Fetal facial bone growth: Post-mortem CT analysis.

OBJECTIVE: To describe and model the normal growth of fetal facial bones and angles. MATERIAL AND METHODS: A total of 118 fetal CT scans obtained at 19 to 41 weeks gestation after in utero fetal death or late miscarriage were analyzed. CT scan was followed by autopsy and pathological examination and only fetuses free from brain disease or abnormal craniofacial development were included. The measurements were taken using software for frontal, sagittal and 3D reconstruction from native axial sections. The optimal plane for bone analysis was chosen and the measurements made by multiplanar reconstruction. RESULTS: There was a statistically significant increase (P<0.001) in all measurements regardless of gestational age (GA) except those of the mandibulo-fronto-maxillary angle (P=0.412), the naso-mandibulo-maxillary angle (P=0.828) and mandibular width (P=0.86). There was no significant difference according to fetal sex. Based on these results, the corresponding growth curves were created. The anteroposterior mandibular diameter (APD) was very strongly correlated with GA (R=0.926, P<0.001). The following equation: GA=(8.187×APD)+4.257 can be used to estimate GA with a confidence interval (CI) of±2.42. The same applies to maxillary width (MW) (R=0.922; P<0.001). The equation GA=(11.059×MW)+7.571 can be used to estimate GA with a CI of 2.17. CONCLUSION: The growth of the mandible, maxilla, zygomatic bone and orbits was measured and the corresponding growth curves were established. Several measurements were strongly correlated with gestational age.

A randomised controlled trial of amnioexchange for fetal gastroschisis.

OBJECTIVE: Morbidity in fetuses affected by gastroschisis is mainly the result of bowel ischaemic and inflammatory processes. Experimental studies on animal models show that clearing amniotic fluid from the digestive secretions by amnioexchange procedures reduces the inflammatory process. We evaluated the benefit of the amnioexchange procedure for fetal gastroschisis in humans. DESIGN: Prospective, interventional, randomised study. SETTING: Eight referral centres for fetal medicine. POPULATION: Pregnant women carrying a fetus with gastroschisis. METHODS: We compared, in utero, amnioexchange with a sham procedure. The protocol included, in both arms, steroid injections at 30 weeks of gestation and the use of postnatal minimal enteral feeding. MAIN OUTCOME MEASURES: The primary outcome was a composite variable based on the duration of ventilation and parenteral nutrition. Secondary outcomes were the effectiveness and safety of the amnioexchange procedure, including the rate of perinatal death, time to full enteral feeding, primary closure, and late feeding disorders. RESULTS: Sixty-four patients were randomised. There was no difference in the composite criteria between the amnioexchange and control groups. Based on an intention-to-treat analysis, there were no significant between-group differences in pregnancy outcome or complications. When studying the relationship between digestive compounds and amniotic fluid inflammatory markers, a clear correlation was found between bile acid and both ferritin and interleukin 1ß (IL1ß). CONCLUSIONS: In humans, amnioexchange, as described in our protocol, is not an option for fetal care; however, we provide supplementary proof of the involvement of inflammation in the pathogenicity of gastroschisis and suggest that future research should aim at reducing inflammation. ClinicalTrials.gov: NCT00127946. TWEETABLE ABSTRACT: A prospective, interventional, randomised study shows no benefit of amnioexchange for fetal gastroschisis in humans.

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.

Molecular diagnosis of bacterial vaginosis: impact on IVF outcome.

Bacterial vaginosis can increase obstetrical complications such as miscarriage, premature rupture of membranes and preterm delivery. The aim of our study was first to assess BV prevalence for infertile patients treated by in vitro fertilisation (IVF) using both the Nugent score and polymerase chain reaction (PCR), and then to assess the impact of BV on the pregnancy rate after IVF. Vaginal samples were obtained from women followed for IVF in our Assisted Reproduction Technology (ART) Unit between August 2010 and April 2011. For each patient, two techniques were performed to diagnose BV: Gram staining to assess the Nugent score and a quantitative molecular analysis using a specific real-time PCR assay. Two groups were studied: normal flora (BV-) and BV (BV+). The primary outcome measure was the implantation rate. The secondary outcomes were clinical pregnancy rate, early and late miscarriage, premature rupture of membranes, preterm delivery, mode of delivery and birthweight. A total of 307 patients were included. PCR revealed a prevalence of BV of 9.45 %. Among women who performed vaginal douching, 22.2 % were BV+, whereas 7.9 % of patients who did not douche were BV+ (p = 0.028). The embryo implantation rate was decreased between the BV- and BV+ groups (36.3 % vs. 27.6 %, p = 0.418), but it was not significant. Obstetrical outcomes did not present significant statistical differences among the groups. Vaginal douching significantly enhanced BV in women treated with IVF. We also observed a non-significant decrease of embryo implantation rate and clinical pregnancy rate for women treated by IVF.

Self-collected vaginal swabs for the quantitative real-time polymerase chain reaction assay of Atopobium vaginae and Gardnerella vaginalis and the diagnosis of bacterial vaginosis.

The aim of this study was to assess the feasibility of using self-collected vaginal specimens for the quantitative real-time polymerase chain reaction (qPCR) assays of bacterial vaginosis (BV)-associated bacteria versus practitioner-collected swabs. A cross-sectional study included 190 pregnant women enrolled before 20 weeks' gestation from September 2008 to November 2009. Self- and practitioner-collected swabs were taken during the same prenatal visit for each woman, qPCR assays performed for each, and the results compared. The quantification of the human albumin gene was used as an internal control to ensure sampling quality and accurate comparisons. The level of agreement of the qPCR assays for each microorganism was calculated with the Spearman product moment correlation coefficient and the kappa statistic. In all, 370 vaginal samples (185 self- and 185 practitioner-collected swabs) had a narrow range of values for the number of albumin gene copies and a significant correlation coefficient (Spearman's rho = 0.532; p < 0.001). The agreement between both sampling methods was excellent (Spearman's rho was 0.748 for Atopobium vaginae, 0.918 for Lactobacillus species, 0.940 for Gardnerella vaginalis; p < 0.001), especially for high concentrations of A. vaginae (≥10(8) copies/mL; kappa value = 0.973; p < 0.001) and G. vaginalis (≥10(9) copies/mL; kappa value = 0.903; p < 0.001). This study demonstrates the validity and reliability of self- versus practitioner-collected swabs for the molecular quantification of Lactobacillus species, G. vaginalis, and A. vaginae.

[Prognostic factors of live-birth after in vitro fertilization for unexplained infertility: A cohort study]. / Facteurs pronostiques des chances de naissance vivante en fécondation in vitro pour infertilité inexpliquée : étude de cohorte.

OBJECTIVES: For 15 to 30% of infertile couples, no etiology can be found, leading to the diagnosis of "unexplained infertility". The aim of our study was to identify prognostic factors for live birth following in vitro fertilization (IVF) for these couples. METHODS: A retrospective, monocentric study on a cohort of couples undergoing IVF for unexplained infertility with the woman aged≤40 years old. Primary analysis compared couples with a live birth following IVF versus childless couples following IVF. RESULTS: Between January 2014 and December 2018, 104 couples were included, 196 transvaginal oocyte pickup were performed, followed by 234 embryo transfers (fresh or cryopreserved) which resulted in 43 deliveries. The cumulative live birth rate was 40.4% per couple. Before IVF attempts, no clinical or paraclinical prognostic factors between the two groups was observed. However, multivariate analysis showed several biological factors of good prognosis in course of treatment, such as a higher number of mature oocytes and better quality embryos in "live birth" group. CONCLUSIONS: For a couple, the chances of having a child following IVF unexplained infertility are 40.4%. However, no clinical characteristic enabled us to identify favourable or unfavourable prognosis factors before starting ART. The prognostic factors identified during IVF cycle are interesting to advise or not to pursue IVF.

Diagnostic accuracy of quantitative real-time PCR assay versus clinical and Gram stain identification of bacterial vaginosis.

The purpose of this investigation was to determine the diagnostic accuracy of quantitative real-time polymerase chain reaction (PCR) assay in diagnosing bacterial vaginosis versus the standard methods, the Amsel criteria and the Nugent score. The Amsel criteria, the Nugent score, and results from the molecular tool were obtained independently from vaginal samples of 163 pregnant women who reported abnormal vaginal symptoms before 20 weeks gestation. To determine the performance of the molecular tool, we calculated the kappa value, sensitivity, specificity, and positive and negative predictive values. Either or both of the Amsel criteria (≥3 criteria) and the Nugent score (score ≥7) indicated that 25 women (15%) had bacterial vaginosis, and the remaining 138 women did not. DNA levels of Gardnerella vaginalis or Atopobium vaginae exceeded 10(9) copies/mL or 10(8) copies/mL, respectively, in 34 (21%) of the 163 samples. Complete agreement between both reference methods and high concentrations of G. vaginalis and A. vaginae was found in 94.5% of women (154/163 samples, kappa value = 0.81, 95% confidence interval 0.70-0.81). The nine samples with discordant results were categorized as intermediate flora by the Nugent score. The molecular tool predicted bacterial vaginosis with a sensitivity of 100%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 100%. The quantitative real-time PCR assay shows excellent agreement with the results of both reference methods for the diagnosis of bacterial vaginosis.

No specific adverse pregnancy outcome in singleton pregnancies after assisted reproductive technology (ART) for unexplained infertility.

OBJECTIVE: To evaluate the obstetrical outcome of pregnancies obtained after assisted reproductive technology (ART).in women with unexplained infertility. MATERIALS AND METHODS: We conducted a retrospective observational case - control cohort study between January 2011 and May 2017. All pregnancies obtained after ART (Intra uterine insemination, In Vitro Fertilization, Intra Cytoplasmic Sperm Injection) were included. The ART pregnancy outcome of women with unexplained infertility was compared to ART pregnancies obtained in a context of male infertility. Cases were matched to controls (1:2) for age, Body Mass Index (BMI), and smoking status. RESULTS: After exclusion of twins, we studied 67 singleton pregnancies in the case group, matched with 129 singleton pregnancies in the control group. The first-trimester complications (miscarriage before 12 weeks gestation (WG), ectopic pregnancy) were similar in the two groups. Concerning the 2nd and the 3rd trimester, the incidence of gestational diabetes mellitus, pre-eclampsia, placenta previa, preterm labor was comparable between the two groups. In singletons, we found a non-significant increase of post-partum hemorrhage (OR=5.5, IC 0.5-50, p=0.13) and small for gestational age new-borns (OR=3.45, IC 0.65-18.1, p=0.14) in women with unexplained infertility. CONCLUSION: More adverse obstetrical outcome are commonly reported after ART, even in singleton pregnancies. Little is known for explaining it and to distingue the own contributions of ART techniques and of the infertility etiology. In our study, we didn't observe a significant negative impact of a history of unexplained infertility on pregnancy. However, further large studies are needed to evaluate more accurately the possible liabilities of the infertility etiology on obstetrical and perinatal outcome.

[CNGOF-SFT Expert Report and Guidelines for Smoking Management during Pregnancy-Short Text]. / Rapport d'experts et recommandations CNGOF-SFT sur la prise en charge du tabagisme en cours de grossesse­texte court.

OBJECTIVES: To provide up-to-date evidence-based guidelines for the management of smoking cessation during pregnancy. METHODS: Systematic review of the international literature. We identified papers published between January 2003 and April 2019 in Cochrane PubMed, and Embase databases with predefined keywords. All reports published in French and English relevant to the areas of focus were included and classified according the level of evidence ranging from 1 (highest) to 4 (lowest). The strength of the recommendations was classified according to the Haute Autorité de santé, France (ranging from A, highest to C, lowest). RESULTS: "Counseling", involving globally all kind of non-pharmacological interventions, has a modest benefit on smoking cessation, birth weight and prematurity. Moderate physical activity did not show a significant effect on smoking cessation. The systematic use of feedback by measuring the expired air carbon monoxide concentration do not influence smoking abstinence but it may be used in establishing a therapeutic alliance. The use of self-help interventions and health education are recommended in helping pregnant smokers quit. The prescription of nicotine replacement therapies (NRT) may be offered to any pregnant woman who has failed stopping smoking without medication This prescription can be initiated by the health care professional taking care of the pregnant woman in early pregnancy. There is no scientific evidence to propose the electronic cigarette for smoking cessation to pregnant smokers; it is recommended to provide the same advice and to use methods that have already been evaluated. The use of waterpipe (shisha/narghile) during pregnancy is associated with decreased fetal growth. It is recommended not to use waterpipe during pregnancy. Breastfeeding is possible in smokers, but less often initiated by them. Although its benefit for the child's development is not demonstrated to date, breastfeeding allows the mother to reduce or stop smoking. The risk of postpartum relapse is high (up to 82% at 1 year). The main factors associated with postpartum abstinence are breastfeeding, not having a smoker at home, and having no symptoms of postpartum depression. CONCLUSIONS: Smoking during pregnancy concerns more than hundred thousand women and their children per year in France. It is a major public health burden. Health care professionals should be mobilized for reducing or even eradicating it.

Smoking and smoking cessation in pregnancy. Synthesis of a systematic review.

OBJECTIVES: To provide up-to-date evidence-based guidelines for the management of smoking cessation during pregnancy and the post-partum period. STUDY DESIGN: A systematic review of the international literature was undertaken between January 2003 and April 2019. MEDLINE, EMBASE databases and the Cochrane library were searched for a range of predefined key words. All relevant reports in English and French were classified according to their level of evidence ranging from 1(highest) to 4(lowest). The strength of each recommendation was classified according to the Haute Autorité de Santé (French National Authority for Health) ranging from A (highest) to C (lowest). RESULTS: "Counselling", including all types of non-pharmacological interventions, has a moderate benefit on smoking cessation, birth weight and prematurity. The systematic use of measuring expired air CO concentration does not influence smoking abstinence, however, it may be useful in assessing smoked tobacco exposure prior to and after quitting. The use of self-help therapies and health education are recommended in helping pregnant smokers quit and should be advised by healthcare professionals. Nicotine replacement therapies (NRT) may be prescribed to pregnant women who have failed to stop smoking after trying non-pharmacological interventions. Different modes of delivery and dosages can be used in optimizing their efficacy. Smoking in the postpartum period is essential to consider. The same treatment options as during pregnancy can be used. CONCLUSION: Smoking during pregnancy concerns more than a hundred thousand women each year in France resulting in a major public health burden. Healthcare professionals should be mobilised to employ a range of methods to reduce or even eradicate it.

Total and fetal cell-free DNA analysis in maternal blood as markers of placental insufficiency in intrauterine growth restriction.

OBJECTIVE: To compare total and fetal DNA levels in the maternal plasma in three groups: pregnancies with intrauterine growth restriction (IUGR) due to placental insufficiency (PI) and other causes, and in control pregnancies. METHODS: Total as well as fetal DNA was quantified in 78 maternal plasma samples. In 19 pregnancies, the fetus presented IUGR due to PI (group A), and in 31 pregnancies due to other causes (group B). The control group comprised 28 patients (group C). DNA quantification was done using real-time quantitative PCR with a standardized pool of plasmid calibrators. DNA concentrations of the three groups were compared using non-parametric tests (Kruskal-Wallis or Mann-Whitney tests). RESULTS: The three groups did not statistically differ regarding maternal age (mean +/- SD: 30.5 +/- 5.4 years), gestational age (30 +/- 5.3 weeks) or the proportion of male fetuses (48.2%). Plasma total DNA was significantly higher in group A compared to groups B and C (p = 0.001 for both). An increase in fetal DNA was only observed in group A for patients beyond 28 weeks of gestation. CONCLUSIONS: The plasma total DNA level is higher in patients with IUGR due to PI. These results suggest the presence of maternal endothelial damage independently of preeclampsia.

[Pathophysiology, diagnosis and management of occiput posterior presentation during labor]. / Variétés postérieures au cours du travail : mécanique obstétricale, diagnostic et prise en charge.

Persistant occiput posterior (OP) positions are the commonest malpresentations of the fetal head during labor and their diagnosis remains challenging. They are associated to prolonged second stage of labor, prolonged expulsive efforts, labor augmentation, cesarean sections and instrumental deliveries. On the maternal side, severe perineal tears, post-partum hemorrhage or chorioamnionitis are more frequent. Currently, prevention of persistent OP positions is based on the maintain of precise maternal positions. Several positions have been evaluated but only lateral position on the same side of the fetal spine has proved its effectiveness. Fetal head rotation can also be achieved with extraction instruments though none has ever been evaluated by a randomized controlled trial. Obstetrical forceps seem more efficient than vacuum but are associated with severe perineal tears. Evaluation of rotation with Thierry's spatulas is scarce. Last, manual rotation is of routine use in many wards. This management is associated with a twofold reduction of operative delivery rate and rare adverse outcomes but has never been evaluated through randomized control trial.

Taxono-genomics description of 'Lactobacillus raoultii sp. nov.', strain Marseille-P4006T, a new Lactobacillus species isolated from the female genital tract of a patient with bacterial vaginosis.

Strain Marseille-P4006T, a Gram-stain-positive, rod-shaped, non-sporulating, facultatively anaerobic bacterium, was isolated from the vaginal swab of a 45-year-old woman with recurrent bacterial vaginosis. We studied its phenotypic characteristics and sequenced its whole genome. The major fatty acids were C16:0 (48%), C19:1n9 (14%) and C18:0 (11%). The 3 070 142-bp-long genome contains 2855 protein-coding genes and 68 RNAs. Strain Marseille-P4006T exhibited 98.1% 16S rRNA similarity with Lactobacillus farraginis, the closest species phylogenetically. Thus, strain Marseille-P4006 is distinct enough to represent a new species for which we propose the name Lactobacillus raoultii sp. nov. The type strain is Marseille-P4006T.

[Maternal morbidity after Thierry's spatulas and vacuum deliveries]. / Morbidité maternelle immédiate après extraction instrumentale par spatules de Thierry et par ventouse obstétricale.

OBJECTIVE: To compare maternal morbidity after Thierry's spatulas or vacuum-assisted deliveries. PATIENTS AND METHODS: Retrospective study, at the French hospital la Conception, in Marseilles. All successful instrumental deliveries between November 2003 and May 2005 were reviewed, that is to say 264. Univariate and multivariate analysis were performed comparing maternal morbidity in the two groups. The primary outcome measure was perineal trauma. Secondary outcomes were blood loss and duration of hospitalization. RESULTS: Among the 264 deliveries, there were 96 vacuum deliveries and 168 Thierry's spatulas extraction. Thierry's spatulas were use more often in nulliparous patient (<0.001). Patients in the group of Thierry's spatulas have a higher rate of epidural analgesia (p=0.05), a longer duration of first (p=0.002) and second stage of labor (p=0.03). There was no difference in incidence of sphincter tears between women who underwent Thierry's spatulas and those who underwent vacuum delivery with respective incidence of 4.2 and 3.2% (p=0.67). There was a significant difference in post-partum hemoglobin value with a higher blood loss in the group of Thierry's spatulas (<0.001). Mean duration of hospitalization was longer in the group with Thierry's spatulas (5.6 days) than in the group who underwent vacuum delivery (4.7 days) (p<0.001). DISCUSSION AND CONCLUSION: Incidence of third degree tears was similar between the vacuum and Thierry's spatulas group. Deliveries with vacuum are associated with less blood loss and a shorter hospitalization stay.

[Modality of fetal heart monitoring during labor (continuous or intermittent), telemetry and central fetal monitoring]. / Surveillance foetale continue ou discontinue, télémétrie et centrale d'analyse.

Fetal heart monitoring during labor is almost systematic today. Continuous monitoring decreases neonatal convulsions, but increases caesarean section and forceps deliveries without impact on long term neonatal prognosis. Overall, there is no proved impact of cardiac fetal monitoring (continuous or intermittent) on perinatal mortality. The most recent study shows neonatal benefits of continuous monitoring associated with an overall increase of caesarean section rate. Continuous fetal monitoring has a better sensitivity to detect acidosis. Many arguments for continuous fetal monitoring will be reported in this review. In specific conditions, intermittent fetal auscultation can be realised, but in current practice such conditions can rarely be applied. Telemetry has been poorly evaluated to date but experiences are currently undertaken. Central fetal monitoring does not improve neonatal issue but could increase caesarean section rate. Central of fetal monitoring could help in the organisation and the conservation of fetal heart monitoring.

[Length of pushing efforts: pushing is not playing. Reply to the article of C. Le Ray and F. Audibert]. / Durée des efforts expulsifs : pousser n'est pas jouer. Réponse à l'article de C. Le Ray et F. Audibert.

The aim of this work is to answer constructively to C. Le Ray and F. Audibert who were surprised that the French guidelines recommended an assisted delivery after 30 min pushing, even if the fetal heart rate is reassuring. We first resumed the definition of "second stage of labor", this word including the first phase with no pushing efforts and the second phase with active pushing of the mother. With that definition, the length of the second stage is around 60 min for the primipara and 20 min for the multipara, this length being modified by the use of peridural. We then specified the physiological mechanisms influencing the acidobasic equilibrium during the pushing time. Those mechanisms are difficult to consider because foetal heart rate monitoring is often "lost" during that phase. Altogether, these factors bring incertitude about progressive foetal acidosis and incapacity to diagnose it. Finally, the literature analysis teaches us that increasing the second stage of labor (inactive plus active phases) during the normal pregnancy seems to be at low risk for the foetus within the primiparas, but display a risk for the mother and so might be limited. Comparing the delayed pushing with the immediate pushing only lead us to conclude that delayed pushing is dangerous, as is prolonged second stage. In conclusion, we think that prolonging the second stage of labor is possible but must be by increasing the inactive first phase of the second stage, especially as long as we will not get a noninvasive and reliable method allowing assessing the well-being of the foetus.

Sex and bacterial infectious diseases.

Most infectious diseases are unequally distributed between male and female subjects. This sex dimorphism is confirmed by epidemiologic studies which suggest an increased number of male septic patients, while, due to the class age of septic patients, an overrepresentation of female patients would be expected. Lifestyle, recreational activities, professional exposition and access to care are plausible reasons for this dimorphism. However, biological differences should be carefully considered, particularly the weight of X-linked variability and the role of sex hormones. Animal models clearly show that clinical response to infection is more exuberant in males than in females. This is partly explained by an attenuation of the inflammatory response by female sex hormones. However, the translation from experimental studies to the bedside remains challenging as a result of confounding factors like age, hormone changes and response to treatment.

'Lactobacillus raoultii' sp. nov., a new bacterium isolated from the vaginal flora of a woman with bacterial vaginosis.

We report the isolation of a new bacterium species, 'Lactobacillus raoultii' strain Marseille P4006 (CSUR P4006), isolated from a vaginal sample of a 45-year-old woman with bacterial vaginosis.