First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS.

OBJECTIVE: To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy. METHODS: This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., between October 2019 and October 2020. Following CMV serology screening in early pregnancy, CVS was offered to women at 11-14 weeks' gestation after CMV-MPI ≤ 10 weeks. Array-comparative genomic hybridization and amplification of the viral genome by PCR were performed on the trophoblasts obtained by CVS. All cases also underwent amniocentesis from 17 weeks onwards and PCR was performed on the amniotic fluid. Secondary prevention with valacyclovir was initiated as soon as MPI was diagnosed, to decrease the risk of vertical transmission. We evaluated the diagnostic performance of CMV-PCR of trophoblast obtained by CVS, using as the reference standard PCR of amniotic fluid obtained by amniocentesis. RESULTS: CVS was performed in 37 pregnancies, at a median (range) gestational age of 12.7 (11.3-14.4) weeks. CMV-PCR in chorionic villi was positive in three and negative in 34 cases. CMV-PCR following amniocentesis, performed at a median (range) gestational age of 17.6 (16.7-29.9) weeks, was positive for the three cases which were positive following CVS and, of the 34 patients with a negative finding following CVS, amniocentesis was negative in 31 and positive in three. The sensitivity of CMV-PCR analysis of trophoblast obtained by CVS for the diagnosis of CMV, using as the reference standard PCR analysis of amniotic fluid obtained by amniocentesis, was 50% (95% CI, 19-81%), specificity was 100% (95% CI, 89-100%), positive predictive value was 100% (95% CI, 44-100%) and negative predictive value was 91% (95% CI, 77-97%). CONCLUSIONS: Diagnosis of placental infection following MPI in early pregnancy can be achieved by PCR amplification of the CMV genome in chorionic villi. We propose that negative CMV-PCR in the trophoblast after 12 weeks could be used to exclude CMV-related embryopathy leading to sequelae. However, this needs to be confirmed through long-term follow-up evaluation. These findings could help to establish CVS as the diagnostic test of choice following maternal serology screening in early pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

[Isolated right aortic arch: prenatal diagnosis characteristics, pregnancy outcomes and systematic review]. / Crosse aortique droite isolée : caractéristiques du diagnostic anténatal, issues de grossesses et revue de la littérature.

OBJECTIVE: To investigate prenatal diagnosis characteristics and pregnancy outcomes associated with isolated right aortic arch (RAA). METHODS: A retrospective study including fetuses with isolated RAA, managed between January 2010 and February 2018. Cases were identified from the ultrasound databases of the expert pediatric cardiologists, who made the aforementioned diagnosis. All fetuses were examined by a fetal medicine imaging expert to exclude any extracardiac abnormality. A systematic review was performed to assess the prenatal diagnosis and outcomes of fetuses with isolated RAA. RESULTS: Fifty-six fetuses were diagnosed with an isolated RAA. An isolated double aortic arch (DAA) was diagnosed in one fetus. Mean gestational age at diagnosis was 24 weeks. The sex ratio (boy/girl) was 0.89. No significant abnormality was detected in invasive tests (karyotype and FISH or microarray). Only one fetus was misdiagnosed with isolated RAA. He was the only symptomatic (stridor) newborn baby and was later diagnosed with DAA. Four studies were included in our systematic review representing 115 cases of isolated RAA. One significant chromosomal abnormality was detected: a 22q11 deletion in a newborn baby who had a postnatal finding of a soft palate cleft. There was one major obstetric complication: an intrauterine fetal demise at 41 gestational weeks. CONCLUSION: Diagnosis of isolated RAA can be challenging. Invasive tests are to be discussed. The diagnosis of isolated RAA should not change obstetric monitoring. Nevertheless, an echocardiography should be performed systematically in these new newborn babies within their first month of life.

Is training sufficient for ultrasound operators to diagnose deep infiltrating endometriosis and bowel involvement by transvaginal ultrasound?

OBJECTIVES: To assess and compare the diagnostic accuracy of transvaginal ultrasonography (TVUS) by trained or untrained ultrasound operators in deep infiltrating endometriosis (DIE) imaging, for diagnosing DIE and bowel involvement. METHODS: This was an observational study of patients with clinically suspected DIE operated in a reference center. TVUS was performed pre-operatively by a trained or/and untrained ultrasound operator to search for DIE and rectal involvement. During surgery, DIE was diagnosed according to macroscopic and histological criteria. Sensitivity (Se), specificity (Sp) and c-index were calculated with 95% confidence intervals for trained and untrained operators, if TVUS results were significantly predictive of DIE and rectal involvement at p<0.05. RESULTS: 115 patients were included: 100 (87%) had DIE and 34 (29.6%) had bowel involvement. TVUS was performed by a trained ultrasound operator for 70 patients and by an untrained one for 56 patients. When performed by a trained operator, TVUS significantly predicted DIE with a Se of 58% (95% CI, 46-70), a Sp of 87.5% (95% CI, 63-100) and a c-index of 0.73 (95% CI, 0.59-0.87). TVUS performed by an untrained operator was not significantly predictive of DIE (p=0.58). Rectal involvement was significantly predicted by TVUS performed by a trained operator with a Se of 40% (95% CI, 23-59), a Sp of 93% (95% CI, 86-100) and a c-index of 0.67 (95% CI, 0.56-0.77). None of the untrained ultrasound operators diagnosed a bowel involvement. CONCLUSION: TVUS is not sufficient to diagnose DIE and bowel involvement, in particular when performed by untrained ultrasound operators.

Far-infrared observations of a massive cluster forming in the Monoceros R2 filament hub⋆.

We present far-infrared observations of Monoceros R2 (a giant molecular cloud at approximately 830 pc distance, containing several sites of active star formation), as observed at 70 µm, 160 µm, 250 µm, 350 µm, and 500 µm by the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) instruments on the Herschel Space Observatory as part of the Herschel imaging survey of OB young stellar objects (HOBYS) Key programme. The Herschel data are complemented by SCUBA-2 data in the submillimetre range, and WISE and Spitzer data in the mid-infrared. In addition, C18O data from the IRAM 30-m Telescope are presented, and used for kinematic information. Sources were extracted from the maps with getsources, and from the fluxes measured, spectral energy distributions were constructed, allowing measurements of source mass and dust temperature. Of 177 Herschel sources robustly detected in the region (a detection with high signal-to-noise and low axis ratio at multiple wavelengths), including protostars and starless cores, 29 are found in a filamentary hub at the centre of the region (a little over 1% of the observed area). These objects are on average smaller, more massive, and more luminous than those in the surrounding regions (which together suggest that they are at a later stage of evolution), a result that cannot be explained entirely by selection effects. These results suggest a picture in which the hub may have begun star formation at a point significantly earlier than the outer regions, possibly forming as a result of feedback from earlier star formation. Furthermore, the hub may be sustaining its star formation by accreting material from the surrounding filaments.

[Outcome of triplet pregnancies managed for twin-to-twin transfusion syndrome: A single center experience]. / Issues des grossesses triples compliquées d'un syndrome transfuseur-transfusé : expérience d'un centre.

OBJECTIVES: Study the outcomes of triplet pregnancies (GGG) complicated with twin-to-twin transfusion syndrome (TTTS) treated with laser fetoscopy. METHODS: Retrospective study of interventions, outcomes and perinatal follow-up of GGG treated for TTS. RESULTS: Between 2002 and 2013, 25 GGG complicated by TTTS were seen in our center, 20 dichorionic and 5 monochorionic. The mean gestational age (GA) at diagnosis of TTTS was 19.7 GW (±2.4) with 2, 4, 16 and 1 pregnancies at Quintero's stage I, II, III and V, respectively. They had a fetoscopy at an average GA of 19 GW and 6 days. There were 3 (13.0%) late miscarriages. The average GA at delivery was of 29.6 GW overall (26.3 GW and 31.1 GW in monochorionic and dichorionic pregnancies respectively). The overall fetal survival rate was 57.97% (40% and 66.7% in the group of monochorionic dichorionic pregnancies, respectively). However, neonatal mortality (<28 days) is 17.5%. CONCLUSION: GGG operated by fetoscopy for TTTS have a survival rate of three, at least 2 and at least 1 fetus of 21.7%, 69.6% and 82.6% respectively. The overall fetal survival rate is 59.97%. There is a tendency for better survival rates in dichorionic GGG compared to monochorionic GGG (P=0.079).

[First trimester screening for Down syndrome at Prima facie. A 6-year survey]. / Dépistage de la trisomie 21 au premier trimestre. Bilan de 6 années à Prima facie.

OBJECTIVE: To evaluate the results of screening for trisomy 21 by the combined risk of first trimester (as defined by the decree of June 23, 2009) in the Prima facie structure. METHODS: Single center study involving all patients that were seen for first trimester screening at Prima facie with singleton living pregnancy, not obtained by embryo donation, between 1 January 2009 and 31 December 2014. RESULTS: Eighteen thousand two hundred and fifty-one patients were included, of which underwent screening for trisomy 21 by the combined risk. One thousand and forty-six (6.1%) had a calculated risk higher than 1/250. Seventy-five were affected by trisomy 21, of whom 65 in the high risk group. The sensitivity and specificity of screening are 86.7% and 94.4%. The median nuchal translucency was 0.98 MoM. CONCLUSIONS: Screening for trisomy 21 by calculating the combined risk of first trimester enabled to detect 86.7% of trisomy 21 with a false positive rate of 5.6%.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.

[Second trimester growth restriction and underlying fetal anomalies]. / Retard de croissance intra-utérin du deuxième trimestre : malformations associées et syndromes sous-jacents.

OBJECTIVES: To determine the incidence of chromosomal abnormalities, syndromic association and fetal defects associated with second trimester fetal growth restriction (FGR) in a tertiary referral center. PATIENTS AND METHODS: Retrospective review of all cases referred between 14 and 27 weeks with an abdominal circumference (AC)<5(th) centile between 2008 and 2012. Multiple pregnancies were excluded. Medical records were retrieved to look for the presence of associated malformations, aneuploidy and outcomes. 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 as based on AC measurement. Thirty-seven fetuses had an abnormal karyotype or an identified syndromic association (15%). The most common chromosomal defect was Trisomy 18 (10 cases, 4.2%), 67 had at least one associated morphological abnormality without aneuploidy or syndromic association (28%). Most common associated abnormalities were relative short femur (5%), omphalocele (5%) and gastroschisis (4%). Last 135 cases were isolated fetal growth retardation (5%). Maternal age was higher (33 yr ± 5 yr versus 31 yr ± 5.6 yr, P < 0.01) 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 associated 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 < 0.01). DISCUSSION AND CONCLUSION: This study describes abnormalities and outcomes associated with second trimester fetal growth retardation in a large population of patients. Our results suggest that the absence of associated malformation, degree of growth restriction, maternal age and the amniotic fluid index may help in the prenatal management and counseling of this high risk population.

Optimal risk assessment of small-for-gestational-age fetuses using 31-34-week biometry in a low-risk population.

OBJECTIVE: To compare the performance of traditional growth charts for estimated fetal weight (EFW) and a validated pragmatic probabilistic approach using biometry at 31-34 weeks' gestation to screen for late pregnancy small-for-gestational age (SGA) fetuses in a low-risk population. METHODS: Records of ultrasound biometry at 31-34 weeks were reviewed in 7755 consecutive low-risk women between 2002 and 2011. Fetal malformations, Doppler anomalies and preterm delivery before 37 weeks were excluded. SGA was defined by various percentile cut-offs of birth weight. The probability of SGA was modeled as a function of Z-scores of femur length, abdominal circumference and head circumference. The model was validated on a second independent dataset of 1725 pregnancies from a different screening unit. The screening performance of this probabilistic approach was compared with those of traditional EFW growth charts. The additional value of factoring in maternal characteristics was also ascertained. RESULTS: Using national birth-weight charts, the proportions of newborns at 37-42 weeks with birth weight<3(rd) , <5(th) and<10(th) centiles were 3%, 6% and 12%, respectively, and there was a 2% rate of birth weight<2500 g. For a 10% false-positive rate, a direct probabilistic approach yielded a 51% detection rate of neonates with birth weight<10(th) centile, compared to the 32% and 48% detection rates given by the 10(th) centile cut-off of two reference charts for EFW. Adding maternal characteristics significantly improved detection rate by 2% to 53%. CONCLUSIONS: The suggested validated approach to screening for late SGA fetuses outperforms traditional approaches using growth charts. By adding maternal characteristics, this screening method offers a favorable alternative to customized charts.

[Fetal taking in some particular circumstances]. / Prélèvements fœtaux : à propos de quelques situations problématiques.

Fetal takings still concern about 6 to 7% of the pregnancies. If, in the majority of the cases, the taking does not present difficulty for a trained operator, particular circumstances related to maternal context (anticoagulating treatment, vaginal bleeding, fever…) may make the taking become more difficult. From a questionnaire sent to the French multidisciplinary centers for prenatal diagnosis and a review of the literature, we establish guidelines for fetal taking in these circumstances.

Prognostic value of a hernia sac in congenital diaphragmatic hernia.

OBJECTIVE: To investigate the prognostic value of a hernia sac in isolated congenital diaphragmatic hernia (CDH). METHODS: Our database was searched to identify all consecutive cases of CDH referred to our fetal medicine unit between January 2004 and August 2011. Presence or absence of a hernia sac was assessed in liveborn cases using surgery or postnatal autopsy reports. We studied the correlation between the presence of a hernia sac and prenatal findings and perinatal morbidity and mortality. RESULTS: Over the study period, there were 70 cases with isolated CDH born alive in which either a surgery or autopsy report was available. Neonatal death, either preoperative or postoperative, occurred in 1/18 (5.6%) infants with a hernia sac and in 17/52 (32.7%) cases without a hernia sac (P = 0.03). Patients with a hernia sac had a significantly higher observed to expected pulmonary volume on prenatal magnetic resonance imaging (51.9 vs 39.3%, P = 0.01). Neonatal morbidity in surviving infants was lower in the group with a hernia sac, although not significantly. CONCLUSION: The presence of a hernia sac is associated with a higher pulmonary volume and a better overall prognosis for CDH.

[Standardization of the gynecological emergency ultrasound examination]. / Standardisation de l'échographie aux urgences gynécologiques.

Standardization of the gynecological emergency ultrasound examination could allow more accurate evaluation in gynecologic or general emergency unit. A systematic set of images, "Standardized Acute Female Echography" (SAFE), was defined. In practice, four pictures are realized whatever presenting complaint (set "A"). These pictures describe the normal anatomy and allow verifying the quality of ultrasonography realization. The picture A1 is obtained by abdominal probe and investigates the Morison's pouch. The pictures A2, A3 and A4 are obtained by transvaginal probe and correspond respectively to the mid-sagittal uterus view, the right ovary and the left ovary. For each of these pictures, some quality criteria were defined allowing a control of ultrasound examination. When abnormality is detected, others pictures (set "B)" are required to describe it. These pictures are called B1 in case of intra-uterine abnormality and B2 in case of adnexal abnormality. This standardization of pelvic ultrasonography could allow a quality control and a delegation of the ultrasound examination by training physicians or diagnostic medical sonographers without repetition of the examination. SAFE could be a reference in the field of gynecological emergencies imaging picture by improving diagnostic and therapeutic management.

[Nuchal translucency thickness at 11-14 weeks of gestation: French charts and equations]. / Epaisseur de la clarté nucale A 11-14SA : courbes et équations françaises.

OBJECTIVES: To construct French reference charts and equations for nuchal translucency thickness (NT) using a large sample of fetuses. To compare this new reference with previous ones. MATERIALS AND METHODS: The study data were obtained from a single large screening center over seven years. Only measurements taken by trained and certified (Fetal Medicine Foundation) operators, with crown rump length (CRL) between of 45 to 84 mm were used. Multiple pregnancies, abnormal karyotype, cystic hygroma or measurements performed by operators performing less than 500 examinations over the study period were excluded. Raw centiles were computed for each CRL. They were then fitted using a least square regression model with high order polynomials. Predicted median values for NT were compared to previously published references and the impact of deviation in median NT was evaluated. RESULTS: There were 19,198 measurements included for NT modelling. New charts and equations for NT centiles calculations are reported. Median values were comparable to those reported in other populations. The small discrepancy in median NT did not impact on screening efficiency. CONCLUSION: We present new French reference charts and equations for NT at first trimester. These may serve as a basis for ongoing audit and quality control. Although they were derived from a very and unselected sample, they do not show clinically relevant difference as compared to existing references. Our results do no support the use or development of customized French reference charts and algorithm for first trimester screening.

[Prenatal management of uncomplicated monochorionic biamniotic pregnancies]. / Surveillance des grossesses gémellaires monochoriales biamniotiques non compliquées.

Monochorionic pregnancies accounts for only 20% of twins but are responsible for most of their morbidity and mortality. There is no randomized study evaluating management of monochorionic pregnancies. Based on expert opinion, it is recommended that monochorionic pregnancies should be followed-up by practionners working with specialized centers with expertise in monochorionic pregnancies. Optimal follow-up should include a bi-monthly ultrasound evaluation.

Outcome of anaemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome.

OBJECTIVE: To evaluate the outcome of severely anaemic monochorionic (MC) twins surviving the death of their co-twin following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome (FFTS). STUDY DESIGN: We reviewed all MC pregnancies complicated with FFTS following primary management, in which a single intrauterine fetal death (IUFD) was diagnosed with certainty within 24 hours between January 1999 and December 2006. We included MC survivors who presented ultrasound or Doppler features of fetal anaemia following the death of their co-twin. Intrauterine transfusion (IUT) was given to all survivors who were anaemic. RESULTS: Nineteen MC twin pregnancies presented a single intrauterine death (IUD) associated with an anaemic co-twin. Median gestational age at IUD was 23 [20-28] weeks. The median interval between IUD and IUT was 12 [8-24] hours. There were 58% (11/19) healthy survivors. Perinatal death rate was 26% (5/19) including 16% (3/19) intrauterine and 10% (2/19) neonatal deaths. Abnormal prenatal cerebral findings developed in 21% (4/19) cases, always within 1 month after the death of the co-twin. Considering occlusive techniques and other management separately, there were 64% (7/11) and 50% (4/8) healthy survivors, respectively, and perinatal death occurred in 36% (4/11) and 12.5% (1/8) of fetuses, respectively. Prenatal fetal cerebral lesions developed in 9% (1/11) of cases following occlusive techniques and in 37.5% (3/8) of fetuses when managed differently. The median gestational age at delivery in the survivors was 31 [25-38] weeks. CONCLUSION: In cases of FFTS with single anaemic survivors, early IUT could be offered following extensive counselling and close follow up.

Histone deacetylase (HDAC) encoding gene expression in pancreatic cancer cell lines and cell sensitivity to HDAC inhibitors.

PURPOSE: Multiple biochemical and molecular alterations occur in pancreatic cancer cells. In the present study, attempts were made for the first time, to explore the level of expression of members of histone deacetylase encoding genes (HDACs) in four pancreatic tumor cell lines: Panc-1, BxPC-3, SOJ-6 and MiaPaCa-2; and two non-related tumor cells: Jurkat and HeLa. Furthermore, we examined the possible relationship between the levels of HDACs expression and the sensitivity/resistance to HDAC inhibitors (TSA, Nicotinamide and Sirtinol). RESULTS: We have found that although a slight variation in the profiles of gene expression among cell lines could be evidenced, HDACs protein synthesis seem to be similar. Furthermore, the cells were equally sensitive to inhibition by Sirtinol whereas some variation in the IC(50) could be seen in the case of TSA. We also demonstrate that the drugs had the capacity to induce the death of cells by apoptosis. METHODS: We have used four human pancreatic tumor cell lines and two-non related tumor cells, to evaluate the expression of HDAC encoding genes by RT-PCR and Western blot analysis. We also measured the effect of certain HDAC inhibitors (HDIs) on cell growth, cell cycle alteration, membrane phosphatidyl-serine exposure, DNA fragmentation and mitochondrial membrane potential loss. CONCLUSIONS: Taken together, our data support the notion that the level of cell sensitivity to the HDIs might be related to the level of expression of genes such as those encoding proteins playing a role in cell cycle checkpoints control but not HDAC per se.

Twins discordant for fetal skeletal abnormalities: a natural confrontation between the two siblings.

BACKGROUND: Skeletal abnormalities encompass a heterogeneous group of disorders characterized by anomalies of cartilage as well as bone growth and development. Some are lethal and express early during fetal life, making them amenable to prenatal diagnosis. The increasing use of routine ultrasonography (US) during pregnancy permits a reliable primary evaluation of the fetal skeleton. However, when a skeletal dysplasia is suspected, it is more difficult to establish a specific diagnosis. Moreover, detailed ultrasonographic evaluation of the whole fetal skeleton may be limited in some circumstances, especially during the third trimester due to the fetal position and in the case of multiple pregnancies. METHODS: Retrospective study of twin pregnancies complicated with skeletal abnormalities. RESULTS: 6 twin pregnancies were reviewed. The prenatal diagnosis was correctly made in 66.66% (4/6) with the primary use of combined 2D and 3D-US. 3D-HCT permits to improve the simultaneous assessment of both fetuses, and is of greater value than US in 16.66% (1/6). CONCLUSION: The combined use of 2D or 3D-US with 3D-HCT permits the best imaging evaluation.

[Screening for Down syndrome using first-trimester combined screening followed by second trimester ultrasound examination in an unselected population]. / Dépistage de la trisomie 21 par le test combiné du premier trimestre suivi par l'échographie du second trimestre en population générale.

BACKGROUND: Recent studies have reported the efficacy of first trimester combined screening for Down Syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 week anomaly scan. STUDY DESIGN: We carried out a multi-centre, interventional study in the unselected population of a single health authority in order to assess the performance of first trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein and unconjugated estriol measurement) when incidentally performed. Detection and screen positive rates were estimated using a correction method for non verified issues. A cost analysis was also performed. RESULTS: During the study period, 14,934 women were included. Fifty-one cases of Down Syndrome were observed, giving a prevalence of 3.4 per 1000 pregnancies. Of these, 46 were diagnosed through first (N=41) or second (N=5) trimester screening. Among the 5 screen-negative Down syndrome cases, all were diagnosed postnatally after an uneventful pregnancy. Detection and screen positive rates of first trimester combined screening were 79.6% and 2.7%, respectively. These features reached 89.7 and 4.2%, respectively when combined with second trimester ultrasound screening. The average cost of the full screening procedure was 108 euro (120 $) per woman and the cost per diagnosed Down syndrome pregnancy was 7,118 euro (7,909 $). CONCLUSION: Our findings suggest that one pragmatic interventional two-step approach using first-trimester combined screening followed by second trimester detailed ultrasound examination is a suitable and acceptable option for Down syndrome screening in pregnancy.

Intertwin discordance in umbilical venous volume flow: a reflection of blood volume imbalance in twin-to-twin transfusion syndrome.

OBJECTIVES: To compare umbilical venous volume flow (UVVF) between donor and recipient twins in twin-to-twin transfusion syndrome (TTTS) using an index that is independent of gestational age and to correlate changes in this index with outcome following endoscopic laser surgery. METHODS: UVVF was calculated in 84 cases of TTTS by multiplying the umbilical vein cross-sectional area at its entry into the fetal abdomen by time averaged blood velocity. All cases were classified according to the Quintero staging system. The ratio between UVVF in recipients and donors (R/D-UVVF) in each pair of twins was calculated before and 48 h after laser treatment, and changes in R/D-UVVF were correlated with pregnancy outcome. Intraobserver and interobserver UVVF measurement reliability was assessed in 19 singletons, and 13 donor and recipient twins before laser treatment using the intraclass correlation coefficient (ICC). RESULTS: Twenty-five, 32, 21 and six cases presented as Quintero Stages 1, 2, 3 and 4, respectively, at a median gestational age of 20 (range, 15-26) weeks. Intraobserver and interobserver ICC for UVVF measurement in twins were 0.97 and 0.67, respectively. UVVF was a median of 2.13-fold (range, 0.3-19-fold) higher in recipients than in donors (137 mL/min vs. 64 mL/min, P < 0.001) and increased with gestational age (r = 0.58, P < 0.001 for recipients, r = 0.62, P < 0.001 for donors). From 68 cases in which R/D-UVVF could be measured 48 h following laser surgery, cases with a favorable outcome showed a significant decrease in R/D-UVVF from a median of 1.97 to 1.27 (P < 0.01) and cases with recurrent TTTS (n = 6) did not (decrease in R/D-UVVF from a median of 2.32 to 2.19, P = 0.17). Using a cut-off of < 30% reduction of R/D-UVVF, 66% of the cases with recurrence could be predicted, and the odds ratio for recurrence was 3.13 (95% CI, 0.52-18.29). A significant UVVF imbalance between recipient and donor twins was found in cases with Quintero Stages 1-3 but not in those with Stage 4. CONCLUSIONS: In TTTS, UVVF is significantly higher in recipients than in their donor cotwins and the R/D-UVVF seems adequately to indicate the flow imbalance between twins, regardless of gestational age. A decrease in R/D-UVVF could be predictive of a favorable evolution following laser treatment.