Papers by Annalisa Tempesta
Prenatal Diagnosis, 2011
To determine the gene expression profile in chorionic villous samples (CVSs) of women destined to... more To determine the gene expression profile in chorionic villous samples (CVSs) of women destined to develop pre-eclampsia (PE). Case-control study encompassing five women destined to develop PE [cases matched for gestational age with 30 controls]. We quantified mRNA expression on tissue samples from CVS of normal and PE patients. We then assessed mRNA expressions of cathepsin (CTSD), angiopoietin 2 (ANGPT2), interleukin 8, chemokine (C-X-C motif) ligand 10, neurokinin B (NKB), matrix metallopeptidase 9, major histocompatibility complex, class I, C (HLA-C)and human leukocyte antigen-G (HLA-G). Data were analyzed by nonparametric rank analysis. For all the mRNA species considered in this study, except CTSD and ANGPT2, all the mean observed ranks in the PE group were significantly altered compared with the rank expectation among controls. mRNA for NKB and HLA-C were the markers with the highest degree of aberration in PE, compared with those in controls. Our study has directly showed that gene expressions relating to trophoblastic cell invasion or utero-placental hemodynamic adaptation are altered in the first trimester trophoblasts that go on to develop PE later. These results posit the use of residual CVS as a possible screening method for PE.
Prenatal Diagnosis, 2006
To retrospectively evaluate whether increased serum levels of total activin A (t-activin A) are f... more To retrospectively evaluate whether increased serum levels of total activin A (t-activin A) are found in women who subsequently experience preterm delivery (PTD). Data on maternal serum t-activin A concentrations were available from a total of 84 singleton pregnant women and included 14 PTD pregnancies, each matched for gestational age and length of freezer storage, with 5 control pregnancies having term delivery (TD). Analyte values were expressed as multiple(s) of the control median. The median t-activin A for controls and cases was 1.00 +/- 0.45 and 1.27 +/- 0.53 MoM, respectively. Univariate analysis of the MoM values was performed using the Kaplan-Meier algorithm. Differences in the rate of delivery using a t-activin A MoM cut-off of > or = 1 SD (equivalent to 1.26 MoM) were analysed using the log rank test. The cumulative rate of PTD (< 37 weeks) was significantly higher for women with t-activin A concentrations > or = 1.26 MoM than those with t-activin A concentrations below this cut-off (40% vs.. 10%, p-value = 0.0218 log rank test). T-activin A concentration is higher in women who will develop PTD in a low-risk population. T-activin A values are inversely proportional to the time elapsed from blood test to delivery. Prospective studies would determine the precise discriminability of this marker for PTD and the best week for performing the blood test, allowing for a proper calculation of the detection rate and a positive predictive value.
Journal of Ultrasound in Medicine, 2012
etal echocardiography is commonly performed in the second trimester and allows the detection of m... more etal echocardiography is commonly performed in the second trimester and allows the detection of most types of major congenital heart disease as well as some of the minor forms. 1 However, the recognition of increased nuchal translucency at 11 to 14 weeks' gestation as a marker for aneuploidies 2 and its association with an increased risk of congenital heart disease 3,4 have led to sonographic evaluation of the fetal heart at this early stage. 5-7 In fact, with modern sonographic equipment, an accurate evaluation of the heart in a high-risk fetus can be made by experts in the first trimester. 5-8 Although most types of congenital heart disease develop during the first 8 weeks of embryonic life, many of these lesions continue to evolve, and others develop with advancing gestation. 9-12
Ultrasound in Obstetrics & Gynecology, 2011
To define the feasibility of assessing the right subcalavian artery (RSA) in 1 st and 2 nd trimes... more To define the feasibility of assessing the right subcalavian artery (RSA) in 1 st and 2 nd trimester ultrasonographic assessment of routine population and the association of ARSA with chromosomal, cardiac and extracardiac anomalies. Methods: RSA was prospectively evaluated since July 2009 in all routine patients booked in our fetal medicine Unit. We included 11-14 weeks assessment, pre-invasive US evaluation in patients that declined 1 st trimester screening at booking and opted directly for fetal karyotyping due to maternal age ≥ 35 y and routine anomaly scan. All patients referred for increased NT, amniocentesis, cardiac or extracardiac abnormalities were excluded. Results: We have assessed 4068 routine patients, 3036 in the 1 st and 3152 in the 2 nd trimester; 2281 patients were assessed in both 1 st and 2 nd trimesters. RSA assessment was feasible in 2529 1 st trimester exams (83%). Feasibility in the first trimester was related to the CRL/BMI ratio. In the 2 nd trimester the feasibility was higher reaching 98%. The overall feasibility in our series was 91.1% (3709 feasible cases, considering both 1 st and 2 nd trimester evaluation). An ARSA was found in 49 fetuses (overall incidence 1.32% of the feasible cases) where 28 were detected in the 1 st and 19 in the 2 nd trimester. Nine of the 2 nd trimester ARSA have been misdiagnosed in the 1 st trimester assessment. Fetal echocardiography always confirmed the initial diagnosis, when an ARSA was detected in the screening scan (no false positive cases). Of the 49 ARSA, 39 were euploid with no other findings; the remaining 10 cases included 5 aneuploidies, 1 genetic syndrome, 1 22q11 microdeletion, 1 cardiac and 2 extracardiac abnormalities. Conclusions: The feasibility of RSA assessment in a routine population depends on gestational age and maternal BMI, with more than 80% feasible cases in the first trimester. A high rate of ARSA are associated with genetic or structural, abnormalities.
Ultrasound in Obstetrics and Gynecology, 2010
To determine the prevalence of the aberrant (right or left) subclavian artery in chromosomally no... more To determine the prevalence of the aberrant (right or left) subclavian artery in chromosomally normal and abnormal fetuses. Methods: The study was performed at two referral centers for CHD. Fetal echocardiography was performed prospectively in the first and second trimester to identify the subclavian artery and to determine whether this was normal or aberrant. Results: Over a period of a two years we were able to identify an aberrant subclavian artery in 0.9% of chromosomally normal fetuses and in 10% of chromosomally abnormal fetuses. Conclusions: The presence of the aberrant subclavian artery is more common in chromosomally abnormal than normal fetuses.
Ultrasound in Obstetrics and Gynecology, 2009
Objective: The use of additional US markers during the first trimester screening permitted an inc... more Objective: The use of additional US markers during the first trimester screening permitted an increase of sensibility of the test and/or reduction of the false positive rate. The objective of this study was to analyze the feasibility and the duration of a complete structural examination of the fetus. Methods: All examinations included evaluation of nuchal translucency, nasal bone, tricuspid valve, ductus venosus, facial angle, head, brain, stomach, bladder, spine, kidneys, abdominal wall, umbilical arteries and extremities. When was not possible to conclude the examination due to the fetal position the patient was invited for a walk and re-examined later. When the visualization of the fetal structures was not satisfactory due to increased maternal MBI or retroverted uterus a TV examination was added. Facial angle was measured in 2D sections or volumes were acquired after a midsagittal section was obtained. Results: In the period May 2008 – January 2009, 838 screening test were performed. Mean CRL was 62mm. The mean duration was 16,8 (5–60) min. TV examination was needed in 12% of cases. 62% of the examinations were done in a single section while 10% were seen in 3 or more sections. The duration was increased with maternal BMI, additional TV approach and number of sections performed. The need of TV scan was associated with maternal BMI while the number of US sections depended on the fetal position. Fetal bladder and kidneys were the most frequently difficult to assess structures. Nuchal translucency, nasal bone and tricuspid valve were successfully examined in all scans. Ductus venosus waves were not satisfactory in 1% of our series. Facial angle was not feasible in 2,5% of the cases. Conclusion: A complete examination of all the fetal structures and of all US markers for abnormalities is feasible with a mean duration of 16–17min. The only factors increasing the time of the examination were maternal BMI and fetal position.
Ultrasound in Obstetrics and Gynecology, 2009
9745 cases complete combined test (NT+ free β-hCG + PAPP-A) and 1978 cases screen NT only. All of... more 9745 cases complete combined test (NT+ free β-hCG + PAPP-A) and 1978 cases screen NT only. All of the sonographers were certificated by Fetal Medicine Foundation and the risk of aneuploides calculated using FMF’s algorithm software. Fetal karyotyping was performed after counsel when the risk was 1 in 300 or over. All of cases were followed up for fetal outcome. Results: In the 12,648 women were enrolled the screening program. Among the screening, there were 662 ineligible cases due to incomplete data or unknown outcome. There were 263 twin pregnancies giving a total of 12,249 fetuses. Night percent of the women were over 35 years old or above. Among the 9745 complete combined test were 287 cases positive (2.95%) and screen NT only 1978 cases were 186 cases positive (9.40%). That included 21,10,6 cases of trisomy21, 18, 13 respectively and 13 cases of Turner syndrome. There were two cases of trisomy 21 were missed but one fetus was diagnosed by genetic sonogram at 21 week of gestation and another was live born. None of trisomy 18, 13 and Turner syndrome was missed in the screening. Conclusions: First-trimester combined screening for chromosomal abnormalities is highly effect, but screening only using NT with high false positive among in Taiwanese of oriental population.
Ultrasound in Obstetrics and Gynecology, 2010
Objectives To analyze fetal two-dimensional (2D) echocardiographic characteristics of interrupted... more Objectives To analyze fetal two-dimensional (2D) echocardiographic characteristics of interrupted aortic arch (IAA) and its different types, to explore whether the use of 4D ultrasound with B-flow imaging and spatiotemporal image correlation (STIC) can improve prenatal diagnostic accuracy, and to describe associations and outcome. Methods The study comprised IAA fetuses examined exclusively by 2D conventional echocardiography during the period from 1994 to 2003, and those identified by conventional echocardiography and examined further by 4D ultrasound with B-flow imaging and STIC during the period January 2004 to July 2008, identified among fetuses examined at two referral centers for congenital heart defects (CHD). Postnatal follow-up was available in all cases. Karyotyping and fluorescent in-situ hybridization (FISH) analysis for the DiGeorge critical region (22q11.2) were performed in all cases. Results Twenty-two cases of isolated IAA (15 Type B and seven Type A, seven and three of which, respectively, underwent B-flow imaging and STIC) were detected among 2520 cases of fetal CHD. In seven of the 15 Type B cases, a right subclavian artery arose anomalously (ARSA). 2D echocardiography failed to distinguish the type of IAA in only two cases and the ARSA in five of the seven cases. B-flow imaging and STIC successfully identified IAA types in all 10 cases examined and clearly visualized the origin and course of the ARSA, including cervical ones. FISH detected 22q11.2 microdeletion in 10 of the 15 Type B cases and an unusual association with Type A in one of the seven cases. Fetal/neonatal outcome included: eight terminations of pregnancy, one intrauterine death and four postoperative deaths in the neonatal period, and nine neonates were alive after surgery at a mean follow-up time of 58 months (range, 4 months-13 years). Conclusion Our results confirm the feasibility of prenatal characterization of IAA and its different types based on 2D echocardiographic examination, albeit with some limitations in the thorough assessment. 4D ultrasound with B-flow imaging and STIC can apparently facilitate visualization and detailed examination of the anatomical features of the IAA types, including visualization of the neck vessels, thus supplying additional information with respect to 2D sonography. As for the known association with microdeletion 22q11.2, our data indicate that Types A and B are distinct, there being a close association only with IAA Type B.
Prenatal Diagnosis, 2011
The aim of this study was to evaluate the detection rate of congenital heart diseases (CHD) in a ... more The aim of this study was to evaluate the detection rate of congenital heart diseases (CHD) in a low-risk population by performing cardiac evaluation during the first-trimester screening for chromosomal abnormalities. In this context, the role of four-chamber view, tricuspid regurgitation and abnormal ductus venosus flow in the screening for cardiac anomalies in a low-risk population was also investigated. The cardiac examination was performed by obstetricians with extensive experience in first- and second-trimester ultrasound (US). Follow-up US evaluations during the second and third trimesters were offered to all patients. In case of abnormal findings during routine assessment, fetal echocardiography was performed by a fetal cardiologist. Among the 4445 fetuses included in the study, 42 CHD were detected (39 diagnosed prenatally and 3 postnatally). In 27 cases, the fetal cardiologist confirmed the type of CHD diagnosed at US screening. In 1 case, the diagnosis was slightly different in the second trimester, and in 3 of the 26 correctly diagnosed in the first-trimester cases, the CHD developed and progressed in severity. A significant association of major CHD and US first-trimester markers was observed. First-trimester assessment of the fetal heart is feasible in a low-risk population when performed by experienced obstetricians. However, although most types of CHD can be diagnosed early in pregnancy, some may become apparent later in gestation.
Annals of the New York Academy of Sciences, 2006
Doppler analysis of the uterine arteries is currently used for pre-eclampsia (PE) screening. PLAC... more Doppler analysis of the uterine arteries is currently used for pre-eclampsia (PE) screening. PLAC1 is a trophoblast-specific gene, and it is known that in normal pregnancies, trophoblastic cells are released into the maternal circulation, where specific trophoblastic mRNA can be detected. In PE, as in women who eventually develop PE, an abnormal passage of fetal and placental cells is also present. In this study, we aimed to verify whether, in normal pregnancies, Doppler waveform of the uterine arteries correlates with PLAC1 mRNA concentrations. Thirteen cases of normal pregnancies at 37 weeks' gestation (23-41) were enrolled in the study. PLAC1 mRNA was extracted from 2 mL of blood by ABI PRISM 6100 nucleic acid Prep Station (Applied Biosystems, Foster City, CA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed by a PE 5700 Sequence detection system. Bulk RNA from normal placental tissue was used as the reference curve, and the amount of PLAC1 mRNA in the study samples was then expressed as the "relative amount" of weight of placental tissue (ng/mL). The uterine arterial mean resistance index (RI) and presence/absence of a dicrote waveform were calculated by using a 5 MHz transabdominal probe (Tecnos, ESAOTE) at the uterine cervico-corporal junction. Doppler measurement was performed on the same day as blood collection. The median of the means of uterine arterial RI was 0.52 (0.39-0.68). RI of uterine arteries and PLAC1 mRNA were significantly correlated in a log-linear regression (R 2 = 0.483, P = 0.024). Our data support that in normal pregnancy, the passage of trophoblast material into the maternal circulation is correlated with the quantitative measurement of uterine hemodynamics.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2007
Objective: This study was conducted to determine whether, in low risk women having labor induced ... more Objective: This study was conducted to determine whether, in low risk women having labor induced using prostaglandin gel (dinoprostone gel), there is a relationship between the concentration of mRNA for the PLAC1 gene (a trophoblast-specific gene) in maternal blood and the time elapsed between the first gel administration and spontaneous delivery. Study design: Blood was collected from 49 selected women at 40.2-41.4 weeks' gestation. Total RNA was extracted by means of an ABI Prism 6100 nucleic acid Prep Station and quantitative real-time PCR analysis was performed by use of a PE Applied Biosystems 5700 Sequence Detection System. Sequence data were obtained from the Genebank Sequence Database. To determine the amount of cDNA, the PLAC1 locus was used. Results: Thirty women (61.2%) had a spontaneous delivery. A caesarean section, either for fetal dystocia or fetal distress, was performed in 19 (38.8%). The crude delivery rates of the women who ended up with a spontaneous delivery were 30% at 24 h and 43% at 48 h. Women (n = 19) with a blood concentration of log PLAC1 mRNA !2.00 displayed a median time to delivery of 23.50 h, (95% CI: 13.13-33.87) while those with a log PLAC1 mRNA <2.00 (n = 30) had a median time of 54 h. (95% CI: 37.86-70.14; p = 0.0043, log-rank test). By means of multivariate analysis, quantitative Bishop score (from 2 to 7) at the time of the first gel administration and log PLAC1 mRNA !2.00 were associated with a higher rate of delivery per unit of time with an odds ratio of 1.35 (95% CI: 1.07-1.71) and 3.48 (95% CI: 1.55-7.80), respectively. Conclusions: In induced term pregnancies, PLAC1 mRNA in maternal blood at the beginning of the treatment correlates with the time elapsed before delivery. This evidence demonstrates that the fetomaternal trafficking of nucleic acids is more consistent when the labor is about to begin.
Prenatal Diagnosis, 2011
Objective The aim of this study was to evaluate the detection rate of congenital heart diseases (... more Objective The aim of this study was to evaluate the detection rate of congenital heart diseases (CHD) in a low-risk population by performing cardiac evaluation during the first-trimester screening for chromosomal abnormalities. In this context, the role of four-chamber view, tricuspid regurgitation and abnormal ductus venosus flow in the screening for cardiac anomalies in a low-risk population was also investigated.
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Papers by Annalisa Tempesta