title: Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.
abstract: Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection.
  
  
  
  The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns.
  
  
  
  The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×106copies/mL (95% CI 7.97×105to 4.02×106). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013).
  
  
  
  We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders.
authors.affiliation: Laboratory of Clinical Research, Saitama Children's Medical Center, Saitama, Japan.|Department of Radiological Technology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Division of Infectious Disease, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oh-Ishi
authors.affiliation: Laboratory of Clinical Research, Saitama Children's Medical Center, Saitama, Japan.|Department of Radiological Technology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.affiliation: Division of Otorhinolaryngology, Kawagoe Otology Institute, Saitama, Japan.|Mejiro University Audiology Clinic, Saitama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sakata
authors.affiliation: Division of Otolaryngology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Nodoka
authors.initials: N
authors.lastname: Adachi
authors.affiliation: Division of Otolaryngology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asanuma
authors.affiliation: Division of Radiology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oguma
authors.affiliation: Division of Pediatrics, Sannoh Doom Clinic, Saitama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kimoto
authors.affiliation: Division of Obstetrics and Gynecology, Sannoh Clinic, Saitama, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Matsumoto
authors.affiliation: Division of Obstetrics and Gynecology, Aiwa Hospital, Saitama, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Division of Obstetrics and Gynecology, Aiwa Hospital, Saitama, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uesato
authors.affiliation: Division of Obstetrics and Gynecology, Aiwa Hospital, Saitama, Japan.
authors.forename: Jutaro
authors.initials: J
authors.lastname: Fujita
authors.affiliation: Department of Molecular Predictive Medicine and Sport Science, School of Medicine, Kyorin University, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shirato
authors.affiliation: Department of Molecular Predictive Medicine and Sport Science, School of Medicine, Kyorin University, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Molecular Predictive Medicine and Sport Science, School of Medicine, Kyorin University, Tokyo, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Kizaki
mesh_terms: D002490:Central Nervous System / Q000002:abnormalities* / Q000821:virology; D000013:Congenital Abnormalities / Q000652:urine / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development; D003586:Cytomegalovirus Infections / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D004279:DNA, Viral / Q000652:urine*; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006309:Hearing; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000209:etiology / Q000821:virology; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D015997:Neonatal Screening; D060888:Real-Time Polymerase Chain Reaction; D066127:White Matter
chemical_list: D004279:DNA, Viral
keywords: congenital cytomegalovirus infection; hearing loss; quantitative real-time PCR; universal screening