{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:21:16Z","timestamp":1793726476853,"version":"4.6.1"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848042002"],"award-info":[{"award-number":["848042002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2025,8]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n Neonates with critical congenital heart disease (CCHD) are at risk for adverse early brain development and long\u2010term neurodevelopmental sequelae. Insulin\u2010like growth factor\u20101 (IGF\u20101) and insulin\u2010like growth factor binding protein\u20103 (IGFBP\u20103) are essential contributors to brain growth and maturation. The present study aimed to compare cord blood levels of IGF\u20101 and IGFBP\u20103 between neonates with CCHD and healthy controls, and to explore their association with perinatal brain development.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This was a prospective, observational study conducted at Wilhelmina Children's Hospital, Utrecht, The Netherlands, between June 2019 and March 2022. The study cohort comprised term neonates diagnosed prenatally with a severe cardiac defect on ultrasound, for which surgical repair within the first month after birth was anticipated. IGF\u20101 and IGFBP\u20103 levels were measured from cord blood samples obtained directly after birth in term neonates with CCHD and healthy control neonates. All cases were stratified into two subgroups according to the predicted cerebral oxygen delivery (COD)\n in utero<\/jats:italic>\n (i.e. normal or lower), based on the expected impact of the cardiac diagnosis on COD. In cases with CCHD, fetal and preoperative neonatal brain magnetic resonance imaging (MRI) scans were performed. Regional and total brain volumes were assessed, after adjustment for sex and postmenstrual age at MRI, using linear regression equations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cord blood samples were collected from 39 neonates with CCHD and 20 healthy controls. IGFBP\u20103 levels were significantly lower in cases of CCHD\n vs<\/jats:italic>\n healthy controls (median, 0.89 mg\/L\n vs<\/jats:italic>\n 1.09 mg\/L;\n P<\/jats:italic>\n \u2009=\u20090.027). When comparing the two subgroups of predicted COD, cases with lower COD (\n n<\/jats:italic>\n \u2009=\u200930) displayed reduced IGF\u20101 (median, 9.7 nmol\/L\n vs<\/jats:italic>\n 11.7 nmol\/L;\n P<\/jats:italic>\n \u2009=\u20090.003) and IGFBP\u20103 (median, 0.88 mg\/L\n vs<\/jats:italic>\n 1.07 mg\/L;\n P<\/jats:italic>\n \u2009=\u20090.005) levels compared to those with normal COD (\n n<\/jats:italic>\n \u2009=\u200929). IGF\u20101 levels were associated positively with neonatal cortical gray matter (\n R<\/jats:italic>\n 2<\/jats:sup>\n , 0.13), deep gray matter (\n R<\/jats:italic>\n 2<\/jats:sup>\n , 0.15) and total brain (\n R<\/jats:italic>\n 2<\/jats:sup>\n , 0.10) volumes (all\n P<\/jats:italic>\n \u2009<\u20090.05). Positive associations were identified between IGFBP\u20103 and neonatal cortical gray matter (\n R<\/jats:italic>\n 2<\/jats:sup>\n , 0.07) as well as cerebellar (\n R<\/jats:italic>\n 2<\/jats:sup>\n , 0.11) volumes (both\n P<\/jats:italic>\n \u2009<\u20090.05). Furthermore, IGF\u20101 was correlated positively (\n r<\/jats:italic>\n \u2009=\u20090.47;\n P<\/jats:italic>\n \u2009=\u20090.039) with fetal\u2010to\u2010neonatal cortical gray matter growth per week.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n IGFBP\u20103 levels were demonstrated to be reduced in neonates with CCHD, and cases with lower predicted COD demonstrated decreased levels of IGF\u20101 and IGFBP\u20103. In addition, lower IGF\u20101 and IGFBP\u20103 levels at birth were associated with reduced early volumetric brain development. These results indicate that a compromised oxygenation profile\n in utero<\/jats:italic>\n in fetuses with CCHD may influence the IGF axis, possibly contributing to impaired brain growth in CCHD. \u00a9 2025 The Author(s).\n Ultrasound in Obstetrics & Gynecology<\/jats:italic>\n published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/uog.29271","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T16:59:29Z","timestamp":1751129969000},"page":"200-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cord blood levels of insulin\u2010like growth factor\u20101 and insulin\u2010like growth factor binding protein\u20103 correlate with perinatal brain development in fetal congenital heart disease"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-0291","authenticated-orcid":false,"given":"M.","family":"Nijman","sequence":"first","affiliation":[{"name":"Department of Neonatology Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"},{"name":"Department of Pediatric Cardiology Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4221-2779","authenticated-orcid":false,"given":"N. H. P.","family":"Claessens","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"},{"name":"Department of Pediatrics Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-8869","authenticated-orcid":false,"given":"J. M. P. J.","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Reijn","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3106-3824","authenticated-orcid":false,"given":"N. J. G.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Beatrix Children's Hospital, University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7743-2413","authenticated-orcid":false,"given":"I. M.","family":"van Ooijen","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"},{"name":"Center for Image Sciences High Field MR Research, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"de Heus","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology St Antonius Hospital Utrecht The Netherlands"},{"name":"Department of Obstetrics and Gynecology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-1861","authenticated-orcid":false,"given":"C. H.","family":"Nijboer","sequence":"additional","affiliation":[{"name":"Department for Developmental Origins of Disease Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-4291","authenticated-orcid":false,"given":"M. N.","family":"Bekker","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-9168","authenticated-orcid":false,"given":"M. J. N. 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