An appropriate-for-gestational-age boy is born at 38 and 5/7 weeks to a 33-year-old gravida 2 now para 2 mother by vacuum-assisted vaginal delivery. The results of all antenatal maternal testing are within normal limits, including group B Streptococcus, and she denies a history of herpes simplex virus (HSV) infection. The length of time between rupture of membranes and delivery is 13 hours and 22 minutes. The delivery is complicated by maternal preeclampsia requiring magnesium therapy, and the neonate has Apgar scores of 7 and 8 at 1 and 5 minutes, respectively. His weight is 3,130 g (35th percentile), length is 50.5 cm (59th percentile), and head circumference is 36.5 cm (93rd percentile). The neonate receives vitamin K, hepatitis B vaccination, and ophthalmic erythromycin ointment after delivery. At birth there is a documented caput succedaneum, but no cephalohematoma, scalp bruising, or other signs of trauma. His anterior fontanelle is soft and flat, and there are no abnormalities found on cardiac, pulmonary, neurologic, or skin examination. There are no abdominal masses or hepatosplenomegaly. Vital signs remain within normal limits throughout the hospital stay. Infant blood typing is not completed at birth because the mother is AB+ and direct antiglobulin testing negative. His bilirubin level is 10.5 mg/dL (179.59 µmol/L) at 42 hours of life, which is high intermediate risk for hyperbilirubinemia but below the treatment threshold of 14.5 mg/dL (248.01 µmol/L). Before discharge, the infant’s weight is down 8% from birthweight and head circumference is 35 cm (67th percentile), with resolution of caput succedaneum. The neonate is discharged 48 hours after birth.Four days after birth the neonate presents to the pediatric clinic for follow-up and has an axillary temperature of 103.6°F (39.8°C). The neonate is noted to be wrapped appropriately in a onesie, the mother is afebrile, and the room is not abnormally warm. After unwrapping the neonate, a repeated axillary temperature is 102.1°F (38.9°C). The infant’s heart rate is 190 beats/min, respiratory rate is 44 breaths/min, and oxygen saturation is 99% on room air. The infant’s weight is 2,718 g, down 13% from birthweight. Length and head circumference are not measured during the visit. The mother denies feeding difficulties, fussiness, or lethargy. The patient is breastfeeding for 10 to 30 minutes on each breast every 2.5 to 3 hours. He is making greater than 2 meconium stools per day. Physical examination shows a well-appearing infant with jaundice to the lower extremities. His anterior fontanelle is soft and flat, and there are no other abnormalities noted on cardiac, pulmonary, abdominal, skin, or neurologic examination. The infant is admitted to the pediatric service for evaluation of neonatal fever. The complete blood cell count shows a white blood cell count of 15,880/µL (15.88 × 109/L) (reference range, 900–3,400/µL [9–34 × 109/L]), hemoglobin level of 17.0 g/dL (170 g/L) (reference range, 14.5–18.5 g/dL [145–185 g/L]), platelet count of 314 × 103/µL (314 × 109/L) (reference range, 180–327 × 103/µL [180–327 × 109/L]), red blood cell count of 4.82 × 106/µL (4.82 × 1012/L) (reference range, 3.9–5.5 × 106/µL [3.9–5.5 × 1012/L]), and a normal manual differential cell count. The reticulocyte count is 2.68% (reference range, 1.8%–4.6%). Urinalysis, C-reactive protein level, and coagulation studies are within normal limits. The cerebrospinal fluid (CSF) is grossly bloody, with a white blood cell count greater than 999/µL (>1 × 109/L) and a red blood cell count greater than 0.34 × 106/µL (>0.34 × 1012/L). The total bilirubin level is 22.2 mg/dL (379.71 µmol/L), with a direct bilirubin level of 0.9 mg/dL (15.39 µmol/L), after which the infant is transferred to the NICU for possible exchange transfusion. A type and screen is obtained, and his blood type is A+ and direct antiglobulin test results are negative. The infant is started on ampicillin, gentamicin, and acyclovir. Intravenous fluids containing 10% dextrose are started on admission and are weaned off by hospital day 3, after adequate weight gain with breastfeeding is demonstrated. Antimicrobial therapy is discontinued once the results of the blood culture, urine culture, CSF culture, and CSF meningitis/encephalitis panel by polymerase chain reaction are negative. The first newborn screen is also negative. Additional imaging is obtained and reveals the diagnosis.Because fever in an infant younger than 28 days is concerning for serious bacterial infections, the standard of care includes blood, urine, and CSF cultures as well as admission for antibiotic therapy. In infants younger than 90 days, viral infections can be a significant cause of fever, and some evidence suggests that serious bacterial infection is less common in infants with identified viral syndromes compared with those without identified viral syndromes. Thus, additional viral testing can be helpful in this population. HSV should be considered in neonates with pleocytosis on CSF analysis, increased transaminase levels, seizures, or skin lesions. HSV-2 accounts for most neonatal HSV infections, with 85% of these being acquired during delivery and the remainder being acquired in the postpartum period. (1)Head ultrasonography is performed and shows bilateral grade 3 intraventricular hemorrhage (IVH).IVH is more common in preterm infants compared with term infants due to the fragility of the highly vascularized germinal matrix, which involutes by 36 to 37 weeks of gestation. (2) IVH is a rare form of intracranial hemorrhage (ICH) in term infants and has an estimated incidence of 0.2%. (3) However, the overall incidence of ICH in term infants is difficult to estimate because it is often asymptomatic. The incidence of asymptomatic ICH in term infants has been reported to be 26% to 46%, with subdural hemorrhage being the most common form of ICH. (4)(5) In symptomatic infants, the incidence of ICH has been estimated to be 4.9 in 10,000. (6) Mode of delivery may play a role in ICH incidence, as the highest incidence was associated with forceps use (1 in 664), followed by vacuum extraction (1 in 860), spontaneous vaginal delivery (1 in 1,900), and cesarean delivery without labor (1 in 2,750). (7)In adults, fever occurs in up to 40% of patients after ICH and is associated with poor outcomes. The cause of fever in adults is uncertain and has been linked to infection, stroke, or damage to the hypothalamus. (8) In neonates, the relationship between ICH and fever is not well-described. A prospective study found that of 153 term infants admitted for neonatal fever between 2003 and 2004 without evidence of infection, 11 (7.2%) had ICH. This study also evaluated 28 infants who developed ICH within the first week after birth and found that 11 (39.3%) developed fever within the first 4 days after birth. (9) Other studies have found fever to be a less common presenting feature of ICH. A retrospective review of 24 term neonates admitted to the NICU with ICH reported that the most common presenting symptom was seizure (46%), followed by cyanosis (29%), tachypnea (21%), and fever, hypothermia, and poor feeding (4% each). (10) A cross-sectional study of 30 term infants with IVH found that 3 had a presenting sign of fever. However, this study also found that 50% of infants had coagulopathy. (11) The presented case is unique in that the infant had no signs or symptoms other than fever and hyperbilirubinemia to point toward ICH as the diagnosis.A few mechanisms have been proposed to explain how ICH causes fever. Hemoglobin has been shown to convert arachidonic acid to prostaglandin E2 (PGE2) and prostaglandin F2α, (12) which are known factors in fever production. When hemoglobin is injected into the subarachnoid space of live rabbits, the CSF concentration of PGE2 increases and causes a linear increase in rectal temperature. (13) In addition, interleukin-6 has been shown to be a factor in fever production independent of PGE2, (14) and increased levels of interleukin-6 have been reported in CSF samples of patients with subarachnoid hemorrhage. (15)Currently, no studies have investigated hyperbilirubinemia as an independent cause of fever. In this case, hyperbilirubinemia is likely due to intraventricular red blood cell lysis. The lysis of red blood cells within IVH has also been thought to contribute to its progression to obstructive hydrocephalus. Up to 55% of patients with IVH progress to hydrocephalus, (16) making serial head circumference measurements crucial during follow-up.The infant defervesced within 9 hours of admission. A dilated ophthalmologic examination revealed no retinal or vitreous hemorrhage. He was discharged after 5 days of intensive phototherapy, without the need for an exchange transfusion. He is followed closely in the pediatric clinic after discharge for serial head circumference measurements. Approximately 2 weeks after discharge he is found to have a rapid increase in head circumference from the 56th to the 85th percentile. Repeated head ultrasonography shows resolved IVH but enlarged lateral and third ventricles concerning for obstructive hydrocephalus. The infant is admitted for ventriculoperitoneal shunt placement.Intracranial hemorrhage in term infants is often asymptomatic, making a high index of suspicion necessary for its timely diagnosis.In term infants presenting with isolated fever without other signs of infection, investigation of intracranial hemorrhage may be warranted in addition to antibiotic and antiviral therapy.Patients with intraventricular hemorrhage should be followed with serial head circumference measurements to evaluate for hydrocephalus.