Objective: To investigate whether pathological changes in the umbilical artery (UA), ductus venosus (DV) and short-term fetal heart variation are related to perinatal outcome in severe, early intrauterine growth restriction (IUGR).

Methods: This multicenter, prospective, longitudinal, observational study was carried out in the Departments of Fetal Medicine and Obstetrics in Hamburg, Amsterdam, Utrecht and London. In 70 singleton pregnancies with IUGR fetuses, delivered at 26-33 weeks of gestation because of antepartum fetal distress, short-term variation (STV) of fetal heart rate, pulsatility index of the fetal UA (UA PI) and DV pulsatility index for veins (DV PIV) were assessed at least weekly. The final measurement was performed within 24 h of delivery. Standard cut-off levels (2 SD or 3 SD, absent flow or reversed flow) were used and new cut-off levels were calculated by means of receiver-operating characteristics analysis. Adverse outcome was defined as perinatal death, cerebral hemorrhage (> or = Grade II) or bronchopulmonary dysplasia before discharge. The predictive value for adverse outcome was calculated for different cut-off levels of the monitoring parameters, adjusted for gestational age (GA), by multivariate logistic regression analysis. Data were analyzed separately for three different time blocks, namely 8-14, 2-7 and 0-1 days before delivery.

Results: Adverse perinatal outcome occurred in 18/70 (26%) infants. During the last 24 h before delivery DV PIV and UA PI were significantly higher and STV lower in the adverse outcome group, while 2-7 days before delivery only DV PIV was significantly higher. Adverse perinatal outcome could be predicted at 0-1 days before delivery by DV PIV at a cut-off of three multiples of the SD (odds ratio (OR) 11.3; 95% CI 2.3-57) and GA (OR 0.4; 95% CI 0.3-0.8), at 2-7 days by DV PIV at 2 SD (OR 3.0; 95% CI 0.8-12) and GA (OR 0.5; 95% CI 0.3-0.8) and at 8-14 days by DV PIV at 2 SD (OR 3.9; 95% CI 0.8-20) and GA (OR 0.5; 95% CI 0.3-0.8). Other parameters did not contribute to the multivariate model.

Conclusions: DV PIV measurement is the best predictor of perinatal outcome. This measurement may be useful in timing the delivery of early IUGR fetuses and in improving perinatal outcome, even when delivery may be indicated at an earlier GA. However, as GA was also an important factor influencing outcome, with poorer outcome at earlier gestation at delivery, this hypothesis needs to be tested in a multicenter, prospective, randomized trial.