The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsens

Objective: To test the hypothesis that hemodynamic changes depicted by Doppler precede deteriorating biophysical profile score in severe intrauterine growth restriction. Methods: Intrauterine growth-restricted fetuses with elevated umbilical artery Doppler pulsatility index (PI) > 2 standard deviations above mean for gestational age and birth weight < 10th centile for gestational age were examined longitudinally. Fetal well-being was assessed serially with five-component biophysical profile scoring (tone, movement, breathing, amniotic fluid volume and non-stress test) and concurrent Doppler examination of the umbilical artery, middle cerebral artery and ductus venosus, inferior vena cava and free umbilical vein. For fetuses with a final biophysical profile score < 6/10, progression of biophysical profile scoring, arterial PI and venous peak velocity indices were analyzed longitudinally. Gestational age effect was removed by converting indices to Z-scores (deviation from gestational age mean, in standard deviations). Results: Forty-four of 236 intrauterine growth-restricted fetuses (18.6%) required delivery for abnormal biophysical profile scoring. The median gestational age at entry was 25 weeks and 1 day and at delivery was 29 weeks and 6 days. The median interval between examinations was 1.5 days and the majority had daily testing in the week prior to delivery. Between first examination and delivery, significant deterioration was observed for Doppler criteria (chi-square, P < 0.001) and biophysical parameters (Fisher's exact, P = 0.02) predominantly confined to the week prior to delivery/stillbirth. Doppler variables changed first. In 42 fetuses (95.5%), one or more vascular beds deteriorated, accelerating especially in the umbilical artery and ductus venosus at a median of 4 days before biophysical profile scoring deteriorated. Two to 3 days before delivery, fetal breathing movement began to decline. The next day, amniotic fluid volume began to drop. Composite biophysical profile score dropped abruptly on the day of delivery, with loss of fetal movement and tone. Three principal patterns of Doppler deterioration were observed: (i) worsening umbilical artery PI, advent of brain sparing and venous deterioration (n = 32, 72.7%); (ii) abnormal precordial venous flows, advent of brain sparing (n = 6, 13.6%); and (iii) abnormal ductus venosus only (n = 4, 9.1%). In the majority (31, 70.5%), Doppler deterioration was complete 24 h before biophysical profile score decline. In the remainder (11, 25%), Doppler deterioration and biophysical profile score < 6/10 were simultaneous. Conclusion: In the majority of severely intrauterine growth-restricted fetuses, sequential deterioration of arterial and venous flows precedes biophysical profile score deterioration. Adding serial Doppler evaluation of the umbilical artery, middle cerebral artery and ductus venosus to intrauterine growth restriction surveillance will enhance the performance of the biophysical score in the detection of fetal compromise and therefore optimizing the timing of intervention.