title: Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.
abstract: OBJECTIVE
  To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR.
  
  
  METHODS
  This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT).
  
  
  RESULTS
  50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm).
  
  
  CONCLUSIONS
  Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Clinical Hospital Center "Sestre milosrdnice", Medical School, University of Zagreb, Vinogradska cesta 29, 10000 Zagreb, Croatia.
authors.forename: Mirta
authors.initials: M
authors.lastname: Starčević
authors.affiliation: Department of Obstetrics and Gynecology, Clinical Hospital "Sveti Duh", Medical School, University of Zagreb, Sveti Duh 64, 10000 Zagreb, Croatia. Electronic address: predojevic.maja@gmail.com.
authors.forename: Maja
authors.initials: M
authors.lastname: Predojević
authors.affiliation: Department of Obstetrics and Gynecology, Clinical Hospital Center "Sestre milosrdnice", Medical School, University of Zagreb, Vinogradska cesta 29, 10000 Zagreb, Croatia.
authors.forename: Dražan
authors.initials: D
authors.lastname: Butorac
authors.affiliation: Division of Neonatology, Department of Pediatrics, Clinical Hospital Center "Sestre milosrdnice", Medical School, University of Zagreb, Vinogradska cesta 29, 10000 Zagreb, Croatia.
authors.forename: Jasna
authors.initials: J
authors.lastname: Tumbri
authors.affiliation: Nuclear Magnetic Resonance Center, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
authors.forename: Paško
authors.initials: P
authors.lastname: Konjevoda
authors.affiliation: Department of Physiology, Medical School, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia.
authors.forename: Aida Salihagić
authors.initials: AS
authors.lastname: Kadić
mesh_terms: D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D002657:Child Development; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging*; D006801:Humans; D007231:Infant, Newborn; D021041:Placental Circulation; D010927:Placental Insufficiency / Q000000981:diagnostic imaging*; D011247:Pregnancy
keywords: Doppler; Hypoxia; Intrauterine growth restriction; Neurodevelopment