Feasibility and Added Value of Fetal DTI Tractography in the Evaluation of an Isolated Short Corpus Callosum: Preliminary Results.

BACKGROUND AND PURPOSE: Prognosis of isolated short corpus callosum is challenging. Our aim was to assess whether fetal DTI tractography can distinguish callosal dysplasia from variants of normal callosal development in fetuses with an isolated short corpus callosum. MATERIALS AND METHODS: This was a retrospective study of 37 cases referred for fetal DTI at 30.4 weeks (range, 25-34 weeks) because of an isolated short corpus callosum less than the 5th percentile by sonography at 26 weeks (range, 22-31 weeks). Tractography quality, the presence of Probst bundles, dysmorphic frontal horns, callosal length (internal cranial occipitofrontal dimension/length of the corpus callosum ratio), and callosal thickness were assessed. Cytogenetic data and neurodevelopmental follow-up were systematically reviewed. RESULTS: Thirty-three of 37 fetal DTIs distinguished the 2 groups: those with Probst bundles (Probst bundles+) in 13/33 cases (40%) and without Probst bundles (Probst bundles-) in 20/33 cases (60%). Internal cranial occipitofrontal dimension/length of the corpus callosum was significantly higher in Probst bundles+ than in Probst bundles-, with a threshold value determined at 3.75 for a sensitivity of 92% (95% CI, 77%-100%) and specificity of 85% (95% CI, 63%-100%). Callosal lipomas (4/4) were all in the Probst bundles- group. More genetic anomalies were found in the Probst bundles+ than in Probst bundles- group (23% versus 10%, P = .08). CONCLUSIONS: Fetal DTI, combined with anatomic, cytogenetic, and clinical characteristics could suggest the possibility of classifying an isolated short corpus callosum as callosal dysplasia and a variant of normal callosal development.

[What are the real purpose and scope of screening for aneuploidy?] / Quels sont l'objectif réel et la portée du dépistage des aneuploïdies ?

In France, the recommended method for Down syndrome screening is the first trimester combined test, the risk assessment, based on maternal age, ultrasound measurement of fetal nuchal translucency and maternal serum markers (free ß-hCG and PAPP-A). The Down syndrome detection rate is 78.7% at a screen positive rate of 5%. However, the best screening test is the integrated test using a combination of first trimester combined test and second trimester quadruple test (serum α-fetoprotein, human chorionic gonadotropin, unconjugated E3, and dimeric inhibin-A) and being able to achieve a detection rate for Down syndrome of approximately 96% at a screen-positive rate of 5%. In recent years, the isolation of small fragments of "fetal" cell-free DNA in the maternal blood dramatically changed the screening strategy paradigm allowing a Down syndrome detection rate and false positive rate of 99.2 and 0.09%, respectively. However, aneuploidy screening based on cell-free DNA presents two major limitations which must be taken into account because they considerably limit its benefit: (i) not every woman will receive an interpretable result and that those who fail to receive a result are at increased risk for fetal aneuploidy: whether an inconclusive result is treated as screen positive or screen negative affects the overall detection rate (sensitivity) and false-positive rate (specificity) of the test; (ii) the limited number of targeted aneuploidies (trisomies 21, 18, 13 and common sex chromosome aneuploidies) in contrast to conventional noninvasive screening which is also able to detect rare aneuploidies, duplications, deletions, and other structural rearrangements. Of course, genetic counseling has to include a discussion about benefits and limitations of aneuploidy screening based on cell-free DNA. However, it should not be considered as a new screening test to substitute for conventional noninvasive screening. Moreover, if the ultimate goal is to deliver the most information about potential risk of various chromosomal abnormalities associated with adverse perinatal outcomes, then current cell-free DNA screening strategies may not be the best approach. These data highlight the limitations of cell-free DNA screening and the importance of a clear and fair information during pretest genetic counseling about benefits and limitations of any prenatal noninvasive screening (whether conventional or by cell-free DNA), but also about risks and benefits of invasive diagnostic procedures (in first- or second-line), especially since the cytogenetic analysis with chromosomal microarray analysis has improved the detection of genome microdeletions and microduplications (variants of the copy number) that can not be detected by standard cytogenetic analysis.

Pregnancy loss: French clinical practice guidelines.

In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women with a threatened late miscarriage and an isolated undilated shortened cervix (<25mm on ultrasound), cerclage is only indicated for those with a history of either late miscarriage or preterm delivery (Grade A). Among women with a threatened late miscarriage, an isolated undilated shortened cervix (<25mm on ultrasound) and no uterine contractions, daily treatment with vaginal progesterone up to 34 weeks of gestation is recommended (Grade A). Hysteroscopic section of the septum is recommended for women with a uterine septum and a history of late miscarriage (Grade C). Correction of acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is recommended after three early or late miscarriages (Grade C). Prophylactic cerclage is recommended for women with a history of three late miscarriages or preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin at a preventive dose are recommended for women with obstetric antiphospholipid syndrome (Grade A). Glycaemic levels should be controlled before conception in women with diabetes (Grade A).

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

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

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.

[Epidemiology of loss pregnancy]. / Épidémiologie des pertes de grossesse.

OBJECTIVES: Study of epidemiology of pregnancy loss. MATERIALS AND METHOD: A systematic review of the literature was performed using Pubmed and the Cochrane library databases and the guidelines from main international societies. RESULTS: The occurrence of first trimester miscarriage is 12% of pregnancies and 25% of women. Miscarriage risk factors are ages of woman and man, body mass index greater than or equal to 25kg/m(2), excessive coffee drinking, smoking and alcohol consumption, exposure to magnetic fields and ionizing radiation, history of abortion, some fertility disorders and impaired ovarian reserve. Late miscarriage (LM) complicates less than 1% of pregnancies. Identified risk factors are maternal age, low level of education, living alone, history of previous miscarriage, of premature delivery and of previous termination of pregnancy, any uterine malformation, trachelectomy, existing bacterial vaginosis, amniocentesis, a shortened cervix and a dilated cervical os with prolapsed membranes. Fetal death in utero has a prevalence of 2% in the world and 5/1000 in France. Its main risk factors are detailed in the chapter.

[In utero fetal death]. / Morts fœtales in utero.

OBJECTIVES: To give consistent data of the prevalence of intrauterine fetal death (IUFD), to assess risk factors and causes related to IUFD, to evaluate prevention of IUFD, to evaluate fetal autopsy and MRI and to determine the management of inhibition of lactation. METHODS: French and English publications were searched using PubMed, Cochrane Library. RESULTS: Intrauterine fetal death occurs in 2% of the pregnancies worldwide, and in around 0,5% of pregnancies in France (NP1). Major risk factors related to IUFD are maternal overweight, maternal age, and smoking, small for gestational age fetuses or placental abruption, and pre-gestational maternal diseases such as hypertension and diabetes (NP1). The most relevant causes of IUFD are placental anomalies, followed by abnormal karyotypes and congenital malformations (NP3). Data are insufficient to recommend a classification for causes of IUFD. Data concerning primary and secondary prevention do not recommend a specific management for the following of pregnancy. Fetal autopsy is still the gold standard of fetal examination, but fetal post-mortem MRI can be offered when fetal autopsy is refused (NP4). Inhibition of lactation should be started within 24hours postpartum with cabergoline, if the patient demands a treatment (NP4).

Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.

OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology. METHODS: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured. RESULTS: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1). CONCLUSION: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness. KEY POINTS: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.

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.

Specific complications of monochorionic twin pregnancies: twin-twin transfusion syndrome and twin reversed arterial perfusion sequence.

Monochorionic twins are subjected to specific complications which originate in either imbalance or abnormality of the single placenta serving two twins. This unequal placental sharing can cause complications including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), selective intrauterine growth restriction or twin reversed arterial perfusion sequence (TRAP). Monochorionicity also makes the management of these specific complications as well as that of a severe malformation in one twin hazardous since the spontaneous death of one twin exposes the co-twin to a risk of exsanguination into the dead twin and its placenta. The latter is responsible for the death of the co-twin in up to 20% of the cases and in ischemic sequelae in about the same proportions in the survivors. Although the symptoms of all these complications are very different, the keystone of their management comes down to either surgical destruction of the inter-twin anastomoses on the chorionic plate when aiming at dual survival or selective and permanent occlusion of the cord of a severely affected twin aiming at protecting the normal co-twin. This can be best achieved by fetoscopic selective laser coagulation and bipolar forceps cord coagulation respectively.