Diagnosis of Neonatal Herpes Simplex Infection from the Placenta

Abstract

Due to a high rate of fetal demise and premature birth in intrauterine HSV infection, the outcome in neonates is usually adverse. A female preterm infant with a gestational age of 25 1/7 weeks with expected early clinical course tested positive for neonatal herpes simplex virus (HSV) 2 after the neonatologist was informed of positive immunohistochemistry for the virus on the fifth day of life by the pathologist. Pathological examination of the placenta had revealed subacute necrotizing inflammation with stromal cell necrosis suggestive of intrauterine infection, possibly ascending due to prolonged rupture of membranes. To the best of our knowledge, this is the first case wherein placental pathology indicated exposure to HSV in utero before the infant presented with signs or symptoms of neonatal HSV resulting in a favorable outcome for the infant. Due to the variability of presentation of intrauterine HSV infection, pathological examination of the placenta in the first 2–5 days of life in premature infants can provide clues to the diagnosis of neonatal HSV which may significantly impact the outcome.

Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model

“…Indeed, unlike gd7.5 where HSV-2 infection of implantation sites resulted in relatively little histopathology, by gd12.5, we saw gross histological pathologies including leukocyte infiltration, hemorrhage, edema, and necrosis in the placenta. Importantly, these same findings, particularly cell necrosis, have been reported in the placenta of a neonate diagnosed with intrauterine HSV infection [60]. Thus, our model appears to recapitulate the clinical effects of HSV-2 infection on placental tissues.…”

Congenital Herpes Simplex Virus: A Histopathological View of the Placenta

“…The teratogenic effect of HSV on an embryo may provoke a variety of clinical outcomes, namely, ventriculomegaly, microcephaly, intracerebral calcifications, limb dysplasia [1], eye defects [4], and fetal loss [11,14]. As previously reported, primary infection in late pregnancy increases the risk of vertical transmission [13].…”

“…HSV could be transmitted to the fetus through the transplacental or the ascending route of acquisition from the vagina or cervix, even when the amniotic membranes remain intact [10,11]. Despite that, the intrapartum transmission of HSV through contact with a virus-shedding lesion in the genital tract tends to be the most commonly detected transmission route [12].…”

“…During pregnancy, most of the infected women are asymptomatic or present with nonspecific symptoms. The absence of clinical characteristics could result in a late diagnosis of congenital or neonatal HSV infection, increasing both morbidity and mortality [11,17]. The placenta may be macroscopically normal [19], and its histopathological manifestations may be nonspecific for the HSV infection.…”

Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives

“…Identification of HSV within the placenta is relatively uncommon, with a large study identifying a total of 64 cases between 1963 and 2009, supporting the rarity of intrauterine infection [ 139 ]. Histological manifestations of a placental HSV infection can include subacute necrotizing inflammation with stromal cell necrosis involving the umbilical cord and fetal surface/chorionic plate ( Figure 5 D) [ 140 ]. Additional investigation has described chronic chorioamnionitis with degradation of the amniotic lining, chorionic villi that are appropriate for gestational age, delayed villous maturation, and a HSV Cowdry type B intranuclear inclusion within subamniotic tissue [ 141 ].…”