[show abstract][hide abstract] ABSTRACT: Our primary objective was to establish a cutoff value for the soluble fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured using the Elecsys assay to predict late-onset preeclampsia in low-risk pregnancies. Our secondary objective was to evaluate the ability of combination models using Elecsys data, second trimester uterine artery (UtA) Doppler ultrasonography measurements, and the serum fetoplacental protein levels used for Down's syndrome screening, to predict preeclampsia.
This prospective cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation.
Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver operating characteristic curve analysis showed that the third trimester sFlt-1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used to determine the five best combination models for early detection of late-onset preeclampsia. The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed FPR of 10%, the combination of body mass index and the second trimester sFlt-1 level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded a DR of 62.5% at a fixed FPR of 10%.
The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio, and the combination of the second trimester sFlt-1 level with body mass index, were better predictors of late-onset preeclampsia than any individual marker.
BMC Pregnancy and Childbirth 01/2014; 14(1):35. · 2.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this short manuscript we comment that circulating mRNA species possibly originating from both the trophoblast and the mesenchymal axis of the chorionic villi can be used to screen for CHD.
Ultrasound in Obstetrics and Gynecology 11/2013; · 3.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract Objective: To derive a birth weight predictive equation and to compare its diagnostic value with that of ultrasound. Methods: A longitudinal observational cohort study, including singleton pregnancies at term, was performed at St. Orsola-Malpighi Hospital, University of Bologna, (Italy). A birth weight prediction formula, including symphysis-fundal height (SFH), BMI, maternal abdominal circumference (mAC) and parity was derived from a general linear model (GLM) (retrospective study). Moreover, on a new series of patients, the fetal weight was estimated by using both GLM and ultrasound using Hadlock formula (prospective study). The residual analysis and the intraclass correlation coefficient (ICC) were used to test the accuracy of methods in predicting birth weight. Results: Between January and November 2012, 1034 patients were included in the retrospective study and 44 in the prospective one. The following GLM was derived: estimated birth weight (g)=1485.61+(SFH(cm)×23.37)+(11.62(cm)×mAC)+[BMI×(-6.81)]+(parity (0=nulliparous, 1=multiparous) × 72.25). When prospectively applied, the GLM and ultrasound provided a percentage of prediction within ± 10% of the actual weight of 73% and 84% respectively. Ultrasound estimation, as opposite of GLM one, was significantly associated with neonatal weight (R(2)=0.388, F=26.607, p-value<0.001, ICC=0.767). Conclusions: Although ultrasound biometry has provided the best values in fetal weight estimation, the predictive performance of both methods is limited.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2013; · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim: The aim of this paper was to evaluate the lower uterine segment (LUS) thickness through transvaginal sonography in late preterm and full term pregnancies with a single previous Cesarean section, to correlate the obtained LUS measurements with intraoperative observations, and to identify a predictive cut-off value in order to select the best candidates for a vaginal birth after Cesarean delivery (VBAC). Methods: Two hundred and fourteen women with a single previous Cesarean section who had an ultrasound measurement of the LUS thickness (stratified in S1, S2 and S3) in pregnancy were enrolled. The outcome of interest was the visual finding of a thin uterine scar at the time of the iterative Cesarean section. Linear regression was used to correlate the LUS thickness with gestational age (GA). A ROC curve has been used to determine the detection rate (DR) and the risk of each actual value of LUS thickness versus a thin uterine scar (outcome of interest). Results: The LUS thickness was correlated with the gestational age (R2=0.034, P-value =0.005). The DR as estimated by ROC curves to detect a translucent lower uterine segment (S3) was 94.1% at a false positive rate (FPR) of 20%. The correspondent cut-off value was 1.8 mm. Finally a likelihood ratio (LR) of observing S3 was estimated. At the quoted cut-off of 1.8 mm the LR was 3. As demonstrated, for a segment of 1 mm the LR was instead about 13. Conclusion: The obtained values lead us to the conclusion that a thickness less than 1.8 mm can be reasonably considered a valid cut-off value to identify patients with a higher risk of thin uterine scar.
[show abstract][hide abstract] ABSTRACT: Aim: The study aims to calculate the probability of a successful vaginal delivery in post-term low-risk women by using a set of predictors (maternal, fetal, and ultrasonographic) according to the number of dinoprostone gel applications. Methods: This was an observational study of a cohort of 174 low-risk post-term singleton pregnancies. Parity, cervical status and length, and amniotic fluid volume (AFI) were evaluated immediately before prostaglandin gel induction at the Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy between January 2010 and October 2011. Results: A consistent difference in vaginal delivery rates was observed for women who had one gel administration (Group 1) versus those who received either two or three gel administrations (Group 2): 77.5% at 24 hours and 97.4% at 48 hours vs. 27% at 24 hours and 54% at 48 hours (P <0.001 for both the comparisons) respectively. The predictors of a vaginal delivery were cervix dilatation and short cervix for Group 1, lower AFI for Group 2, and parity for both groups. Conclusion: Women who require more than one gel administration have a lower rate of vaginal delivery at 24 and 48 hours. Maternal, fetal, and ultrasonographic parameters can predict a successful vaginal delivery.
[show abstract][hide abstract] ABSTRACT: Ursodeoxycholic acid (UDCA) administration in intrahepatic cholestasis of pregnancy (ICP) induces bile acids (BA) efflux from the foetal compartment, but the molecular basis of this transplacental transport is only partially defined.
To determine if placental breast cancer resistance protein (BCRP), able to transport BA, is regulated by UDCA in ICP.
32 pregnant women with ICP (14 untreated, 34.9±5.17 years; 18 treated with UDCA - 25 mg/Kg/day, 32.7±4.62 years,) and 12 healthy controls (33.4±3.32 years) agreed to participate in the study. Placentas were obtained at delivery and processed for membrane extraction. BCRP protein expression was evaluated by immunoblotting techniques and chemiluminescence quantified with a luminograph measuring emitted photons; mRNA expression with real time PCR. Statistical differences between groups were evaluated by ANOVA with Dunn's Multiple Comparison test.
BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed among the three groups both for mRNA (ANOVA, p = 0.0074) and protein (ANOVA, p<0.0001) expression. BCRP expression was similar in controls and in the untreated ICP group. UDCA induced a significant increase in placental BCRP mRNA and protein expression compared to controls (350.7±106.3 vs 100±18.68% of controls, p<0.05 and 397.8±56.02 vs 100±11.44% of controls, p<0.001, respectively) and untreated ICP (90.29±17.59% of controls, p<0.05 and 155.0±13.87%, p<0.01).
Our results confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast and show that ICP treatment with high dose UDCA significantly upregulates placental BCRP expression favouring BA efflux from the foetal compartment.
PLoS ONE 01/2013; 8(5):e64101. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: We aimed to clarify whether the short-term adverse neonatal outcomes associated with epidural analgesia are due to the epidural analgesia itself or to the instrumental delivery. METHODS: A retrospective case-control study was conducted to evaluate the relationship between epidural analgesia, labor length, and perinatal outcomes. A total of 350 pregnant women at term who delivered under epidural analgesia (cases) were compared with 1400 patients without epidural analgesia (controls). RESULTS: Vacuum extraction (6.5 vs. 2.9 %) and cesarean section (19.9 vs. 11.1 %) were more frequently performed in the cases than controls (p < 0.001). Using a Kaplan-Meier algorithm, it was determined that the mean lengths of the 1st and 2nd stages of labor and the overall durations of labor and delivery were significantly longer in cases compared with controls. A Cox regression analysis showed that the longer labor remained even after adjustment for parity. The neonatal variables stratified by mode of delivery were not different in cases and controls, except for a slightly lower umbilical arterial pH in spontaneous delivery for the cases group. However, the Apgar scores and umbilical arterial pH were significantly lower in the neonates delivered by vacuum extraction compared with those in the neonates delivered by spontaneous delivery or cesarean section, regardless of whether epidural analgesia was performed. A multivariable analysis showed that vacuum extraction much more consistently affected the arterial pH than the analgesia itself (the β coefficients were -0.036 for epidural analgesia vs. -0.050 for vacuum extraction). CONCLUSION: Epidural analgesia was associated with slowly progressing labor, thus resulting in an increased rate of instrumental delivery. This instrumental delivery appears to adversely affect the neonatal outcomes more strongly than the analgesia itself.
Journal of Anesthesia 09/2012; · 0.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim was to determine the outcome of pregnancies complicated by maternal Parvovirus B19 (B19) infection.
Among 175 pregnant women referred to our clinic because of suspicion of a B19 infection, 63 with confirmed laboratory diagnosis of acute/recent B19 infection were followed up by ultrasound and Doppler measurement of the middle cerebral artery peak systolic velocity.
The vertical transmission rate was 31.7% (20/63). Of the 20 infected, 8 had hydrops, 1 had signs suggestive of meconium peritonitis and 1 had an isolated hydrothorax. Three fetuses presenting with hydrops were treated with intrauterine blood transfusion. Two of them died while the last showed resolution of anemia. Among the five untreated hydropic fetuses, one presented with mild signs that resolved spontaneously, two died at 16 and 17 weeks of gestation and two had also cardiomegaly and the parents opted for elective termination of pregnancy. All the anemic fetuses had middle cerebral artery peak systolic velocity values more than 1.8 multiples of the median. No stillbirth occurred.
The outcome of uncomplicated cases with B19 infection is good. In the presence of hydrops prognosis was very poor. It seems therefore logical to attempt to pick up this ominous signs early.
[show abstract][hide abstract] ABSTRACT: Septate uterus seems to be strongly associated with an adverse pregnancy outcome. However, the possible relationship between septate uterus and miscarriage has only been retrospectively ascertained. The aim of our study was to describe the reproductive outcome in women with incidental diagnosis of malformed uterus at first trimester scan.
Women at their first pregnancy attending our centre for a routine viability scan with an incidental suspicion of uterine anomaly at standard sonography were submitted to transvaginal volume ultrasound. All the cases with a 3D diagnosis of septate uterus were prospectively recruited and followed up.
Overall 24 patients with a single intrauterine pregnancy were included at a median gestational age of 8.2 weeks. The cumulative pregnancy progression rate, as quoted by Kaplan-Meier algorithm, was 33.3% due to the occurrence of early (≤ 13 weeks) or late miscarriages (14-22 weeks) in 13 and 3 cases, respectively.
The pregnancy outcome is poor if a septate uterus is incidentally diagnosed in the early stage of a viable intrauterine pregnancy.
Human Reproduction 06/2012; 27(9):2671-5. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim: To evaluate pregnancy outcome in women with fetal membranes at or beyond external os who underwent exam-indicated cerclage or conservative management. Material and Methods: Retrospective cohort study including 52 patients with fetal membranes at or beyond external os between 17 and 27 weeks of gestation, treated in two third-level hospitals, between January 2001 and April 2009. The outcomes of interest of the study, prolongation of pregnancy and neonatal survival rate, were stratified according to type of management, parity, clinical conditions and blood tests at admission and calculated using the Kaplan-Meier algorithm. Results: Of 52 women, 37 received exam-indicated cerclage and 15 were managed conservatively. The rate of patients still pregnant beyond 180 days within the cerclage group differed significantly from those of the conservative management group (80% vs 0%, respectively) (P-value < 0.001). No difference has been found according to neonatal survival (82% versus 53%, respectively). Conclusion: Exam-indicated cerclage appears to prolong gestation compared to expectant management.
Journal of Obstetrics and Gynaecology Research 05/2012; · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the benefit of antioxidant supplementation in a cohort of women with low antioxidant status and determine the changes in cell-free mRNA.
This study was a randomized, placebo-controlled trial of 8-12 weeks' pregnant women who had low antioxidant status treated with either antioxidants or control diets daily until 2 weeks' postpartum. The primary end-point was the risk of pre-eclampsia and the secondary end-point was the changes of angiogenic and anti-oxidant mRNA markers related to the outcome (ClinicalTrial.gov, number NCT01232205).
There were 110 women enrolled in the study, randomly assigned to the supplementation (n = 52) and control group (n = 58). The overall rate of pre-eclampsia was 8.7% (nine subjects). There were significant differences (P = 0.034) between the supplementation and control group in the incidence of pre-eclampsia (2.0% [one case] and 14.5% [eight cases], respectively) and mRNA level of superoxide-dismutase, heme oxygenase-1, vascular endothelial growth factor receptor-1, endoglin and placental growth factor after supplementation.
Supplementation of women with low antioxidant status with micronutrients containing antioxidants during early gestation might reduce the risk of pre-eclampsia.
Journal of Obstetrics and Gynaecology Research 05/2012; 38(9):1152-61. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: To standardize the evaluation of normal tentorium insertion and normal rotation of the cerebellar vermis over the brainstem, using two novel measurements: the brainstem-tentorium angle (BT angle) and the brainstem-vermis angle (BV angle). We also aimed to test the reproducibility of these measurements.
Prospective observational study including normal fetuses at routine anomaly scan with confirmed normal follow-up. Three-dimensional volumes of the fetal head were acquired starting from standard trans-cerebellar views. In the sagittal plane, obtained by multiplanar reconstruction, the angle between the brainstem and the tentorium insertion in the fetal skull, and between the brainstem and the lower edge of the vermis were measured twice by two independent operators. Intraobserver and interobserver variations were calculated.
Eighty cases were included. The estimated BT and BV angles lie in a wide interval among normal midtrimester fetuses with a median value (min-max) of 25.65 (20.13-47.39) and 9.29 (3.87-19.36) respectively. Intraobserver and interobserver variation were good for both measurements.
The BT and BV angle may be of help in assessing the fetal posterior fossa at midgestation and gives a standardized and reproducible measurement of normal tentorium insertion and normal rotation of the cerebellar vermis over the brainstem.
[show abstract][hide abstract] ABSTRACT: The aim of the study was to evaluate the accuracy and reproducibility of fetal crown-rump length (CRL) measurement using three-dimensional ultrasound (3DUS).
We included a series of women with singleton pregnancy at 6-13 + 6 weeks. Following CRL measurement by the two-dimensional ultrasound (2DUS), a 3DUS volume was acquired. On the reconstructed midsagittal plane, CRL was measured twice by an operator and once by another. The correlation between CRL measured by 3DUS and 2DUS, as well as the intraobserver and interobserver agreement, was then calculated. Furthermore, the agreement between 2DUS and 3DUS CRL measurements together with intraobserver and interobserver agreement was calculated separately for the groups with a midsagittal acquisition plane (MSAP) and non-midsagittal acquisition plane (NMSAP).
Overall, 137 pregnancies were included in the analysis. CRL measurements performed using 3DUS showed excellent correlation with 2DUS [intraclass correlation coefficient (ICC) = 0.992]. In addition, the 3DUS showed a high intraobserver and interobserver agreement (ICC = 0.999 and 0.993, respectively). Finally, when we divided the acquired volumes according to the plane of acquisition, excellent 2DUS-3DUS, as well as intraobserver and interobserver agreement, was maintained for both MSAP and NMSAP.
3DUS is a highly accurate and reproducible tool for fetal CRL measurement regardless of the fetal position at the time of 3D volume acquisition.
[show abstract][hide abstract] ABSTRACT: To evaluate the role of the brainstem-vermis (BV) and brainstem-tentorium (BT) angles in the differential diagnosis of upward rotation of the fetal cerebellar vermis.
The BV and BT angles were measured retrospectively on median sonographic views of the brain in 31 fetuses at 19-28 weeks' gestation with upward rotation of the cerebellar vermis due to Blake's pouch cyst (n = 12), Dandy-Walker malformation (n = 12) and cerebellar vermian hypoplasia (n = 7). Eighty normal fetuses at 20-24 weeks were included as controls.
In the control group, BV and BT angles were 9.1 ± 3.5° (range, 4-17°) and 29.3 ± 5.8° (range, 21-44°), respectively. The BV angle was significantly increased in each of the three subgroups of anomalies: Blake's pouch cyst (23 ± 2.8°; range, 19-26°), vermian hypoplasia (34.9 ± 5.4°; range, 24-40°) and Dandy-Walker malformation (63.5 ± 17.6°; range, 45-112°), the angle increasing with increasing severity of the condition. The BT angle had a similar pattern but there was overlap among the different groups.
The BV angle and, to a lesser degree, the BT angle are simple and reproducible measurements that provide valuable additional information for the categorization of upward rotation of the fetal cerebellar vermis. From mid gestation, a BV angle > 45° is strongly suggestive of a Dandy-Walker malformation, while a measurement < 30° favors the diagnosis of a Blake's pouch cyst.
Ultrasound in Obstetrics and Gynecology 01/2012; 39(6):632-5. · 3.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyperglycaemia occurring in diabetes is responsible for accelerated arterial remodeling and atherosclerosis, affecting the macro- and the microcirculatory system. Vessel injury is mainly related to deregulation of glucose homeostasis and insulin/insulin-precursors production, generation of advanced glycation end-products, reduction in nitric oxide synthesis, and oxidative and reductive stress. It occurs both at extracellular level with increased calcium and matrix proteins deposition and at intracellular level, with abnormalities of intracellular pathways and increased cell death. Peripheral arterial disease, coronary heart disease, and ischemic stroke are the main causes of morbidity/mortality in diabetic patients representing a major clinical and economic issue. Pharmacological therapies, administration of growth factors, and stem cellular strategies are the most effective approaches and will be discussed in depth in this comprehensive review covering the regenerative therapies of diabetic microangiopathy.
Experimental Diabetes Research 01/2012; 2012:916560. · 1.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine whether supplementation with vitamin B(6) improves nausea and/or vomiting in pregnancy.
This experimental study was conducted with 60 pregnant women experiencing nausea and/or vomiting prior to the 12th gestational week. Of these women, 30 were treated daily with 10mg and the remaining 30 with 1.28 mg of pyridoxine hydrochloride for 2 weeks. The primary outcome was the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score in each group at the end of treatment.
The women experiencing nausea and/or vomiting in pregnancy had significantly lower levels of circulating vitamin B(6) (P=0.007) compared with those without this symptom. Vitamin B(6) supplementation significantly increased plasma vitamin B(6) concentration (P<0.05 in both groups). There were no significant differences in PUQE score or in plasma concentration levels of protein, dopamine, serotonin, unconjugated estriol, and ghrelin after supplementation between the 2 groups at baseline, but there was a significantly lesser decrease in PUQE score and a greater increase in vitamin B(6) level and vitamin B(6) concentration to plasma protein concentration ratios in group 1 than in group 2 after supplementation (P<0.05 for all).
Although the high-supplementation group had a greater decrease in PUQE score in comparison to the low-supplementation group, the difference is unlikely to affect the severity of symptoms.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 12/2011; 116(3):206-10. · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Prospective assignment at 11 + 0 to 13 + 6 weeks of risk for late pre-eclampsia (PE) using eight logistic regression-based statistical models.
Five hundred and fifty-four pregnancies. Uterine artery pulsatility index, parity, body mass index, mean arterial pressure, pregnancy-associated plasma protein-A, free β-human chorionic gonadotrophin and maternal age, were combined to obtain 'a posteriori risk of PE'.
We observed 39 cases (7%) of late PE. There were 12 cases of severe PE and 27 of mild PE. According to the models used, the estimated detection rate ranged from 38.5% to 84.6% with a false-positive rate of 10%. The median risk ratio (estimated median risk of PE in affected pregnancies divided by estimated risk of PE in unaffected pregnancies) ranged between 1.66 and 7.61. The most reproducible biochemical-based model was a mixed model encompassing maternal history and pregnancy-associated plasma protein-A.
Some of the multivariable models drawn from the literature accurately predicted the late PE occurrence. The failure of some models may be because of the population in question not bearing several of the risk factors used to generate the models proposed. An effective combined screening at first trimester for late PE seems possible.