Refining the prognosis of fetuses infected with Cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: a single-centre retrospective study.

OBJECTIVE: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT). DESIGN: A retrospective study. SETTING: Reference fetal medicine unit. POPULATION: Sixty-two fetuses infected <14 weeks of gestation. METHODS: We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA. MAIN OUTCOME MEASURES: For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported. RESULTS: The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter. CONCLUSIONS: Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy. TWEETABLE ABSTRACT: Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks.

Vein of Galen aneurysmal malformation (VGAM) in the fetus: retrospective analysis of perinatal prognostic indicators in a two-center series of 49 cases.

OBJECTIVE: Vein of Galen aneurysmal malformation (VGAM) is a rare fetal anomaly, the neurological outcome of which can be good with appropriate perinatal management. However, most fetal series are too small to allow reliable statistical assessment of potential prognostic indicators. Our aim was to assess, in a two-center series of 49 cases, the prognostic value of several prenatal variables, in order to identify possible prenatal indicators of poor outcome, in terms of mortality and cerebral disability. METHODS: This was a retrospective study involving 49 cases of VGAM diagnosed prenatally and managed at two centers over a 17-year period (1999-2015). All cases had undergone detailed prenatal cerebral and cardiac assessment by grayscale ultrasound, color and pulsed-wave Doppler and magnetic resonance imaging (MRI). Ultrasound and MRI examination reports and images were reviewed and outcome information was obtained from medical reports. Volume of the VGAM (on ultrasound and MRI) was calculated and development of straight-sinus dilatation, ventriculomegaly and other major brain abnormalities was noted. Cardiothoracic ratio, tricuspid regurgitation and reversed blood flow across the aortic isthmus were evaluated on fetal echocardiography. Major brain lesions were considered by definition to be associated with poor outcome in all cases. Pregnancy and fetoneonatal outcome were known in all cases. Fetoneonatal outcome and brain damage were considered as dependent variables in the statistical evaluation. Poor outcome was defined as death, late termination of pregnancy due to association with related severe brain anomalies or severe neurological impairment. RESULTS: At a mean follow-up time of 20 (range, 0-72) months, 36.7% of the whole series and 52.9% of the cases which did not undergo late termination were alive and free of adverse sequelae. Five (10.2%) cases showed progression of the lesion between diagnosis and delivery. On univariate analysis, dilatation of the straight sinus, VGAM volume ≥ 20 000 mm3 and tricuspid regurgitation were all significantly related to poor outcome. However, on logistic regression analysis, the only variables associated significantly with poor outcome were tricuspid regurgitation and, to a lesser extent, VGAM volume ≥ 20 000 mm3 . The former was also the only variable associated with brain damage. CONCLUSIONS: Major brain lesions, tricuspid regurgitation and, to a lesser extent, VGAM volume ≥ 20 000 mm3 are the only prenatal variables associated with poor outcome in fetal VGAM. Prenatal multidisciplinary counseling should be based on these variables. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Placental elastography in a murine intrauterine growth restriction model.

OBJECTIVE: To compare placental elasticity in normal versus intrauterine growth restriction (IUGR) murine pregnancies using shear wave elastography (SWE). METHODS: Intrauterine growth restriction was created by ligation of the left uterine artery of Sprague-Dawley rats on E17. Ultrasonography (US) and elastography were performed 2 days later on exteriorized horns after laparotomy. Biparietal diameter (BPD) and abdominal diameter (AD) were measured and compared in each horn. Placental elasticity of each placenta was compared in the right and left horns, respectively, using the Young's modulus, which increases with increasing stiffness of the tissue. RESULTS: Two hundred seventeen feto-placental units from 18 rats were included. Fetuses in the left ligated horn had smaller biometric measurements than those in the right horn (6.7 vs 7.2 mm, p < 0.001, and 9.2 vs 11.2 mm, p < 0.001 for BPD and AD, respectively). Mean fetal weight was lower in the pups from the left than the right horn (1.65 vs 2.11 g; p < 0.001). Mean (SD) Young's modulus was higher for placentas from the left than the right horn (11.7 ± 1.5 kPa vs 8.01 ± 3.8 kPa, respectively; p < 0.001), indicating increased stiffness in placentas from the left than the right horn. There was an inverse relationship between fetal weight and placental elasticity (r = 0.42; p < 0.001). CONCLUSION: Shear wave elastography may be used to provide quantitative elasticity measurements of the placenta. In our model, placentas from IUGR fetuses demonstrated greater stiffness, which correlated with the degree of fetal growth restriction.

In vivo MRI assessment of placental and foetal oxygenation changes in a rat model of growth restriction using blood oxygen level-dependent (BOLD) magnetic resonance imaging.

OBJECTIVES: To evaluate whether changes in BOLD signal intensities following hyperoxygenation are related to intrauterine growth restriction (IUGR) in a rat model. METHODS: IUGR was induced in pregnant rats by ligating the left vascular uterine pedicle at day 16 of gestation. BOLD MR imaging using a balanced steady-state free-precession (balanced-SSFP) sequence on a 1.5-T system was performed on day 19. Signal intensities (SI) before and after maternal hyperoxygenation were compared in the maternal liver and in control and growth-restricted foetoplacental units (FPUs). RESULTS: Maternal hyperoxygenation resulted in a significant increase in SI in all regions of interest (P < 0.05) in the 18 rats. In the control group, the SI (mean ± SD) increased by 21 % ± 15 in placentas (n = 74) and 13 % ± 8.5 in foetuses (n = 53). In the IUGR group, the increase was significantly lower: 6.5 % ± 4 in placentas (n = 36) and 7 %± 5.5 in foetuses (n = 34) (P < 0.05). CONCLUSION: BOLD MRI allows non-invasive assessment of the foetoplacental response to maternal hyperoxygenation in the rat and demonstrates its alteration in an IUGR model. This imaging method may provide a useful adjunct for the early diagnosis, evaluation, and management of human IUGR. KEY POINTS: • Intra-uterine growth restriction is an important cause of perinatal morbidity and mortality. • Blood oxygen level-dependent MRI non-invasively assesses foetoplacental response to maternal hyperoxygenation. • In the rat, foetoplacental response to maternal hyperoxygenation is altered in IUGR. • Functional MRI may help to assess human IUGR.

Active management of selective intrauterine growth restriction with abnormal Doppler in monochorionic diamniotic twin pregnancies diagnosed in the second trimester of pregnancy.

OBJECTIVE: This study aims to compare outcomes of active management of monochorionic diamniotic twin pregnancies complicated with severe intrauterine growth restriction (IUGR) of one twin before 24 weeks with continuous or intermittent absent or reversed end-diastolic flow (AREDF) in the umbilical artery, with or without twin-to-twin transfusion syndrome (TTTS). METHOD: This study is a retrospective comparison of 45 consecutive cases of severe selective IUGR (s-IUGR) defined as an estimated fetal weight at or below the fifth centile with a >25% weight discordance and AREDF in the umbilical artery before 24 weeks and 166 consecutive cases of TTTS stage III, with AREDF in the donor (TTTS3D) and also with s-IUGR. These were treated by either selective laser photocoagulation of chorionic vessels (SLPCV) or cord coagulation (CC). RESULTS: The 166 cases of TTTS3D were treated by SLPCV, whereas 23 and 22 cases of s-IUGR were treated by SLPCV and CC, respectively. Overall survival was 52.17% or 45.45% in s-IUGR treated by SLPCV or CC, respectively, and 48.49% in TTTS3D. The survival of appropriately grown for gestational age (AGA) twins following CC (90.9%) was higher than that following SLPCV in s-IUGR (74%) or in recipient twins of TTTS3D (55.42%) (p = 0.001). Survival of the IUGR twin was 30% and 41.56% with SLPCV in s-IUGR and TTTS3D, respectively. CONCLUSIONS: Active management of severe IUGR with AREDF in the umbilical artery seems beneficial. Survival rates with SLPCV were similar in s-IUGR and TTTS3D. However, there was a trend for higher survival rates in the AGA twin for CC. The choice of the technique should be driven by objective counseling on survival of both IUGR and AGA twins and therefore by the utility-based ethical values expressed by the pregnant woman.

SPIO-enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction.

OBJECTIVE: To assess placental perfusion with magnetic resonance imaging (MRI) and superparamagnetic iron oxide (SPIO) in a rat model of intrauterine growth restriction (IUGR). DESIGN: Experimental animal study. SETTING: The study complied with US National Institutes of Health recommendations for animal care. POPULATION: Thirty-two rats at day 16 of gestation underwent surgical ligation of the left uterine vessel to induce IUGR. METHODS: Eighteen rats were examined by MRI 3 days later, after bolus injection of ferucarbotran. MAIN OUTCOME MEASURE: Signal intensities were measured in the maternal left ventricle and in the placentas of the two horns. Quantitative microcirculation parameters were calculated and compared between the placentas of the two horns. RESULTS: Fifty-four kinetic curves of placental perfusion were obtained in 11 rats. The mean placental blood flow was significantly lower in the ligated horns than in the normal horns (108.1 versus 159.4 ml/minute/100 ml, p = 0.0004). The mean fractional volume of the maternal vascular placental compartment did not differ significantly between the pathological (42.8%) and normal placentas (39.2%). CONCLUSIONS: Placental perfusion, including changes during experimental IUGR, can be measured in rats by using MRI with SPIO. These findings could have implications for human studies of placental microcirculation and for the management of disorders related to placental dysfunction.

Hidden mortality of prenatally diagnosed vein of Galen aneurysmal malformation: retrospective study and review of the literature.

OBJECTIVE: To evaluate the prognosis of prenatally diagnosed vein of Galen aneurysmal malformation (VGAM) in a large cohort with this condition and to review the literature on prenatally diagnosed VGAM. METHODS: This was a retrospective study of all cases of prenatally diagnosed VGAM managed in our referral center during a 12-year period. VGAM was categorized as being either isolated or associated with any other abnormality, based on fetal ultrasound and magnetic resonance imaging findings. Poor outcomes comprised termination of pregnancy with confirmation of antenatal findings, perinatal death and severe cardiac and/or neurological impairment in survivors. The literature was also reviewed for similar cases. RESULTS: Twenty-one cases of prenatally diagnosed VGAM were managed in our center. Four (19.0%) cases were isolated and 17 (81.0%) were associated with other anomalies. There were nine terminations (42.9%) and six neonatal deaths (28.6%). Six children (28.6%) were still alive at last follow-up, of whom three had abnormal neurological development. VGAM associated with other anomalies was strongly associated with a poor outcome compared with isolated forms (P < 0.0001). One hundred and nine cases from the literature were also reviewed. CONCLUSION: Fetuses with prenatally diagnosed VGAM have unexpectedly poor outcomes in the presence of cardiac or cerebral anomalies, while those with strictly isolated VGAM tend to have more favorable outcomes. Our literature review corroborates these findings.

Laser therapy for twin-to-twin transfusion syndrome (TTTS).

Monochorionic twins are subjected to specific complications which originate in either imbalance or abnormality of the single placenta serving two twins including twin-to-twin transfusion syndrome. The diagnosis is well established in overt clinical forms with the association of polyuric polyhydramnios and oliguric oligohydramnios. The best treatment of cases presenting before 26 weeks of gestion is fetoscopic laser ablation of the intertwin anastomoses on the chorionic plate. Although subjected to subtle variations, the core technique follows robust guidelines which could help understanding and acquiring the required skills and experience to perform this procedure. However appropriate and tailored hands-on training and appropriate perinatal set-up are critical not only for surgical management but also for the follow-up and management of related complications.

Prenatally diagnosed periventricular nodular heterotopia: Further delineation of the imaging phenotype and outcome.

OBJECTIVES: Periventricular nodular heterotopia (PNH) is a malformation of cortical development which presents with heterogeneous imaging, neurological phenotype and outcome. There is a paucity of comprehensive description detailing the prenatal diagnosis of PNH. The aim of this study is to report neuroimaging features and correlated outcomes in order to delineate the spectrum of prenatally diagnosed PNH. METHODS: It was a retrospective study over 15 years in five tertiary centers. All fetuses with prenatally diagnosed PNH were collected. Fetal ultrasound and MRI were reviewed and genetic screening collected. Prenatal findings were analyzed in correlation to fetopathological analyses and post-natal follow up. RESULTS: Thirty fetuses (22 females and 8 males) with PNH were identified. The two major ultrasound signs were ventriculomegaly associated with dysmorphic frontal horns (60%) and posterior fossa anomalies (73.3%). On MRI, two groups of PNH were identified: the contiguous and diffuse PNH (n = 15, 50%), often associated with megacisterna magna, and the non-diffuse, either anterior, posterior or unilateral PNH. FLNA mutations were found in 6/11 cases with diffuse PNH. Additional cortical malformations were exclusively observed in non diffuse PNH (9/15; 60%). Twenty-four pregnancies (80%) were terminated. Six children aged 6 months to 5 years are alive. Five have normal neurodevelopment (all had diffuse PNH) whereas one case with non diffuse PNH has developmental delay and epilepsy. CONCLUSION: PNH is heterogeneous but patients with diffuse PNH are a common subgroup with specific findings on prenatal imaging and implications for prenatal counseling.

Dynamic contrast enhanced MRI of the placenta: A tool for prenatal diagnosis of placenta accreta?

BACKGROUND: Ultrasound (US) is the primary imaging modality for the diagnosis of placenta accreta, but it is not sufficiently accurate. MRI morphologic criteria have recently emerged as a useful tool in this setting, but their analysis is too subjective. Recent studies suggest that gadolinium enhancement may help to distinguish between the stretched myometrium and placenta within a scar area. However, objective MRI criteria are still required for prenatal diagnosis of placenta accreta. The purpose of this study was to assess the diagnostic value of dynamic contrast gadolinium enhancement (DCE) MRI patterns for placenta accreta. MATERIALS AND METHODS: MR images were acquired with a 1.5-T unit at 30-35 weeks of gestation in women with a history of Caesarian section, a low-lying anterior placenta, and US features compatible with placenta accreta. Sagittal, axial and coronal SSFP (Steady State Free Precession) sequences were acquired before injection. Then, contrast-enhanced dynamic T1-weighted images were acquired through the entire cross-sectional area of the placenta. Images were obtained sequentially at 10- to 14-s intervals for 2 min, beginning simultaneously with the bolus injection. Functional analysis was performed retrospectively, and tissular relative enhancement parameters were extracted from the recorded images. The suspected area of accreta (SAA) was placed in the region of the previous scar, and a control area (CA) of similar size was placed on the same image plane, as far as possible from the SAA. Semi-quantitative analysis of DCE-MR images was based on the kinetic enhancement curves in these two regions of interest (ROI). Three tissular relative enhancement parameters were compared according to the pregnancy outcomes, namely time to peak, maximal signal intensity, and area under the enhancement curve. RESULTS: We studied 9 women (43%) with accreta and 12 women (57%) with a normal placenta. All three tissular relative enhancement parameters differed significantly between the two groups (p < 10-3). CONCLUSION: The use of dynamic contrast-enhanced MRI at 30-35 weeks of gestation in women with a high risk of placenta accreta allows the extraction of tissular enhancement parameters that differ significantly between placenta accreta and normal placenta. It therefore provides objective parameters on which to base the diagnosis and patient management.

[Prenatal discovery of Joubert syndrome associated with small bowel volvulus]. / Découverte anténatale d'un syndrome de Joubert associé à un volvulus du grêle.

Joubert syndrome and prenatal volvulus are difficult to diagnose during pregnancy. Joubert syndrome and related diseases should be considered in case of prenatal abnormal features of the fourth ventricle. Small bowel volvulus is also a surgical emergency because of the risk of intestinal necrosis before or after delivery. This type of condition justifies the transfer of pregnant women to a specialized hospital where the newborn may receive appropriate care. We report the case of a 31-week and 4-day gestational-age fetus in whom intrauterine growth retardation and small-bowel volvulus were diagnosed. Additional imaging revealed associated Joubert syndrome. This highlights the need for regular ultrasound monitoring during pregnancy and the comanagement of obstetricians and pediatricians to provide appropriate care before and after delivery.

Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications.

INTRODUCTION: In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. MATERIAL AND METHODS: To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. RESULTS: The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour. CONCLUSION: Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB.

[Placental MRI: physiology and pathology]. / IRM placentaire: physiologie et pathologie.

The placenta is essential for fetal development but its in vivo study, including the study of placental perfusion is still very limited to date. MRI is a safe examination that offers new perspectives for the study of placental function that is altered in many conditions (IUGR, preeclampsia…) and placental anatomy (placenta accreta…). The different MRI sequences (DCE, IVIM, BOLD, ASL…) are new tools that may soon allow us to assess precisely placental function and anatomy, in vivo and non-invasively.

[Management of twin-to-twin transfusion syndrome]. / Prise en charge du syndrome transfuseur-transfusé.

Twin-to-twin transfusion syndrome (TTTS), also called twin oligoamnios polyhydramnios sequence (TOPS) complicates around 15% of monochorionic pregnancies irrespective of the mode of conception. It is a hemodynamic, and probably hormonal, discordance secondary to imbalanced blood flow through the vascular anastomoses aforementioned. During the last 15 years, a lot of progress has been made in the understanding, diagnosis and treatment of TTTS. Nevertheless, many questions remain unanswered and research is still active in this domain. Fetoscopic laser coagulation of placental vessels is the only treatment addressing the pathophysiology of the syndrome as proven through a randomized controlled study against amnioreduction. This technique has definitely improved overall survival as well as the rate of neurologically intact survival but it still lacks preoperative prognostic markers.

Dynamic contrast-enhanced magnetic resonance imaging: definitive imaging of placental function?

The placenta constitutes a complex circulatory interface between the mother and fetus, but the relationship between the maternal and fetal circulation is still very difficult to study in vivo. There is growing evidence that magnetic resonance imaging (MRI) is useful and safe during pregnancy, and MRI is increasingly used for fetal and placental anatomical imaging. MRI functional imaging is now a modern obstetric tool and has the potential to provide new insights into the physiology of the human placenta. Placental perfusion has been studied during the first pass of an MR contrast agent, by arterial spin labeling, diffusion imaging, T1 and T2 relaxation time measurement using echo-planar imaging, and by a combination of magnetization transfer with established stereological methods. The BOLD (blood oxygen level-dependent) effect offers new perspectives for functional MRI evaluation of the placenta.