{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:20:09Z","timestamp":1789996809968,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T00:00:00Z","timestamp":1501286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hypospadias is more common among male infants with growth restriction, defined as a birth weight less than the 10<jats:sup>th<\/jats:sup> centile, than in infants with a normal birth weight. Intrauterine growth retardation (IUGR) has been associated, also, with abnormalities of the placenta, such as maternal vascular malperfusion. In a consecutive sample of newborn infants, the association between hypospadias, IUGR and abnormalities of the placenta could be analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Affected infants were identified among 289,365 liveborn and stillborn infants in the Active Malformations Surveillance Program between 1972 and 2012. The four anatomic locations of the ectopic urethral opening, based on the recorded physical examination findings, were: (1) glandular; (2) subcoronal; (3) penile; (4) penoscrotal. Affected infants with associated malformations, a chromosome abnormality, teratogenic exposure, maternal diabetes mellitus, or multiple gestations were excluded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three hundred sixteen affected infants were identified: 52.2% glandular, 11.7% subcoronal, 27.8% penile, and 8.2% penoscrotal. The highest frequency of IUGR (34.6%) was in the infants with the most severe hypospadias (penoscrotal). The 39 reports of placenta findings showed a high frequency of abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>An increased rate of occurrence of hypospadias and abnormalities of the placenta were present in infants with intrauterine growth restriction. The postulated cause of this association is a deficiency in the function of the placenta during weeks 10 to 14 of gestation when normal masculinization occurs due to an increase in the level of placental human chorionic gonadotropin and fetal testosterone. The cause of the placental deficiency has not been established. Birth Defects Research 110:122\u2013127, 2018.\u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1087","type":"journal-article","created":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T07:02:45Z","timestamp":1501311765000},"page":"122-127","source":"Crossref","is-referenced-by-count":28,"title":["Hypospadias, Intrauterine Growth Restriction, and Abnormalities of the Placenta"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4264-1730","authenticated-orcid":false,"given":"M. Hassan","family":"Toufaily","sequence":"first","affiliation":[{"name":"Active Malformations Surveillance Program, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"},{"name":"Medical Genetics Unit, MassGeneral Hospital for Children Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drucilla J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital, and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Noel","family":"Westgate","sequence":"additional","affiliation":[{"name":"Active Malformations Surveillance Program, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"},{"name":"Medical Genetics Unit, MassGeneral Hospital for Children Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Therese","family":"Hunt","sequence":"additional","affiliation":[{"name":"Hunt Consulting Associates Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-4848","authenticated-orcid":false,"given":"Lewis B.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Active Malformations Surveillance Program, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"},{"name":"Medical Genetics Unit, MassGeneral Hospital for Children Harvard Medical School Boston Massachusetts"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1002\/ajmg.a.37947","article-title":"Maternal hypertension and risk for hypospadias in offspring","volume":"170","author":"Agopian AJ","year":"2016","journal-title":"Am J Med Genet Part A"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den098"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.011091175"},{"key":"e_1_2_5_5_1","first-page":"262","article-title":"Obstetrically important lesions of the umbilical cord","volume":"39","author":"Benirschke K","year":"1994","journal-title":"J Reprod Med"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0304-z"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.2350\/12-06-1211-OA.1"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070380"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0994"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65334-7"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2007.10.046"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.2001.00088.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.12864"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003081-199609000-00007"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182574f39"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2008.01.001"},{"key":"e_1_2_5_17_1","volume-title":"Common Malformations","author":"Holmes LB","year":"2012"},{"key":"e_1_2_5_18_1","doi-asserted-by":"crossref","unstructured":"HolmesLB NasriH WestgateM-N ToufailyMH LinAE.2018.The Active Malformations Surveillance Program Boston in 1972-2012: Methodology and Demographic Characteristics. Birth Defects Research110:148\u2013156.","DOI":"10.1002\/bdr2.1156"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(82)80343-0"},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1002\/ajmg.a.36050","article-title":"Severe hypospadias and its association with maternal\u2010placental factors","volume":"161","author":"Huisma F","year":"2013","journal-title":"Am J Med Genet Part A"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.3.473"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.2350\/13-06-1351-CR.1"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10084"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.2000.00436.x"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-3-6"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.7308"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2008.055236"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-999316"},{"key":"e_1_2_5_29_1","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1016\/S0022-5347(05)68863-5","article-title":"In vitro fertilization is associated with an increased risk of hypospadias","volume":"16","author":"Silver RI","year":"1999","journal-title":"J Urol"},{"issue":"2","key":"e_1_2_5_30_1","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S0022-5347(01)65830-0","article-title":"Androgen receptor gene mutations are rarely associated with isolated penile hypospadias","volume":"156","author":"Sutherland RW","year":"1996","journal-title":"J Urol"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1979.tb05060.x"},{"key":"e_1_2_5_32_1","first-page":"52","article-title":"Study of the incidence of hypospadias in Rochester, Minnesota, 1940\u20131970, and a case\u2010control comparison of possible etiologic factors","volume":"49","author":"Sweet RA","year":"1974","journal-title":"Mayo Clin Proc"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.09.005"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.2350\/09-06-0669-CR.1"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201232"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33140"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdr2.1087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:51:01Z","timestamp":1694652661000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.1087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,29]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1002\/bdr2.1087"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.1087","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,29]]}}}