Irene Cameroni

Prevention of Developmental Delays in a Down Syndrome Mouse Model

OBJECTIVE: To estimate whether prenatal treatment with neuroprotective peptides prevents the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome and to explore the peptides’ effects on achievement of normal development. METHODS: Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8–12. Offspring were tested from postnatal day 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup’s treatment and genotype. The pup’s genotype was determined after completion of all tests. Activity-dependent neurotrophic factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real-time polymerase chain reaction. RESULTS: Trisomic mice achieved milestones with a significant delay in four of five motor and sensory milestones. Trisomic mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in three of four motor and one of four sensory milestones (P<.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent neurotrophic factor expression was significantly downregulated in the Ts65Dn brains compared with the controls, prenatal treatment with NAPVSIPQ+ SALLRSIPA prevented the activity-dependent neurotrophic factor decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+ SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the trisomic brains, whereas treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. CONCLUSION: Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome.

Can adverse neonatal outcome be predicted in late preterm or term fetal growth restriction

To identify independent predictors of adverse neonatal outcome in cases of fetal growth restriction (FGR) at ≥ 34 weeks.

Prediction of superimposed preeclampsia using uterine artery Doppler velocimetry in women with chronic hypertension.

To assess the role of uterine artery (UtA) Doppler to predict superimposed preeclampsia in women with chronic hypertension.

Alterations in phosphorylated cyclic adenosine monophosphate response element of binding protein activity: a pathway for fetal alcohol syndrome-related neurotoxicity.

OBJECTIVEnFetal alcohol syndrome (FAS) is the leading cause of a spectrum of preventable nongenetic learning and behavioral disorders. In adult (FAS) mice, we measured phosphorylated cyclic adenosine monophosphate response element of binding protein (pCREB) staining in hippocampal subregions to evaluate a possible mechanism underlying FAS learning deficits.nnnSTUDY DESIGNnPregnant C57BL6/J mice were treated on gestational day 8 with alcohol or control (saline). After learning assessment, the offspring were perfused for immunohistochemistry and brain sections probed using SER 133 pCREB antibody. Relative staining density was assessed using National Institutes of Health Image software. Statistical analysis included analysis of variance with P < .05 considered significant.nnnRESULTSnIn all hippocampal subregions, pCREB staining was greater in the control animals than in the alcohol-treated group (P < or = .0001).nnnCONCLUSIONnIn utero alcohol exposure decreased pCREB activity in hippocampal subregions of adult mice. The dentate gyrus had the most robust cumulative decrease in pCREB staining, suggesting FAS adult learning deficits may correlate to enhanced dentate gyrus neurodegeneration.

P32.05: Uterine artery Doppler in a risk population: What's its role in the prediction of severe pregnancy complications?

Objective: The aim of this study was to evaluate the efficacy of uterine artery Doppler velocimetry in predicting placenta previa-accreta. Methods: Clinical records of all deliveries between April 1991 and June 2007 were retrospectively analyzed. Cases with small for gestational age, pregnancy-induced hypertension, multiple pregnancies, fetal anomalies, chromosomal abnormalities, and maternal medical illnesses such as cardiovascular disease, renal disease or diabetes mellitus were excluded. Out of 10,977 total cases evaluated, 173 had placenta previa without accreta (PP) and 28 placenta previa with accreta (PPA), diagnosed by histological confirmation. All patients underwent uterine artery Doppler flow velocimetry to measure the mean resistance index (RI) at third trimester, and age, parity, previous abortion history, previous cesarean section history, gestational age at delivery, child sex and birth weight were reviewed. Multiple logistic regression was performed to adjust for potentially confounding variables. Results: Statistically significant differences were found in age, parity, previous abortion, previous cesarean section, gestational age at delivery, and birth weight (P < 0.001, respectively) between the normal group (n = 10,776) and the placenta previa group (n = 201, PP + PPA). Uterine artery Doppler mean RI and sex were similar in both groups (P > 0.05). In placenta previa group, no difference was observed in all variables except uterine artery Doppler mean RI between PP and PPA. In cases of uterine artery Doppler mean RI lesser than 0.40, women who had placenta previa were at increased risk of having placenta accreta (odds ratio [OR] 3.39; 95% confidence interval [CI] 1.41, 8.16). Conclusions: This study shows that uterine artery Doppler RI is reduced in PPA compared with PP. Low uterine artery Doppler RI is independent risk factor of placenta accreta in placenta previa patients.

O6. Uterine artery Doppler in a risk population: What’s its role in the prediction of small for gestational age fetuses?

Objective: The aim of this retrospective study was to assess the role of uterine artery (UtA) Doppler velocimetry in the prediction of small for gestational age (SGA) fetuses in a high risk population. Methods: A population of 145 singleton high risk pregnancies was evaluated with serial UtA Doppler performed within 23 weeks (I UtADoppler) and between 23 and 30 weeks’ gestation (II UtA Doppler). Risk population was composed by women with chronic hypertension or with a previous pregnancy complicated by one of the following: preeclampsia, stillbirth, abruptio placentae, small for gestational age newborns. The association between an abnormal UtA velocimetry (Resistance Index > 0.58 and/or bilateral notch) and the probability to develop SGA fetuses was analysed. SGA fetuses were diagnosed on the base of ultrasonographic measurement of abdominal circumference below the 10 centile. Therapy with low-dose aspirin and/or Low Weight Molecular Heparin was prescribed according with a clinical protocol. Results: Gestational age at delivery, mean birth weight, abnormal UtA Doppler and Umbilical artery Doppler were significantly different between SGA fetuses and not SGA fetuses (Table 1). Particularly 30% of SGA fetuses with an abnormal UtA Doppler had also an abnormal Umbilical artery Doppler (defined as a Pulsatility Index >95 centile). Logistic regression analysis showed that only the abnormal UtA Doppler test performed between 23 and 30 weeks’ gestation independently correlated with SGA fetuses, otherwise ASA was a significant protective factor for SGA fetuses (Table 2). Persistence of abnormal UtA Doppler was associated with a statistically higher rate of SGA. Conclusion: An abnormal UtA Doppler in the late second or early third trimester remained the variable significantly related with SGA fetuses; therefore UtA Doppler evaluation between 23 and 30 weeks could be useful for the management of high risk population. ASA was a significant protective factor for intrauterine growth.

OP14.14: Small for gestational age fetuses: Does presence of preeclampsia affect neonatal outcome?

Objectives: To evaluate the independent and combined contribution to short-term predictive value for mortality in severe IUGR of clinically used and recently described cardiovascular Doppler parameters. Methods: Umbilical artery, middle cerebral artery, ductus venosus (DV), aortic isthmus flow index and modified-myocardial performance index (Mod-MPI) were measured in a cohort of 97 preterm IUGR fetuses. Logistic regression was performed to select those variables that were independently associated to perinatal mortality, and an algorithm to estimate probabilities of death was constructed including the best combination of parameters. Results: A combination of gestational age (below or above 28 weeks), DV atrial flow (positive or absent-reverse) and ModMPI (normal or above 95th percentile) had the highest predictive value for perinatal mortality in IUGR cases. An algorithm including these 3 parameters had a better predictive accuracy than any single parameter. The risk for death below and above 28 weeks respectively was: normal DV and Mod-MPI, 18% and 0.1%; either abnormal, 70–73% and 6–7%; both abnormal, 97% and 45%. Conclusions: The use of composite cardiovascular Doppler scores may help to refine considerably the short-term prediction of perinatal mortality at different gestational ages in severe IUGR fetuses.