognized agent. Pregnant sows experimentally inoculated with Virus X (ISUYP604671) or homogenate (filtrate) of tissues from a clinically affected animal developed clinical signs and pathological changes similar to field observations including the loss of pregnancy. Furthermore, caesarian-derived, colostrum-deprived young pigs developed mild encephalomyelitis lesions in brains after experimental inoculation with the virus or the tissue homogenate although clinical neurologic signs were not observed. More importantly, Virus X was re-isolated from all inoculated animals while control pigs remained negative for the virus during the study. Collectively, Virus X is a novel viral agent responsible for PRNS and remains to be further characterized for taxonomical identity.

Background: The effect of pityriasis rosea (PR) on the outcome of pregnancy has not been previously reported., Objective: We sought to investigate the possible impact of PR in pregnant women., Methods: In all, 38 women who developed PR during pregnancy were observed. In one of them, who developed PR at 10 weeks' gestation and aborted 2 weeks later, plasma, peripheral blood mononuclear cells, maternal skin, and placental and embryonic tissues were studied by quantitative calibrated real-time polymerase chain reaction for human herpesviruses (HHV)-6 and -7. Controls included plasma from 36 healthy blood donors, plasma and paraffin-embedded tissue sections from 12 patients with other dermatitides, and from placental and embryonic tissues from one woman who presented with a 19-week intrauterine fetal death., Results: Of the 38 women, 9 had a premature delivery and 5 miscarried. In particular, 62% of the women who developed PR within 15 weeks' gestation aborted. Neonatal hypotonia, weak motility, and hyporeactivity were noted in 6 cases. In the patient studied in detail, HHV-6 DNA was detected in plasma, peripheral blood mononuclear cells, skin, and placenta and embryonic tissues, whereas HHV-7 DNA was absent. HHV-6 p41 antigen was detected by immunohistochemistry in skin lesions, placenta, and embryonic tissues. No herpesvirus DNA was detected in plasma and tissues from control subjects., Limitations: This is a case series study with a small number of patients., Conclusion: PR may be associated with an active HHV-6 infection. In pregnancy, PR may foreshadow premature delivery with neonatal hypotonia and even fetal demise especially if it develops within 15 weeks' gestation.

In Australia, as in other developed countries, approximately 40-50% of stillbirths are of unknown aetiology. Emerging evidence suggests stillbirths are often multifactorial. The absence of a known cause leads to uncertainty regarding the risk of recurrence, which can cause extreme anguish for parents that may manifest as guilt, anger or bewilderment. Further, clinical endeavours to prevent recurrences in future pregnancies are impaired by lack of a defined aetiology. Therefore, efforts to provide an aetiological diagnosis of stillbirth impact upon all aspects of care of the mother, and inform many parts of clinical decision making. Despite the magnitude of the problem, that is 7 stillbirths per 1000 births in Australia, diagnostic efforts to discover viral aetiologies are often minimal. Viruses and other difficult to culture organisms have been postulated as the aetiology of a number of obstetric and paediatric conditions of unknown cause, including stillbirth. Reasons forwarded for testing stillbirth cases for infectious agents are non-medical factors, including addressing all parents' need for diagnostic closure, identifying infectious agents as a sporadic cause of stillbirth to reassure parents and clinicians regarding risk for future pregnancies, and to reduce unnecessary testing. It is clear that viral agents including rubella, human cytomegalovirus (CMV), parvovirus B19, herpes simplex virus (HSV), lymphocytic choriomeningitis virus (LCMV), and varicella zoster virus (VZV) may cause intrauterine deaths. Evidence for many other agents is that minimal or asymptomatic infections also occur, so improved markers of adverse outcomes are needed. The role of other viruses and difficult-to-culture organisms in stillbirth is uncertain, and needs more research. However, testing stillborn babies for some viral agents remains a useful adjunct to histopathological and other examinations at autopsy. Modern molecular techniques such as multiplex PCR, allow searches for multiple agents. Now that such testing is available, it is important to assess the clinical usefulness of such testing.

Objective: To augment the understanding of parvovirus B19 infection in pregnancy with respect to maternal characteristics and their corresponding fetal outcomes., Study Design: Retrospective case-series of all women referred to Magee-Women&#95;s Hospital with serologically-documented parvovirus B19 infection during pregnancy from 1998-2001., Results: All 25 cases that are available for analysis occurred from January through June. The frequency of cases varied substantially from year to year, with 14 cases in 1998, 0 cases in 1999 and 2000, and 11 cases in 2001. In contrast to previous reports, the minority of women [4/25(16%)] experienced symptoms attributable to parvovirus B-19 infection although 3 of 25 (12%) fetuses developed hydrops fetalis and 4/25 (16%) suffered an intrauterine of fetal death., Conclusions: These findings suggest that parvovirus B19 infection in pregnancy follows seasonal and annual trend variation, may produce a lower frequency of maternal symptoms and a higher fetal loss rate than previously reported. Synopsis. Maternal parvovirus B19 infection follows seasonal and annual variation is often asymptomatic and may have higher fetal loss rates than previously reported. Continued surveillance is warranted.

Background: Haemophilus influenzae is a rare cause of intrauterine infection, with the potential to cause severe morbidity and mortality in the perinate., Case: An 18-year-old primigravida presented at 32 weeks' gestation with sudden-onset abdominal pain and abrupt cessation of fetal movements. Intrauterine fetal death was confirmed. At necropsy the fetus had multiorgan hemorrhage. H influenzae was cultured from the amniotic membranes and ear canal fluid. The mother was readmitted on postpartum day 2 with fever. Her blood cultures were also positive for H influenzae., Conclusion: H influenzae may cause ascending fetal infection and death and may cause maternal sepsis by fetomaternal transmission.

Objectives: The human cytomegalovirus (CMV) is universally distributed among human populations as one of the most common cause of congenital infection with an incidence of about 0.15-2.0% in developed countries. However, controversial data concerning intrauterine fetal death caused by CMV infection exist., Method: A case report., Results: In this case report we present a stillbirth in the 18th week of pregnancy, caused by a maternal serological and fetal histological congenital CMV infection., Conclusion: Every attending physician and obstetrician should be aware of the possibility of a primary or even recurrent congenital CMV infection that could be a reason for sudden unknown congenital fetal death.

Bovine viral diarrhea virus (BVDV) infections cause substantial economic losses to the cattle industries. Persistently infected (PI) cattle are the most important reservoir for BVDV. White-tailed deer (Odocoileus virginianus) are the most abundant species of wild ruminants in the United States and contact between cattle and deer is common. If the outcome of fetal infection of white-tailed deer is similar to cattle, PI white-tailed deer may pose a threat to BVDV control programs. The objective of this study was to determine if experimental infection of pregnant white-tailed deer with BVDV would result in the birth of PI offspring. Nine female and one male white-tailed deer were captured and housed at a captive deer isolation facility. After natural mating had occurred, all does were inoculated intranasally at approximately 50 days of pregnancy with 10(6) CCID(50) each of a BVDV 1 (BJ) and BVDV 2 (PA131) strain. Although no clinical signs of BVDV infection were observed or abortions detected, only one pregnancy advanced to term. On day 167 post-inoculation, one doe delivered a live fawn and a mummified fetus. The fawn was translocated to an isolation facility to be hand-raised. The fawn was determined to be PI with BVDV 2 by serial virus isolation from serum and white blood cells, immunohistochemistry on skin biopsy, and RT-PCR. This is the first report of persistent infection of white-tailed deer with BVDV. Further research is needed to assess the impact of PI white-tailed deer on BVDV control programs in cattle.

Eighteen pregnant sheep, six at 45 days gestation and twelve at 75 days gestation, were infected with foot-and-mouth disease virus (FMDV) type O UKG 34/2001. Two sheep from each gestational group were killed at 2, 4, and 7 days post-inoculation (dpi). Three sheep, pregnant for 75 days at infection, were killed at 17 and 18 dpi. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and virus isolation (VI) were used to detect viral RNA and infectious virus, respectively, in fetal tissues taken post mortem. Eleven fetuses were obtained from the six sheep inoculated at day 45 of gestation. Of these, two of three fetuses at 2 dpi had viral RNA detected by RT-PCR and virus was detected in one by VI. Viral RNA was detected in two of four fetuses at 4 dpi, while viral RNA and virus were detected in all four fetuses at 7 dpi. No gross abnormalities were evident in these fetuses. In the group inoculated at day 75 of gestation, viral RNA was detected in three of four fetuses at 4 dpi. Virus and viral RNA were detected in three of four fetuses at 7 dpi. Of the seven fetuses examined at 17 and 18 dpi, viral RNA was detected in five, and four of these had died in utero. Gross abnormalities including haemorrhage and oedema in a number of tissues were evident in many of the fetuses in this group, but no vesicular lesions were found. Viral RNA and virus were detected in the amniotic fluid associated with infected fetuses. This study is the first to demonstrate that FMDV may cause transplacental infection and fetal death.

Objective: To describe the pathological findings in stillborn piglets and fetuses delivered by sows naturally infected with Menangle virus, a recently recognised Paramyxovirus., Design: Observations of the gross and microscopic pathology of natural disease., Procedure: Postmortem examinations were performed on 49 stillborn piglets, 35 mummified or semi-mummified full-term fetuses and 6 aborted fetuses from 20 litters at a 2600-sow intensive piggery in New South Wales during an outbreak of reproductive disease from June to September 1997. Body weights, crown-rump lengths and gross pathological changes were recorded. Tissues, including brain and spinal cord, were processed for histopathological examination., Results: Litters with reduced numbers of live born piglets had mummified fetuses and stillborn piglets. Affected stillborn and aborted piglets frequently had arthrogryposis, craniofacial and spinal deformities, pulmonary hypoplasia and degeneration of the brain and spinal cord. Intranuclear and intracytoplasmic inclusion bodies were observed in neurones and other cells in the brain and spinal cord in association with extensive degeneration, necrosis, infiltration of macrophages and gliosis., Conclusions: In utero infection of piglets with Menangle virus is associated with severe skeletal and neurological malformations.

Varicella belongs to the most common vaccine-preventable diseases in Germany. During pregnancy, varicella may have serious consequences for the pregnant women and for the fetus or newborn. Pregnant women who contract varicella are at risk of pneumonia which must be regarded as a medical emergency. Chicken pox between the 5th and 24th weeks of pregnancy may lead to the congenital varicella syndrome. In case of maternal varicella during the last few weeks of pregnancy or shortly after delivery, the virus can cause chicken pox in the newborn. Life-threaten ing disseminated neonatal varicella must be expected if the mother develops chicken pox between 5 days before and 2 days after delivery. Using currently available diagnostics, immuno-prophylactic and therapeutic opportunities, these serious consequences of varicella during pregnancy can be prevented.

In this case report we describe a fatal intrauterine HSV-2 infection in a mother with insulin-dependent diabetes mellitus without signs, symptoms or serological evidence of infection with this virus during pregnancy. A normally developed infant was delivered by caesarean section and the course of the viral infection was rapid and fatal within the first d. Histopathology demonstrated disseminated intravascular coagulation in several organs. The diagnosis was confirmed by PCR amplifications of HSV-2 DNA from several organs of the child at autopsy and further supported by DNA sequencing of the viral amplicon derived from brain. Despite a significant IgG titre rise to a type-common HSV IgG antigen being seen in the mother, no IgG response to the HSV-2 type-specific glycoprotein G (gG) could be documented during long-term follow-up.

Parvovirus B19 is a significant human pathogen that causes a wide spectrum of clinical complications ranging from mild, self-limiting erythema infectiosum in immunocompetent children to lethal cytopenias in immunocompromised patients and intrauterine foetal death in primary infected pregnant women. The infection may also be persistent and can mimic or trigger autoimmune inflammatory disorders. Another important clinical aspect to consider is the risk of infection through B19-contaminated blood products. Recent advances in diagnosis and pathogenesis, new insights in the cellular immune response and newly discovered genotypes of human parvoviruses form a platform for the development of modern therapeutic and prophylactic alternatives.

This study demonstrated that a multivalent vaccine containing modified-live bovine herpesvirus type 1 (BHV-1) protected pregnant heifers and their fetuses against virulent BHV-1 challenge exposure at 365 days after vaccination. The percentage of abortions or fetal deaths caused by BHV-1 was significantly higher in control heifers (10 of 10 [100.0%]) than BHV-1-vaccinated heifers (three of 19 [15.8%]).

Vertical transmission of viruses is an important cause of morbidity in the fetus and neonate. Placental viral infection indicates risk of vertical transmission, but not always transmission to, or disease of the fetus. Specimens from mothers and babies from three groups-two prospective and one retrospective cohort-were tested for pathogens of teratogenic potential using multiplex PCR. Placental infection was present in 13% of the 105 samples collected. Assessment of the prospective cohorts showed cytomegalovirus (CMV) detected in 4% of placentae from unselected women, parvovirus B19 in 1% and Ureaplasma parvum in 1% of placentae. In a retrospective cohort of women at high risk of transmitting congenital infection due to seroconversion during pregnancy, miscarriage or stillbirth, CMV was detected in 64% and human herpes virus type 7 in 9% of placentae. Of 14 PCR-positive placentae, two were associated with the birth of a living symptomatic infant, two with stillbirth, one with miscarriage, and two with elective terminations of pregnancy. Directed laboratory assessment of women at high risk of transmitting congenital infection, on the basis of clinical or laboratory markers, is important for accurate diagnosis of adverse outcomes of pregnancy. However, routine screening for viruses in the placentae from women with a low-risk serological profile for transmitting congenital infection is unlikely to result in significant numbers of additional diagnoses and is confounded by inadequacy of current diagnostic methods. The major pathogen detected in all cases of placental infection associated with fetal death was human CMV.

Objectives: To study the association between Epstein-Barr virus (EBV) antibody status in early pregnancy and pregnancy outcomes including fetal death, length of gestation and fetal weight and length at birth., Design: Nested control study., Setting: Population based health registers., Population: The source population comprised 35,940 pregnant women. Cases were all (280) women with fetal death and a random sample of 940 women with a live born child., Method: Information on pregnancy outcome was obtained from the Norwegian Medical Birth Registry. Serum samples from the first trimester were tested for EBV antibodies. In women seronegative for EBV, further serum from late pregnancy was analysed to detect seroconversion. Main outcome measures Vital status, length of gestation, weight and length at birth., Results: There was no association between EBV antibody status and fetal death. Women with significant EBV reactivation had a significantly shorter duration of pregnancy, and associated lighter babies, compared with women without significant reactivation (stillborn: 176 vs 197 days, P=0.16, and live born: 271 vs 279 days, P=0.03, respectively)., Conclusion: Significant reactivation of EBV infection during pregnancy may influence pregnancy duration.

Background: The aim of this study was to assess the impact of maternal cytomegalovirus (CMV) antibody status in pregnancy on the risk of fetal death and of low birth weight., Methods: The study of fetal death risk was a nested case-control study. Cases were all women within a cohort of 35,940 pregnant women in Norway 1992--94, who experienced fetal death after 16th week of gestation (n=281). Controls were 957 randomly selected women with live born children. Both groups were identified through linkage to the Norwegian Medical Birth Registry. The risk of low birth weight was studied in the live born children., Results: Seventy-two percent (203/281) of the cases and 69% (662/957) of the controls had CMV immunoglobulin G (IgG) antibodies in the first trimester (P=0.3). 0.4% (1/281) of the cases and 0.7% (7/957) had CMV IgM antibodies in the first trimester (P=0.7). Among 322 initially CMV antibody-negative women, 11% (6/55) of the cases and 9% (24/267) of the controls had occurrence of CMV IgG and/or IgM antibodies (P=0.7) during pregnancy. Also, after control for maternal age, parity, and follow-up time, no association between CMV antibodies and fetal death was found. CMV antibody status was not associated with low birth weight., Conclusions: This study does not support a causal relation between CMV infection in pregnancy and fetal death or low birth weight.

Problem: Pediatric human immunodeficiency virus (HIV) infection is largely a result of transplacental transmission, and pregnancy perturbation is more frequent in HIV-infected women. Dysregulation of placental immunology may occur during HIV infection, possibly facilitating HIV vertical transfer and miscarriage. The (FIV)-infected cat is a useful small-animal model for HIV pathogenesis because the viruses share common biological and clinical features. Transplacental transmission is readily achieved experimentally, resulting in a high proportion of infected offspring and frequent reproductive failure., Method of Study: We are using this model to examine lentivirus-induced placental immunopathology to determine the role aberrant immunology plays in intrauterine transmission and pregnancy perturbation., Results: Kittens were cesarean delivered from FIV-B-2542-infected and control queens at week 8 gestation (1 week short of term), and placental and fetal specimens were collected. On average, control queens delivered 3.8 kittens/litter, and 1 of 31 kittens (3.2%) was non-viable. FIV-infected queens produced 2.7 kittens/litter with 15 of 25 fetuses (60%) non-viable. The virus was detected in 14 of 15 placentas (93%) and 21 of 22 fetuses (95%) using polymerase chain reaction (PCR). Using a one-step, real time reverse transcriptase (RT)-PCR, we measured expression of representative placental T helper 1 (Th1) cytokines, interleukin (IL)-1beta and interferon (IFN)-gamma, a Th2 cytokine, IL-10, and chemokine receptor CXCR4. A comparison of placental cytokine expression between infected and control queens did not reveal differences between the two groups. However, elevated expression of Th1 cytokines and increased Th1/Th2 ratios (IL-1beta/IL-10) occurred in placentas from resorptions, indicating that increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat., Conclusion: The potential to establish efficient FIV in utero transmission, coupled with the parallels in immunopathology between FIV-infected cats and HIV-infected humans, suggests the usefulness of the FIV-infected cat as a cost-effective, small-animal model to study lentivirus-induced immunopathology, transplacental infection, and reproductive failure.

In utero viral infections have been associated with an adverse pregnancy outcome and may have a causative role in the unexplained fetal death file. Parvovirus B19 and cytomegalovirus are among the most common pathogens implicated in fetal loss cases. Parvovirus B19 has been reported to account for cases of spontaneous abortions, intrauterine fetal death and nonimmune hydrops fetalis, whereas cytomegalovirus accounts for nonimmune hydrops fetalis, intrauterine growth retardation and congenital anomalies. This review aims to summarize the current literature in an attempt to underline the need for routine screening, close follow-up and prevention. A better understanding of the pathogenetic mechanisms of viral infections during the crucial time of organogenesis, along with early detection, may contribute to the reduction in stillbirth rate.

Objective: To determine whether cell-mediated immunity against porcine reproductive and respiratory syndrome (PRRS) virus is correlated with protection against reproductive failure in sows during clinical outbreaks of PRRS in commercial herds., Design: Outbreak investigation in 4 swine breeding herds., Animals: 97 sows., Procedures: On each farm, blood samples were collected from sows with clinical signs (abortion or increased fetal death; case sows) and from clinically normal sows (control sows). The intensity of the cell-mediated immune (CMI) response was determined by use of an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. Multiple logistic regression analyses and t tests were used to compare ELISPOT assay values between case and control sows. Multiple linear regression was used to investigate associations between cell-mediated immunity and the magnitude of clinical signs., Results: In 2 farms, case sows had lower ELISPOT assay values than control sows. A negative association between the intensity of the CMI response and the number of pigs born dead per litter was detected on 1 farm. In 1 farm, no association was detected between the intensity of the CMI response and protection against reproductive failure., Conclusions and Clinical Relevance: Evidence that a strong CMI response was correlated with protection against clinical PRRS was detected in 3 of 4 farms. However, farms and sows within farms varied considerably in their immune responsiveness and in the degree to which they were protected clinically. Increasing cell-mediated immunity within infected herds has the potential to decrease clinical reproductive disease, but only if the sources of intra- and interfarm variation in the intensity of cell-mediated immunity to PRRS virus can be identified.

Objective: We investigated gender-specific risks of mother-to-child transmission (MTCT) at birth and at 6 to 8 weeks among infants born to HIV-infected African women., Design: Follow-up study of infants enrolled in 2 randomized, phase III, clinical trials to prevent MTCT, conducted in Blantyre, Malawi, in southeast Africa., Methods: Infants were enrolled at birth and monitored postnatally, and their HIV status was assessed at birth and at 6 to 8 weeks (assessment beyond 6-8 weeks is ongoing). Statistical analyses were stratified according to gender, and comparisons were made with descriptive, univariate, and multivariate statistical tests. MTCT was estimated at birth and at 6 to 8 weeks among infants who were not infected at birth., Results: Overall, 966 boys and 998 girls were enrolled. The rate of HIV transmission at birth was 9.5% (187 of 1964 infants). However, at birth significantly more girls (12.6%) than boys (6.3%) were infected with HIV. This association remained significant after controlling for maternal viral load and other factors. Among infants who were uninfected at birth, 8.7% (135 of 1554 infants) acquired HIV by 6 to 8 weeks; of these infants, more girls acquired HIV (10.0%), compared with boys (7.4%)., Conclusions: Female infants may be more susceptible to HIV infection before birth and continuing after birth. Alternatively, in utero mortality rates of HIV-infected male infants may be disproportionately higher and thus more HIV-infected female infants are born. In areas of sub-Saharan Africa, where HIV infection rates are high among women of reproductive age, the magnitude of the gender transmission differences observed in this study could have clinical, preventive, and demographic implications.

A retrospective study of natural cases of abortion, recorded between October 2000 and September 2002, was made to determine the prevalence of abortions associated with porcine circovirus type 2 (PCV-2). The virus was detected by PCR, immunohistochemistry and in situ hybridisation. A total of 46 (13.1 per cent) of 350 aborted fetuses and stillborn piglets were positive for PCV-2 by PCR, and the virus was detected in fetuses at all stages of gestation. Viral antigen was detected in macrophages from the aborted fetuses and stillborn piglets by immunohistochemistry, and viral DNA was detected by in situ hybridisation.

The equine herpesvirus 1 (EHV-1) was isolated in Argentina from an aborted equine foetus in 1979. This virus (SPv) has special restriction patterns (RP) in comparison with other Argentine isolates. In addition, SPv could be distinguished on the basis of its pathogenicity in baby mice inoculated intracerebrally. We studied the growth properties of the SPv in cell culture and its effects in a mouse respiratory and abortion model. We observed that SPv did not modify its capacity to grow in cell culture with respect to reference HH1 strain. Nevertheless, we found significant differences between the titres of the two strains at 8-14 h post-infection (PI). In this work we demonstrated that SPv showed low virulence in female at different stages of gestation, consistently, with results found in the mouse respiratory model. We considered that this low virulence of SPv could be related to its RP because the RP of HH1 strain are similar to those of the HVS25A strain and both showed effect on pregnant mice. More specific studies about genomic alterations to the SPv are necessary for identifying, more clearly, if the intra-strain variations have relation with the low virulence in the mouse respiratory and abortion model.