A longitudinal analysis of arterial dopler parameters in growth restricted fetuses
Authors: Mikovic Zeljko , Mandic Vesna , Djukic Milan , Egic Amira , Filimonovic Dejan , Cerovic Nikola , Popovac Mirjana 
Published: July 2008

Doppler parameters enable noninvasive and direct detection of placental insufficiency and brain sparing effect, which occurs as an adaptive mechanism to chronic hypoxemia. It is of great interest if further changes of Doppler parameters, which occur after the detection of the first pathologic value, can anticipate a moment of fetal distress. We investigated growth-restricted fetuses with the brain sparing effect in the time interval between the detection of blood flow redistribution until the distress. The aim of our study was to evaluate longitudinally Doppler parameters in umbilical (Aum), medial cerebral (MCA), renal (AR) and femoral (AF) artery and find: 1) if there are significant changes in their value; 2) the character and time interval of these changes; and 3) if they differ from changes in biophysical profile (BFP). MATERIALS AND METHODS Prospective clinical study evaluated 35 pregnancies with fetal growth restriction. Fetuses were selected for the study if: 1) there were pathologic cerebral/umbilical (C/U) ratio, 2) at least four Doppler examinations in 3-4 days interval were performed and 3) prepartal fetal distress, defined as silent fetal heart rate pattern with spontaneous and late decelerations, was present. In 28 neonates after delivery umbilical artery gas and acid-base status was determined. Blood flow velocity waveforms were evaluated in Aum MCA, AR, and AF. Arterial blood flow was estimated by pulsatility index (Pi), while in Aum we also used: present end-diastolic velocity (PEDV) absent end-diastolic velocity (AEDV) and reverse end-diastolic velocity (REDV). All of the fetuses were monitored by cardiotocogram (CTG) once to twice a day and by BFP twice a week. Elective Cesarean section was done in the presence of distress, except if severe immaturity or extreme malnutrition occurred. RESULTS Etiological factors of placental insufficiency were: 1) hypertensive syndrome (n=26), 2) chronic renal disease (n=3), 3) primary antiphospholipid syndrome (n=2), 4) diabetes mellitus (n=1), 5) cardiac disease (n=1) and 6) unknown (n=2). Initial Doppler examination, with the detection of pathological C/U, was done in time interval between 26. to 32. weeks of gestation (wg) (29.4 ? 2.5) delivery was between 29. to 34. wg (32.2 ? 1.9); and average body weight was 1327 ? 245g. Pathological BFP was registered in 91.4% of fetuses. Cesarian section has not been done, in spite of distress, in two fetuses (5.7%) due to their extreme immaturity and/or malnutrition, so they died "in utero". Hypoxemia was registered in 96.4% (27/28) neonates, while acidosis in 71.4% (20/28). Neonatal morbidity was 93.9% (31/33), neonatal mortality 8.6% while perinatal mortality was 14.3%. We found high significant difference (P<0.001) in Pi Aum, Pi ACM and Pi AR in the time interval between the detection of pathological C/U ratio and fetal distress, while the difference was insignificant for the values of Pi AF (table). The value changes are characterized by: continuing increase of Pi Aum, with a maximum in the last week before the distress; biphasic character of PI MCA - tendency to decrease in the first two and significant increase in the last week; and significant increase of Pi AR one and a half week before the distress (table, graphic). Three weeks before the distress in 7 (53.8%) cases we registered PEDV, in 6 (46.2%) AEDV, while we didn`t register REDV in any case. In the last week there were 3 (8.6%) PEDV, 23 (65.7%) AEDV and 9 (25.7%) REDV.. DISSCUSSION Significant changes in Doppler parameters suggest that even after the blood redistribution in growth restricted hypoxemic fetuses further haemodynamic changes occur. Preterminal increase in Pi Aum can be due to: 1) release of leucotrien, tromboxan and free oxygen radicals and consecutive vasoconstriction in villous arteries; 2) increase of diastolic arterial pressure as a result of hypoxic-ishemic central nervous system (CNS) insult; 3) decreased combined heart minute volume in preterminal phase of hypoxemia. The increase of Pi MCA values is a result of hypoxic-ishemic CNS insult. As a consequence of hypoxia ischemia occurs by two mechanisms: local vasodilatatory agents production decrease, or due to the brain edema. The increase of Pi AR values can be explained by severe hypoxemia with the failure of local autoregulation of renal blood flow. The greatest changes in BFP values were registered in the first half, while in Doppler parameters in the second half of the studied interval suggesting that Doppler parameters more accurately announce fetal distress. We can conclude the following: 1) fetal distress appears after the presence hypoxic-ischemic CNS insult, and therefore late when sequels are concerned; 2) if the fetus is mature, elective delivery should be planed after the appearance of pathological C/U ratio, or with the pathological BFP at the latest, in order to avoid post-hypoxic sequels; 3) if the fetus is immature, pregnancy can be prolonged safely, in spite of pathological C/U ratio and BFP, with intensive monitoring of Doppler parameters until the detection of their increased values.