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Cited by 79Urological Disorders and TreatmentsPregnancy and preeclampsia studiesCongenital Anomalies and Fetal Surgery

Hypospadias in males with intrauterine growth restriction due to placental insufficiency: the placental role in the embryogenesis of male external genitalia

Yinon, Yoav, Kingdom, John C.P., Proctor, Leslie K., Kelly, Edmond N., Salle, Joao L. Pippi, Wherrett, Diane, Keating, Sarah, Nevo, Ori +1 more·2010·American Journal of Medical Genetics Part A
DOI 10.1002/ajmg.a.33140
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Abstract

Our aim was to define the association between early onset intra-uterine growth restriction (IUGR) due to placental insufficiency and hypospadias in males. We prospectively studied a cohort of small-for-gestational age (SGA) male infants with hypospadias managed by a multidisciplinary team over a 5-year period. Thirty SGA male infants were diagnosed with hypospadias/abnormal genitalia after birth, and four of them were diagnosed antenatally. Five cases occurred in the smaller pair of discordant IUGR twins, where the larger co-twin had normal male genitalia. Serial ultrasounds demonstrated features of early-onset IUGR in all cases at a median gestational age of 21 weeks (range 14-31weeks). Twenty-one (70%) pregnancies were subsequently complicated by absent/reversed end-diastolic flow in the umbilical arteries indicating severe IUGR, and 17 (57%) women developed severe pre-eclampsia. There were 27 (90%) live births at a median gestational age of 31 weeks (range 27-37); 23 (77%) of the neonates had birth weights <3rd centile. All newborns had normal male karyotypes. In 62% (18/29) the hypospadias was severe. A correlation was found between the severity of the IUGR and the severity of hypospadias as significantly more infants with severe hypospadias were less than the 3rd centile compared to the mild-moderate hypospadias group: 94% (17/18) versus 55% (6/11), respectively (P = 0.02). In conclusion, SGA male newborns with hypospadias exhibit a high rate of early-onset severe IUGR due to placental insufficiency. Early placental development likely influences male external genitalia formation. Careful sonographic evaluation of the genitalia is advised when early-onset placentally mediated IUGR is found.

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  • Placental insufficiency, associated with intrauterine growth restriction (IUGR), is associated with abnormalities in development of the male external genitalia, and hypospadias in particular.

    “placental insufficiency, associated with intrauterine growth restriction (IUGR), is associated with abnormalities in development of the male external genitalia, and hypospadias in particular [60,61]”

    From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [60]

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Authors
Yinon, Y., Kingdom, J. C. P., Proctor, L. K., Kelly, E. N., Salle, J. L. P., Wherrett, D., Keating, S., Nevo, O., & Chitayat, D.
Affiliations
  • Mount Sinai Hospital (CA)
  • University of Toronto (CA)
  • Sunnybrook Health Science Centre (CA)
Corresponding author
Chitayat, David
ORCID
Venue
American Journal of Medical Genetics Part A
Publisher
Wiley
Published
2009-12-23
Volume
152A
Issue
1
Pages
75-83
ISSN
  • 1552-4825 (ISSN-L)
  • 1552-4833
DOI
10.1002/ajmg.a.33140
OpenAlex
W2007661620
Cited by
79
References
28
Citations by year
2026: 2 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 2 · 2017: 6 · 2016: 7 · 2015: 5 · 2014: 9 · 2013: 6 · 2012: 4
FWCI
3.17
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • American Journal of Medical Genetics Part A (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Urology › Urological Disorders and Treatments
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Surgery › Congenital Anomalies and Fetal Surgery
Keywords
hypospadias, fetal growth restriction, placental insufficiency, umbilical artery Doppler, preeclampsia, prenatal diagnosis, hypospadias severity
MeSH terms
Adult, Female, Fetal Growth Retardation, Genitalia, Male, Humans, Hypospadias, Infant, Newborn, Infant, Small for Gestational Age, Male, Placental Insufficiency, Pregnancy, Prospective Studies

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