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BACKGROUND: Uterine fibroids are the most frequent female benign tumor, which can cause complications during pregnancy, mainly pain. Differential diagnosis may be challenging and a standardized management approach is lacking. We aim to propose an algorithm for the differential diagnosis of pain during pregnancy and for management of fibroid-related pain. METHODS: A retrospective cohort study of all pregnant women admitted to our center for complications related to fibroids between 2008 and 2019. Data regarding clinical examination, laboratory results, imaging parameters, as well as perinatal outcomes, were collected and assessed (Fisher exact test). RESULTS: Twenty-four pregnant patients were admitted for fibroid-related complications. Six patients were admitted more than one times, for a total of 34 admissions. The main cause of hospital admission was pain (n=33, 94.1%), which was successfully managed with acetaminophen and/or ketoprofen in 91.2%. In two cases, conservative management failed and a surgical approach was undertaken. Most women (n=20, 90.9%) delivered at term, with a cesarean delivery and post-partum hemorrhage rate of 22.7%. All newborns had normal APGAR score, umbilical artery pH and birth weight. CONCLUSIONS: Pain is the most common complication of fibroids during pregnancy. Accurate differential diagnosis and adequate management are pivotal to ensure good perinatal outcomes.

Objective To identify independent predictors of adverse neonatal outcome in cases of fetal growth restriction (FGR) at ≥34 weeks. Methods From a cohort of 481 FGR cases delivered at ≥34 weeks, demographic and obstetric variables, fetal biometry and Doppler indices of the uterine, umbilical and fetal middle cerebral arteries available within 2 weeks of delivery, were related to adverse neonatal outcome, defined as admission to the neonatal intensive care unit for indications other than low birth weight alone. Results Logistic regression analysis showed that gestational age (GA) at delivery (odds ratio (OR) = 0.59; 95% CI, 0.50‐0.70), abdominal circumference (AC) centile (OR = 0.69; 95% CI, 0.59‐0.81) and umbilical artery (UA) pulsatility index (PI) centile (OR = 1.02; 95% CI, 1.01‐1.04) significantly correlated with adverse neonatal outcome.From thismodel we calculateda scoreof adverse neonatal outcome expressed by the formula: (UA-PI centile/3) − (10 × AC centile) + (10 × (40 − GA at delivery in weeks)). Receiver‐operating characteristics curve analysis demonstrated that a score of ≥25 optimally predicted adverse neonatal outcome (sensitivity of 75%, falsepositive rate of 18%). Beyond 37.5 weeks, gestational age no longer had an independent impact on outcome. Conclusions In late preterm or term FGR, GA at delivery is the most important predictor of adverse neonatal outcome. At >37.5 weeks, delivery may be the best option to minimize adverse outcome in all FGR cases. At 34‐37 weeks, a score based on GA at delivery, UA-PI centile and AC centile optimally predicts adverse neonatal outcome. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd.

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.

Background: Intrahepatic cholestasis of pregnancy is a liver disorder with a multifactorial etiology characterized by maternal pruritus, abnormal liver function tests and increased fetal risk. The main biochemical finding is the increase in total serum bile acid concentrations. In a subgroup of women, the serum gamma-glutamyl transpeptidase level is also increased. There is evidence that dysfunction of the ABCB4 gene might play a role in intrahepatic cholestasis of pregnancy development. Aim: To investigate the role of the ABCB4 gene in Italian women with intrahepatic cholestasis of pregnancy and raised gamma-glutamyl transpeptidase by, analyzing the complete coding sequence and mRNA splicing products. Methods: Among 299 women with intrahepatic cholestasis of pregnancy, 10 showing raised gamma-glutamyl transpeptidase were enrolled in this study. DNA and RNA were extracted from peripheral blood mononuclear cells using standard procedures. The 27 coding exons and the promoter region were amplified by polymerase chain reaction and analyzed by sequencing. Reverse transcript-polymerase chain reaction analysis of ABCB4 mRNA and cDNA analysis were also performed. Results: A novel splicing mutation that causes a truncated protein of 249 amino acid was identified in a woman who had the highest serum levels of gamma-glutamyl transpeptidase, alkaline phosphatase, bile acids, and the highest pruritus score. We identified also one already described p.R590Q mutation in a woman who had significantly higher serum levels of alkaline phosphatase, aspartate, and alanine aminotransferase. Conclusions: Our study demonstrates that splicing mutations in the ABCB4 gene can cause ICP in women with high gamma-glutamyl transpeptidase and thus a complete analysis of coding sequence and cDNA products is required. © 2009 Editrice Gastroenterologica Italiana S.r.l.

ANALYSIS OSCAR SADAN, MOSHE LESHNO, AHUVA GOTTREICH, MICHAL DISHI, ABRAHAM GOLAN, SAMUEL LURIE, Sackler University, Holon, Israel, Sackler Faculty of Medicine, Tel-Aviv, Faculty of Management, Tel Aviv, Israel, Tel-Aviv University, Holon, Israel, Wolfson Medical Center, Sackler University, Obstetrics & Gynecology, Holon, Israel, E. Wolfson Medical Center, Tel Aviv University, Obstetrics and Gynecology, Holon, Israel, Tel-Aviv University, Obstetrics & Gynecology, Holon, Israel OBJECTIVE: A previous decision analysis models for two strategic choices for trial of labor or repeated cesarean section after a prior cesarean concluded that the degree of wish for an additional future pregnancy appeared to be a major determinant for the choice between the two strategic options. We had extended the analysis model to stillbirth and hypoxic-ischemic encephalopathy in addition to placental complications while updating most of the outcomes in the decision tree. STUDY DESIGN: A model was formulated using a decision tree based on reported probabilities for various outcomes and estimated utilities. The question asked was should a trial of labor or repeated cesarean section be performed after a prior cesarean, with a varying desire for an additional pregnancy. RESULTS: Our model favors repeated elective cesarean section (0.9947) over trial of labor (0.9917) after a previous cesarean and is the preferred approach. This approach was preferable irrespective of the probability of additional pregnancy. CONCLUSION: In contrary to previous models, when taking into account occurrence of a live infant birth, birth of an infant with hypoxic-ischemic encephalopathy stillbirth, neonatal death, abnormal placental implantation, hysterectomy, and maternal death the preferred approach for women with previous cesarean section is an elective repeated cesarean section rather then trial of vaginal delivery.

NEUROTOXITICITY ROBIN ROBERSON, IRENE CAMERONI, LAURA TOSO, DANIEL ABEBE, STEPHANIE BISSELL, CATHERINE SPONG, National Institutes of Health (NIH), Unit on Perinatal and Develomental Neurobiology, NICHD&NIAAA, Bethesda, Maryland, University of Milano-Bicocca, Obstetrics and Gynecology, Monza, Milan, Italy OBJECTIVE: Fetal alcohol syndrome (FAS) is the leading cause of a spectrum of preventable non-genetic learning disorders. In the adult, neurogenesis occurs in the hippocampal dentate gyrus, which is thought to be important for learning and memory. Previously we have shown alterations in the NMDA receptor underlie some of the learning abnormalities in FAS. NMDA exerts it action through CREB. CREB is a transcription factor that controls gene expression via phosphorylation promoting neuronal survival. Using a model for FAS, we measured P-CREB levels in hippocampal subregions to evaluate if alterations in P-CREB underlie the FAS learning abnormalities after in utero alcohol exposure. STUDY DESIGN: Pregnant C57Bl6/J mice were treated on gestational day 8 with alcohol, n = 10 or control (saline) n = 5. Adult males were assessed in the Morris water maze for learning on days 50-56. On day 57, 5 males/ treatment were perfused for immunohistochemistry, and stained with SER 144 P-CREB antibody with relative densities of staining assessed using NIH Image software. Statistical analysis ANOVA, P!.05 significant. RESULTS: The hippocampal areas CA1, dentate and CA3 were quantitated. In the control, P-CREB staining was greatest in dentate granule cells and lowest in CA1. In all of the hippocampal subregions, alcohol exposure in utero resulted in significant downregulation of P-CREB (P!.001).

Objective To assess the role of uterine artery (UtA) Doppler to predict superimposed preeclampsia in women with chronic hypertension. Methods In a cohort of 182 women with chronic hypertension, UtA Doppler studies were performed before 25 weeks (mean 19.7 ± 2.1 weeks) and repeated later in pregnancy (mean 28.5 ± 3.7 weeks). Results The incidence of preeclampsia was 13% (24/182). Rates of preeclampsia increased with advancing gestation of abnormal UtA Doppler: 7% when UtA Doppler were normal at early exam, 18% when abnormal at early exam, and 28% when abnormal at late exam (Chi-square for trend: P < 0.001). The rate of preeclampsia among 40 women with abnormal early but normal late UtA Doppler was similar to that of women with normal findings at early exam (8 vs 7%; P = 1.00). Logistic regression analysis showed that the ability of UtA Doppler to predict preeclampsia was independent from other variables [Odds Ratio (OR) 7.1, 95% Confidence Interval (CI) 2.6–18.9). Receiver operating characteristic (ROC) curve identified a UtA value of 0.58 as the optimal threshold for the prediction of preeclampsia. Conclusion The later in pregnancy the abnormal UtA Doppler findings are observed, the greater the risk of preeclampsia. Normalization of UtA Doppler after 25 weeks reduces the risk of preeclampsia to 8%. Copyright © 2008 John Wiley & Sons, Ltd.