title: Fetal growth restriction but not preterm birth is a risk factor for severe hypospadias.
abstract: BACKGROUND
  Hypospadias has multifactorial causes and occurs at a high frequency among very low-birthweight infants. Placental insufficiency is hypothesized to be one cause of hypospadias; that is, decreased human chorionic gonadotropin (hCG) secretion caused by placental insufficiency is suspected to result in abnormal male external genitalia, but there is little direct evidence to support this. The aim of this study was therefore to identify the features of hypospadias and to clarify the male genital abnormalities caused by fetal growth restriction (FGR).
  
  
  METHODS
  We reviewed the clinical data of boys who underwent hypospadias repair between 2005 and 2011 at Kyoto University Hospital.
  
  
  RESULTS
  Twenty boys were included in this study. Fifteen (75%) of the subjects were preterm or low-birthweight infants. Thirteen (65%) had FGR, 60% of whom had severe hypospadias regardless of gestational age. In addition, 92% of the FGR infants also had other genital anomalies, such as cryptorchidism, bifid scrotum, or micropenis. In contrast, only 14% and 43% of the non-FGR infants had severe hypospadias or genital anomalies other than hypospadias, respectively. Placental histopathology was available in eight FGR infants, in seven of whom it was suggestive of blood flow deficiency such as infarction and single umbilical artery.
  
  
  CONCLUSIONS
  Infants with FGR have a high incidence of hypospadias. FGR caused by placental dysfunction, but not low birthweight, is a risk factor for severe hypospadias associated with multiple genital anomalies.
authors.affiliation: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.|Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Sizuyo
authors.initials: S
authors.lastname: Nagai
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukura
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Niwa
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
mesh_terms: D000293:Adolescent; D002648:Child; D005317:Fetal Growth Retardation; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007021:Hypospadias / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D015994:Incidence; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007564:Japan / Q000453:epidemiology; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
keywords: fetal growth restriction; human chorionic gonadotropin; hypospadias; placental insufficiency