Stillbirth following severe symmetric fetal growth restriction due to reactivation of Epstein–Barr virus infection in pregnancy

Tomai, Xuan-Hong

doi:10.1111/j.1447-0756.2011.01662.x

Cited by 64 publications

(4 citation statements)

References 16 publications

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“…Haeri et al who investigated the prevalence of EBV seropositivity in 64 healthy pregnant women [ 36 ], demonstrated that 22 (35%) women showed EBV reactivation during pregnancy, regardless of maternal age, race, parity, or insurance type [ 36 ]. Moreover, previous reports have clarified that EBV reactivation during pregnancy lead to poor obstetrical outcomes, such as fetal growth restriction [ 37 ], shorter pregnancy duration [ 38 ], and lower birth weight [ 38 ], despite not showing any symptoms. Thus, we recommend transabdominal ultrasound and/or nonstress tests to determine the presence of these complications.…”

Section: Discussionmentioning

confidence: 99%

Chronic active Epstein–Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report

Takahashi

Makino

Iizuka

et al. 2021

BMC Pregnancy Childbirth

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Background Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare and fatal disease characterized by uncontrolled immune cell activation that can lead to a cytokine storm. Unfortunately, this condition can occur even during pregnancy, threatening both maternal and fetal lives. Case presentation A 23-year-old nulliparous woman at 26 weeks of gestation presented with continuous fever, coughing, and sore throat. Upon arrival at our hospital, her temperature was >38°C and laboratory findings indicated cytopenia (neutrophil count, 779/μL; hemoglobin level, 10.2 g/dL; platelet count, 29,000/μL), elevated ferritin level (1,308 ng/mL), and elevated soluble interleukin-2 receptor level (11,200 U/mL). Computed tomography showed marked splenomegaly. Bone marrow examination revealed hemophagocytosis, and blood examination showed a plasma Epstein–Barr virus (EBV) DNA level of 8.9 × 105 copies/μg. The monoclonal proliferation of EBV-infected T cells was confirmed by Southern blotting, and the patient was diagnosed with chronic active EBV-associated sHLH and T-cell lymphoproliferative disease. Immediately after admission, the patient’s condition suddenly deteriorated. She developed shock and disseminated intravascular coagulation, requiring endotracheal intubation along with methylprednisolone pulse and etoposide therapy. Although the patient recovered, she delivered a stillborn baby. After delivery, she was treated with reduced-dose dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) and steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapies. Five months after diagnosis, she received human leukocyte antigen-haploidentical allogeneic bone marrow transplantation from her sister. She remains in remission for 5 months from the time of transplantation to the present. Conclusions sHLH, which may cause maternal and fetal death, should be carefully considered in critically ill pregnant women, particularly those presenting with continuous fever and cytopenia.

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Section: Discussionmentioning

confidence: 99%

Chronic active Epstein–Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report

Takahashi

Makino

Iizuka

et al. 2021

BMC Pregnancy Childbirth

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“…Our results, together with that of previous study18, indicated that prenatal depression was associated with maternal EBV reactivation. In view of the link between EBV reactivation during pregnancy and adverse offspring development234, it is plausible that prenatal psychosocial stress may promote maternal latent EBV reactivation, which increases the risk of fetal exposure to the virus, and contributes to adverse offspring development. However, EBV reactivation during pregnancy was also considered as a non-causal marker of impaired cellmediated immune function, which could contribute to adverse perinatal health outcomes27.…”

Section: Discussionmentioning

confidence: 99%

“…Like other herpes viruses, EBV has the ability to remain latent in the body and becomes reactivated at a later time. It has been reported that maternal EBV reactivation in pregnancy is related to the adverse offspring development including severe symmetrical fetal growth restriction, lower birthweight, and leukemia234.…”

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confidence: 99%

Maternal depressive symptoms related to Epstein-Barr virus reactivation in late pregnancy

Zhu

Chen

Hao

et al. 2013

Sci Rep

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We examined the relationship between maternal depressive symptoms in late pregnancy and Epstein-Barr virus reactivation before delivery. In this prospective observational study, prevalence of Epstein-Barr virus reactivation within one week before delivery was compared between 163 pregnant women with depressive symptoms at 33 to 34 weeks of gestation and a computer-generated control group of 163 pregnant healthy women without depressive symptoms. Depressive symptoms at 33 to 34 weeks of gestation were significantly related to the prevalence of Epstein-Barr virus reactivation before delivery after adjustment for potential confounders (adjusted OR52.74, 95%CI: 1.23-6.08). Compared to that in the control group, the prevalence of Epstein-Barr virus reactivation was higher in women with depressive symptoms accompanied by higher negative coping (24.2% compared with 7.9%; adjusted OR53.67, 95%CI: 1.47-9.16). Maternal depressive symptoms in late pregnancy are associated with Epstein-Barr virus reactivation, and this association could be moderated by maternal coping style.E pstein-Barr virus (EBV) is a member of the herpesvirus family, and about 90% of women have serologic evidence of previous infection 1 . Like other herpes viruses, EBV has the ability to remain latent in the body and becomes reactivated at a later time. It has been reported that maternal EBV reactivation in pregnancy is related to the adverse offspring development including severe symmetrical fetal growth restriction, lower birthweight, and leukemia 2-4 .Maternal depression is a mood disorder that begins before or immediately after childbirth. Between 12.7% and 23% of pregnant women will experience a depressive disorder 5,6 . Epidemiological evidence demonstrates that elevated levels of depressive symptoms in mothers are related to the adverse offspring development, such as lower birth weight, small for gestational age and child maladjustment 7-9 . However, the possible mechanisms underlying the association between maternal depression and adverse offspring development remain unclear. Results from animal studies suggested that maternal stress might negatively influence offspring outcomes through a process known as fetal programming 10 . Prenatal stress can lead to increased fetal exposure to glucocorticoids, which could permanently alter the HPA function of the offspring 11,12 . But the evidence from human studies about fetal programming is limited and inconsistent yet [13][14][15][16][17] .Recently, Haeri et al found that women with depression had higher prevalence of EBV reactivation 18 . Their research seems to suggest a potential novel viral model which may elucidate biological pathways underlying how maternal psychosocial stress impacts fetal development. However, this result hasn't been repeated in heterogeneous pregnant women populations. Thus, it would be helpful to support this hypothesis by adding evidence about the relationship between prenatal psychosocial stress and EBV reactivation in pregnant women during different stages of gestation from...

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“…Identification and characteristics of the EBV infection in the placenta has been elusive. A few papers argued that the EBV infection is associated with various pathologic conditions during pregnancy, including depression, preeclampsia, and stillbirth ( 7 8 9 ). These findings are mostly thought to be associated with EBV infection of the B lymphocytes; confirmed by polymerase chain reaction (PCR) or serological tests with blood samples which do not involve histopathological information.…”

Section: Introductionmentioning

confidence: 99%

Identification of Epstein-Barr Virus in the Human Placenta and Its Pathologic Characteristics

Kim

Park

et al. 2017

J Korean Med Sci

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Epstein-Barr virus (EBV), a common pathogen in humans, is suspected as the cause of multiple pregnancy-related pathologies including depression, preeclampsia, and stillbirth. Moreover, transmission of EBV through the placenta has been reported. However, the focus of EBV infection within the placenta has remained unknown to date. In this study, we proved the expression of latent EBV genes in the endometrial glandular epithelial cells of the placenta and investigated the cytological characteristics of these cells. Sixty-eight placentas were obtained from pregnant women. Tissue microarray was constructed. EBV latent genes including EBV-encoding RNA-1 (EBER1), Epstein-Barr virus nuclear antigen 1 (EBNA1), late membrane antigen (LMP1), and RPMS1 were detected with silver in situ hybridization and/or mRNA in situ hybridization. Nuclear features of EBV-positive cells in EBV-infected placenta were compared with those of EBV-negative cells via image analysis. Sixteen placentas (23.5%) showed positive expression of all 4 EBV latent genes; only the glandular epithelial cells of the decidua showed EBV gene expression. EBV infection status was not significantly correlated with maternal, fetal, or placental factors. The nuclei of EBV-positive cells were significantly larger, longer, and round-shaped than those of EBV-negative cells regardless of EBV-infection status of the placenta. For the first time, evidence of EBV gene expression has been shown in placental tissues. Furthermore, we have characterized its cytological features, allowing screening of EBV infection through microscopic examination.

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Stillbirth following severe symmetric fetal growth restriction due to reactivation of Epstein–Barr virus infection in pregnancy

Cited by 64 publications

References 16 publications

Chronic active Epstein–Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report

Chronic active Epstein–Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report

Maternal depressive symptoms related to Epstein-Barr virus reactivation in late pregnancy

Identification of Epstein-Barr Virus in the Human Placenta and Its Pathologic Characteristics

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