Intrauterine Herpes Simplex Virus Infection in a Monochorionic Twin Gestation.

Abstract

Herpes simplex virus (HSV) of the newborn affects 1 in 3200 [1] live births in the United States, and can be acquired by the intrauterine or intrapartum route, or postnatally. Intrauterine or congenital infection represents the rarest form (5% of cases) [2] and frequently has devastating consequences such as congenital brain malformation and severe neurocognitive impairment leading to fetal or neonatal death [3]. Here we present two cases of fatal intrauterine HSV infection in monochorionic twin infants. CASE A 21-year-old secundigravida mother with twin gestation of 26-4/7 weeks presented with spontaneous rupture of membranes of clear amniotic fluid 11 hours prior to delivery. She had negative prenatal laboratory studies for hepatitis B, syphilis, human immunodeficiency virus (HIV), and an unknown group B streptococcus status. Her sexually transmitted infection history included chlamydia trachomatis infection treated during early pregnancy and no history of HSV in herself or her sexual partner. A structural survey 1 week prior to delivery revealed severe hydrops and hydranencephaly in the first twin, and moderate hydrocephalus in the second twin. The mother was afebrile, well-appearing, and reported no history of recent illness or genital lesions before or during either of her pregnancies. Both mother and father refused HSV serologic testing. The first twin boy was delivered via cesarean section with Apgar scores of 1, 2, and 3, at 1, 5, and 10 minutes, respectively. The infant was apneic, unresponsive to resuscitation efforts, and died shortly after birth. On autopsy, gestation was shown to be monochorionic–monoamniotic, and the placenta had evidence of acute chorioamnionitis; however, it was not tested for the presence of HSV. The intracranial cavity was composed of hemorrhagic fluid and fragments of parenchymal tissue with extensive necrosis and chronic inflammation, consistent with meningoencephalitis, and the liver was calcified and necrotic. Viral immunostaining revealed the presence of HSV in the adrenal gland and brain parenchyma, and no virus was detected in the liver. No viral cultures were performed on autopsy tissue due to formalin fixation, and surface cultures for HSV were not performed. The second twin boy had Apgar scores of 5, 7, and 8 at 1, 5, and 10 minutes, respectively. He was immediately intubated for respiratory distress, received inotropes and intravenous fluids for hypotension, and was given ampicillin and gentamicin for presumed sepsis. At 5 hours of life, vesicular skin lesions on the neck were noted on physical examination (PE). PE was otherwise unremarkable. HSV studies were sent from the skin lesion (neck), mucosal surfaces (eyes, mouth, rectum), and cerebrospinal fluid (CSF), and empiric acyclovir 20 mg/kg every 8 hours was started. Initial white blood cell (WBC) count, platelet count, liver function, and serum electrolytes were normal. The CSF revealed 111 WBC/mm 3 with a lymphocytic predominance, 7600 red blood cells/mm 3 , protein 1245 mg/dL, and glucose 21 mg/dL. Blood and CSF bacterial cultures were sterile. Toxoplasma immunoglobulin M antibody, cytomegalovirus (CMV), and parvovirus B-19 polymerase chain reaction (PCR) yielded negative results. PCR was positive for HSV type 2 (HSV-2) and negative for HSV type l from all five tested sites.