D. Di Martino

Neurite outgrowth and cell cycle kinetic changes induced by cis-diamminedichloroplatinum II and retinoic acid in a human neuroblastoma cell line

The aim of this study was to analyze by flow cytometry the effect of cis-diamminedichloroplatinum II (CDDP) and retinoic acid (RA) on the cell cycle of a neuroblastoma cell line (SK-N-BE (2)C NB) and to correlate the kinetic data with cell morphology. CDDP at 1 microgram/ml induced a dramatic G2 + M cell cycle phases block (nearly 200% increase with respect to control) 2 days after treatment. The G2 + M block was spontaneously reversed starting from the 4th day. The cells treated with 10 microM RA were, instead, induced to irreversibly enter the G0 + G1 phase of the cell cycle (nearly 20% increase with respect to control) 48 h after treatment. Neurite-like structures were observed for both CDDP and RA treated cells. These data suggest different cell cycle dependent molecular mechanisms and different degrees of differentiation during CDDP or RA treatment of NB cells.

OP09.01: First trimester uterine artery Doppler velocimetry and arterial tonometry

antral follicles. After the year of observation the ovary volume reduced (6.7 ± 1.2/5.1 ± 1.2 ml) with no significant difference from initial data noted in both groups. At the same period the follicular size was normal in the 1st group, in the 2nd group the maximal size of the follicles exceeded 9 mm (significant difference from the initial data P < 0.05). Initially the hormone level in both groups was normal. In 6 months the level of AMH in both groups reduced, but the difference was insignificant with no changes in FSH and E2 levels. By the end of the observation the hormone level didn’t change in the 1st group, in the 2nd group was registered a reduction of AMH level remaining in the range of age norm, but significantly lower than initial (1.98 ± 0.57/1.02 ± 0.30 ng/ml P < 0.05). Conclusions: The influence of UAE on ovary function of fertile patients cannot be ruled out, the risk of reduction of ovarian reserve increases in the older age group.

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.

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.

Maternal cardiac deceleration capacity: a novel insight into maternal autonomic function in pregnancies complicated by hypertensive disorders and intrauterine growth restriction

OBJECTIVE To explore maternal cardiac deceleration capacity (DC), a marker of autonomic function derived from electrocardiographic (ECG) signals, in pregnancies complicated by intrauterine growth restriction (IUGR) and hypertensive disorders of pregnancy (HDP) associated to IUGR (HDP-IUGR) or to appropriate for gestational age fetal growth (HDP-AGAf). METHODS Prospective single center case-control study conducted at Buzzi Childrens Hospital, Milan. Maternal ECGs were analyzed by Phase Rectified Signal Averaging (PRSA) method to obtain cardiac DC in women with: HDP-IUGR, HDP-AGAf, severe-IUGR, mild-IUGR and uncomplicated pregnancies. IUGR was defined as abdominal circumference <5th centile; severe-IUGR was associated with umbilical artery Doppler pulsatility index >2 standard deviations. Non-parametric tests were adopted. RESULTS 269 women were recruited. Women with HDP-IUGR (n=35) showed significantly higher cardiac DC compared both to controls (n=141) (p=0.003) and women with HDP-AGAf (n=18) (p=0.01). Women with severe-IUGR (n=14) showed significantly higher DC than controls (p=0.01). Women with mild-IUGR (n=61) as well as women with HDP-AGAf showed no differences in DC compared to controls (both p=0.3). CONCLUSIONS Women with pregnancy complicated by severe placental failure, such as HDP-IUGR and severe IUGR, show significant autonomic alterations, as indicated by elevated cardiac DC. On the contrary, pregnancy complications such as HDP-AGAf and mild IUGR show no impact on maternal autonomic balance. We present a new approach to explore maternal autonomic cardiovascular regulation that might reflect the severity of placental vascular insufficiency.

OP09.05: Pulse wave analysis: evaluation of arterial stiffness in first trimester for prediction of placental and maternal pre‐eclampsia (PE)

care in a tertiary Brazilian hospital. The base-cohort population was 487 singleton pregnancies, including 9 case subjects who developed PE requiring delivery before 34 weeks (early PE) and 22 with late PE, 47 with gestational hypertension, and 409 cases subjects (84%) who were unaffected by PE or gestational hypertension. Maternal history, body mass index (BMI), mean arterial pressure (MAP), and uterine artery pulsatility index were recorded in all of the cases. Univariate and logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. Results: The maternal characteristics selected by regression analysis to be part of the final predictive model were nulliparity, previous personal and family history of PE. MAP was higher (86 versus 78 mmHg) in patients who developed PE (P < 0.01). The uterine artery percentile of mean PI was higher in the PE than in the control group (50.3% ± 31.7% versus 37.4% ± 30.0%; P < 0.01). It was estimated that, with the algorithm for PE, 78%, 45%, and 26% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 10% false-positive rate. Conclusions: The traditional approach to screening for PE, which is based on maternal demographic characteristics and medical history, identifies ∼60% of cases destined to develop early PE for a falsepositive rate of 10%. This study proposes that a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, for the same false-positive rate of 10%, could identify 78% of cases of early PE.

OP09.06: Hypertensive disorders (HD) of placental and maternal origin: evaluation by applanation tonometry

care in a tertiary Brazilian hospital. The base-cohort population was 487 singleton pregnancies, including 9 case subjects who developed PE requiring delivery before 34 weeks (early PE) and 22 with late PE, 47 with gestational hypertension, and 409 cases subjects (84%) who were unaffected by PE or gestational hypertension. Maternal history, body mass index (BMI), mean arterial pressure (MAP), and uterine artery pulsatility index were recorded in all of the cases. Univariate and logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. Results: The maternal characteristics selected by regression analysis to be part of the final predictive model were nulliparity, previous personal and family history of PE. MAP was higher (86 versus 78 mmHg) in patients who developed PE (P < 0.01). The uterine artery percentile of mean PI was higher in the PE than in the control group (50.3% ± 31.7% versus 37.4% ± 30.0%; P < 0.01). It was estimated that, with the algorithm for PE, 78%, 45%, and 26% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 10% false-positive rate. Conclusions: The traditional approach to screening for PE, which is based on maternal demographic characteristics and medical history, identifies ∼60% of cases destined to develop early PE for a falsepositive rate of 10%. This study proposes that a combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, for the same false-positive rate of 10%, could identify 78% of cases of early PE.

OP01.02: Increased cardiovascular risk in hypertensive disorders (HD) of placental origin

Objectives: To determine the incidence of chromosomal abnormalities, syndromic association and fetal defects in second trimester fetal growth restriction (FGR) in a tertiary referral center for prenatal diagnosis. Methods: Retrospective review of all cases referred between 14 and 27 weeks with an abdominal circumference (AC) < 5th centile between 2008 and 2012. The presence of aneuploidy and associated malformations was also assessed. Multiple pregnancies were excluded. Results: A total of 8626 fetuses had ultrasonographic examination between 14 and 27 weeks. Of these, there were 239 cases (2.8%) with evidence of FGR. Thirty-seven fetuses had an abnormal karyotype or an identified syndromic association (15%), 67 had at least one morphological abnormality without aneuploidy or syndromic association (28%), 135 cases were isolated fetal growth retardation (57%). The most common chromosomal defect was Trisomy 18. Most common morphological abnormalities were relative short femur (5%), omphalocele (5%) and gastroschisis (4%). The Maternal age was higher (33 yr ± 5 yr versus 31 yr ± 5, 6 yr, P = 0.007) and the z-score for the AC lower (2.5 ± 1 versus 2.15 ± 0.6) in the group with abnormal karyotype or syndromic association than in the group without malformation. Amniotic fluid was more often increased in the group with an abnormal karyotype or associated malformation (14% and 17%) than in the group without malformations (0%, P = 0.0003 and 0.0001). Conclusions: This study describes abnormalities and outcomes associated with second trimester fetal growth retardation in a large population of patients referred for that purpose. Our results suggest that the degree of growth restriction, maternal age and the amniotic fluid index may help in the prenatal management and counseling of this high risk population.

OP09.02: Placental volume and uterine artery Doppler correlation in first trimester of pregnancy

antral follicles. After the year of observation the ovary volume reduced (6.7 ± 1.2/5.1 ± 1.2 ml) with no significant difference from initial data noted in both groups. At the same period the follicular size was normal in the 1st group, in the 2nd group the maximal size of the follicles exceeded 9 mm (significant difference from the initial data P < 0.05). Initially the hormone level in both groups was normal. In 6 months the level of AMH in both groups reduced, but the difference was insignificant with no changes in FSH and E2 levels. By the end of the observation the hormone level didn’t change in the 1st group, in the 2nd group was registered a reduction of AMH level remaining in the range of age norm, but significantly lower than initial (1.98 ± 0.57/1.02 ± 0.30 ng/ml P < 0.05). Conclusions: The influence of UAE on ovary function of fertile patients cannot be ruled out, the risk of reduction of ovarian reserve increases in the older age group.