1 Vol.:(0123456789) Scientific Reports | (2020) 10:19706 | https://doi.org/10.1038/s41598-020-76772-1 www.nature.com/scientificreports Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high‑risk pregnancies Hitomi Imafuku 1 , Hideto Yamada 1* , Akiko Uchida 1 , Masashi Deguchi 1 , Tokuro Shirakawa 1 , Yuki Sasagawa 1 , Yutoku Shi 1 , Kazumichi Fujioka 2 , Ichiro Morioka 3 & Kenji Tanimura 1 This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV‑DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu‑like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1–6.6; p < 0.05), the presence of maternal fever or flu‑like symptoms (5.4, 2.6–11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8–27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1–6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu‑like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV‑DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity. Cytomegalovirus (CMV) is the most common mother-to-child transmission in humans. Approximately 20% of neonates with cCMV are symptomatic. ese clinical manifestations include fetal growth restriction (FGR), low birth weight (LBW), and central nervous system and multiple organ involvement with petechiae, hepatomegaly, splenomegaly, jaundice, pneumonia, and encephalitis. Infants with symptomatic cCMV develop neurological sequelae including hearing dysfunction, neuromuscular disorder, psychomotor retardation, ocular abnormal- ity, delayed language development, and intellectual disability at incidences of 70–90% 1–3 . In addition, 10–15% of infants with asymptomatic cCMV develop long-term sequelae, such as progressive sensorineural hearing difficulty and mental retardation 2,4 . Observational studies have shown higher incidences of cCMV in pregnancies with obstetric complications than in uncomplicated pregnancies. cCMV have been found in 1–4% of newborns with FGR, light-for-date, LBW, threatened premature labor, preterm delivery, and multiple pregnancy 5–8 . A prospective study involving 11,715 newborns screened by PCR tests for CMV-DNA in the saliva has found that socioeconomic factors such as younger age (< 25 years old), parous mothers born in high resources countries, and higher income are risk factors for cCMV due to maternal primary CMV infection 9 . On the other hand, younger and unemployed mothers are found to be risk factors for cCMV caused by non-primary CMV infection 9 . A recent study at a primary maternity hospital, where high-risk pregnancies are transferred to perinatal medical centers, has identified that maternal OPEN 1 Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. 2 Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. 3 Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan. * email: yhideto@med.kobe-u.ac.jp