Comparison of the performance of estimated fetal weight charts for the detection of small- and large-for-gestational age newborns with adverse outcomes: a French population-based study.

OBJECTIVE: To compare the performance of estimated fetal weight (EFW) charts at the third trimester ultrasound for detecting small- and large-for-gestational age (SGA/LGA) newborns with adverse outcomes. DESIGN: Nationally representative observational study. SETTING: French maternity units in 2016. POPULATION: 9940 singleton live births with an ultrasound between 30 and 35 weeks of gestation. METHODS: We compared three prescriptive charts (INTERGROWTH-21st, World Health Organization (WHO), Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD]), four descriptive charts (Hadlock, Fetal Medicine Foundation, two French charts) and a French customised growth model (Epopé). MAIN OUTCOME MEASURES: SGA and LGA (birthweights <10th and >90th percentiles) associated with adverse outcomes (low Apgar score, delivery-room resuscitation, neonatal unit admission). RESULTS: 2.1% and 1.1% of infants had SGA and LGA and adverse outcomes, respectively. The sensitivity and specificity for detecting these infants with an EFW <10th and >90th percentile varied from 29-65% and 84-96% for descriptive charts versus 27-60% and 83-96% for prescriptive charts. WHO and French charts were closest to the EFW distribution, yielding a balance between sensitivity and specificity for SGA and LGA births. INTERGROWTH-21st and Epopé had low sensitivity for SGA with high sensitivity for LGA. Areas under the receiving operator characteristics curve ranged from 0.62 to 0.74, showing low to moderate predictive ability, and diagnostic odds ratios varied from 7 to 16. CONCLUSION: Marked differences in the performance of descriptive as well as prescriptive EFW charts highlight the importance of evaluating them for their ability to detect high-risk fetuses. TWEETABLE ABSTRACT: Choice of growth chart strongly affected identification of high-risk fetuses at the third trimester ultrasound.

Association between extremely preterm caesarean delivery and maternal depressive and anxious symptoms: a national population-based cohort study.

OBJECTIVE: To evaluate whether caesarean delivery before 26 weeks of gestation was associated with symptoms of depression and anxiety in mothers in comparison with deliveries between 26 and 34 weeks. DESIGN: Prospective national population-based EPIPAGE-2 cohort study. SETTING: 268 neonatology departments in France, March to December 2011. POPULATION: Mothers who delivered between 22 and 34 weeks and whose self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (State-Trait Anxiety Inventory: STAI) were assessed at the moment of neonatal discharge. METHODS: The association of caesarean delivery before 26 weeks with severe symptoms of depression (CES-D ≥16) and anxiety (STAI ≥45) was assessed by weighted and design-based log-linear regression model. MAIN OUTCOME MEASURES: Severe symptoms of depression and anxiety in mothers of preterm infants. RESULTS: Among the 2270 women completing CES-D and STAI questionnaires at the time of neonatal discharge, severe symptoms of depression occurred in 25 (65.8%) women having a caesarean before 26 weeks versus in 748 (50.6%) women having a caesarean after 26 weeks. Caesarean delivery before 26 weeks was associated with severe symptoms of depression compared with caesarean delivery after 26 weeks (adjusted relative risk [aRR] 1.42, 95% CI 1.12-1.81) adjusted to neonatal birthweight and severe neonatal morbidity among other factors. There was no evidence of an association between mode of delivery and symptoms of anxiety. CONCLUSIONS: Mothers having a caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression and may benefit from specific preventive care. TWEETABLE ABSTRACT: Mothers having caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression.

The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study.

OBJECTIVE: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. TWEETABLE ABSTRACT: Monochorionicity is associated with adverse perinatal outcomes, but outcomes for preterm twins are comparable irrespective of their chorionicity.

Perinatal outcome after planned vaginal delivery in monochorionic compared with dichorionic twin pregnancy.

OBJECTIVE: To assess, according to chorionicity, the perinatal outcome of twin pregnancy in which vaginal delivery is planned. METHODS: JUMODA (JUmeaux MODe d'Accouchement) was a national prospective population-based cohort study of twin pregnancies, delivered in 176 maternity units in France, from February 2014 to March 2015. In this planned secondary analysis, we assessed, according to chorionicity, the perinatal outcome of twin pregnancies, in which vaginal delivery was planned, that delivered at or after 32 weeks of gestation with the first twin in cephalic presentation. In order to select a population with well-recognized indications for planned vaginal delivery, we applied the same exclusion criteria as those in the Twin Birth Study, an international randomized trial. Monochorionic twin pregnancies with twin-to-twin transfusion syndrome or twin anemia-polycythemia sequence were defined as complicated and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. Multivariable logistic regression models were used to control for potential confounders. Subgroup analyses were conducted according to birth order (first or second twin) and gestational age at delivery (< 37 or ≥ 37 weeks of gestation). RESULTS: Among 3873 twin pregnancies, in which vaginal delivery was planned, that delivered at ≥ 32 weeks' gestation with the first twin in cephalic presentation, meeting the inclusion criteria of the Twin Birth Study, 729 (18.8%) were uncomplicated monochorionic twin pregnancies and 3144 (81.2%) were dichorionic twin pregnancies. The rate of composite intrapartum mortality and neonatal morbidity and mortality did not differ between uncomplicated monochorionic (27/1458 (1.9%)) and dichorionic (107/6288 (1.7%)) twin pregnancies when adjusting for conception by assisted reproductive technologies (adjusted relative risk, 1.07 (95% CI, 0.66-1.75)). No significant difference in the primary outcome was found between the groups on subgroup analyses according to birth order and gestational age at delivery. CONCLUSION: When vaginal delivery is planned, and delivery occurs at ≥ 32 weeks of gestation with the first twin in cephalic presentation, uncomplicated monochorionic twin pregnancy is not associated with a higher rate of composite intrapartum mortality and neonatal morbidity and mortality compared with dichorionic twin pregnancy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Risk of preterm birth in a twin pregnancy after an early-term birth in the preceding singleton pregnancy: a retrospective cohort study.

OBJECTIVE: To evaluate whether a history of spontaneous early-term birth (37+0 -38+6  weeks of gestation) in the previous singleton pregnancy is a risk factor for preterm birth (PTB) in a subsequent twin pregnancy. DESIGN: Retrospective cohort study. SETTINGS: Two French university hospitals (2006-2016). POPULATION: All women who delivered twins from 24+0  weeks after a preceding singleton pregnancy birth at 37+0 to 41+6  weeks. METHODS: Multivariate logistic regression analysis of association between twin PTB and a previous spontaneous singleton early-term birth. MAIN OUTCOME MEASURES: Twin PTB rate before 37, 34 and 32 weeks of gestation. RESULTS: Among 618 twin pregnancies, 270 were born preterm, 92 of them with a preceding spontaneous singleton early-term birth. The univariate analysis showed a significantly higher risk of twin PTB before 37, 34 and 32 weeks among those 92 women compared with those with a full- or late-term birth in their previous singleton pregnancy. This association remained significant after logistic regression (odds ratio [OR] between 2.42 and 3.88). The secondary analysis, restricted to the twin pregnancies with spontaneous PTB found similar results, with a risk of PTB before 37, 34 and 32 weeks significantly higher among women with a previous spontaneous singleton early-term birth, including after logistic regression analysis (OR between 3.51 and 3.56). CONCLUSION: A preceding spontaneous singleton early-term birth is a strong and easily identified risk factor for PTB in twin pregnancies. TWEETABLE ABSTRACT: Spontaneous 'early-term' birth of a singleton is a significant risk factor for future preterm births in twin pregnancies.

Neurodevelopment at 2 years and umbilical artery Doppler in cases of very preterm birth after prenatal hypertensive disorder or suspected fetal growth restriction: EPIPAGE-2 prospective population-based cohort study.

OBJECTIVE: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. METHODS: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. RESULTS: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9). CONCLUSION: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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.

Women and academic careers in obstetrics and gynaecology: aspirations and obstacles among postgraduate trainees - a mixed-methods study.

OBJECTIVE: To examine the relationship between gender and a career in academic medicine. DESIGN: Mixed-methods study. SETTING: Obstetrics-gynaecology postgraduate training programme in Paris, France. SAMPLE: Postgraduate trainees in obstetrics-gynaecology (n = 204). METHODS: Statistical analysis of quantitative survey data, thematic analysis of qualitative interview data and integrative analysis. MAIN OUTCOME MEASURES: Women's aspirations and obstacles related to their decision about a career in academic medicine. RESULTS: A career in academic medicine was envisaged by 13% of the women residents and 27% of the men (P = 0.01). Women reported receiving advice from a mentor less often than men (38.8% versus 52.9%, P = 0.002). Overall, 40.6% of women and 2.9% of men reported experiencing gender discrimination (P < 0.001). In response to the question 'Do you have doubts about your ability to pursue or succeed at an academic career?', 62.4% of the women and only 17.7% of the men answered yes (P < 0.001). The global analysis identified the following obstacles: persistent gender stereotypes that produce everyday sexism, lack of identification with male role models, lack of mentors, perceived discrimination, an ideal of professional excellence that is difficult to attain, constraining professional organisational norms, inequality between men and women in the domestic and family spheres, and finally self-censorship and important doubts about their ability to combine a demanding career and a fulfilling personal life. CONCLUSIONS: Women reported the desire to follow a career in academic medicine half as often as men. Improving the presence and visibility of role models for residents and combating workplace discrimination will address some of the barriers to women choosing a career in academic medicine. TWEETABLE ABSTRACT: Women obstetric trainees in France are only half as likely as men to envisage following an academic path.

Planned delivery route of preterm breech singletons, and neonatal and 2-year outcomes: a population-based cohort study.

OBJECTIVE: To assess whether planned route of delivery is associated with perinatal and 2-year outcomes for preterm breech singletons. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: France, 2011. SAMPLE: Three hundred and ninety women with breech singletons born at 26-34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes. METHODS: Propensity-score analysis. MAIN OUTCOME MEASURES: Survival at discharge, survival at discharge without severe morbidity, and survival at 2 years of corrected age without neurosensory impairment. RESULTS: Vaginal and caesarean deliveries were planned in 143 and 247 women, respectively. Neonates with planned vaginal delivery and planned caesarean delivery did not differ in survival (93.0 versus 95.7%, P = 0.14), survival at discharge without severe morbidity (90.4 versus 89.9%, P = 0.85), or survival at 2 years without neurosensory impairment (86.6 versus 91.6%, P = 0.11). After applying propensity scores and assigning inverse probability of treatment weighting, as compared with planned vaginal delivery, planned caesarean delivery was not associated with improved survival (odds ratio, OR 1.31; 95% confidence interval, 95% CI 0.67-2.59), survival without severe morbidity (OR 0.75, 95% CI 0.45-1.27), or survival at 2 years without neurosensory impairment (OR 1.04, 95% CI 0.60-1.80). Results were similar after matching on propensity score. CONCLUSIONS: No association between planned caesarean delivery and improved outcomes for preterm breech singletons born at 26-34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes was found. The route of delivery should be discussed with women, balancing neonatal outcomes with the higher risks of maternal morbidity associated with caesarean section performed at low gestational age.

Intrapartum group B Streptococcus screening in the labor ward by Xpert® GBS real-time PCR.

Group B Streptococcus (GBS) is the leading cause of neonatal infections in industrialized countries. Intrapartum antibiotic prophylaxis (IAP) given to colonized parturients is a key step for the prevention of neonatal early-onset infection. We compared the performances of Xpert® GBS polymerase chain reaction (PCR) (Cepheid, Sunnyvale, CA, USA) as a point-of-care system in labor wards to standard culture for intrapartum GBS detection. Pregnant women with a GBS-positive antenatal screening were prospectively included. A vaginal double swab was collected at the time of delivery for point-of-care Xpert® GBS PCR and GBS culture. A total of 565 pregnant women were included. Valid Xpert® GBS results were obtained for 488 (86.4%) women on the first attempt. Repeat testing improved the PCR success to 516 (91.3%) women. Among the 305 women positive for GBS by culture at delivery, only 238 (78.0%) were positive by Xpert® GBS PCR, cycle thresholds being correlated to culture quantification. Among 260 women negative for GBS culture, 56 (21.5%) were positive by Xpert® GBS PCR, including 50 where IAP was initiated before vaginal sampling. Overall, among the 565 women with GBS antenatal positive culture, only 335 (59.3%) were still positive at delivery whatever the technique used, resulting in unnecessary IAP for 40% of them. This large cohort study comparing intrapartum to antepartum GBS detection provides evidence that (i) Xpert® GBS PCR might be a valuable solution for intrapartum GBS detection compared to culture-based strategies and (ii) laboratory training of non-specialized staff is mandatory to reach the performances required for point-of-care tests.

Efficacy of antenatal corticosteroids in preterm twins: the EPIPAGE-2 cohort study.

OBJECTIVES: To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval. DESIGN: EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation. SETTING: All French maternity units, except in a single administrative region, between March and December 2011. POPULATION: A total of 750 twin neonates born between 24 and 31 weeks of gestation. METHODS: Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment. MAIN OUTCOME MEASURES: Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes. RESULTS: Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1-0.5), in-hospital mortality (0.3; 0.1-0.6), and the composite indicator (0.1; 0.1-0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3-1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course. CONCLUSION: In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days. TWEETABLE ABSTRACT: A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24-31 weeks).

Gestational age at diagnosis of early-onset fetal growth restriction and impact on management and survival: a population-based cohort study.

OBJECTIVE: To investigate the impact of gestational age (GA) at diagnosis of fetal growth restriction (FGR) on obstetric management and rates of live birth and survival for very preterm infants with early-onset FGR. DESIGN: Population-based cohort study. SETTING: All maternity units in 25 French regions in 2011. POPULATION: Fetuses diagnosed with FGR before 28 weeks of gestation among singleton births between 22 and 31 weeks of gestation without severe congenital anomalies. METHODS: We studied the effects of GA at diagnosis on perinatal management and outcomes. We used multivariable regression to identify antenatal factors (maternal characteristics, ultrasound measurements and sex) associated with the probability of live birth. MAIN OUTCOMES MEASURES: Live birth and survival to discharge from neonatal care. RESULTS: A total of 436 of 3698 fetuses were diagnosed with FGR before 28 weeks (11.8%); 66.9% were live born and 54.4% survived to discharge. 50% were live born when diagnosis occurred before 25 weeks, 66% at 25 weeks and >90% at 26 and 27 weeks of gestation. In all, 94.1% of live births were by prelabour caesarean, principally for maternal indications before 26 weeks. Low GA at diagnosis, an estimated fetal weight or abdominal circumference below the third centile and male sex were adversely associated with live birth in adjusted models. CONCLUSION: Gestational age at FGR diagnosis had an impact on the probability of live birth and survival, after consideration of other perinatal characteristics. Investigations of the outcomes of births with early-onset FGR need to include stillbirths and information on the GA at which FGR is diagnosed. TWEETABLE ABSTRACT: Evaluations of active management of pregnancies with early onset growth restriction should include stillbirths.

Why women with previous caesarean and eligible for a trial of labour have an elective repeat caesarean delivery? A national study in France.

OBJECTIVE: To identify the characteristics of women and maternity units associated with elective repeat caesarean delivery (ERCD) in women eligible for trial of labour after caesarean (TOLAC). DESIGN: Cross-sectional study. SETTING: France. POPULATION AND SAMPLE: Using data from the 2010 French National Perinatal Survey, a representative sample of births in France (n = 14 681 women), we studied two groups of women with prior caesarean section: (i) women eligible for TOLAC according to guidelines (n = 1179) and (ii) a subgroup of these women without any medical characteristics that might indicate ERCD (n = 575). METHODS: Associations were analysed by multilevel logistic regression. MAIN OUTCOME MEASURES: Adjusted odds ratios. RESULTS: Among the 1584 women with a previous caesarean, 1179 (74.4%) were eligible for TOLAC according to guidelines (group 1); 490 (41.6%) had ERCD. Risk of ERCD increased with increasing maternal age and body mass index, pre-existing condition and suspected macrosomia and decreased with previous vaginal deliveries. Among the unit characteristics, private status (aOR = 2.3, 95% CI 1.3-4.1) and low level of care (aOR = 2.5, 95% CI 1.4-4.5]) were independently associated with a higher risk of ERCD after adjustment on patient/pregnancy characteristics. The variability of ERCD rate between hospitals was mainly (78%) explained by the status and level of care, and not (0%) by patient/pregnancy characteristics. Associations with unit characteristics were similar for group 2. CONCLUSION: For women eligible for TOLAC, the rate of ERCD is high and not in agreement with guidelines. Some characteristics of women are associated with ERCD, but the main determinants are at the unit level, which suggests that non-medical reasons are involved in the decision process. TWEETABLE ABSTRACT: Elective repeat caesarean in women eligible for trial of labour mainly depends on maternity unit characteristics.

Variation in transplacental transfer of tyrosine kinase inhibitors in the human perfused cotyledon model.

BACKGROUND: The use of tyrosine kinase inhibitors (TKis) during pregnancy in humans remains rare, and little data are available on their transplacental passage. Erlotinib and gefitinib are the first-line targeted therapy in case of stage IV nonsmall-cell lung cancer with an EGFR-activating mutation. There are no data available regarding the comparative use of these TKis in pregnant patients. We aimed to compare the transplacental transfer of gefitinib, imatinib and erlotinib, using the ex vivo method of human perfused cotyledon, and to determine the placental accumulation of TKis. MATERIALS AND METHODS: Term placentas were perfused after delivery with gefitinib, imatinib and erlotinib at targeted maternal concentrations around the steady-state plasma trough concentration (i.e. 500, 1000 and 1500 ng/ml, respectively). Samples from fetal and maternal circulations were collected in order to monitor TKis concentrations. Main transfer parameters such as fetal transfer rate (FTR), clearance index (CI) and placental uptake were assessed. RESULTS: Mean FTR of gefitinib, imatinib and erlotinib were 16.8%, 10.6% and 31.4%, respectively. Mean CI of gefitinib, imatinib and erlotinib were 0.59, 0.48 and 0.93, respectively. Placental uptake in cotyledon was 0.030% %, 0.010% and 0.003% for gefitinib, imatinib and erlotinib, respectively, corresponding to a mean mass of 27.7 µg for gefitinib, 15.7 µg for imatinib and 6.8 µg for erlotinib. CONCLUSION: The results suggest that TKis cross the placenta at therapeutic level. Particularly, erlotinib crosses the placenta at a higher rate than gefitinib or imatinib. All of them have a very low placental uptake. These data may suggest that gefitinib should be preferred to erlotinib for the treatment of pregnant woman with lung cancer harboring an EGFR-activating mutation, during the second and third trimesters of pregnancy.

Endometriosis also affects the decidua in contact with the fetal membranes during pregnancy.

STUDY QUESTION: Are the fetal membranes of women affected with endometriosis similar to those from disease-free women? SUMMARY ANSWER: Decidua of women with endometriosis is able to generate endometriotic-like lesions in contact with the fetal membranes. WHAT IS KNOWN ALREADY: Eutopic endometrium of women affected with endometriosis presents compromised properties. Endometrium undergoes decidualisation to accept and to further control the conceptus development during pregnancy. Decidualized endometrium is in close contact with the chorionic membrane and forms the choriodecidual layer, a major maternal-fetal interface. STUDY DESIGN, SIZE, DURATION: This is a laboratory case-control study involving diseased versus control samples. Eleven case samples and 11 control samples were collected from women in a tertiary care/research center between November 2011 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were consecutive pregnant women affected with confirmed endometriosis and disease free women, who underwent Cesarean section before labor for obstetrical indication. The choriodecidual tissues were characterized using histology, immunohistochemistry, transcriptomic and whole genome CpG methylation analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We demonstrate for the first time the presence of endometriotic-like lesions within the decidual side of the choriodecidua of the fetal membranes from women affected with severe endometriosis. Fetal membranes from women affected with endometriosis exhibited glandular components in the choriodecidual layer surrounded by enlarged decidualized cells disseminated along the entire membrane surface. Significant deregulation (variation of expression ≥2, P-value ≤0.05) was observed for 2773 genes known to be enriched in processes involved in glandular function, endocrine and nervous system, neoangiogenesis, and autoimmune disease. CpG methylation analysis revealed 5999 differentially methylated regions with a P-value ≤0.05. LIMITATIONS, REASONS FOR CAUTION: We studied women who delivered at term by Cesarean section before labor, following an uneventful pregnancy. Notwithstanding this, one cannot exclude that the presence of disseminated endometriotic lesions within the choriodecidual layer of the fetal membranes may disturb the anatomical integrity and/or the function of the membranes in some women with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our results shed new light on the capability of the diseased decidua to develop lesions not only at ectopic autologous locations, but also on the semi-allogenous fetal membranes, a particularly immunotolerant environment.

Is the probability of prenatal diagnosis or termination of pregnancy different for fetuses with congenital anomalies conceived following assisted reproductive techniques? A population-based evaluation of fetuses with congenital heart defects.

OBJECTIVE: To compare the probability of prenatal diagnosis (PND) and termination of pregnancy for fetal anomaly (TOPFA) between fetuses conceived by assisted reproductive techniques (ART) and spontaneously-conceived fetuses with congenital heart defects (CHD). DESIGN: Population-based observational study. SETTING: Paris and surrounding suburbs. POPULATION: Fetuses with CHD in the Paris registry of congenital malformations and cohort of children with CHD (Epicard). METHODS: Comparison of ART-conceived and spontaneously conceived fetuses taking into account potential confounders (maternal characteristics, multiplicity and year of birth or TOPFA). MAIN OUTCOME MEASURES: Probability and gestational age at PND and TOPFA for ART-conceived versus spontaneously conceived fetuses. RESULTS: The probability of PND (28.1% versus 34.6%, P = 0.077) and TOPFA (36.2% versus 39.2%, P = 0.677) were not statistically different between ART-conceived (n = 171) and spontaneously conceived (n = 4620) fetuses. Estimates were similar after adjustment for potential confounders. Gestational age at PND tended to be earlier for ART fetuses (23.1 versus 24.8 weeks, P = 0.05) but no statistical difference was found after adjustment for confounders. Gestational age at TOPFA was comparable between ART-conceived and spontaneously conceived fetuses. CONCLUSIONS: In our population, ART conception was not significantly associated with the probability of PND or TOPFA for CHD. One implication of our results is that live births may be adequate for assessing the overall risk of CHD related to ART. However, total prevalence, in particular of severe CHD, would not be adequately assessed if TOPFA are not included.

Poor effectiveness of antenatal detection of fetal growth restriction and consequences for obstetric management and neonatal outcomes: a French national study.

OBJECTIVE: To assess the proportion of small for gestational age (SGA) and normal birthweight infants suspected of fetal growth restriction (FGR) during pregnancy, and to investigate obstetric and neonatal outcomes by suspicion of FGR and SGA status at birth. DESIGN: Population-based study. SETTING: All French maternity units in 2010. POPULATION: Representative sample of singleton births (n = 14,100). METHODS: We compared SGA infants with a birthweight of less than the 10th percentile suspected of FGR, defined as mention of FGR in medical charts (true positives), non-SGA infants suspected of FGR (false positives), SGA infants without suspicion of FGR (false negatives) and non-SGA infants without suspicion of FGR (true negatives). Multivariable analyses were adjusted for maternal and neonatal characteristics hypothesised to affect closer surveillance for FGR and our outcomes. MAIN OUTCOME MEASURES: Obstetric management (caesarean, provider-initiated preterm and early term delivery) and neonatal outcomes (late fetal death, preterm birth, Apgar score, resuscitation at birth). RESULTS: 21.7% of SGA infants (n = 265) and 2.1% of non-SGA infants (n = 271) were suspected of FGR during pregnancy. Compared with true negatives, provider-initiated preterm deliveries were higher for true and false positives (adjusted risk ratio [aRR], 6.1 [95% CI, 3.8-9.8] and 4.6 [95% CI, 3.2-6.7]), but not for false negatives (aRR, 1.1 [95% CI, 0.6-1.9]). Neonatal outcomes were not better for SGA infants if FGR was suspected. CONCLUSION: Antenatal suspicion of FGR among SGA infants was low and one-half of infants suspected of FGR were not SGA. The increased risk of provider-initiated delivery observed in non-SGA infants suspected of FGR raises concerns about the iatrogenic consequences of screening.

Stabilising the caesarean rate: which target population?

OBJECTIVE: Caesarean rate increased in France between 1995 and 2003, but remained stable between 2003 and 2010. Our objective was to analyse these trends by identifying the groups of women who contributed to the increase and those who contributed to the stabilisation. DESIGN: Cross-sectional population-based study from the French national perinatal surveys. SETTING: All maternity units in France. POPULATION: Representative samples of women delivering in 1995 (n = 13 147), 2003 (n = 14 482), and 2010 (n = 14 681). METHODS: Robson classification, based on pregnancy and delivery characteristics, was used for each group. MAIN OUTCOME MEASURES: Caesarean rate for each group, its contribution to the overall caesarean rate, and the differences (Δ) in these contributions between 1995 and 2003 and between 2003 and 2010. RESULTS: Overall caesarean rates were 15.4% in 1995, 19.7% in 2003 and 20.5% in 2010. Between 1995 and 2003, the contribution to the overall caesarean rate of all groups but one rose. Between 2003 and 2010, the contribution of all groups but three stabilised or decreased: nulliparous women in spontaneous labour with singleton cephalic fetuses at term (Δ = + 0.5%, 95% CI 0.1-0.9%), an increase explained by their higher caesarean rate; nulliparous women with induced labour at term (Δ = + 1.1%, 95% CI 0.8-1.4%) caused by an increase in both the caesarean rate and the relative size of this group; and women with previous caesarean (Δ = + 0.8%, 95% CI 0.3-1.3%), because of the growing size of this group. CONCLUSION: Proposing and evaluating interventions for improving the management of labour in nulliparous women could help to maintain caesarean rates and mitigate increases among multiparous women in the future.

Tranexamic acid for the prevention and treatment of postpartum haemorrhage.

Postpartum haemorrhage (PPH) is a major cause of maternal mortality, accounting for one-quarter of all maternal deaths worldwide. Uterotonics after birth are the only intervention that has been shown to be effective for PPH prevention. Tranexamic acid (TXA), an antifibrinolytic agent, has therefore been investigated as a potentially useful complement to this for both prevention and treatment because its hypothesized mechanism of action in PPH supplements that of uterotonics and because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. This review covers evidence from randomized controlled trials (RCTs) for PPH prevention after caesarean (n=10) and vaginal (n=2) deliveries and for PPH treatment after vaginal delivery (n=1). It discusses its efficacy and side effects overall and in relation to the various doses studied for both indications. TXA appears to be a promising drug for the prevention and treatment of PPH after both vaginal and caesarean delivery. Nevertheless, the current level of evidence supporting its efficacy is insufficient, as are the data about its benefit:harm ratio. Large, adequately powered multicentre RCTs are required before its widespread use for preventing and treating PPH can be recommended.

Severe postpartum hemorrhage and the risk of adverse maternal outcome: A comparative analysis of two population-based studies in France and the Netherlands.

Objectives: Among women with severe PPH (sPPH) in France and the Netherlands, we compared incidence of adverse maternal outcome (major obstetric hemorrhage (≥2.5L blood loss) and/or hysterectomy and/or mortality) by mode of delivery. Second, we compared use and timing of resuscitation and transfusion management, second-line uterotonics and uterine-sparing interventions (intra-uterine tamponade, compression sutures, vascular ligation, arterial embolization) by mode of delivery. Methods:  Secondary analysis of two population-based studies of women with sPPH in France and the Netherlands. Women were selected by a harmonized definition for sPPH: (total blood loss ≥ 1500 ml) AND (blood transfusion of ≥ 4 units packed red blood cells and/or multicomponent blood transfusion). Findings: Incidence of adverse maternal outcome after vaginal birth was 793/1002, 9.1 % in the Netherlands versus 88/214, 41.1 % in France and 259/342, 76.2% versus 160/270, 59.3% after cesarean. Hemostatic agents such as fibrinogen were administered less frequently (p < 0.001) in the Netherlands (vaginal birth: 83/1002, 8.3% versus 105/2014, 49.5% in France; cesarean: 47/342, 13.7% and 152/270, 55.6%). Second-line uterotonics were started significantly later after PPH-onset in the Netherlands than France (vaginal birth: 46 versus 25 min; cesarean: 45 versus 18 min). Uterine-sparing interventions were less frequently (p < 0.001) applied in the Netherlands after vaginal birth (394/1002,39.3 %, 134/214, 62.6%) and cesarean (133/342, 38.9 % and 155/270, 57.4%), all initiated later after onset of refractory PPH in the Netherlands. Interpretation: Incidence of adverse maternal outcome was higher among women with sPPH in the Netherlands than France regardless mode of birth. Possible explanatory mechanisms are earlier and more frequent use of second-line uterotonics and uterine-sparing interventions in France compared to the Netherlands.