Static and dynamic responses to hyperoxia of normal placenta across gestation with T2*-weighted sequences.

OBJECTIVES: T2*-weighted sequences have been identified as non-invasive tools to study the placental oxygenation in-vivo. This study aims to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. METHODS: We conducted a single-center prospective study including 52 uncomplicated pregnancies. Two T2*-weighted sequences were performed: T2*-relaxometry was performed before and after maternal hyperoxia. The histogram distribution of T2* values was assessed by fitting a gamma distribution as T2*~Γ(αß). A dynamic acquisition (BOLD protocol) was also performed before and during oxygen supply, until placental oxygen saturation. The signal change over time was modeled using a sigmoid function, used to determine the intensity of enhancement (∆BOLD,%), a temporal variation coefficient (λ,min-1 , controlling the slope of the curve), and the maximal steepness (Vmax, ∆BOLD.min-1 ) of placental enhancement. RESULTS: The histogram analysis of the T2* values in normoxia showed a whole-placenta variation, with a decreasing linear trend in the mean T2* value (R= -0.83, 95% CI [-0.9, -0.71], p<0.001) along with a more peaked and narrower distribution of T2* values across gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia / mean T2*baseline ) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar aspect. The ∆BOLD showed a non-linear increase across gestation. Conversely, the λ(min-1 ) parameter, showed an inverted trend across gestation, with a significantly weaker correlation (R = -0.33, 95% CI [-0.58, -0.02], p=0.04, R2 = 0.1). As a combination of ∆BOLD and λ, the changes in Vmax throughout gestation were mainly influenced by the changes in ∆BOLD and resulted in a positive non-linear correlation with gestational age. CONCLUSION: Our results suggest that the decrease in the T2* placental signal over gestation does not reflect a dysfunction. The BOLD effect, representative of a free-diffusion model of oxygenation, highlights the growing differences in oxygen saturation between mother and fetus across gestation (∆BOLD), and placental permeability to oxygen (λ). This article is protected by copyright. All rights reserved.

Quantitative fetal MRI with diffusion tensor imaging in cases with 'short' corpus callosum.

OBJECTIVES: It has been suggested previously that the presence of Probst bundles (PB) in cases with a short corpus callosum (SCC) on diffusion tensor imaging (DTI) may help to differentiate between corpus callosal (CC) dysplasia and a variant of normal CC development. The objectives of this study were to compare DTI parameters between cases of SCC vs normal CC and between cases of SCC with PB (SCC-PB+) vs SCC without PB (SCC-PB-). METHODS: This was a retrospective study of patients referred to the Necker Hospital in Paris, France, for magnetic resonance imaging (MRI) evaluation of an apparently isolated SCC detected by sonography between November 2016 and December 2022 (IRB: 00011928). MRI was performed using a 1.5-Tesla Signa system. T2-weighted axial and sagittal sequences of the fetal brain were used to measure the length and thickness of the CC. 16-direction DTI axial brain sequences were performed to identify the presence of PB and to generate quantitative imaging parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the entire CC, genu, body and splenium. Cases in which other associated brain abnormalities were detected on MRI were excluded. Cases were matched for fetal gender and gestational age with controls in a 1:3 ratio. Control cases were normal fetuses included in the LUMIERE on the FETUS trial (NCT04142606) that underwent the same DTI evaluation of the brain. Comparisons between SCC and normal CC cases, and between SCC-PB+ and SCC-PB- cases were performed using ANOVA and adjusted for potential confounders using ANCOVA. RESULTS: Twenty-two SCC cases were included and compared with 66 fetuses with a normal CC. In 10/22 (45.5%) cases of SCC, PB were identified. As expected, dimensions of the CC were significantly smaller in SCC compared with normal CC cases (all P < 0.01). In SCC-PB+ vs SCC-PB- cases, FA values were significantly lower in the entire CC (median, 0.21 (range, 0.19-0.24) vs 0.24 (range, 0.22-0.28); P < 0.01), genu (median, 0.21 (range, 0.15-0.29) vs 0.24 (range, 0.17-0.29); P = 0.04), body (median, 0.21 (range, 0.18-0.23) vs 0.23 (range, 0.21-0.27); P = 0.04) and splenium (median, 0.22 (range, 0.16-0.30) vs 0.25 (range, 0.20-0.29); P = 0.03). ADC values were significantly higher in the entire CC, genu and body in SCC-PB+ vs SCC-PB- cases (all P < 0.05). In SCC-PB+ cases, all FA values were significantly lower, and ADC values in the CC body were significantly higher compared with normal CC cases (all P < 0.05). In SCC-PB- cases, there was no significant difference in FA and ADC compared with normal CC cases (all P > 0.05). CONCLUSIONS: Fetal DTI evaluation of the CC showed that FA values were significantly lower and ADC values tended to be significantly higher in SCC-PB+ compared with normal CC cases. This may highlight alterations of the white matter microstructure in SCC-PB+. In contrast, isolated SCC-PB- did not demonstrate significant changes in DTI parameters, strengthening the possibility that this is a normal CC variant. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Placental T2* and BOLD effect in response to hyperoxia in normal and growth-restricted pregnancies: multicenter cohort study.

OBJECTIVES: Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non-invasive in-vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). METHODS: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non-FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5-Tesla MRI system, the same multi-echo gradient-recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* - baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non-FGR), presence/absence of Doppler anomalies and birth weight (small-for-gestational age (SGA) vs non-SGA). RESULTS: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5-48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1-48.5%) vs 33.7% (22.7-47.4%); P = 0.95). Baseline T2* Z-score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non-FGR pregnancies (median, -1.27 (IQR, -4.87 to -0.10) vs 0.33 (IQR, -0.81 to 1.02); P = 0.001). Baseline T2* Z-score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non-SGA neonate (n = 62) (median, -0.75 (IQR, -3.48 to 0.29) vs 0.35 (IQR, -0.79 to 1.05); P = 0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diffusion tensor imaging of fetal spinal cord: feasibility and gestational-age-related changes.

OBJECTIVES: Diffusion tensor imaging (DTI) of the fetal brain is a relatively new technique that allows evaluation of white matter tracts of the central nervous system throughout pregnancy, as well as in certain pathological conditions. The objectives of this study were to evaluate the feasibility of DTI of the spinal cord in utero and to examine gestational-age (GA)-related changes in DTI parameters during pregnancy. METHODS: This was a prospective study conducted between December 2021 and June 2022 in the LUMIERE Platform, Necker-Enfants Malades Hospital, Paris, France, as part of the LUMIERE SUR LE FETUS trial. Women with a pregnancy between 18 and 36 weeks of gestation without fetal or maternal abnormality were eligible for inclusion. Sagittal diffusion-weighted scans of the fetal spine were acquired, without sedation, using a 1.5-Tesla magnetic resonance imaging scanner. The imaging parameters were as follows: 15 non-collinear direction diffusion-weighted magnetic-pulsed gradients with a b-value 700 s/mm2 and one B0 image without diffusion-weighting; slice thickness, 3 mm; field of view (FOV), 36 mm; phase FOV, 1.00; voxel size, 4.5 × 2.8 × 3 mm3 ; number of slices, 7-10; repetition time, 2800 ms; echo time, minimum; and total acquisition time, 2.3 min. DTI parameters, including fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were extracted at the cervical, upper thoracic, lower thoracic and lumbar levels of the spinal cord. Cases with motion degradation and those with aberrant reconstruction of the spinal cord on tractography were excluded. Pearson's correlation analysis was performed to evaluate GA-related changes of DTI parameters during pregnancy. RESULTS: During the study period, 42 pregnant women were included at a median GA of 29.3 (range, 22.0-35.7) weeks. Five (11.9%) patients were not included in the analysis because of fetal movement. Two (4.8%) patients with aberrant tractography reconstruction were also excluded from analysis. Acquisition of DTI parameters was feasible in all remaining cases (35/35). Increasing GA correlated with increasing FA averaged over the entire fetal spinal cord (r, 0.37; P < 0.01), as well as at the individual cervical (r, 0.519; P < 0.01), upper thoracic (r, 0.468; P < 0.01), lower thoracic (r, 0.425; P = 0.02) and lumbar (r, 0.427; P = 0.02) levels. There was no correlation between GA and ADC averaged over the entire spinal cord (r, 0.01; P = 0.99) or at the individual cervical (r, -0.109; P = 0.56), upper thoracic (r, -0.226; P = 0.22), lower thoracic (r, -0.052; P = 0.78) or lumbar (r, -0.11; P = 0.95) levels. CONCLUSIONS: This study shows that DTI of the spinal cord is feasible in normal fetuses in typical clinical practice and allows extraction of DTI parameters of the spinal cord. There is a significant GA-related change in FA in the fetal spinal cord during pregnancy, which may result from decreasing water content as observed during myelination of fiber tracts occurring in utero. This study may serve as a basis for further investigation of DTI in the fetus, including research into its potential in pathological conditions that impact spinal cord development. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of different prenatal management strategies in short- and long-term outcomes in monochorionic twin pregnancies with selective intrauterine growth restriction and abnormal flow velocity waveforms in the umbilical artery Doppler: a retrospective observational study of 108 cases.

OBJECTIVES: To review perinatal and neurodevelopmental outcome (NDO) following selective fetoscopic laser coagulation (SFLC), cord coagulation (CC) or expectant management of monochorionic diamniotic twin pregnancies complicated with selective intrauterine growth restriction (sIUGR) and absent or reverse end-diastolic flow (AREDF) in the umbilical arteries (UA). DESIGN AND SETTING: Single-centre retrospective observational study. POPULATION: 108 cases of sIUGR diagnosed before 26+6  weeks' gestation with AREDF in the UA. METHODS: Survival rate and potential risk factors were analysed. NDO was assessed using parental questionnaires. MAIN OUTCOMES MEASURES: Survival, gestational age at delivery and NDO. RESULTS: SFLC, CC and EM were performed in 13, 50 and 45 cases, respectively, with an overall survival of 23.1, 40 and 77.8% and intrauterine demise of the co-twin of 30.8, 10 and 6.7% respectively. Intrauterine demise of the sIUGR twin occurred in 76.9 and 17.8% following SFLC and EM, respectively. The discordance in EFW at diagnosis was higher and absent/negative a-wave in the ductus venosus (DV) was more prevalent in the surgical groups. NDO in survivors at follow up was abnormal in 0 and 18% in the smaller twin following SFLC and EM, respectively, and in 25, 24 and 21% in the larger twin following SFLC, CC and EM, respectively. CONCLUSION: SFLC yielded a poor result. EM seems a valid option when EFW discordance is <30% and a-wave in DV is positive. Otherwise, CC should be considered to protect the AGA co-twin. The long-term outcome of both small and large twins seems unaffected by the choice in primary prenatal management strategy. TWEETABLE ABSTRACT: In type II sIUGR in MC twins, long-term neurodevelopment is normal in over 80% of the survivors.

Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae.

OBJECTIVES: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae. METHODS: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally. RESULTS: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae. CONCLUSIONS: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Cost-effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model-based analysis.

OBJECTIVE: To evaluate the cost-effectiveness of five prenatal screening strategies for trisomies (13/18/21) and other unbalanced chromosomal abnormalities (UBCA), following the introduction of cell-free DNA (cfDNA) analysis. METHODS: A model-based cost-effectiveness analysis was performed to estimate prevalence, safety, screening-program costs and healthcare costs of five different prenatal screening strategies, using a virtual cohort of 652 653 pregnant women in France. Data were derived from the French Biomedicine Agency and published articles. Uncertainty was addressed using one-way sensitivity analysis. The five strategies compared were: (i) cfDNA testing for women with a risk following first-trimester screening of ≥ 1/250; (ii) cfDNA testing for women with a risk of ≥ 1/1000 (currently recommended); (iii) cfDNA testing in the general population (regardless of risk); (iv) invasive testing for women with a risk of ≥ 1/250 (historical strategy); and (v) invasive testing for women with a risk of ≥ 1/1000. RESULTS: In our virtual population, at similar risk thresholds, cfDNA testing compared with invasive testing was cheaper but less effective. Compared with the historical strategy, cfDNA testing at the ≥ 1/1000 risk threshold was a more expensive strategy that detected 158 additional trisomies, but also 175 fewer other UBCA. Implementation of cfDNA testing in the general population would give an incremental cost-effectiveness ratio of €9 166 689 per additional anomaly detected compared with the historical strategy. CONCLUSION: Extending cfDNA to lower risk thresholds or even to all pregnancies would detect more trisomies, but at greater expense and with lower detection rate of other UBCA, compared with the historical strategy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Relación costo-eficacia de cinco estrategias de cribado prenatal para trisomías y otras anomalías cromosómicas no equilibradas: un análisis basado en modelos OBJETIVO: Evaluar la eficacia en función de los costos de cinco estrategias de cribado prenatal para trisomías (13/18/21) y otras anomalías cromosómicas no equilibradas (UBCA, por sus siglas en inglés), tras la introducción del análisis de ADN fetal (cfDNA, por sus siglas en inglés). MÉTODOS: Se realizó un análisis de la relación costo-eficacia basado en modelos para estimar la prevalencia, la seguridad, los costos de los programas de cribado y los costos sanitarios de cinco estrategias diferentes de cribado prenatal, para lo cual se usó una cohorte virtual de 652 653 mujeres embarazadas en Francia. Los datos se obtuvieron de la Agencia Francesa de Biomedicina y de artículos publicados. La incertidumbre se abordó mediante un análisis de sensibilidad unidireccional. Las cinco estrategias comparadas fueron: (i) pruebas de cfDNA para mujeres con un riesgo ≥1/250 después del examen del primer trimestre; (ii) pruebas de cfDNA para mujeres con un riesgo ≥1/1000 (las recomendadas actualmente); (iii) pruebas de cfDNA en la población general (independientemente del riesgo); (iv) pruebas invasivas para mujeres con un riesgo ≥1/250 (estrategia histórica); y (v) pruebas invasivas para mujeres con un riesgo ≥1/1000. RESULTADOS: En esta población virtual, con umbrales de riesgo similares, la prueba de cfDNA fue más barata pero menos efectiva en comparación con la prueba invasiva. En comparación con la estrategia histórica, la prueba de cfDNA para el umbral de riesgo de ≥1/1000 fue una estrategia más costosa que detectó 158 trisomías adicionales, pero también 175 menos de otras UBCA. La aplicación de las pruebas de cfDNA en la población general daría una relación costo-eficacia incremental de 9 166 689 EUR por cada anomalía adicional detectada en comparación con la estrategia histórica. CONCLUSIÓN: Extender las pruebas de cfDNA a umbrales de riesgo más bajos o incluso a todos los embarazos detectaría más trisomías, pero a un costo mayor y con una tasa de detección más baja de otras UBCA, en comparación con la estrategia histórica.

Preterm premature rupture of membranes is a collateral effect of improvement in perinatal outcomes following fetoscopic coagulation of chorionic vessels for twin-twin transfusion syndrome: a retrospective observational study of 1092 cases.

OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a leading complication following fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS). Our primary objective was to describe the impact of improvements in surgical technique on survival and rate of PPROM over time. The secondary objective was to assess potential risk factors for PPROM. DESIGN AND SETTING: Single-centre retrospective observational study. POPULATION: 1092 consecutive cases of TTTS operated by FLC between 2000 and 2016, with a 6.8% rate of loss to follow up. METHODS: The incidence of PPROM and potential risk factors were analysed using competing risks models. MAIN OUTCOME MEASURES: PPROM, neonatal survival and neurological damage at 28 days. RESULTS: PPROM <32 weeks increased from 15 to 40% between 2000 and 2016 along with an overall improvement of perinatal outcomes: dual survival rose from 42 to 66% whereas dual losses dropped two-fold, from 19 to 9%. Gestational age at surgery at <17 weeks was a significant risk-factor for PPROM, with an additional risk of 10% within the first week of surgery. Although early PPROM at <20 weeks carried a 56% risk of miscarriage, the occurrence of PPROM at >20 weeks did not affect survival, despite an increase in preterm birth at <32 weeks. CONCLUSIONS: With significant improvement in perinatal outcomes, possibly related to improvements in surgical technique, postoperative complications have shifted to non-lethal obstetric complications such as PPROM, with rather reassuring postnatal outcomes, despite an increase in preterm birth and, potentially, morbidity. Early surgeries (<17 weeks) are at higher risk of postoperative PPROM. TWEETABLE ABSTRACT: Following laser/TTTS, rates of PPROM increased with perinatal survival; surgeries at <17 weeks are at highest risk.

Cellular origin of intrinsic optical signals in the rabbit retina.

Optical imaging of retinal intrinsic signals is a relatively new method that provides spatiotemporal patterns of retinal activity through activity-dependent changes in light reflectance of the retina. The exact physiological mechanisms at the origin of retinal intrinsic signals are poorly understood and there are significant inter-species differences in their characteristics and cellular origins. In this study, we re-examined this issue through pharmacological dissection of retinal intrinsic signals in the rabbit with simultaneous ERG recordings. Retinal intrinsic signals faithfully reflected retinal activity as their amplitude was strongly associated with stimulation intensity (r2=0.85). Further, a strong linear relation was found using linear regression (r2=0.98) between retinal intrinsic signal amplitude and the ERG b wave, which suggests common cellular origins. Intravitreal injections of pharmacological agents were performed to isolate the activity of the retina's major cell types. Retinal intrinsic signals were abolished when the photoreceptors' activity was isolated with aspartate, indicative that they are not at the origin of this signal. A small but significant decrease in intrinsic response (20%) was observed when ganglion and amacrine cells' activity was inhibited by TTX injections. The remaining intrinsic responses were abolished in a dose-dependent manner through the inhibition of ON-bipolar cells by APB. Our results indicate that, in rabbits, retinal intrinsic signals reflect stimulation intensity and originate from the inner retina with a major contribution of bipolar cells and a minor one from ganglion or amacrine cells.

Neural Processing of Second-Order Motion in the Suprasylvian Cortex of the Cat.

Neuronal responses to second-order motion, that is, to spatiotemporal variations of texture or contrast, have been reported in several cortical areas of mammals, including the middle-temporal (MT) area in primates. In this study, we investigated whether second-order responses are present in the cat posteromedial lateral suprasylvian (PMLS) cortex, a possible homolog of the primate area MT. The stimuli used were luminance-based sine-wave gratings (first-order) and contrast-modulated carrier stimuli (second-order), which consisted of a high-spatial-frequency static grating (carrier) whose contrast was modulated by a low-spatial-frequency drifting grating (envelope). Results indicate that most PMLS neurons responded to second-order motion and for the vast majority of cells, first- and second-order preferred directions were conserved. However, responses to second-order stimuli were significantly reduced when compared to those evoked by first-order gratings. Circular variance was increased for second-order stimuli, indicating that PMLS direction selectivity was weaker for this type of stimulus. Finally, carrier orientation selectivity was either absent or very broad and had no influence on the envelope's orientation selectivity. In conclusion, our data show that PMLS neurons exhibit similar first- and second-order response profiles and that, akin primate area MT cells, they perform a form-cue invariant analysis of motion signals.

Non-invasive prenatal testing for trisomy 21 based on analysis of cell-free fetal DNA circulating in the maternal plasma.

OBJECTIVE: By-the-book implementation of non-invasive prenatal test and clinical validation for trisomy 21. STUDY DESIGN: Publicly funded prospective study of 225 cases. Women at risk for trisomy 21 > 1/250 based on combined ultrasound and serum markers during first or second trimester were eligible following an informed consent. The technique was established from the available literature and performed on 10 mL of venous blood collected prior to chorionic villus sampling or amniocentesis. Investigators were blinded to the fetal karyotype. Results were expressed in Z-scores of the percentage of each chromosome. RESULTS: Among 976 eligible cases, 225 were processed: 8 were used for pretesting phase and 23 to build a reference set. One hundred thirty six euploid cases and 47 with trisomy 21 were then run randomly. Eleven cases yielded no result (4.8%). Z-scores were above 3 (7.58+/-2.41) for chromosome 21 in all 47 trisomies and in none of the euploid cases (0.11+/-1.0). Z-scores were within normal range for the other chromosomes in both groups. Using a cut-off of 3, sensitivity and specificity were of 100% 95% CI [94.1, 100] and 100% 95% CI [98, 100], respectively. CONCLUSION: Non-invasive prenatal test for trisomy 21 is a robust strategy that can be translated from seminal publications. Publicly funded studies should refine its indications and cost-effectiveness in prenatal screening and diagnosis. © 2015 John Wiley & Sons, Ltd.

A nomogram for perioperative prognostic risk-assessment in twin-twin transfusion syndrome.

OBJECTIVE: Prognostic assessment in twin-to-twin transfusion syndrome (TTTS) is ill-defined. The objective of this study is to define a perioperative prognostic score for TTTS treated by percutaneous laser coagulation. METHODS: Consecutive cases of TTTS treated by percutaneous fetoscopic laser coagulation over a 6-year period were reviewed. Twin survival at 28 days was considered using a 3-level polytomous variable defined by 0, 1, or 2 fatal events. A multivariate prognostic analysis with internal validation was conducted using gestational age at diagnosis, weight discordance, umbilical artery, and ductus venosus abnormalities in the donor and the recipient respectively, cervical length, selectivity of surgery, and transplacental approach. RESULTS: On the basis of 507 cases, the perinatal survival rate of 2 and 1 twin was 46.2% and 31.5%, respectively. Statistically significant factors included umbilical artery abnormalities in the donor, gestational age, and transplacental approach, but with different effects regarding survival of 0, 1, or 2 twins. A scoring chart was subsequently constructed together with a nomogram for both a preoperative and immediate post-operative prognostic assessment. CONCLUSION: Part of the prognosis can be anticipated by perioperative findings. Although further validation is required, the presented nomogram should help unify the prognostic assessment in TTTS.

Emergency cerclage in cases of twin-to-twin transfusion syndrome with a short cervix at the time of surgery and relationship to perinatal outcome.

OBJECTIVE: To evaluate the impact of emergency cerclage on perinatal outcome in cases presenting with cervical length less than fifth centile at the time of laser surgery. POPULATION AND METHODS: Observational study of severe twin-to-twin transfusion syndrome (TTTS) cases diagnosed before 26 weeks of gestation and treated by fetoscopic selective laser coagulation (FSLC). Transvaginal sonographic measurement of cervical length prior to treatment identified cases with cervical length less than fifth centile (15 mm). Expectant management was followed in these cases prior to 2004, and a McDonald suture was performed immediately after laser surgery from 2004 onwards. Outcome was compared in patients with and without cerclage. RESULTS: Cervical length was a strong predictor for gestational age (GA) at delivery (p = 0.005). Mean GA at laser therapy was comparable [22.4 ( +/- 2.1) and 22.1 ( +/- 2) in patients with (n = 9) and without cerclage (n = 5), respectively, (p = 0.8)], whereas mean (SD) GA at delivery was 30.5 ( +/- 4.3) and 23.1 ( +/- 2.6) weeks in patients with and without cerclage, respectively, (p = 0.004). There were 16 (89%) and 4 (40%) surviving twins in cases with and without cerclage, respectively (p = 0.01). CONCLUSIONS: In TTTS treated by laser, cervical length before treatment is significantly associated with GA at delivery. In cases with cervix < 15 mm, emergency cerclage may prolong the pregnancy and allow for better outcome.

[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.

[Down syndrome screening in France: the worst consensus]. / Dépistage de la trisomie 21 en France: le consensus du pire.

Down syndrome screening has been based on second trimester maternal serum markers assay for many years. Another late strategy was based on the "genetic sonogram" performed in early second trimester in high-risk populations selected on maternal age or second trimester maternal serum markers. New strategies for Down syndrome screening have emerged over the last 10 years, with higher sensitivity and lower false-positive rates. First trimester ultrasound examination is a successful screening test; the sensitivity of nuchal translucency measurement is of 60 to 77% for a 5% false-positive rate. Combining nuchal translucency measurement with PAPP-A and free beta-hCG assay (first trimester combined screening) increases the sensitivity up to 82%. The most specific strategy is based on the integrated test, i.e., the integration of the quadruple test performed in second trimester (inhibine dimeric A, total beta-hCG, AFP, and uE3 assay) to the first trimester combined screening: for a 85% detection rate, the false-positive rate is estimated to 0.9%. However, it is ethical only with the patient agreement because it prevents access to the results of first trimester combined screening, and deprives the patient of an early diagnosis by CVS. Therefore, alternative strategies were proposed: step-wise sequential screening and contingent sequential screening. In the step-wise screening, karyotype is offered when the result of the combined test is beyond a specified threshold. If the combined test result is below this threshold, quadruple test is offered, and the final risk is calculated in the second trimester by integrating the results of the quadruple test with those of the combined test. Contingent screening also begins with the first trimester-combined test. According to its results, the patients are considered in one of the 3 following risk groups: high, intermediate, or low risk. An early karyotype is proposed to the high-risk group after combined testing. The low risk group is reassured and thus the quadruple test is not performed. The quadruple test is proposed to the intermediate risk group and final risk is calculated by the integration of the combined test result into the quadruple test result. The global detection rate of the step-wise or contingent sequential screening is estimated to 84% for a false-positive rate of 2%.

[First trimester Down syndrome screening program using nuchal translucency and maternal serum markers: the Echo PAPP-A.78 study]. / Programme de dépistage de la trisomie 21 dans les Yvelines par mesure échographique de la clarté nucale et mesure des marqueurs sériques maternels au 1er trimestre de la grossesse. Etude Echo PAPP-A.78.

Successive development of different methods to screen down syndrome (DS) have had unexpected effects, leading to an inflation in the number of karyotypes ordered and the number of induced abortions. In our district (Yvelines, France), DS screening leads to perform 16% karyotypes rate. Rapid progress in biology and ultrasonography has enabled us to correct this overprescription by conducting an early screening program using a combination of ultrasound graphic and new biochemical markers (Pregnancy-associated plasma protein A and the free fraction of ss-hCG) which allow an overall evaluation of risk. This method has high sensitivity (85%) and leads to a false positive rate karyotypes in about 5% of pregnancies. The purpose of the study conducted between January 1, 2001 and December 31, 2002 in the Yvelines was to confirm the validity of this method and determine its reproducibility in routine practice. Five partners contributed to the study: the Regional delegation for clinical research of the Paris-public assistance hospitals (AP-HP), the district health insurance fund (CPAM 78), the Yvelines maternity network which includes all ten maternity wards in the district, and the Echo 78 association which includes all ultrasoundgraphists working in the district who accepted to participate as investigators, as well as five biology laboratories where DS screening was performed.

Effect of diazepam treatment on metabolic indices in trained and untrained rats.

Exercise training, like diazepam, is commonly employed as a means of reducing anxiety. Both diazepam and exercise training have been shown to modify carbohydrate and lipid metabolism as well as influence calcium metabolism in skeletal muscle. As receptor binding and thereby efficacy of diazepam has been demonstrated to be modulated by the lipid environment of the receptor, and changes in calcium levels can affect a number of intracellular signalling pathways, we sought to determine if the interaction of both chronic diazepam and exercise training would modify selected metabolic indices in an animal model. For this purpose, muscle and liver glycogen, blood glucose and plasma free fatty acids (FFA) were measured in sedentary, exercise trained and exercise trained, acutely exhausted animals. Alterations in lipid and carbohydrate metabolism were observed in all experimental groups. Diazepam treatment alone exerts metabolic consequences, such as elevated muscle glycogen and plasma FFA and depressed blood glucose levels, which are similar to those observed with exercise training. When animals are acutely exercised to exhaustion, however, differences appear, including a reduced rise in plasma FFA, which suggests that long-term diazepam treatment does influence exercise metabolism, possibly as a result of effects on the sympatho-adrenal system.