[Fetal cytomegalovirus infection diagnosed on autopsy: a case report]. / Infection fœtale à cytomégalovirus de diagnostic autopsique: à propos d'un cas.

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.

Viral infections: contributions to late fetal death, stillbirth, and infant death.

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.

Pathogenesis of Korean type 1 (European genotype) porcine reproductive and respiratory syndrome virus in experimentally infected pregnant gilts.

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.

Selective uptake of influenza vaccine and pregnancy outcomes.

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.

Reproductive parameters following a PRRS outbreak where a whole-herd PRRS MLV vaccination strategy was instituted post-outbreak.

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.

Parvovirus B19 infection in the first trimester of pregnancy and risk of fetal loss: a population-based case-control study.

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 - diagnosis, management, and outcome.

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.

Seroprevalence of cytomegalovirus infection in pregnant women and associated role in obstetric complications: a preliminary study.

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.

Human cytomegalovirus infection is detected frequently in stillbirths and is associated with fetal thrombotic vasculopathy.

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.

Viral detection in hydrops fetalis, spontaneous abortion, and unexplained fetal death in utero.

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.

Pregnancy loss ascribable to parvovirus B19/erythrovirus is associated with a high prevalence of trisomy.

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%.

Impact of porcine epidemic diarrhea virus infection at different periods of pregnancy on subsequent reproductive performance in gilts and sows.

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.

Selection of method is crucial for the diagnosis of porcine circovirus type 2 associated reproductive failures.

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.

Maternal human parvovirus B19 infection and the risk of fetal death and low birthweight: a case-control study within 35 940 pregnant women.

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.