Prenatal diagnosis of recurrent hypoplastic left heart syndrome associated with MYH6 variants: a case report.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a rare but genetically complex and clinically and anatomically severe form of congenital heart disease (CHD). CASE PRESENTATION: Here, we report on the use of rapid prenatal whole-exome sequencing for the prenatal diagnosis of a severe case of neonatal recurrent HLHS caused by heterozygous compound variants in the MYH6 gene inherited from the (healthy) parents. MYH6 is known to be highly polymorphic; a large number of rare and common variants have variable effects on protein levels. We postulated that two hypomorphic variants led to severe CHD when associated in trans; this was consistent with the autosomal recessive pattern of inheritance. In the literature, dominant transmission of MYH6-related CHD is more frequent and is probably linked to synergistic heterozygosity or the specific combination of a single, pathogenic variant with common MYH6 variants. CONCLUSIONS: The present report illustrates the major contribution of whole-exome sequencing (WES) in the characterization of an unusually recurrent fetal disorder and considered the role of WES in the prenatal diagnosis of disorders that do not usually have a genetic etiology.

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.

[Evolution of the cesarean delivery rate from 37 weeks of gestation among nulliparas or how to evaluate the external validity of a randomized North American trial about induction of labor]. / Évolution du taux de césariennes à partir de 37 semaines d'aménorrhée parmi les nullipares ou comment évaluer la validité externe d'un essai randomisé nord-américain sur le déclenchement artificiel du travail.

OBJECTIVE: To determine the risk of caesarean delivery (CD) when an expectant management is considered for a nulliparous reaching≥37 weeks of gestation (wog). METHODS: This is a prospective study, including all nulliparous women who delivered at≥37 wog a singleton fetus in a cephalic presentation between the first January 2017 and the 31st December 2017 in a French perinatal network (Mypa). For each week of gestation from 37 wog to 41 wog, the rate of CD was determined according the onset of labor (spontaneous or induced). The risk of CD when expectant management was considered at a specific gestational age was calculated by taking all the population who reached this gestational age, minus all women who had an induction of labor or underwent a caesarean delivery before labor. RESULTS: In total, 16,085 women delivered at≥24 wog, and 5498 (34.1%) were nulliparous with a singleton fetus in a cephalic presentation reaching 37SA. The risk of CD increased from 40 wog, whatever the labor was spontaneous or induced (when labor was spontaneous, the risk of CD was stable till 39 wog around 11%, and increased from 14% at 40 wog to 20% at 41 wog; similarly, when labor was induced, the risk of CD was stable till 39 wog around 28%, and increased from 40% at 40 wog to 38% at 41 wog. The risk of CD for a nulliparous reaching>37 Wog when expectant management is considered was stable around 22.3%. CONCLUSION: The risk of CD for a nulliparous reaching≥37SA when expectant management is considered is similar than the one in the United States of America.

Prognostic value of diffusion-weighted magnetic resonance imaging of brain in fetal growth restriction: results of prospective multicenter study.

OBJECTIVE: To measure prospectively apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5th centile, and analyze their association with adverse perinatal outcome. METHODS: This was a prospective study involving six tertiary-level perinatal centers. In the period 22 November 2016 to 11 September 2017, we included singleton, small-for-gestational-age (SGA) fetuses with EFW ≤ 5th percentile, between 28 and 32 weeks of gestation, regardless of the umbilical artery Doppler and maternal uterine artery Doppler findings. A fetal magnetic resonance imaging (MRI) examination with diffusion-weighted sequences (DWI) was performed within 14 days following inclusion and before 32 weeks. ADC values were calculated in the frontal and occipital white matter, basal ganglia and cerebellar hemispheres. An ultrasound examination was performed within 1 week prior to the MRI examination. The primary outcome was a composite measure of adverse perinatal outcome, defined as any of the following: perinatal death; admission to neonatal intensive care unit with mechanical ventilation > 48 h; necrotizing enterocolitis; Grade III-IV intraventricular hemorrhage; periventricular leukomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with and those without adverse perinatal outcome was performed. The association between ADC values and adverse perinatal outcome was then analyzed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses. RESULTS: MRI was performed in 64 patients, of whom five were excluded owing to fetal movement artifacts on DWI and two were excluded for termination of pregnancy with no link to fetal growth restriction (FGR). One intrauterine death occurred secondary to severe FGR. Among the 56 liveborn neonates, delivered at a mean ± SD gestational age of 33.6 ± 3.0 weeks, with a mean birth weight of 1441 ± 566 g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotizing enterocolitis. Overall, therefore, seven out of 57 (12.3%) cases had an adverse perinatal outcome (95% CI, 3.8-20.8%). The ADC values in the frontal region were significantly lower in the group with adverse perinatal outcome vs those in the group with favorable outcome (mean values of both hemispheres, 1.68 vs 1.78 × 10-3 mm2 /s; P = 0.04). No significant difference in ADC values was observed between the two groups in any other cerebral territory. A cut-off value of 1.70 × 10-3 mm2 /s was associated with a sensitivity of 57% (95% CI, 18-90%), a specificity of 78% (95% CI, 63-88%), a positive predictive value of 27% (95% CI, 8-55%) and a negative predictive value of 93% (95% CI, 80-98%) for the prediction of adverse perinatal outcome. A mean frontal ADC value < 1.70 × 10-3 mm2 /s was not associated significantly with an increased risk of adverse perinatal outcome, either in the univariate analysis (P = 0.07), or when adjusting for gestational age at MRI and fetal sex (odds ratio (OR), 6.06 (95% CI, 0.9-37.1), P = 0.051) or for umbilical artery Doppler (OR, 6.08 (95% CI, 0.89-41.44)). CONCLUSION: This first prospective, multicenter, cohort study using DWI in the setting of SGA found lower ADC values in the frontal white-matter territory in fetuses with, compared with those without, adverse perinatal outcome. To determine the prognostic value of these changes, further standardized evaluation of the neurodevelopment of children born with growth restriction is required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

[Cell-free DNA fraction: Can it be used to evaluate the risk of obstetrical issues?] / L'ADN fœtal libre circulant : un outil d'évaluation du risque de survenue de complications obstétricales ?

OBJECTIVE: The aim of the study was to evaluate if fetal cell-free DNA (cfDNA) fraction circulating in maternal blood at the beginning of the second trimester is associated with obstetrical complications. METHODS: This is a retrospective unicentric study conducted at the hospital of Poissy Saint Germain between the 1st January 2015, and the 31st. December 2016, Each woman who had a genetic counseling in order to realize a non-invasive prenatal test (NIPT) was included. Only singleton pregnancies with a documented-issue were analysed. The primary criteria was a composite criteria, defined as the occurrence of preeclampsia, in utero fetal growth, or a spontaneous preterm delivery. A descriptive analyse was first conducted, secondly completed by a sub-group one: "high fetal fraction" (>90th percentile) group, "low fetal-fraction" group (<10th percentile) and "medium fetal-fraction" (control group) group. RESULTS: A total of 417 women had a cfDNA test, which was performed at a mean gestational age of 17.1 weeks of gestation. A total of 17% of pregnancies met the primary criteria. Among them, there were 8 (1.9%) pre-eclampsia, 49 (11.8%) intra-uterine growth restriction and 14 (3.4%) preterm births. There was no significant difference for the occurrence of the primary criteria (P>0.99) and of each obstetrical complication between each group. CONCLUSION: Fetal cf-DNA fraction measured at the beginning of the second trimester is not associated with common obstetrical 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.

[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.

Diagnostic yield of chromosomal microarray analysis in fetuses with isolated increased nuchal translucency: a French multicenter study.

OBJECTIVE: To determine the frequency and nature of copy number variants (CNVs) identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses with isolated increased nuchal translucency thickness (NT) ≥ 3.5 mm. METHODS: This was a retrospective, multicenter study, including 11 French hospitals, of data from the period between April 2012 and December 2015. In total, 720 fetuses were analyzed by rapid aneuploidy test and the fetuses identified as euploid underwent CMA. CNVs detected were evaluated for clinical significance and classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs not related to the phenotype (i.e. incidental findings). RESULTS: In 121 (16.8%) fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53 (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic, including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599 (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%) were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the reason for referral diagnosis (i.e. an incidental finding) and the remaining 21 were benign CNVs, without clinical consequence. Interestingly, we identified five genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with congenital heart defects. CONCLUSION: Our study demonstrates the benefit of CMA in the etiological diagnosis of fetuses with isolated increased NT. It is worth noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

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).

[Obstetrical ultrasound simulator as a tool for improving teaching strategies for beginners: Pilot study and review of the literature]. / La simulation pour améliorer l'apprentissage de l'échographie obstétricale chez les débutants : étude pilote et revue de la littérature.

OBJECTIVES: The aim of this study was to evaluate the obstetrical ultrasound simulator as an initiation tool for teaching obstetrical ultrasound scanning for beginners. METHODS: Twenty medical students with no experience in ultrasound scan (US) received a basic theoretical ultrasonography course on US principles and 2nd trimester biometrical measurements. The participants were then divided into 2 groups (A, B). Only group A received a practical 2nd trimester scan training session on the simulator where they were asked to determine fetal and placental position, and to take the 3 biometrical standardized measurements. Group B had the same training session but with a real ultrasound machine and a pregnant volunteer. The 2 groups were then asked to perform an US session on real patients (22 weeks) during which they had to do the same US study. The time needed to complete the whole scan was analyzed. The quality of the measurements was compared based on the previously published Objective Quality Criteria scoring. RESULTS: The mean total score was significantly (P=0.001) better for group A (14.3±1.4) compared to group B 10.3 (±2.75) for group A and B respectively. The time needed to accomplish the whole exam tended to be longer for group A (569±174s) compared to group A (479±104s) (P=0.18). CONCLUSIONS: The simulator might be a useful initiation tool to obstetric ultrasound for those who never practiced. It might prove a time sparing procedure in the training process and allow trainees to reach a basic practice level before performing examinations on actual patients.

Angle of fetal head progression measured using transperineal ultrasound as a predictive factor of vacuum extraction failure.

OBJECTIVE: To evaluate the predictive value of angle of progression (AoP) of the fetal head for a failed vacuum delivery. METHODS: This was a prospective observational study that included women with a singleton pregnancy of ≥ 37 weeks' gestation, in cephalic presentation requiring vacuum extraction. Transperineal ultrasound was performed immediately before vacuum extraction, although AoP was measured on stored images after delivery. Vacuum extraction was defined as failed when the duration of extraction exceeded 20 min or the vacuum cup detached more than three times. We compared the demographic and ultrasound data of failed vacuum deliveries with those that were successful. The predictive value of AoP for failure of vacuum delivery was calculated. RESULTS: AoP was measured in 235 women. Vacuum extractions failed in 30 (12.8%) women (29/184 nulliparous and 1/51 parous) and resulted in 28 vaginal deliveries by forceps and two Cesarean deliveries. Median AoP was significantly lower in the vacuum failure group compared with those with successful vacuum delivery (136.6° (interquartile range (IQR), 129.8-144.1°) vs 145.9° (IQR, 135.0-158.4°); P < 0.01). As all but one failed vacuum extraction occurred among nulliparous women, the predictive value of AoP was calculated in this subgroup of women. The area under the receiver-operating characteristics curve for prediction of vacuum extraction failure was 0.67 (95% CI, 0.57-0.77) and the optimal AoP cut-off was 145.5°. Above this value, the rate of vacuum extraction failure fell below 5%. CONCLUSION: AoP is a predictive factor of failed vacuum extraction, especially among nulliparous women whose risk of failure is high. AoP measurement may help in choosing between forceps and vacuum extraction. Copyright © 2015 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.

[Definition of pregnancy losses: Standardization of terminology from the French National College of Obstetricians and Gynecologists (CNGOF)]. / Standardisation de la terminologie des pertes de grossesse : consensus d'experts du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: While a number of glossaries have been produced by various authorities in different countries, at present there is no internationally accepted common set of definitions for many terms used to describe pregnancy losses. The objective of the current study was to provide a standardized French/English terminology/glossary relating to pregnancy losses. METHODS: Literature review, construction of a glossary and rating of proposals using a formal consensus method. The glossary was subject of a critical comprehensive review by a meeting of professionals (multidisciplinary panel). RESULTS: A miscarriage is a spontaneous evacuation of an intra-uterine pregnancy<22WG. A missed early miscarriage is when ultrasound (<14WG) shows no growth of intra-uterine sac/embryo and/or loss of fetal heart activity. An early miscarriage is when spontaneous evacuation of intra-uterine pregnancy occurs <14WG. A complete early miscarriage is when there is no retained products of conception (empty uterus on ultrasound) and no bleeding nor pain. Incomplete early miscarriage is when ultrasonography shows retained products of conception in the uterine cavity (including cervical canal). Repeat miscarriage or recurrent pregnancy loss is when the woman experiences 3 or more consecutive miscarriages <14WG. A late miscarriage is when there is spontaneous evacuation of pregnancy ≥14WG and <22WG. A threatened late miscarriage is when shortening/opening of the cervix±uterine contraction occur ≥14WG and <22WG. An intra-uterine fetal demise is when there is a spontaneous loss of fetal heart activity ≥14 WG. CONCLUSION: The final current terminology should be used by all healthcare professionals.

[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.

[Chronic maternal diseases and pregnancy losses. French guidelines]. / Pathologies maternelles chroniques et pertes de grossesse. Recommandations françaises.

AIM: To review the available data on maternal chronic diseases and pregnancy losses. MATERIAL AND METHODS: We searched PubMed and the Cochrane library with pregnancy loss, stillbirth, intrauterine fetal demise, intrauterine fetal death, miscarriage and each maternal diseases of this paper. RESULTS: Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anticoagulant) should be measured in case of miscarriage after 10WG confirmed by ultrasound (grade B) and an antiphospholipid syndrome should be treated by a combination of aspirin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We do not recommend testing for genetic thrombophilia in case of first trimester miscarriage (grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancy for women with pregestational diabetes to limit the risks of pregnancy loss (grade A) with a goal of prepregnancy HbA1c<7%. Overt and subclinical hypothyroidisms should be treated by L-thyroxin during pregnancy to reduce the risks of pregnancy loss (grade A). Women who are positive for TPOAb should have TSH concentrations follow-up during pregnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism (grade B). CONCLUSIONS: Prepregnancy management of most chronic maternal diseases, ideally through prepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss.

[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).