title: Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus.
abstract: OBJECTIVE
  To identify the temporal sequence of abnormal Doppler changes in the fetal circulation in a subset of early and severely growth-restricted fetuses.
  
  
  METHODS
  This was a prospective observational study in a tertiary care/teaching hospital. Twenty-six women who were diagnosed with growth-restricted fetuses by local standards before 32 weeks' gestation and who had abnormal uterine and umbilical artery Doppler velocimetry were enrolled onto the study. To compare Doppler changes as a function of time, pulsed-wave Doppler ultrasound was performed on five vessels in the fetal peripheral and central circulations. Doppler examinations were performed twice-weekly and on the day of delivery if the fetal heart rate tracing became abnormal. Doppler indices were scored as abnormal when their values were outside the local reference limits on two or more consecutive measurements. Biometry for assessment of fetal growth was performed every 2 weeks. Computerized fetal heart rates were obtained daily. Delivery was based on a non-reactive fetal heart rate tracing and not on Doppler information. Patients with a severely growth-restricted fetus who were delivered for maternal indications such as pre-eclampsia were excluded. Perinatal outcome endpoints included: intrauterine death, gestational age at delivery, newborn weight, central nervous system damage of grade 2 or greater, intraventricular hemorrhage and neonatal mortality.
  
  
  RESULTS
  Mean gestational age and newborn weight at delivery were 29 (standard deviation (SD), 2) weeks and 818 (SD, 150) g, respectively. The sequence of Doppler velocimetric changes was described by onset time cumulative curves that showed two time-related events. First, for each vessel there was a progressive increase in the percent of fetuses developing a Doppler abnormality. Second, severely growth-restricted fetuses followed a progressive sequence of acquiring Doppler abnormalities which were categorized into 'early' and 'late' Doppler changes. Early changes occurred in peripheral vessels (umbilical and middle cerebral arteries; 50% of patients affected 15-16 days prior to delivery). Late changes included umbilical artery reverse flow, and abnormal changes in the ductus venosus, aortic and pulmonary outflow tracts (50% of patients affected 4-5 days prior to delivery). The time interval between the occurrence of early and late changes was significantly different (P < 0.0001) and late changes were significantly associated with perinatal death (P < 0.01).
  
  
  CONCLUSIONS
  Doppler velocimetry abnormalities develop in different vessels of the severely growth-restricted fetus in a sequential fashion. Late changes in vascular adaptation by the severely growth-restricted fetus are the best predictor of perinatal death.
authors.affiliation: Istituto di Scienze Biologiche Luigi Sacco and Clinica Ostetrica e Ginecologica, University of Milan, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferrazzi
authors.forename: M
authors.initials: M
authors.lastname: Bozzo
authors.forename: S
authors.initials: S
authors.lastname: Rigano
authors.forename: M
authors.initials: M
authors.lastname: Bellotti
authors.forename: A
authors.initials: A
authors.lastname: Morabito
authors.forename: G
authors.initials: G
authors.lastname: Pardi
authors.forename: F C
authors.initials: FC
authors.lastname: Battaglia
authors.forename: H L
authors.initials: HL
authors.lastname: Galan
mesh_terms: D001775:Blood Circulation / Q000502:physiology*; D001783:Blood Flow Velocity / Q000502:physiology; D005260:Female; D005313:Fetal Death; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005323:Fetal Monitoring; D005333:Fetus / Q000098:blood supply*; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal