Fetal aortic valvuloplasty for critical aortic stenosis: single-center retrospective study focusing on postnatal outcome.

OBJECTIVE: We aimed to report our experience on fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS) focusing on the postnatal evolution of the patients. METHODS: This retrospective study was approved by our local Institutional Review Board (n°2002-0128143827). All fetuses with critical AS who underwent FAV in a single center between 01/2011 and 06/2022 were included. FAV were performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the anterograde aortic flow across the aortic valve. At birth, biventricular circulation (BVC) strategy was decided assuming the left ventricle (LV) systolic and diastolic functions would ensure the systemic circulation. RESULTS: Sixty-three FAV were performed on 58 fetuses at 24.6[21.4-32.4] weeks of gestation. The procedure was successful in 52/58(89.6%) fetuses. There were 11/58(19%) in utero demises and 9/58(15.5%) terminations of pregnancy. There were no liveborn patients after the unsuccessful procedures. 38/58(65.5%) infants were delivered at a median gestational age of 38.1[29-40.6] weeks and 21/38(55.3%) of them required prostaglandin. 28/38(73.7%) [28/58(48.3%)] children entered the BVC path at birth. Among them, 20 required an aortic valvuloplasty at birth (11 percutaneous, 9 surgical) and 8 did not require any treatment at birth but of those, 5/8 underwent a surgical valvuloplasty between day 26 and day 1200 of life. 11/28(39.3%) infants with BVC at birth required a second intervention and four of them required a third intervention. Two infants who entered the BVC at birth underwent a conversion to UVC. None of the surviving children with BVC developed pulmonary hypertension. The global survival rate in case of BVC was 22/28(78.6%) at 23.3[8-112] months of life. 10 patients had UVC at birth. Among them, 6 received comfort care from birth and only 4 underwent surgery. 3/10 patients were still alive at the latest assessment (48[22-102] months). CONCLUSION: FAV for critical aortic stenosis led to anterograde aortic flow in 89.6% of the fetuses, with BVC being achieved in 48.3% (73.7% of the live born). Among patients with BVC at birth, the rate of reintervention is high but long-term survival is satisfactory. This article is protected by copyright. All rights reserved.

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 fetal growth restricted pregnancies : multicenter cohort.

OBJECTIVES: Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (f-MRI) technique allows a non-invasive in-vivo evaluation of placental oxygenation. The aim of this study was to highlight and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between FGR and non-FGR fetuses (fetal growth restricted). METHODS: In a prospective multicenter study (NCT02238301), we included 19 FGR fetuses (cases defined by an ultrasound-based estimated fetal weight (EFW) <5th centile) and 75 non-FGR fetuses (controls). 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 in baseline and in hyperoxic conditions and the relative BOLD effect according to the following equation: Relative BOLD effect = 100 x (hyperoxicT2*-baseline T2*)/baseline T2*. The baseline T2* values and relative BOLD effect were compared according to fetal weight estimations (between FGR and non-FGR fetuses), presence of Doppler anomalies and according to birth weight (between appropriate and small for gestational age newborns - AGA/SGA). RESULTS: We demonstrate a relative BOLD effect in response to hyperoxia in the human placenta, quantified at 33.8% (22.5;48.0). The relative BOLD effect was not statistically different between FGR and non-FGR fetuses (34.4% (26.1-33.4) versus 33.7% (22.7-139.2), p=0.95). Baseline T2* values Z-score adjusted for gestational age at MRI ​​were significantly lower for FGR fetuses as compared with non-FGR fetuses (-1.27 (-4.87;-0.10) vs 0.33 (-0.81;1.02) respectively, p=0.001). Baseline T2* values Z-score were also significantly lower for the subsequently SGA neonates (-0.75 (-3.48; 0.29 n=23) vs 0.35 (-0.79;-1.05 n=62), p=0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in FGR fetuses. Further studies are needed to evaluate whether such parameters may detect placental insufficiency, before it has a clinical impact on fetal growth. This article is protected by copyright. All rights reserved.

Non-invasive cell-free DNA prenatal screening for trisomy 21 as part of primary screening strategy in twin pregnancies.

OBJECTIVES: The performance of non-invasive prenatal screening using cell-free DNA testing in maternal blood in twin pregnancies is still under-evaluated, while serum marker-based strategies yield poor results. This study aims at assessing the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancies as a first-tier test. The secondary objectives were to assess the failure rate and associated factors. METHODS: This retrospective cohort study included twin pregnancies for which non-invasive prenatal screening using cell-free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in vitro diagnosis and set a fetal fraction cut-off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome was collected from either physicians or midwives through a questionnaire or were retrieved directly on site. We calculated the performance of non-invasive cell free DNA screening for trisomy 21 and analyzed failure rate and factors. RESULTS: We included 2577 multiple pregnancies among which 1885 (84.8%) were retained after excluding vanishing twins and pregnancies without follow-up. Overall, there were six confirmed trisomy 21 cases (0.32%). For trisomy 21, sensitivity was 100% (95% CI, 61-100%) and the false-positive rate 0.2% (95% CI, 0.07-0.6%). The primary failure rate was 4.6% with 4% due to insufficient fetal fraction. After a new blood draw (59.8% of failed cases), failure rate was only 1.5%. Body mass index and chorionicity were significantly correlated with the risk of failure. CONCLUSION: This study adds further evidence on the high performance of NIPS in twins, as part of the primary screening strategy for trisomy 21, at an extremely low false-positive rate. This article is protected by copyright. All rights reserved.

Impact of prenatal estimation of the risk of respiratory distress in neonates with congenital pulmonary malformations on the choice of delivery site.

BACKGROUND: The vast majority of prenatally diagnosed congenital pulmonary malformations (CPM) remain asymptomatic at birth. The maximal value of the CPM volume ratio (CVRmax) predicts the risk of neonatal respiratory distress (NRD), and should allow for better assessment of the level of expertise needed at the delivery site. AIM: This study evaluated the level of maternity units currently chosen for the delivery of CPMs, and determined the impact of the choice of delivery site based on the CVRmax, with a threshold of 0.4 cm2. METHODS: Data were extracted from the French prospective MALFPULM cohort, with inclusion between March 2015 and June 2018. RESULTS: The final study population consisted of 383 women. Deliveries in level 1 or 2 maternity units (n = 98, 25%) involved CPMs with lower CVRmax (p<0.001), causing fewer signs of prenatal compression (p = 0.025). Among the 62 children (16%) who presented with NRD, only seven (11%) were born in level 1 or 2 units (p = 0.0078). Choosing the maternity level according to the CVRmax would have increased the number of births in level 1 or 2 maternity hospitals by 70%. In these maternity units, the percentage of children with NRD would have increased from 8% in the actual distribution to 10% in the new strategy. CONCLUSION: Our results showed an overuse of level 3 maternity hospitals for the delivery of newborns with a prenatal diagnosis of CPM. The use of CVRmax should enable a reduction in the use of expertise centers without an adverse impact on newborns.

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.

Corpus callosal reference ranges: systematic review of methodology of biometric chart construction and measurements obtained.

OBJECTIVE: Adequate reference ranges of size of the corpus callosum (CC) are necessary to improve characterization of CC abnormalities and parental counseling. The objective of this study was to evaluate the methodology used in studies developing references charts for CC biometry. METHODS: We conducted a systematic review of studies on fetal CC biometry using a set of predefined quality criteria of study design, statistical analysis and reporting methods. We included observational studies whose primary aim was to create ultrasound or magnetic resonance imaging charts for CC size in a normal population of fetuses. Studies were scored against a predefined set of independently agreed methodological criteria, and an overall quality score was given for each study. RESULTS: Twelve studies met the inclusion criteria. Quality scores ranged between 17.4% and 95.7%. The greatest potential for bias was noted for the following items: sample selection and sample-size calculation, as only 17% of the studies were population-based and had consecutive or random recruitment of patients and with a justification of the sample size; number of measurements obtained for CC biometry, as only 17% of the studies performed more than one measurement per fetus and per scan; and description of characteristics of the study population, as only 8% of the studies clearly reported a minimum dataset of demographic characteristics. CONCLUSIONS: Our review demonstrates substantial heterogeneity in methods and final biometric values of the fetal CC across the evaluated studies. The use of uniform methodology of the highest quality is essential in order to define a 'short' CC and provide appropriate parental counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.