Muriel Doret

Multifractal analysis of fetal heart rate variability in fetuses with and without severe acidosis during labor.

We performed multifractal analysis of fetal heart rate (FHR) variability in fetuses with and without acidosis during labor. Multifractal analysis was performed on fetal electrocardiograms in 10-minute sliding windows within the last 2 hours before delivery in 45 term fetuses divided in three groups according to umbilical arterial pH and FHR pattern: group A had pH ≥7.30 and normal FHR, group B had pH ≥7.30 and intermediate or abnormal FHR, and group C had acidosis (pH ≤7.05) and intermediate or abnormal FHR. Six multifractal parameters were compared using Wilcoxon rank sum test. Multifractal parameters were significantly different between the three groups in the last 10 minutes before delivery (P <0.05). Two parameters (H(min), zeta(2)) exhibited a significant difference 70 minutes before delivery, and one parameter (C(2)) was different 10 minutes before birth (P <0.05). Multifractal parameters were significantly different in acidotic and nonacidotic fetuses, independently from FHR pattern.

Methodology for multifractal analysis of heart rate variability: From LF/HF ratio to wavelet leaders

The present contribution aims at proposing a comprehensive and tutorial introduction to the practical use of wavelet Leader based multifractal analysis to study heart rate variability. First, the theoretical background is recalled. Second, practical issues and pitfalls related to the selection of the scaling range or statistical orders, minimal regularity, parabolic approximation of spectrum and parameter estimation, are discussed. Third, multifractal analysis is connected explicitly to other standard characterizations of heart rate variability: (mono)fractal analysis, Hurst exponent, spectral analysis and the HF/LF ratio. This review is illustrated on real per partum fetal ECG data, collected at an academic French public hospital, for both healthy fetuses and fetuses suffering from acidosis.

Prevention of spontaneous preterm birth: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF)

In France, 60,000 neonates are born preterm every year (7.4%), half of them after the spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated with decreased prematurity (level of evidence [LE]1). It is therefore recommended (Grade A). Routine screening and treatment of vaginal bacteriosis is not recommended in the general population (Grade A). The only population for which vaginal progesterone is recommended is that comprising asymptomatic women with singleton pregnancies, no history of preterm delivery, and a short cervix at 16-24 weeks of gestation (Grade B). A history-indicated cerclage is not recommended for women with only a history of conization (Grade C), uterine malformation (professional consensus), isolated history of preterm delivery (Grade B), or twin pregnancies for primary (Grade B) or secondary (Grade C) prevention of preterm birth. A history-indicated cerclage is recommended for a singleton pregnancy with a history of at least 3 late miscarriages or preterm deliveries (Grade A). Ultrasound cervical length screening is recommended between 16 and 22 weeks for women with a singleton previously delivered before 34 weeks gestation, so that cerclage can be offered if cervical length <25mm before 24 weeks (Grade C). A cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with twin pregnancies (Grade A) or in populations of asymptomatic women with a short cervix (professional consensus). Although the implementation of universal screening by transvaginal ultrasound for cervical length at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In cases of preterm labor, (i) it is not possible to recommend any one of the several methods (ultrasound of the cervical length, vaginal examination, or fetal fibronectin assay) over any other to predict preterm birth (Grade B); (ii) routine antibiotic therapy is not recommended (Grade A); (iii) prolonged hospitalization (Grade B) and bed rest (Grade C) are not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (Grade B), unlike beta-agonists (Grade C), can be used for tocolysis in spontaneous preterm labor without preterm premature rupture of membranes. Maintenance tocolysis is not recommended (Grade B). Antenatal corticosteroid administration is recommended for all women at risk of preterm delivery before 34 weeks of gestation (Grade A). After 34 weeks, the evidence is insufficiently consistent to justify recommending systematic antenatal corticosteroid treatment (Grade B), but a course of this treatment might be indicated in clinical situations associated with high risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (Grade C). Repeated courses of antenatal corticosteroids are not recommended (Grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended for women at high risk of imminent preterm birth before 32 weeks (Grade A). Cesareans are not recommended for fetuses in vertex presentation (professional consensus). Both planned vaginal and elective cesarean delivery are possible for breech presentations (professional consensus). Delayed cord clamping may be considered if the neonatal or maternal state allows (professional consensus).

Placental site and epithelioid trophoblastic tumours: Diagnostic pitfalls

OBJECTIVE To describe the clinical and histological pitfalls in the diagnosis of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT), two rare types of gestational trophoblastic neoplasia (GTN). METHODS This retrospective, observational, study was carried out in the French Trophoblastic Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two types of tumour were investigated together. Twenty-two patients with PSTT or ETT were analysed. RESULTS The clinical presentation of these two types of tumour was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed as an ectopic pregnancy. Median age at presentation was 35-years, with a median interval of 12months between the antecedent pregnancy and diagnosis of PSTT or ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients; there was a major disagreement with the referral pathologist in five of these seven patients (28%). CONCLUSIONS PSTT and ETT are the most difficult types of GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to significant therapeutic deviations from the recommended first-line treatment, namely hysterectomy. Clinical and histological expertise is essential to avoid the pitfalls in the diagnosis of PSTT and ETT.

Adaptive Multiscale Complexity Analysis of Fetal Heart Rate

Per partum fetal asphyxia is a major cause of neonatal morbidity and mortality. Fetal heart rate monitoring plays an important role in early detection of acidosis, an indicator for asphyxia. This problem is addressed in this paper by introducing a novel complexity analysis of fetal heart rate data, based on producing a collection of piecewise linear approximations of varying dimensions from which a measure of complexity is extracted. This procedure specifically accounts for the highly nonstationary context of labor by being adaptive and multiscale. Using a reference dataset, made of real per partum fetal heart rate data, collected in situ and carefully constituted by obstetricians, the behavior of the proposed approach is analyzed and illustrated. Its performance is evaluated in terms of the rate of correct acidosis detection versus the rate of false detection, as well as how early the detection is made. Computational cost is also discussed. The results are shown to be extremely promising and further potential uses of the tool are discussed. MATLAB routines implementing the procedure will be made available at the time of publication.

In vitro study of tocolytic effect of rofecoxib, a specific cyclo‐oxygenase 2 inhibitor. Comparison and combination with other tocolytic agents

Objective The aim of this work was to study and compare the tocolytic effects of rofecoxib with indomethacin, ritodrine, nicardipine and atosiban. We also studied the combination of rofecoxib with each agent.

Fractal Analysis and Hurst Parameter for Intrapartum Fetal Heart Rate Variability Analysis: A Versatile Alternative to Frequency Bands and LF/HF Ratio

Background The fetal heart rate (FHR) is commonly monitored during labor to detect early fetal acidosis. FHR variability is traditionally investigated using Fourier transform, often with adult predefined frequency band powers and the corresponding LF/HF ratio. However, fetal conditions differ from adults and modify spectrum repartition along frequencies. Aims This study questions the arbitrariness definition and relevance of the frequency band splitting procedure, and thus of the calculation of the underlying LF/HF ratio, as efficient tools for characterizing intrapartum FHR variability. Study Design The last 30 minutes before delivery of the intrapartum FHR were analyzed. Subjects Case-control study. A total of 45 singletons divided into two groups based on umbilical cord arterial pH: the Index group with pH ≤ 7.05 (n = 15) and Control group with pH > 7.05 (n = 30). Outcome Measures Frequency band-based LF/HF ratio and Hurst parameter. Results This study shows that the intrapartum FHR is characterized by fractal temporal dynamics and promotes the Hurst parameter as a potential marker of fetal acidosis. This parameter preserves the intuition of a power frequency balance, while avoiding the frequency band splitting procedure and thus the arbitrary choice of a frequency separating bands. The study also shows that extending the frequency range covered by the adult-based bands to higher and lower frequencies permits the Hurst parameter to achieve better performance for identifying fetal acidosis. Conclusions The Hurst parameter provides a robust and versatile tool for quantifying FHR variability, yields better acidosis detection performance compared to the LF/HF ratio, and avoids arbitrariness in spectral band splitting and definitions.

The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium

Objective To compare the tocolytic potency of ritodrine, nicardipine and atosiban, used alone and in dual combinations, to see whether combinations of these drugs, which act via different pathways, could improve inhibition of uterine contractility.

Risk of gestational trophoblastic neoplasia after hCG normalisation according to hydatidiform mole type.

OBJECTIVE The risk of gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) is well known. However, the risk of GTN after normalisation of hCG in HM is poorly reported. The aim of this study was to evaluate the risk of GTN after normalisation of hCG according to HM types. METHODS This prospective cohort study carried out between 2000 and 2010 used the database of the French Trophoblastic Disease Centre (FTDC). A total of 2008 registered patients with ascertained types of HM were analysed. Cases of GTN occurring after normalisation of hCG were analysed. RESULTS A GTN developed in 239 out of 1980 HMs (12.1%) and 6 out of these 239 post-molar GTN (2.5%) were diagnosed after normalisation of hCG. The risk of GTN after normalisation of hCG was 0.34% (6/1747) following a HM, 0% (0/593) after a partial HM (PHM), 0.36% (4/1122) after a complete HM (CHM), and 9.5% (2/21) after a multiple pregnancy with HM. CONCLUSIONS The risk of post-molar GTN justifies hCG monitoring in all women with HM. However, after normalisation of hCG, monitoring of PHM can be stopped safely while it should be maintained for CHM and more importantly for multiple pregnancies with HM.

Scattering transform for intrapartum fetal heart rate characterization and acidosis detection

Early acidosis detection and asphyxia prediction in intrapartum fetal heart rate is of major concern. This contribution aims at assessing the potential of the Scattering Transform to characterize intrapartum fetal heart rate. Elaborating on discrete wavelet transform, the Scattering Transform performs a non linear and multiscale analysis, thus probing not only the covariance structure of data but also the full dependence structure. Applied to a real database constructed by a French public academic hospital, the Scattering Transform is shown to catch relevant features of intrapartum fetal heart rate time dynamics and to have a satisfactory ability to discriminate Normal subjects from Abnormal.