Serena Rigano

Predictors of neonatal outcome in early-onset placental dysfunction

OBJECTIVE: To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. METHODS: Prospective multicenter study of prenataly diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships between perinatal variables (arterial and venous Dopplers, gestational age, birth weight, acid-base status, and Apgar scores) and major neonatal complications, neonatal death, and intact survival were analyzed by logistic regression. Predictive cutoffs were determined by receiver operating characteristic curves. RESULTS: Major morbidity occurred in 35.9% of 604 neonates: bronchopulmonary dysplasia in 23.2% (n=140), intraventricular hemorrhage in 15.2% (n=92), and necrotizing enterocolitis in 12.4% (n=75). Total mortality was 21.5 % (n=130), and 58.3% survived without complication (n=352). From 24 to 32 weeks, major morbidity declined (56.6% to 10.5%), coinciding with survival that exceeded 50% after 26 weeks. Gestational age was the most significant determinant (P<.005) of total survival until 266/7 weeks (r2=0.27), and intact survival until 292/7 weeks (r2=0.42). Beyond these gestational-age cutoffs, and above birth weight of 600 g, ductus venosus Doppler and cord artery pH predicted neonatal mortality (P<.001, r2=0.38), and ductus venosus Doppler alone predicted intact survival (P<.001, r2=0.34). CONCLUSION: This study provides neonatal outcomes specific for early-onset placenta-based fetal growth restriction quantifying the impact of gestational age, birth weight, and fetal cardiovascular parameters. Early gestational age and birth weight are the primary quantifying parameters. Beyond these thresholds, ductus venosus Doppler parameters emerge as the primary cardiovascular factor in predicting neonatal outcome. LEVEL OF EVIDENCE: II

Doppler Investigation in Intrauterine Growth Restriction—From Qualitative Indices to Flow Measurements

In 1997 we started a collaboration among three groups, combining our experience with Doppler examination of the human fetus, blood flow studies on fetal lamb, and mathematical modeling of human circulation. In preliminary investigations on fetal lambs, the same Doppler method designed for the human fetus was used to measure venous blood flow in the umbilical veins of seven fetal lambs. Doppler measurements and diffusion technique groups for umbilical venous flow were 210.8 ± 18.8 and 205.7 ± 38.5 ml/min/kg, respectively (p= 0.881). In human pregnancy the interobserver variabilities for the vein diameter, mean velocity, and absolute umbilical venous blood were 2.9%, 7.9%, and 12.7%, respectively. A cross‐sectional study allowed us to establish normal reference values. Venous blood flow/kg of estimated fetal weight showed a nonsignificant linear reduction with gestational age, from 128.7 ml/min/kg at 20 weeks to 104.2 ml/min/kg at 38 weeks. In a series of 37 growth‐restricted fetuses, the UV flow per kilogram was significantly lower in the more severe growth‐restricted fetuses (abdominal circumference below the second percentile and abnormal umbilical arterial p.i.) than in normal comparable fetuses (p < 0.001). In a series of 140 normal fetuses, we calculated that the absolute blood flow rate in the ductus venosus (DV) increases significantly with advancing gestational age from 20 to 38 weeks of gestation (from 23.2 ± 9.6 ml/min to 43.5 ± 21.5 ml/min). This means that the percentage of umbilical blood flow shunted through the DV decreases significantly during gestation (from 50% at midgestation to 20% at 38 weeks). In a series of 45 growthrestricted fetuses, delivered because of nonreactive fetal heart rate (group 2) and for other reasons but still with a normal heart rate pattern (group 1), we measured the ductal inlet diameter. In these fetuses, the diameters at the ductal isthmus, normalized for the dimension of the abdominal circumference (inlet diameter/abdominal circumference), were significantly larger (group 1 = 6.8 ± 2.3; group 29.4 ± 2.8) than in the control group (6.1 ± 0.3). This means that in this subset of fetuses the amount of blood shunted can be increased as a compensatory mechanism.

Growth of fetal lean mass and fetal fat mass in gestational diabetes

This study was carried out to investigate growth indicators of fetal lean mass and fat mass in the second half of the gestational period in pregnancies complicated by gestational diabetes mellitus (GDM) in comparison to normal control pregnancies.

Small size‐specific umbilical vein diameter in severe growth restricted fetuses that die in utero

To study changes in umbilical vein (UV) blood flow velocity, diameter and blood flow volume in intrauterine growth retardation (IUGR) fetuses who die in utero (IUD‐IUGR).

Computational Patient-Specific Models Based on 3-D Ultrasound Data to Quantify Uterine Arterial Flow During Pregnancy

Information on uterine blood flow rate during pregnancy would widely improve our knowledge on feto-placental patho-physiology. Ultrasonographic flow rate evaluation requires the knowledge of the spatial velocity profiles throughout the investigated vessel; these data may be obtained from hemodynamic simulations with accurate computational models. Recently, computational models of superficial vessels have been created using 3-D ultrasound data; unfortunately, common reconstruction methods are unsuitable for the uterine arteries due to the low quality achievable of imaged deep vessels. In this paper a simplified spline-based technique was applied to create computational models for patient-specific simulations of uterine arterial heamodynamics. Moreover, a novel method to quantify the uterine flow rates was developed based on echo-Doppler measurements and computational data. Preliminary results obtained for four patients indicated a quite narrow range for the blood flow rate through the main uterine artery with large variability in the flow split between corporal and cervical branches. Furthermore, parabolic-like velocity profiles were obtained in the branching region of the different patients, suggesting a clinical use of averaged, not patient-specific, spatial velocity distribution coefficients for the blood flow rate calculation. The developed reconstruction method based on 3-D ultrasound imaging is efficient for creating realistic custom models of the uterine arteries. The results of the fluid dynamic simulations allowed us to quantify the uterine arterial flow and its repartition in normal pregnancies.

OC27.04: Intervention thresholds for severe early onset growth restriction (IUGR)

intraventricular hemorrhagia and elevated nucleated red blood cell counts at delivery. Results: 8 stillbirths (10.7%), 12 perinatal (16%) and 2 neonatal death (2%) occurred among 74 fetuses. Logistic regression analysis confirmed that abnormal Ductus venosus waveforms (R2 = 0.57, p < 0.001) together with gestational age (R2 = 0.57, p < 0.001) showed the strongest association with perinatal death, whereas gestational age only was significantly related with neonatal death (R2 = 0.67, p < 0.05). Abnormal ductus venosus Doppler waveforms (R2 = 0.86, p < 0.001) and gestation age (R2 = 0.49, p < 0.05) were strongly associated with adverse outcome. Abnormal venous Doppler flow patterns performed better in the prediction of fetal or perinatal demise than died ARED flow or brain sparing. Conclusion: Abnormal Ductus venosus waveforms in preterm growth-related fetuses with ARED flow are strongly relates to adverse fetal and perinatal outcomes below 32 weeks of gestational age. The possible benefit of these pregnancies to be prolonged can only be evaluated in a prospective randomized study.

OP15.01: Absolute uterine artery blood flow volume is increased in twin human pregnancies compared to singletons

Objectives: To compare (1) absolute and (2) weight-specific blood flow volume of uterine arteries (UtA) in normal twin pregnancies to normal singleton pregnancies. Methods: Twelve twin pregnancies (10 dichorionic, two monochorionic) with normal UtA PI and normal weight at birth were included. UtA diameter and time-averaged maximum velocity were obtained to calculate flow (mL/min) and UtA flow/EFW (mL/min/kg) in each UtA. UtA flow was estimated by the formula Q = hV · πD2/4; a patient-specific coefficient, h, was obtained by an ad hoc mathematical model. Total UtA flow was calculated as a sum of right and left vessel flow volume. Twins’ UtA flow was expressed per unit EFW considering the sum of the two EFWs. Twins were compared to 48 normal age-matched singletons. Results: Gestational age at exam was similar in twins and in singletons (25.9 ± 6.4 vs. 25.2 ± 6.2 weeks, NS). UtA flow (mL/min) was significantly increased in twins (509.3 ± 240.7 mL/min) compared to singletons (337.2 ± 257.0 mL/min) (P = 0.04). UtA flow (mL/min) exponentially increased along gestation in twins and in singletons. The twins’ trend was above the third interquartile range of singletons’ reference values. UtA diameter was significantly increased in twins (0.33 ± 0.07 cm) than in singletons (0.28 ± 0.05 cm), while no differences in UtA mean velocity were observed (77.5 ± 29.9 vs. 76.7 ± 29.1 cm/sec, respectively, NS). UtA flow per EFW did not differ between twins and singletons (384.4 ± 198.6 vs. 460.9 ± 302.9 mL/min/kg, respectively, NS). Conclusions: (1) UtA flow volume (mL/min) in twin pregnancies was significantly increased. This was determined by larger vessel diameter, compared to singletons. (2) Each twin proved to share an amount of UtA flow per unit estimated fetal weight not significantly different from singletons.

WS02: Prenatal diagnosis WS02‐01Sonographic measurement of fetal subcutaneous tissue of gestational diabetic mothers: a new criteria for therapy

Objective

OP01.06: Reduction of uterine artery blood flow volume is correlated to reduced fetal mass in pregnancies with abnormal uterine resistance index

Total vascular resistance (dyne s/cm5) 1623 (1287–3125) 1163 (944–1785) 0.008 Stroke volume (mL) 69 (36–81) 67 (57–86) 0.95 Cardiac output (L/min) 5.40 (4.4–7.0) 6.1 (4.0–8.1) 0.08 Ejection fraction (%) 69 (64–83) 71 (65–79) 0.59 Midwall fractional shortening (% of predicted value) 118 (94–126) 122 (106–140) 0.04 Isovolumetric relaxation time (ms) 78 (50–90) 60 (45–75) 0.006 24 h ambulatory heart rate (bpm) 74 (61–82) 79 (76–92) 0.003 24 h ambulatory systolic blood pressure (mmHg) 117 (104–136) 106 (101–121) 0.031 24 h ambulatory diastolic blood pressure (mmHg) 75 (65–88) 66 (56–73) 0.012 24 h ambulatory mean arterial pressure (mmHg) 87 (79–104) 79 (72–87) 0.016

P07.05: Uterine artery blood flow volume growth rate in uncomplicated human pregnancies

Objective: 1) To study uterine artery (UtA) flow (ml/min) growth rate along gestation in normal human pregnancies; 2) to evaluate longitudinal changes of UtA flow expressed per unit estimated fetal weight (EFW) (ml/min/kg). Methods: A cohort of twelve singleton uneventful human pregnancies, with a normal mean UtA PI, was included in this longitudinal study. UtA was evidenced by power-Doppler mode and sampled 10–15 mm prior to bifurcation. UtA diameter was measured on a perpendicular view after removing power-Doppler. UtA PI and velocity were measured with a Doppler beam angle < 30◦. The average of three consecutive diameters and velocities was considered. UtA flow was estimated by the formula Q = hV · πD2/4; h coefficient (0.5) was obtained by an ad hoc mathematical model. UtA total flow (ml/min) (right plus left UtA flow) was then expressed per EFW (ml/min/kg). Using linear interpolation, including random effects for the intercept and the slope of gestational age for each fetus, a linear mixed effects model was fitted. Results: Forty-seven ultrasound examinations were performed. Ultrasound exams were performed at 14.3,b1.2 weeks and every 4 weeks until delivery. Each case was definitively included in the study after recording normal perinatal and neonatal outcomes. UtA total flow (ml/min) showed a significant correlation to gestational age (133.6 ml/min at 15 weeks; 415.9 ml/min at 35 weeks) (p < 0.001), with a linear increase of 14.1 ml/min per week (right UtA 5.4 vs. left UtA 8.7 ml/min per week, p NS). UtA flow per unit EFW (ml/min/kg) showed a significant reduction from 780.3 ml/min/kg at 15 weeks to 144.1 ml/min/kg at 35 weeks (reduction rate 40.3 ml/min/kg per week). Conclusions: UtA flow (ml/min) significantly increased along gestation in this longitudinal cohort of normal pregnancies. UtA flow per unit EFW (ml/min/kg) significantly decreased longitudinally, since UtA flow (ml/min) growth rate was lower than fetal weight gain rate along gestation.