title: Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.
abstract: BACKGROUND
  Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort.
  
  
  OBJECTIVE
  The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome.
  
  
  METHODS
  In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death.
  
  
  RESULTS
  Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001).
  
  
  CONCLUSIONS
  The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome.
authors.affiliation: Obstetrics and Gynecology, Royal College of Surgeons, Dublin, Ireland. Electronic address: cathymonteith@rcsi.ie.
authors.forename: Cathy
authors.initials: C
authors.lastname: Monteith
authors.affiliation: Obstetrics and Gynecology, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Karen
authors.initials: K
authors.lastname: Flood
authors.affiliation: Obstetrics and Gynecology, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Sieglinde
authors.initials: S
authors.lastname: Mullers
authors.affiliation: Obstetrics and Gynecology, University of Melbourne, Royal Women's Hospital, Melbourne, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Unterscheider
authors.affiliation: Obstetrics and Gynecology, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Breathnach
authors.affiliation: Obstetrics and Gynecology, Coombe Women and Infants University Hospital, Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Daly
authors.affiliation: Obstetrics and Gynecology, Rotunda Hospital, Dublin, Ireland.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Geary
authors.affiliation: University College Dublin Center for Human Reproduction, Coombe Women and Infants University Hospital, Dublin, Ireland.
authors.forename: Mairead M
authors.initials: MM
authors.lastname: Kennelly
authors.affiliation: Obstetrics and Gynecology, University College Dublin School of Medicine and Medical Science, National Maternity Hospital, Dublin, Ireland.
authors.forename: Fionnuala M
authors.initials: FM
authors.lastname: McAuliffe
authors.affiliation: Obstetrics and Gynecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland.
authors.forename: Keelin
authors.initials: K
authors.lastname: O'Donoghue
authors.affiliation: Obstetrics and Gynecology, Royal Jubilee Maternity Hospital, Belfast, Ireland.
authors.forename: Alison
authors.initials: A
authors.lastname: Hunter
authors.affiliation: Obstetrics and Gynecology, National University of Ireland, Galway, Ireland.
authors.forename: John J
authors.initials: JJ
authors.lastname: Morrison
authors.affiliation: Obstetrics and Gynecology, Graduate Entry Medical School, University of Limerick, Limerick, Ireland.
authors.forename: Gerald
authors.initials: G
authors.lastname: Burke
authors.affiliation: Epidemiology and Public Health, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.affiliation: Obstetrics and Gynecology, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Tully
authors.affiliation: Obstetrics and Gynecology, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Fergal D
authors.initials: FD
authors.lastname: Malone
mesh_terms: D000328:Adult; D002536:Cerebral Arteries / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000098:blood supply; D011237:Predictive Value of Tests; D011247:Pregnancy; D011379:Prognosis; D011446:Prospective Studies; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal; D014469:Umbilical Arteries / Q000000981:diagnostic imaging* / Q000503:physiopathology
keywords: adverse neonatal outcome; brain sparing; brain-sparing effect; cerebroplacental ratio; intrauterine growth restriction; middle cerebral artery Doppler; small for gestational age; umbilical artery Doppler