Fetal infection: a pragmatic approach to recognition and management

Viruses and parasites can be transmitted from a pregnant woman to her fetus via the placenta and can affect development of the fetus. Maternal infection is often asymptomatic or mild. The implications for the fetus are dependent on gestation, stage of organogenesis, the presence of maternal immunity and the virus type. Fetal infections are a potentially preventable cause of perinatal morbidity and mortality. Prenatal diagnosis is often initiated due to exposure of mother to an infectious contact. Management involves confirmation of maternal infection and careful consideration of the risks and benefits of fetal diagnosis, fetal surveillance, intrauterine treatment and possibly termination of pregnancy. Empathic and effective counselling of the parents is crucial and a multidisciplinary approach is important for optimal care. This review uses cases of two fetal infections to highlight a pragmatic approach to prenatal diagnosis and management. There is also an overview of three other fetal infections which can potentially cause serious morbidity and mortality.     

Fetal infection: a pragmatic approach to recognition and management

Viruses and parasites can be transmitted from a pregnant woman to her fetus via the placenta and can affect development of the fetus. Maternal infection is often asymptomatic or mild. The implications for the fetus are dependent on gestation and the presence of maternal immunity. Fetal infections are a potentially preventable cause of perinatal mortality. Prenatal diagnosis is often initiated due to exposure of mother to an infectious contact. Management involves confirmation of maternal infection and careful consideration of the risks and benefits of fetal diagnosis, fetal surveillance, intrauterine treatment and possibly a termination of pregnancy. Empathic and effective counselling of the parents is crucial and a multidisciplinary approach is important for optimal care. This review uses cases of two fetal infections to highlight a pragmatic approach to prenatal diagnosis and management. There is also an overview of three other fetal infections which can potentially cause serious morbidity and mortality.     

Detection of cytomegalovirus,herpes virus simplex,and parvovirus b19 in spontaneous abortion placentas

Objective: This study aims to investigate the presence of Cytomegalovirus (CMV), herpes virus simplex (HSV), and parvovirus B19 (PVB19) in the placental tissue of patients who underwent abortions without an otherwise-defined aetiology.

Study design: This cross-sectional study was conducted in a high-risk obstetric maternity facility at a University Hospital in Belo Horizonte, Brazil, from January 2013 to December 2015. We included placenta samples obtained from spontaneous abortions of unknown aetiology. Seventy placenta samples were identified and were classified according to histopathological characteristics. All samples were analysed using immunohistochemistry and polymerase chain reaction for CMV, PVB19, and HSV. The clinical variables were collected from the medical records of patients to verify the association of infection with villitis. The patients were divided into the following groups: I) with villitis (n?=?28) and II) without villitis (n?=?42).

Methods: Immunohistochemistry used monoclonal anti-CMV antibody (NCL-CMVpp65, Leica Biosystems, Wetzlar, Germany), anti-PVB19 antibody (NCL-PARVO, Leica Biosystems, Wetzlar, Germany), and anti-HSV1/HSV2 antibodies (NCL-HSV-1 and HSV2, Leica Biosystems, Wetzlar, Germany). The data were analysed using the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL) 19.0.

Results: Viral agents were detected in five patients (7.14%) in the villitis group. Three patients were positive for CMV, one for PVB19, and one for HSV type 2. Foetal and maternal complications were significantly higher in the group with villitis compared with those in the group without villitis (p?=?.002).

Conclusions: The prevalence of transplacental viral infections as a cause of spontaneous abortion should be considered high in the placenta with villitis. Thus, this study highlights the need for developing diagnostic tests to clarify the aetiology of abortion and foetal loss.     

Cytomegalovirus infection in infants admitted to a neonatal intensive care unit

Abstract

Objectives: To determine the incidence of congenital cytomegalovirus (CMV) infection and the frequency of postnatal infection in a neonatal intensive care unit (NICU).

Methods: Urine samples of 135 infants who were admitted to the NICU during a 6 month period were evaluated to detect CMV using a nested PCR assay. A breast milk sample was obtained to determine viral excretion. Clinical characteristics of infected and non-infected infants were compared.

Results: Congenital CMV infection was confirmed in two (1.48%) infants. Post-natal infection was documented in four of 36 (11.1%) infants that were evaluated. CMV excretion was detected in 43 of 116 mothers. Gestational age of infants born to mothers who excreted CMV was shorter than that of infants of mothers with negative results (33.1 versus 34.2 weeks; p?=?0.07).

Conclusions: CMV excretion in breast milk is frequent and is associated to congenital and postnatal infection. Further studies are necessary to assess the impact of CMV infection during pregnancy and neonatal outcomes.     

Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies

OBJECTIVE: To study the outcome of 20 twin pregnancies with evidence of primary or recurrent cytomegalovirus (CMV) infection during pregnancy. DESIGN: Observational study. SETTING: Two tertiary perinatal departments in Israel. POPULATION: Twenty women with twin pregnancies who were referred because of serologic investigation indicating CMV infection. Seventeen women had evidence of primary CMV infection, and three women appeared to have recurrent CMV infection. METHODS: Prenatal diagnosis was made by amniocentesis of both sacs after 21 weeks of gestation. CMV isolation was performed by culture on fibroblasts, shell vial technique and polymerase chain reaction (PCR) amplification of CMV DNA. After birth, the neonatal urine and saliva were cultured for CMV. MAIN OUTCOME MEASURES: Intrauterine CMV infection defined as positive PCR at amniotic fluid analysis and congenital CMV infection defined as positive CMV cultures after birth. RESULTS: Except for one, all women underwent amniocentesis of both gestational sacs. In 14 (70%) women, no evidence of vertical transmission to any of the 28 fetuses was found and none of the newborns had evidence of congenital CMV infection. Intrauterine infection was detected by amniocentesis in five women and by ultrasound findings with positive maternal serology in one. In three women, CMV was detected in only one amniotic sac. In five of our six total cases, both twins were found to have congenital CMV infection at birth, all of whom had dichorionic-diamniotic placentation, three fused and two separate. CONCLUSIONS: In twin gestations, as in singletons, intrauterine and congenital CMV infection occurs in about 30% of women with primary or recurrent infection. The placenta type did not predict if one or both twins would be infected. Our data do not exclude the possibility that intrauterine transmission of the virus from one fetus to the other can occur.     

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.     

Management of an obstetric health care provider with acute parvovirus B19 infection

We report a case of an obstetrician with acute parvovirus B19 infection and the series of exposed pregnant women. Currently, there are no established guidelines regarding management of an obstetric health care provider with acute parvovirus B19 infection. We propose a management scheme of this clinical scenario.     

Fetal manifestations and poor outcomes of congenital cytomegalovirus infections: possible candidates for intrauterine antiviral treatments

AIM: This retrospective study was performed to reveal the natural history of cytomegalovirus (CMV) infected fetuses during the perinatal period and to find prenatal findings associated with poor outcomes. METHODS: 33 neonates with CMV infection, born after 30 weeks of gestation, were registered from a total of 12 414 infants between 1995 and 2003. Maternal and neonatal medical records were reviewed regarding fetal growth; abdominal signs including ascites and hepatosplenomegaly; cerebral signs including ventriculomegaly, microcephaly, and calcification; and fetal heart rate monitoring, for signs which may have been detected by the standard obstetric ultrasonography. Univariate and multivariate analyses were performed to test for any associations between these manifestations and poor outcomes such as death and neurological damages. RESULTS: Among the 33 infants, 6 died, 10 developed neurological damage including cerebral palsy (n = 8), epilepsy (n = 5), and hearing difficulties (n = 5), and the remaining 17 were normal. After adjusting for ganciclovir treatment and gender, death was 40-fold more likely associated with infants having abdominal signs (OR 40, 95%CI 4.6-930) than those without abdominal signs. Similarly, poor outcomes (death or neurological damage) were more likely associated with infants having either abdominal or cerebral signs (OR 39, 95%CI 3.8-1323). Fetal growth restriction and non-reassuring fetal heart rate patterns were not significantly associated with poor outcomes. CONCLUSION: The absence of abdominal signs guarantees the infant's survival. The presence of abdominal or cerebral signs is associated with poor outcomes, suggesting that these fetuses are possible candidates to receive in-utero therapy of congenital CMV infection.     

Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature

Objective: Rubella virus infection during the first trimester of pregnancy can cause congenital rubella syndrome (CRS). We aimed to describe the abnormalities in order to define the ultrasound features to look for when performing prenatal scans. The goal of this review is to focus specifically on the signs of CRS accessible to prenatal diagnosis.

Methods: We analyzed every case of CRS described before and/or after birth that we identified in the Pubmed database and classified them as accessible or not to prenatal diagnosis.

Results: The most frequently reported malformations accessible to prenatal diagnosis were: cardiac septal defects, pulmonary artery stenosis, microcephaly, cataract, microphtalmia, and hepatosplenomegaly.

Conclusion: This extensive literature review shows that the ultrasound features of CRS are not well known, even though rubella was the first teratogenic virus described. This review will help clinicians in the management of rubella during pregnancy by clarifying the findings to be sought.     

Diagnosis of fetal parvovirus B19 infection: value of virological assays in fetal specimens

Objective  The purpose of our work was to examine the most reliable laboratory diagnosis of fetal parvovirus B19 infection in hydropic fetuses by evaluating the most appropriate clinical sample and laboratory test.
Design  B19 DNA detection in fetal samples and serological signs of B19 infection in the respective mothers. Samples collected between January 2000 and July 2008.
Setting  Microbiology, University of Bologna, Bologna, Italy.
Samples One hundred thirty-five fetal samples (58 fetal cord blood and 77 amniotic fluid samples) and 109 serum samples collected from 109 pregnant women.
Methods  Validated and certified in situ hybridisation assay (ISH) and polymerase chain reaction–enzyme-linked immunosorbent assay (PCR-ELISA) were performed on fetal samples to detect B19 DNA. B19-specific antibodies were investigated in maternal serum samples by a commercial enzyme immunoassay.
Main outcome measures  Parvovirus B19 DNA detection in fetal specimens was analysed in relation to maternal serological signs of infection.
Results  Parvovirus B19 DNA was detected in 22.41% of fetal cord blood and 36.36% of amniotic fluid samples. A statistically significant difference was found between DNA detection by ISH (23.70%) and PCR-ELISA (14.81%) ( P = 0.004). Only 11.76% of fetuses with virological diagnosis of B19 infection were from women with serological signs of acute/recent B19 infection.
Conclusions  Diagnosis of fetal parvovirus B19 infection cannot always rely on maternal serological investigations but rather on the virological analysis of fetal samples. Both fetal cord blood and amniotic fluid samples are suitable for diagnosis, but the detection of B19 DNA in the cells of amniotic fluid samples by ISH proved to be the most reliable diagnostic system.     

Anti-viral therapy for congenital cytomegalovirus infection: pharmacokinetics,efficacy and side effects

Congenital cytomegalovirus (CMV) infection is the most common congenital infection in the world with approximately 0.5–2% of all live born infants, and can cause early or late severe neurological and neurisensorial damage. Although no drug has been licensed for therapy of congenital CMV infection, ganciclovir (GCV) and its oral pro-drug, valganciclovir (val-GCV), is increasingly being administrated to symptomatic infants, to improve neurodevelopmental and auditory outcome. Other potentially efficacious for therapy of congenital CMV disease are foscarnet and cidofovir, which have only been administered in few cases. A literature search was performed to look for evidence based or scientific articles evaluating pharmacokinetics, efficacy, and side effects of GCV/val-GCVand the other two anti-viral drugs.     

妊娠合并乙型肝炎病毒感染围分娩期管理

对乙型肝炎(乙肝)病毒感染孕妇采取合理的围分娩期管理以阻断母婴垂直传播是降低我国慢性乙肝感染率的关键。新生儿出生后及时注射乙肝免疫球蛋白,并按照0、1、6方案接种乙肝疫苗,可有效阻断乙肝的围分娩期传播。孕妇在晚孕期进行抗病毒治疗可能通过降低母体病毒水平而减少围分娩期传播风险,但抗病毒药物对胎儿的安全性仍需进一步验证。     

Prenatal diagnosis and management of a ranula

A ranula is a mucous extravasation cyst which appears as a swelling in the submental and submandibular regions. We describe a case of congenital ranula or retention salivary cyst diagnosed at 22 weeks' gestation. The fetal growth was normal, as was the amniotic fluid volume. Follow-up ultrasound scans revealed no changes in the size or the position of the cyst. Surgical treatment was performed two days after the delivery. There were no complications and no recurrences have occurred to date.     

孕期TORCH感染产前筛查、诊断和临床咨询

弓形虫、风疹病毒、巨细胞病毒及疱疹病毒是最常见的引起孕妇感染的病原体,可经胎盘垂直传播导致胎儿宫内感染,最终造成胎儿及新生儿结构的畸形及神经系统的损伤。尽管目前可以对上述先天性感染进行产前筛查和诊断,但尚缺乏统一的临床咨询及诊治指南。文章主要对近年来在上述先天性感染产前筛查、诊断和临床咨询领域的最新进展进行阐述。