Perinatal/Neonatal Case Presentation Nonimmune Hydrops Fetalis and Fulminant Fatal Disease Due to Congenital Cytomegalovirus Infection in a Premature Infant Venkatesh Sampath, MD Vivek Narendran, MD Edward F. Donovan, MD Jerzy Stanek, MD, PhD Mark R. Schleiss, MD We report a case of fatal congenital cytomegalovirus (CMV) disease in a 695 gm, 29 weeks estimated gestational age premature infant. The newborn presented with hydrops fetalis, an unusual presentation of congenital CMV infection. In spite of ganciclovir therapy, the infant succumbed to his illness. Autopsy findings revealed the presence of widespread CMV disease, including pneumonitis, enteritis, and myocarditis. Congenital CMV infection should be considered in the differential diagnosis of hydrops fetalis. Journal of Perinatology (2005) 25, 608 – 611. doi:10.1038/sj.jp.7211357 INTRODUCTION Given the diversity of potential etiologies, 1 the investigation of nonimmune hydrops fetalis requires a multidisciplinary approach. Infectious pathogens acquired in utero represent an important category of the identifiable causes of hydrops fetalis 2 among which parvovirus B19 is the most common agent. 3 Among the other viral etiologies of hydrops fetalis, cytomegalovirus (CMV) infection, although uncommon, is important to identify, since specific antiviral therapy is available. 4 We report a case of congenital CMV infection presenting as fetal hydrops, in an infant who died of severe pneumonitis, despite the use of ganciclovir therapy. CASE REPORT The patient was a male infant born at 29 weeks gestation with a birth weight of 695 g. The infant was the third pregnancy of a 21- year-old Caucasian with a history of hypothyroidism and alcohol and cocaine abuse. She had one prior uneventful term pregnancy and one spontaneous abortion. She had received very little antenatal care and presented with a pregnancy that was estimated, by dates, to be 28 weeks estimated gestational age (EGA) with possible preterm labor. An ultrasound confirmed a singleton pregnancy with oligohydraminos, pericardial effusion and ascites. Antenatal serologic testing performed for varicella-zoster virus, toxoplasmosis, syphilis, rubella, herpes simplex virus, and HIV were negative. Maternal IgG, but not IgM, antibodies to parvovirus B19, and cytomegalovirus were detected. Antiplatelet antibodies, ANCA, and ANA antibodies were all negative. Fetal echocardiogram revealed a moderate pericardial effusion and a structurally normal heart. A fetal MRI performed to better evaluate the fetal hydrops (Figure 1) revealed oligohydramnios, cardiomegaly, pericardial effusion, and ascites with hepatosplenomegaly, confirming the diagnosis. A peri-umbilical blood sample revealed a white blood cell count of 2900/mm 3 , a hemoglobin concentration of 8.6 g/dl, and a platelet count of 16,000/mm 3 . While a fetal blood transfusion was being attempted to correct the anemia fetal bradycardia ensued, necessitating emergent caesarean section. The infants Apgars were 1, 1, 2, and 4 at 1, 5, 10, and 15 min, respectively. He was resuscitated with high inflation pressures, 20 ml/kg of normal saline and sodium bicarbonate. Physical examination on admission was remarkable for symmetrical IUGR (<10th centile), based on the EGA of 28 weeks. Since the estimation of gestational age was based on dates of a woman who had very little prenatal care, the possibility of a younger gestational age (e.g., 25 to 26 weeks) could not definitively be excluded. The initial physical exam was also remarkable for severe hepatosplenomegaly, and pallor. The initial CBC had a hematocrit of 14%, platelets of 29 and absolute neutrophil count of 800. Chest X-ray was consistent with respiratory distress syndrome and an enlarged cardiac silhouette. Echocardiography performed on day of life (DOL) 2 to evaluate the cardiomegaly revealed the presence of a small to moderate pericardial effusion, structurally normal heart, and normal ventricular function. The infant’s respiratory status initially improved after surfactant and high-frequency oscillation, and he was extubated by DOL 2. A clinical diagnosis of congenital CMV was entertained because of the physical findings, and a work-up was instituted. Histopathological analysis of the placenta (Figure 2) revealed plasmacytic villitis consistent with CMV infection, confirmed by immunohistochemistry and in-situ hybridization. Head ultrasound Address correspondence and reprint requests to Mark R. Schleiss, Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Minnesota School of Medicine, 420 Delaware Street SE, MMC 296, 55455, Minneapolis, MN, USA. Department of Pediatrics (V.S., V.N., E.F.D.), Division of Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Department of Pathology (J.S.), University of Cincinnati School of Medicine, Cincinnati, OH, USA; and Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Minnesota School of Medicine, Minneapolis, MN, USA. Journal of Perinatology 2005; 25:608 – 611 r 2005 Nature Publishing Group All rights reserved. 0743-8346/05 $30 www.nature.com/jp 608