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.

Fetal brain imaging following laser surgery in twin-to-twin surgery.

OBJECTIVE: To describe the incidence and nature of prenatal brain damage following fetoscopic laser selective coagulation (FLSC) of placental vessels for twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective observational study. SETTING: Single center cohort. POPULATION: All consecutive cases referred for TTTS treated by FLSC between 2003 and 2015. METHODS: After the FLSC, patients were followed weekly by ultrasound. Fetal magnetic resonance imaging (MRI) scans were systematically planned at 30-32 weeks of gestation. MAIN OUTCOME MEASURES: Brain damage diagnosed prenatally by ultrasound or MRI. RESULTS: In total, 1023 cases were reviewed. Brain damage was diagnosed prenatally in 22/1023 (2.1%) cases. Diagnosis was performed by ultrasound prior to MRI in 18 (82%) cases. All lesions were within the spectrum of ischaemic haemorrhagic lesions. Postoperative twin anaemia polycythaemia sequence and recurrence of TTTS were significantly associated with brain damage. CONCLUSION: The incidence of prenatal brain damage is low following FSLC, and is strongly associated with incomplete surgery. TWEETABLE ABSTRACT: Following FSLC for TTTS, prenatal brain damage occurs in 2% of cases and is associated with incomplete surgery.

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.

Fetal urine biochemistry at 13-23 weeks of gestation in lower urinary tract obstruction: criteria for in-utero treatment.

OBJECTIVES: To assess the value of fetal urine biochemistry before 23 weeks of gestation in cases of lower urinary tract obstruction (LUTO) to refine prognosis and to select potential candidates for in-utero intervention. METHODS: This was a retrospective study including 72 cases of LUTO with fetal urine sampled before 23 weeks and assayed for total protein, ß-2-microglobulin, sodium, chloride, calcium, phosphorus, glucose and gamma-glutamyl transpeptidase (GGTP). Two groups were defined according to renal outcome: 1) bilateral renal dysplasia on histological examination or renal failure at birth; 2) normal postnatal renal function or histologically normal appearance of the kidneys. Correlations between fetal urinary biochemical markers and postnatal renal function were studied. RESULTS: LUTO was isolated in 56/72 (77.8%) cases and was associated with other malformations in 16/72 (22.2%) cases. High GGTP levels (236 IU/L vs 5 IU/L; P < 0.0001) were observed in fetal urine in the five cases of urodigestive fistula. A significant difference between outcome groups was observed for ß-2-microglobulin (P = 0.0017), sodium (P = 0.0008), chloride (P = 0.0028) and calcium (P = 0.0092) but not for protein, glucose or phosphorus. Sensitivity and specificity in defining a poor renal prognosis were 80.6% and 89% for ß-2-microglobulin, 61.3% and 100% for sodium and 64.5% and 100% for calcium, respectively. CONCLUSIONS: Fetal urinalysis before 23 weeks of gestation allowed distinction between three groups: 1) fetuses with normal urine biochemistry for which fetal therapy should be discussed; 2) fetuses with abnormal urine biochemistry for which prognosis for renal outcome is poor and for which the benefit of fetal therapy is likely to be compromised; 3) fetuses with urodigestive fistula.

Pulmonary stenosis in complicated monochorionic twin pregnancies: prevalence, management and outcome.

OBJECTIVE: To review prevalence, management and prognostic factors of pulmonary stenosis (PS) in monochorionic diamniotic (MCDA) pregnancies complicated by twin-to-twin transfusion syndrome (TTTS). METHODS: Retrospective study over the last 10 years in a single referral center. We reviewed fetal echocardiography data of all MC twin cases with diagnosis of isolated PS. We assessed fetoscopy characteristics of those that underwent laser coagulation. We collected data regarding perinatal outcome, neonatal echocardiography and cardiac management. RESULTS: We found 24 cases of isolated PS among 2091 MCDA pregnancies. Among 1052 complicated MCDA that underwent fetal laser surgery, 22 (2.09%) developed PS of which 20 were diagnosed prenatally. Two cases were diagnosed in uncomplicated MCDA pregnancies (0.2%). Four of 22 (18.18%) cases with TTTS showed in utero regression after laser treatment. Thirteen newborns (65%) required valvular dilatation. Peak systolic velocities in the pulmonary artery trunk (PSV-PA) at diagnosis and the interval between the diagnosis of TTTS and that of PS were significantly different (p < 0.001 and p = 0.05 respectively) between PS requiring cardiac intervention and those who did not. CONCLUSION: An elevated PSV-PA at the time of PS diagnosis and a short time-interval between fetoscopic laser surgery and PS diagnosis are predictive of the need for interventional treatment after birth.

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.

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.

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.

Secondary bladder herniation in isolated gastroschisis justifies increased surveillance.

OBJECTIVES: To assess the perinatal outcome of fetuses with gastroschisis complicated by secondary bladder herniation. POPULATION AND MATERIALS: This was a retrospective study of all cases of isolated gastroschisis associated with bladder herniation managed at our institution. Prenatal ultrasound, obstetrical and perinatal information were collected. Pathology reports were also gathered. RESULTS: Out of 105 cases of gastroschisis managed at our institution, six (5.7%) were associated with secondary bladder herniation, two of them being diagnosed postnatally. Median gestational age at diagnosis of bladder herniation was 33.6 weeks (range 31-36) in five female and one male fetuses. Bladder herniation was associated with bowel dilatation in four cases (67%) and with pyelic dilatation in one case (17%). Despite increased surveillance, one male fetus died in utero. In four other cases, cesarean section was performed for fetal distress (three cases) or hyperechogenic bowels (one case). The five survivors had primary abdominal closure (n = 2) or staged repair (n = 3) with uneventful follow-up. CONCLUSION: Bladder herniation was present in 6% of apparently isolated gastroschisis. There was one intrauterine fetal death and four other cases were delivered for fetal distress. Increased surveillance seems justified.

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.