Quels sont l'objectif réel et la portée du dépistage des aneuploïdies ?

International audienceIn 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 β-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

Variation between hospital caesarean delivery rates when Robson's classification is considered: An observational study from a French perinatal network

International audienceIntroduction WHO has recommended using Robson's Ten Group Classification System (TGCS) to monitor and analyze CD rates. Its failure to take some maternal and organizational factors into account, however, could limit the interpretation of CD rate comparisons, because it may contribute to variations in hospital CD rates. Objective To study the contribution of maternal socioeconomic and clinical characteristics and hospital organizational factors to the variation in CD rates when using Robson's ten-group classification system for CD rate comparisons. Methods This prospective, observational, population-based study included all deliveries at a gestational age > 24 weeks at the 10 hospitals of the French MYPA perinatal network in the Paris area. CD rates were calculated for each TGCS group in each hospital. Interhospital variations in these rates were investigated with hierarchical logistic regression models to quantify the variation explained by differences in patient and hospital characteristics when the TGCS is considered. Variations in CD rates between hospitals were estimated with median odds ratios (MOR) to express interhospital variance on the standard odds ratio scale. The percentage of variation explained by TGCS and maternal and hospital characteristics was also calculated. Results The global CD rate was 24.0% (interhospital range: 17-32%). CD rates within each TGCS group differed significantly between hospitals (P40 years), severe preeclampsia, and two organizational factors: Hospital status (private maternities) and the deliveries per staff member per 24 hours. The MOR in the empty model was 1.27 and did not change after taking the TGCS into account. Adding maternal characteristics and hospital organizational factors lowered the MOR to 1.14 and reduced the variation between hospital CD rates by 70%. Conclusion Maternal characteristics and hospital factors are needed to address variation in CD rates among the TGCS groups. Therefore, comparisons of these rates that do not consider these factors should be interpreted carefully

Is gestational age at term a risk factor for ongoing pregnancies in nulliparous women: A prospective cohort study

International audienceBACKGROUND: The results of American observational studies and 1 large, randomized trial show that elective induction of labor among nulliparous women can reduce cesarean delivery rates and suggest that gestational age at delivery may be a risk factor for cesarean delivery in pregnancies managed expectantly. However, data on the risk of cesarean delivery at term in ongoing pregnancies are sparse, especially in high-income countries, and further information is needed to explore the external validity of these previous studies. OBJECTIVE: This study aimed to evaluate the risk of cesarean delivery for each gestational week of ongoing pregnancy in nulliparous women with a singleton fetus in the cephalic presentation at term in a French population. STUDY DESIGN: This retrospective study was conducted in a perinatal network of 10 maternity units from January 1, 2016, to December 31, 2017, and included all nulliparous women with a singleton fetus in the cephalic presentation who gave birth at term (≥37 0/7 weeks of gestation). From the start of term (37 completed weeks) and at the start of each subsequent week of completed gestation (each week + 0 days), ongoing pregnancy was defined as that of a woman who was still pregnant and who gave birth at any time after that date. For each week of gestation for these ongoing pregnancies, the cesarean delivery rate was defined as the number of cesarean deliveries performed in each ongoing pregnancy group divided by the number of women in this group. Separate models for each week of gestation, adjusted by maternal characteristics and hospital status, were used to compare the cesarean delivery risk between ongoing pregnancies and those delivered the preceding week. The same methods were applied to subgroups defined according to the mode of labor onset. Odds ratios were calculated after adjusting for maternal age and educational level, presence of severe preeclampsia, and maternity unit status. RESULTS: The study included 11,308 nulliparous women, 2544 (22.5%) of whom had a cesarean delivery. These rates remained stable for ongoing pregnancies at 37 0/7, 38 0/7, and 39 0/7 weeks of gestation; the rates were 22.5% (95% confidence interval, 21.7–23.2), 22.6% (95% confidence interval, 21.8–23.3); and 22.7% (95% confidence interval, 21.9–23.6), respectively. The risk of cesarean delivery started to increase in ongoing pregnancies at 40 0/7 weeks of gestation (24.3%; 95% confidence interval, 23.1–25.4) and especially at 41 0/7 weeks of gestation (30.7%; 95% confidence interval, 28.9–32.5). Similar trends were also shown for all modes of labor onset and in every maternity unit. In univariate and multivariate analyses, ongoing pregnancy at or beyond 40 0/7 weeks of gestation was associated with a higher risk of cesarean delivery than pregnancy delivered the previous week: 24.3% of ongoing pregnancies at 40 0/7 weeks of gestation vs 19.9% of deliveries between 39 0/7 weeks of gestation and 39 6/7 weeks of gestation. The odds ratios were 1.28 (95% confidence interval, 1.15–1.44) or 30.4% of ongoing pregnancies at 41 0/7 weeks of gestation vs 1.73 (95% confidence interval, 1.51–1.96) or 19.6% of deliveries between 40 0/7 weeks of gestation and 40 6/7 weeks of gestation. CONCLUSION: Cesarean delivery rates increased starting at 40 0/7 weeks of gestation in ongoing pregnancies regardless of the mode of labor onset

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

International audienceOBJECTIVE: 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. Copyrigh

L'ADN fœtal libre circulant : un outil d’évaluation du risque de survenue de complications obstétricales ?

International audienceObjective: 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” (&gt; 90th percentile) group, “low fetal-fraction” group (&lt; 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 &gt; 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

Active Management of the Third Stage of Labor with a Combination of Oxytocin and Misoprostol to Prevent Postpartum Hemorrhage: A Randomized Controlled Trial

International audienceOBJECTIVE: To evaluate the effectiveness and safety of misoprostol administered simultaneously with oxytocin as part of the active management of the third stage of labor. METHODS: This multicenter, double-blind, randomized, placebo-controlled trial recruited women in the first stage of labor with expected vaginal deliveries at 36-42 weeks of gestation. Exclusion criteria were multiple pregnancies, hypersensitivity to misoprostol, and cesarean delivery. Participants received routine intravenous oxytocin and were randomly allocated to receive 400 micrograms misoprostol or placebo orally immediately after delivery of the newborn. The primary outcome was postpartum hemorrhage (500 mL or greater within 2 hours of birth). Secondary outcomes included severe postpartum hemorrhage (1,000 mL or greater) and adverse maternal events such as fever, shivering, and nausea. Two groups of 1,550 women were required to demonstrate a 33% decrease of postpartum hemorrhage according to a two-tailed α at 0.05 with 80% power. An interim analysis was planned after 50% enrollment. RESULTS: Participant enrollment occurred from April 2010 to September 2013. Baseline characteristics were similar in the two groups. The study was discontinued after the planned interim analysis including 1,721 patients showed that misoprostol was not effective and was associated with significantly more adverse effects. The rate of postpartum hemorrhage was 8.4% (68/806) in the misoprostol and 8.3% (66/797) in the placebo group (P.98), and rates of severe postpartum hemorrhage were 1.8% and 2.4%, respectively (P.57). Maternal adverse events occurred significantly more frequently in the misoprostol group (for fever 30.4% in the misoprostol group compared with 6.3% in the placebo group, P<.001; for shivering 10.8% in the misoprostol group compared with 0.6% in the placebo group, P<.001). CONCLUSION: Misoprostol administered with prophylactic routine oxytocin did not reduce the rate of postpartum hemorrhage risk and increased the rate of adverse events

Cervical Dilators Used Concurrently With Misoprostol to Shorten Labor in Second-Trimester Termination of Pregnancy

International audienceOBJECTIVE: To evaluate the use of cervical dilators concurrently with misoprostol to shorten labor in second-trimester medical termination of pregnancy.METHODS: This multicenter randomized controlled trial compared the efficacy of cervical dilators inserted concurrently with misoprostol with that of misoprostol, alone, to shorten labor for women undergoing termination of pregnancy between 15 0/7 and 27 6/7 weeks of gestation. The primary outcome was the proportion of women with a duration of labor exceeding 12 hours. Secondary outcomes included median duration of labor, time to amniotomy, side effects, complications, NPRS (Numeric Pain Rating Scale) score, and women's distress as measured by the IES-R (Impact of Event Scale-Revised). These outcomes also were studied separately in the nulliparous subgroup. To demonstrate a reduction of 50% of the proportion of women with a duration of labor exceeding 12 hours in the dilator group, with a power of 80% and a 2-sided 0.05 significance level, a sample of 268 women (134 in each group) was required.RESULTS: Between December 2017 and September 2019, this study enrolled and analyzed 347 women: 174 in the dilator group and 173 in the control group, including 87 and 93 nulliparous patients, respectively. Sociodemographic and obstetric characteristics were similar between groups. The proportion of women with labor exceeding 12 hours was not different between groups (49/174 [28.2%] in the dilator group vs 53/173 [30.6%] in the control group [P=.61] for the whole population, and 37/87 [42.5%] vs 42/93 [45.2%] [P=.72], respectively, among nulliparous patients). Median duration of labor was 8.5 hours in the dilator group compared with 9.2 hours in the control group (P=.65) for the whole population, and 10.5 hours compared with 11.8 hours, respectively, among nulliparous patients (P=.33). Median time to amniotomy was 3.6 hours in the dilator group compared with 5.0 hours in the control group (P=.08) for the whole population, and 3.5 hours compared with 6.7 hours, respectively, among nulliparous patients (P=.003). Side effects, complications, NPRS score, and IES-R score were similar between groups

Pathologies maternelles chroniques et pertes de grossesse. Recommandations françaises

International audienceAim.-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 maternaldiseases of this paper.Results-Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anti-coagulant) should be measured in case of miscarriage after 10 WG confirmed by ultrasound(grade B) and an antiphospholipid syndrome should be treated by a combination of aspi-rin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We donot recommend testing for genetic thrombophilia in case of first trimester miscarriage(grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancyfor 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 betreated 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 pre-gnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism(grade B).Conclusions.-Prepregnancy management of most chronic maternal diseases, ideally throughprepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss

Impact of COVID-19-Related Lockdown on Delivery and Perinatal Outcomes: A Retrospective Cohort Study

International audienceObjective: The magnitude and direction of effects on pregnancy outcomes of the lockdown imposed during COVID-19 have been uncertain and debated. Therefore, we aimed to quantify delivery and perinatal outcomes during the first nationwide lockdown due to the COVID-19 pandemic compared with the same durations of time for the pre-and post-lockdown periods.Study design: This was a retrospective cohort study of six university hospital maternity units distributed across France, each of which serves as the obstetric care referral unit within its respective perinatal network. Maternal and perinatal outcomes were compared between the lockdown period and same-duration (i.e., 55-day) periods before and after the 2020 lockdown (pre-lockdown: 22 January– 16 March; lockdown: 17 March–10 May; post-lockdown: 11 May–4 July). We compared the overall rates of Caesarean delivery (CD), pre-labor CD, labor induction, operative vaginal delivery, severe postpartum hemorrhage (≥1 L), severe perineal tear, maternal transfusion, and neonatal mortality and morbidity (1-and 5-min Apgar scores < 7), hypoxia and anoxia (umbilical arterial pH < 7.20 or <7.10, respectively), and admission to a neonatal intensive care unit before discharge. Adjusted odds ratios were estimated using logistic regression, controlling for region of birth, maternal age category, multiparity, multiple pregnancies, diabetes, and hypertensive disorders.Results: The study sample consisted of 11,929 women who delivered consecutively at one of the six maternity units studied (4093 pre-lockdown, 3829 during lockdown, and 4007 post-lockdown) and their 12,179 neonates (4169 pre-lockdown, 3905 during lockdown, and 4105 post-lockdown). The maternal and obstetric characteristics of the women delivering during the lockdown period were alike those delivering pre-and post-lockdown on maternal age, parity, body mass index, rate of complication by hypertensive disorders or insulin-treated diabetes, and gestational age at delivery. Overall CD rates were similar during the three periods (23.6%, 24.8%, and 24.3% pre-lockdown, lockdown, and post-lockdown, respectively) and no outcome differed significantly during lockdown compared to pre-and post-lockdown. These findings were consistent across maternity units.Conclusion: The maternal and perinatal outcomes are reassuring regarding the performance of the health-care system during the COVID-19 lockdown studied. Such information is crucial, because additional COVID-19-related lockdowns might still be needed. They are also instructive regarding potential future pandemics

Impact of COVID-19 lockdown on preterm births, low birth weights and stillbirths: A retrospective cohort study

International audienceObjective: The effect of lockdowns during the coronavirus (COVID-19) pandemic on pregnancy outcomes remains uncertain. We aimed to evaluate the association between the COVID-19-related lockdown and pregnancy outcomes in maternity hospitals in France. Study design: This was a retrospective cohort study from six tertiary referral hospitals in different regions of France. Three 55-day periods were compared: Pre-lockdown from 22 January 2020, lockdown from 17 March 2020, and post-lockdown from 11 May 2020 to 4 July 2020. We included all women who delivered singleton or multiple pregnancies, who delivered at ≥24 weeks of gestation and with birthweights ≥500 g. We documented gestational ages at the delivery of liveborn and stillborn infants (‘stillbirths’). These were categorized as having a very low birthweight (VLBW, <1500 g), or a low birthweight (LBW, <2500 g). Adjustments were made for place of birth, maternal age, parity and diabetes, and hypertensive disorders, as well as for multiple pregnancies. Results: In total, 11,929 women delivered in the six selected centers. This figure is constituted of 4093, 3829, and 4007 deliveries in the pre-lockdown (1), peri-lockdown (2), and post-lockdown (3) periods, respectively. There were no differences in pregnancy outcomes between these three periods. Overall, birth rates <27+6 weeks, between weeks 28+0 and 31+6, and between 32+0 and weeks 36+6 were 1.0%, 1.9%, and 4.4%, respectively. After adjustment, these rates were stable between periods 1 and 2 (adjusted odds ratio, aOR 0.90; 95% confidence interval, CI 0.69–1.19) and between periods 2 and 3 (aOR 1.04; 95% CI 0.80–1.36). Although more VLBW neonates were born during lockdown (3.5% vs. 2.6%, p = 0.03), this difference did not persist after adjustment (aOR 0.84, CI 95% 0.64–1.10). The LBW rates were similar during the three periods at 12.5% overall. The stillbirth rate was unaffected by the lockdown. Conclusion: The pregnancy outcomes (preterm birth, LBW, VLBW, and stillbirth rates) were not modified by the COVID-19 lockdown in our cohort study in France. Considering the discrepancies in results and methodological issues in previous published studies, there is not sufficient evidence to conclude that such lockdowns have any impact on perinatal outcomes