Kathryn Drennan

The Transitional Phase of Ductus Venosus Reversed Flow in Severely Premature IUGR Fetuses

The guiding hypothesis for this work is that in severe intrauterine growth-restricted (IUGR) fetuses, the time from ductus venosus (DV) reversed flow (RF) appearance to intrauterine fetal demise (IUFD) or nonreassuring fetal testing is variable. As such, there must be a transitional phase between the presence of end-diastolic forward flow (FF) and absent or reversed end-diastolic flow (A/REDF). Ductus venosus Doppler was serially studied in 19 IUGR fetuses (estimated fetal weight < 10th percentile and umbilical artery pulsatility index > 95th percentile) from diagnosis until demise or delivery occurring for nonreassuring fetal testing. Ductus venosus waveforms were assessed qualitatively: forward flow versus absent or reversed flow in diastole. Two sets of at least 30 consecutive ductus venosus waveforms were obtained at each examination. If the waveforms differed between the two sets, they were defined as alternating. Cord arterial pH and base excess (BE) were obtained at birth. In 14 cases, DVRF occurred intermittently between periods of FF during the same clinical visit. Intermittent DVRF was present from 2 to 57 days (median, 13 days) and became continuous from 1 to 23 days (median, 7 days) before the occurrence of delivery for nonreassuring fetal testing or fetal demise. One fetus had an abnormal arterial pH (< 7.0) and one had an abnormal BE (< -12). These data show that (1) there is a transitional phase in which DV alternates FF and A/RF before RF becomes persistent; (2) the time from the appearance of DVRF to delivery or IUFD is variable, and (3) not all very preterm IUGR fetuses with continuous DVRF are acidemic. Because of these findings, the decision of delivery regarding early severe IUGR fetuses should be individualized, and the DVRF Doppler information has to be integrated with other antenatal fetal parameters.

Nuclear Matrix Association: Switching to the Invasive Cytotrophoblast

Abnormal trophoblast invasion is associated with the most common and most severe complications of human pregnancy. The biology of invasion, as well as the etiology of abnormal invasion remains poorly understood. The aim of this study was to characterize the transcriptome of the HTR-8/SVneo human cytotrophoblast cell line which displays well characterized invasive and non-invasive behavior, and to correlate the activity of the transcriptome with nuclear matrix attachment and cell phenotype. Comparison of the invasive to non-invasive HTR transcriptomes was unremarkable. In contrast, comparison of the MARs on chromosomes 14-18 revealed an increased number of MARs associated with the invasive phenotype. These attachment areas were more likely to be associated with silent rather than actively transcribed genes. This study supports the view that nuclear matrix attachment may play an important role in cytotrophoblast invasion by ensuring specific silencing that facilitates invasion.

OC252: Sequence of cardiovascular changes occurring in severe IUGR fetuses in pregnancies complicated by pre‐eclampsia and in pregnancies without this complication

Objectives: To examine the relationship between smallness, assessed by customized standards, and the predictive value of a normal umbilical artery Doppler. Methods: A cohort was created of 7645 singleton pregnancies without congenital anomalies. Fetuses suspected antenatally of being small for gestational age were referred for assessment by umbilical artery Doppler. The associations with adverse outcome were assessed for small-for-gestational age babies who had normal and abnormal Doppler, compared with neonates who were not small for gestational age. Perinatal outcome indicators were collected, including fetal distress requiring Cesarean section and neonatal morbidity (neonatal intensive care > 14 days, neonatal seizures, intraventricular hemorrhage Grade III or more, periventricular leucomalacia, hypoxic–ischemic encephalopathy, or necrotizing enterocolitis). Results: Of the 369 small-for-gestational age fetuses which had been identified antenatally, 70 (19%) had an abnormal umbilical artery Doppler and the babies from these pregnancies had an elevated risk of fetal distress requiring Cesarean section (OR 5.89; CI, 2.64–11.84) and neonatal morbidity (OR 3.99; CI, 1.04–11.03). However the 299 fetuses (81%) with normal umbilical artery Doppler also had elevated risk of fetal distress (OR 4.49; CI, 2.96–6.66) and neonatal morbidity (OR 2.26; CI, 1.04–4.39). Because of the higher prevalence, many more instances of adverse outcome were attributable to this group than to the group with abnormal Dopper (fetal distress – population attributable risk (PAR): normal Doppler 8.6 vs. abnormal Doppler 2.7; neonatal morbidity – PAR: normal Doppler 4.0 vs. abnormal Doppler 2.2. Conclusions: Smallness for gestational age according to customized weight standards defines a group of pregnancies with significantly elevated risk of adverse perinatal outcome. Normal antenatal umbilical artery Doppler cannot be taken as an indicator of low risk in these pregnancies.

OC116: Ductus venosus SIA Index and a‐wave reversed flow in severely premature growth‐restricted fetuses

test. Results: There were 8 fetal demises (FD), 9 neonatal demises (ND), and 32 neonates survived (NS) at the time of hospital discharge. An ROC curve for the SIA Index in all cases showed less than −1.25 correlated with FD and greater than −1.25 correlated with live birth with 100% sensitivity and 100% specificity. A second ROC curve of live births showed less than 2.07 correlated with NS and greater than 2.07 correlated with ND with a sensitivity of 67% and a specificity of 94%. DV A/REDF correlated with FD and ND with sensitivities of 88% and 78%, respectively, and with NS 32%. Of the 32 NS, 11 (34%) possessed A/REDF at some time, with a median of 11 days before delivery. Conclusions: The SIA Index is a novel Doppler parameter in the assessment of severely premature IUGR fetuses that allows a much more accurate prediction of fetal outcome compared to A/REDF alone. Assessment of the SIA Index should therefore be considered part of the evaluation of IUGR fetuses.

OC117: Are double pulsations in the umbilical vein equivalent to a-wave reversal in the ductus venosus in the management of IUGR?

Objectives: Doppler waveforms of the Ductus Venosus (DV) demonstrate two periods of decreased blood velocity. These occur during isovolumetric relaxation at the end of ventricular systole and during atrial contraction at the end of ventricular diastole (a wave). In IUGR fetuses, both the isovolumetric relaxation velocity (IRV) and the end-diastolic velocity (EDV) may become abnormal. The hypothesis of this study is that in severely premature IUGR fetuses, Doppler assessment of both the IRV and the EDV allows a more accurate prediction of fetal outcome than A/REDF alone. Methods: DV Doppler was serially studied in 49 severely premature IUGR fetuses from diagnosis until demise or delivery. DV waveforms were assessed quantitatively for peak systolic velocity (PSV), IRV, and EDV and qualitatively for forward or A/REDF. The SIA Index [PSV/(IRV+EDV)] was calculated for each fetus and compared to fetal/neonatal outcomes. Data was analyzed by Kruskal-Wallis non-parametric one-way ANOVA with post-hoc Mann-Whitney U test. Results: There were 8 fetal demises (FD), 9 neonatal demises (ND), and 32 neonates survived (NS) at the time of hospital discharge. An ROC curve for the SIA Index in all cases showed less than −1.25 correlated with FD and greater than −1.25 correlated with live birth with 100% sensitivity and 100% specificity. A second ROC curve of live births showed less than 2.07 correlated with NS and greater than 2.07 correlated with ND with a sensitivity of 67% and a specificity of 94%. DV A/REDF correlated with FD and ND with sensitivities of 88% and 78%, respectively, and with NS 32%. Of the 32 NS, 11 (34%) possessed A/REDF at some time, with a median of 11 days before delivery. Conclusions: The SIA Index is a novel Doppler parameter in the assessment of severely premature IUGR fetuses that allows a much more accurate prediction of fetal outcome compared to A/REDF alone. Assessment of the SIA Index should therefore be considered part of the evaluation of IUGR fetuses.