F. Fuse

Italian Advisory Board: sFlt-1/PlGF ratio and preeclampsia, state of the art and developments in diagnostic, therapeutic and clinical management

Extensive research has been published, showing the usefulness of angiogenic markers in both diagnosis and subsequent prediction and management of preeclampsia and placenta-related disorders. Recent evidence provides a helpful cut off for the Elecsys ratio sFlt-1 to PlGF, that predicts preeclampsia development in women with sign and symptoms, before its clinical onset in the short term. In Europe, no accordance exists for the use of such kind of test in clinical practice; only German guidelines have recently taken it into account, as a diagnostic aid for preeclampsia, in conjunction with other clinical findings. This panel of Italian experts recently met, in order to review the literature and to promote the evaluation of the clinical utility of sFlt-1/PlGF ratio at the Italian country level, as regards: prediction of preeclampsia during the first trimester, prediction or exclusion of new onset or recurrence in patients with risk factors for preeclampsia, triage of patients suffering from gestational hypertension, evaluation of disease severity, prediction of adverse maternal and fetal outcomes.

Multivariable evaluation of the maternal hemodynamic profile in pregnancies complicated by intrauterine growth restriction: a prospective study: Maternal hemodynamics in IUGR.

To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre‐eclampsia and gestational hypertension).

P05.04: Placental histology and sFlt-1/PlGF in pregnancies complicated by hypertensive disorders

males. (Mean fetal weight: 0,65g vs 0,84g, p<.001 at ED17,5 and 1,01g vs 1,14g, p=.02 at ED18,5). Measured by ultrasounds, uterine artery resistance index (RI) was higher in late gestation in transgenic group. (mean RI: 0,63 vs 0,58, p= .029). In 29 mice studied by BOLD MRI, change in T2* differed significantly between STOX 1 and wild type in placental inner layer (8.2 msec vs 5.8 msec; p < .025), placental outer layer (6.1 msec vs 3.07msec; p < .005), and fetal brain (5.29 msec vs 9.09 msec; P = .004). There was no significant difference in the fetal liver (2.42 msec vs 2.5 msec; P = .25). Conclusions: STOX1-overexpressing mice constitute a reliable model of PE. BOLD MRI has the potential to pick up placental changes in such mice pre-eclamptic pregnancies as compared to normal ones.

OP06.02: Three‐dimensional automated measure of the fetal thigh in high‐risk pregnancies to predict fetal weight

Results: At admission of suspected preterm birth, both preterm and term-born after suspected preterm labour pregnancies present a higher rate of SGA (12,4 % vs 6,6% vs 0,9%; p<0,001) compared to the control group. The proportion of SGA neonates was also increased in both groups after suspected preterm labour (11,8% vs. 7,7% vs. 5,6%; p=0.024), as well as the rate on neonatal intensive care admission (75% vs. 16,5% vs. 3,1%; p<0,001) compared with controls. Conclusions: Suspected preterm labour is a risk factor for fetal growth restriction and adverse perinatal outcomes even in term-born neonates. Fetal growth surveillance would be recommended after admission for suspected preterm labour.

P25.08: Maternal hemodynamic profile in pregnancies complicated by intrauterine growth restriction

Objectives: To compare published reference charts of Umbilical Artery (UA), Middle Cerebral Artery (MCA) Doppler and Cerebroplacental Ratio (CPR), in order to assess the clinical impact in management arising from the variation between different reference charts. Methods: MEDLINE was searched for all the studies published between 1988 and 2016 whose only aim was to create fetal Doppler reference values. The search yielded 725 possible citations, of which 21 studies reporting normal Doppler reference values were finally included in the review for Umbilical Artery (11), Middle Cerebral Artery (12) and Cerebroplacental Ratio (3). The differences between Pulsatility Index (PI) cut-off values at clinically relevant centiles were expressed in percentage form by subtracting the lowest from the highest PI and dividing by the highest. A simulation analysis was performed on a historical cohort of SGA fetuses (n= 617) to evaluate the impact of this variability on clinical management. Results: Wide discrepancies in reported Doppler references values were found. Middle cerebral artery showed the greatest differences between clinically relevant PI cut-off values: for the 5th centile of MCA PI there was up to 47.2% variation between published references at 36-37 weeks of gestation. Differences between the 95th PI umbilical artery cut-off centile were above 20% at 28-38 weeks. For the CPR the 5th centile values varied from 17% (at 39 weeks) to 35% (at 37 weeks). Simulation analysis showed that, depending on the chart used, the prevalence of abnormal UA, MCA and CPR varied in our historical cohort from 18.2% to 2.1%, 0.7% to 22.6% and 4.3% to 26.5% respectively. Conclusions: Large differences exist in current fetal Doppler reference charts at clinically relevant cut-offs. The choice of chart used could lead to a significant change in clinical management. Therefore, an attempt to standardise fetal Doppler reference ranges is mandatory, as this variability may lead to suboptimal outcomes in clinical practice and research.

OP01.03: Placental histology and sFlt‐1/PlGF ratio in intrauterine growth restriction

Objectives: Evaluation of the fetus at risk for uteroplacental insufficiency and growth restriction applies spectral Doppler measurements of the fetal circulation. Our objective is to determine if fetuses with abdominal circumference (AC) below the 5th or weight (EFW) below the 10th percentile will have lower values for the cerebroplacental ratio or the cerebrorenal ratio. Methods: We evaluated 2900 unselected women with multiple associated fetal and maternal co morbidities in whom we measured both the CPR and the CRR using previously standardised methodology. Results: No discernible differences were found between fetuses with low AC <5 or 10 percentile and fetuses with EFW <10% and the CRR or CPR of the appropriately grown fetuses. We plotted the values of each on previously created reference curves (figure). Conclusions: The measurement of the CPR or the CRR among fetuses with AC <10th percentile was not better than EFW <10th percentile to identify fetuses that would ultimately have a lower value consistent with centralisation of fetal blood flow.

OP01.11: Maternal hemodynamic in pregnancies complicated by intrauterine growth restriction and hypertensive disorders

Methods: 10733 women with a complete first trimester screening were included. Potential predictors for birth weight included maternal age, BMI, parity, smoking status, type of conception, time difference (days) between date of pregnancy based on CRL and LMP (CRL-LMP), uterine artery lowest PI (UtA-LPI), PAPP-A and bHCG (MoM) as well as abdominal circumference (AC, Z-score). Bootstrap methods were used for model selection and estimation, under an approximately uniform distribution of birth weight. A model was built to predict individual birthweight using first trimester variables. The additional value of these variables was quantified by comparing the birthweight absolute percent prediction error (APPE) given by the model to the percent error using the average weight reference provided by the Intergrowth study. Small and large for gestational age (SGA and LGA) were defined by birth weight <10th centile and >90th centile respectively. Results: The prediction model included BMI, parity, smoking status, time difference between date of pregnancy based on CRL and LMP, UtA-LPI, PAPP-A, bHCG and AC. in SGA newborns, first trimester individual birthweight predictions were significantly closer to the actual birthweight (median APPE=17% IQR=10-23) compared to population references (median APPE 24% IQR=20-30). However, in the overall population as in LGA newborns, first trimester did not improve birthweight prediction compared to the average weight reference. Conclusions: Birthweight predictions based on a combination of maternal history, ultrasound, and biochemistry in the first trimester significantly improved screening for SGA with a significant contribution of CRL-LMP.