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Background: The long-term follow-up of very preterm and very low birthweight cohorts contributes to valuable evidence to understand life-course outcomes in these vulnerable populations. However, attrition is a major challenge in long-term outcome studies. Examining the techniques used by existing cohorts may help to reveal practices that enhance willingness to continue participation over time., Objectives: To evaluate the effect of data collection methods and retention strategies on overall retention in European birth cohorts of individuals born very preterm and very low birthweight., Methods: A survey of European cohorts integrated in the RECAP-preterm Consortium provided data on study characteristics, retention at the most recent follow-up, data collection methods and retention strategies. Cohorts were classified according to participants' age at most recent follow-up as child (<18) or adult cohorts (≥18 years old)., Results: Data were obtained for 17 (81%) cohorts (7 adult and 10 child) in 12 countries. Considering the baseline, at the most recent follow-up, overall retention ranged from 10% to 99%. Child cohorts presented higher median retention (68% versus 38% or 52% for adult cohorts with ≤5 or >5 follow-ups) and used relatively more retention strategies. For contact and invitation, cohorts mostly resorted to invitation letters, and to face-to-face interviews for assessments. Study duration was negatively correlated with retention and positively associated with the number of follow-up evaluation. We identified 109 retention strategies, with a median of 6 per cohort; bond-building (n = 41; 38%) was the most utilised, followed by barrier-reduction (n = 36; 33%) and reminders (n = 32; 29%). Retention was not influenced by category or number of strategies., Conclusions: Regular contact with cohort participants favour retention whilst neither the number nor the categories of retention strategies used seemed to have an influence, suggesting that tailored strategies focussed on participants at higher risk of dropout might be a more effective approach., (© 2021 John Wiley & Sons Ltd.)

Background: Migrant-native disparities in perinatal health and care utilization are well-established, yet most evidence comes from countries without universal health coverage. Migrant-specific factors potentially contributing to such disparities are seldom examined. We investigated the association between migration and host-country language proficiency and inadequate utilization of prenatal care (PNC) in Portugal., Methods: We used robust Poisson regression to analyze data from 1419 migrant and 2477 native women enrolled in the Portuguese Bambino cohort study who had given birth at a Portuguese public hospital between 2017 and 2019. Migrant women's language proficiency was self-rated for understanding, speaking, reading, and writing skills. PNC utilization inadequacy was assessed using three dimensions: initiation, number of visits, and the modified Adequacy of Prenatal Care Utilization (mAPNCU) Index score., Results: Migrant women were overall more likely to initiate PNC late and have inadequate/intermediate mAPNCU scores than natives. Migrant-native disparities in the number of PNC visits were only observed among recent migrants (≤5 years in Portugal). Full, intermediate, and limited Portuguese skills were associated with increasingly higher risks of late PNC initiation (aRR 1.34 [95%CI 1.20-1.50]); (aRR 1.52 [95%CI 1.28-1.80]); (aRR 1.91 [95%CI 1.52-2.40]), inadequate number of PNC visits (aRR 1.06 [95%CI 0.93-1.22]); (aRR 1.14 [95%CI 0.97-1.34]); (aRR 1.57 [95%CI 1.19-2.07]), and inadequate/intermediate mAPNCU scores (aRR 1.18 [95%CI 1.07-1.32]); (aRR 1.30 [95%CI 1.11-1.53]); (aRR 1.69 [95%CI 1.38-2.07]) compared with native Portuguese skills, respectively., Conclusions: Migrant-native disparities in PNC utilization are present in Portugal, despite universal health coverage. Recent migrants and women with limited language competence are the most vulnerable to inadequate PNC use., (© 2022 Wiley Periodicals LLC.)

Objectives: To report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school., Methods: As part of a longitudinal, prospective, school-based surveillance study, this investigation involved repeated testing of 73 pupils, 9 teachers, 13 non-teaching staff and 26 household members of participants who tested positive, with rapid antigen tests and/or RT-PCR (Day 0-2 and Day 5-7), serologies on dried capillary blood samples (Day 0-2 and Day 30), contact tracing interviews and SARS-CoV-2 whole genome sequencing., Results: We identified 20 children (aged 4 to 6 years from 4 school classes), 2 teachers and a total of 4 household members who were infected by the Alpha variant during this outbreak. Infection attack rates were between 11.8 and 62.0% among pupils from the 4 school classes, 22.2% among teachers and 0% among non-teaching staff. Secondary attack rate among household members was 15.4%. Symptoms were reported by 63% of infected children, 100% of teachers and 50% of household members. All analysed sequences but one showed 100% identity. Serological tests detected 8 seroconversions unidentified by SARS-CoV-2 virological tests., Conclusions: This study confirmed child-to-child and child-to-adult SARS-CoV-2 transmission and introduction into households. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation., Competing Interests: The authors have declared that no competing interests exist.

Background: We examined the determinants of adolescents' Health-Related Quality of Life (HRQoL) and psychological distress (self-reported and parent-reported) during the COVID-19 pandemic, using a random sample of the population of Geneva, Switzerland., Methods: Data was drawn from participants aged 14-17 years, who participated with their families to a serosurvey conducted in November and December 2020. Adolescents' HRQoL was evaluated using the validated adolescent-reported KIDSCREEN-10 and parent-reported KINDL® scales. Psychological distress was assessed with self-reported sadness and loneliness, and using the KINDL® emotional well-being scale. Using generalized estimating equations, we examined the role of socio-demographic, family and behavioural characteristics in influencing adolescents' mental health status and wellbeing., Results: Among 240 adolescents, 11% had a low HRQoL, 35% reported sadness and 23% reported loneliness. Based on parents' perception, 12% of the adolescents had a low HRQoL and 16% a low emotional well-being. Being a girl (aOR = 3.20; 95%CI: 1.67-6.16), increased time on social media (aOR = 2.07; 95%CI: 1.08-3.97), parents' average to poor mood (aOR = 2.62; 95%CI: 1.10-6.23) and average to poor household financial situation (aOR = 2.31; IC95%: 1.01-6.10) were associated with an increased risk of sadness. Mismatches between adolescents' and their parents' perception of HRQoL were more likely for girls (aOR = 2.88; 95%CI: 1.54-5.41) and in households with lower family well-being (aOR = 0.91; 95%CI: 0.86-0.96)., Conclusions: A meaningful proportion of adolescents experienced low well-being during the second wave of COVID-19, and average well-being was lower than pre-pandemic estimates. Adolescents living in underprivileged or distressed families seemed particularly affected. Monitoring is necessary to evaluate the long-term effects of the pandemic on adolescents., Competing Interests: The authors have declare that they have no competing interests.

Objective: To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine whether any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at 2 years of corrected age., Design: Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants., Setting: France, 2011., Sample: We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24-31 weeks. Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorised as amoxicillin (n = 345), macrolide (n = 30), third-generation cephalosporin (n = 45) or any combinations covering Streptococcus agalactiae and >90% of Escherichia coli (n = 72), initiated within 24 hours after preterm premature rupture of membranes., Methods: Population-averaged robust Poisson models., Main Outcome Measures: Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment., Results: With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08-1.45] and 1.10 [95 % confidence interval 1.01-1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen., Conclusion: In preterm premature rupture of membranes at 24-31 weeks, antibiotic prophylaxis based on third-generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen., Tweetable Abstract: Antibiotic prophylaxis after PPROM at 24-31 weeks: 3rd-generation cephalosporins associated with improved neonatal outcomes., (© 2022 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS)., Study Design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores., Results: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38)., Conclusions: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To describe the rationale, organization, and procedures of the Corona Immunitas Digital Follow-Up (CI-DFU) eCohort and to characterize participants at baseline. Methods: Participants of Corona Immunitas, a population-based nationwide SARS-CoV-2 seroprevalence study in Switzerland, were invited to join the CI-DFU eCohort in 11 study centres. Weekly online questonnaires cover health status changes, prevention measures adherence, and social impacts. Monthly questionnaires cover additional prevention adherence, contact tracing apps use, vaccination and vaccine hesitancy, and socio-economic changes. Results: We report data from the 5 centres that enrolled in the CI-DFU between June and October 2020 (covering Basel City/Land, Fribourg, Neuchâtel, Ticino, Zurich). As of February 2021, 4636 participants were enrolled and 85,693 weekly and 27,817 monthly questionnaires were collected. Design-based oversampling led to overrepresentation of individuals aged 65+ years. People with higher education and income were more likely to enroll and be retained. Conclusion: Broad enrolment and robust retention of participants enables scientifically sound monitoring of pandemic impacts, prevention, and vaccination progress. The CI-DFU eCohort demonstrates proof-of-principle for large-scale, federated eCohort study designs based on jointly agreed principles and transparent governance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Speierer, Chocano-Bedoya, Anker, Schmid, Keidel, Vermes, Imboden, Levati, Franscella, Corna, Amati, Harju, Luedi, Michel, Veys-Takeuchi, Zuppinger, Nusslé, D’Acremont, Tall, Salberg, Baysson, Lorthe, Pennacchio, Frei, Kaufmann, Geigges, West, Schwab, Cullati, Chiolero, Kahlert, Stringhini, Vollrath, Probst-Hensch, Rodondi, Puhan and von Wyl.)

Introduction: The COVID-19 pandemic has affected billions of people around the world both directly through the infection itself and indirectly through its economic, social and sanitary impact. Collecting data over time is essential for the understanding of the disease spread, the incidence of COVID-19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. The objective of the study was to set up a longitudinal follow-up of adult participants of serosurveys carried out in the canton of Geneva, Switzerland, during the COVID-19 pandemic. This follow-up aims at monitoring COVID-19 related symptoms and SARS-CoV-2 seroconversion, as well as the overall impact of the pandemic on several dimensions of health and on socioeconomic factors over a period of at least 2 years., Methods and Analysis: Serosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https://www.specchio-covid19.ch/). On registration, an initial questionnaire assessed sociodemographic and lifestyle characteristics (including housing conditions, physical activity, diet, alcohol and tobacco consumption), anthropometry, general health and experience related to COVID-19 (symptoms, COVID-19 test results, quarantines, hospitalisations). Weekly, participants were invited to fill in a short questionnaire with updates on self-reported COVID-19-compatible symptoms, SARS-CoV-2 infection testing and vaccination. A more detailed questionnaire about mental health, well-being, risk perception and changes in working conditions was proposed monthly. Supplementary questionnaires were proposed at regular intervals to assess more in depth the impact of the pandemic on physical and mental health, vaccination adherence, healthcare consumption and changes in health behaviours. At baseline, serology testing allowed to assess the spread of SARS-CoV-2 infection among the general population and subgroups of workers. Additionally, seropositive participants and a sample of randomly selected participants were invited for serologic testing at regular intervals in order to monitor both the seropersistance of anti-SARS-CoV-2 antibodies and the seroprevalence of anti-SARS-CoV-2 antibodies in the population of the canton of Geneva., Ethics and Dissemination: The study was approved by the Cantonal Research Ethics Commission of Geneva, Switzerland (CCER Project ID 2020-00881). Results will be disseminated in a variety of ways, via the Specchio-COVID-19 platform, social media posts, press releases and through regular scientific dissemination methods (open-access articles, conferences)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prelabour rupture of membranes (PROM) exposes both foetuses and mothers to the risk of infection. Induction of labour has been proposed to reduce this risk, but its neonatal and maternal risks and benefits must be balanced against those of expectant management (EM). Recent randomized studies of preterm PROM show that EM until 37 weeks of gestation is associated with lower overall neonatal morbidity. In term PROM, active management is associated with a shorter birth interval but not with lower rates of neonatal infection. Similar maternal and neonatal outcomes are reported regardless of whether induction uses oxytocin, PGE2, or oral misoprostol., Competing Interests: Declaration of competing interest Authors have no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions.AimWe estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign.MethodsWe conducted a population-based cross-sectional serosurvey between 1 June and 7 July 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins using the Roche Elecsys immunoassays. We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies).ResultsAmong 3,355 individuals (54.1% women; 20.8% aged < 18 years and 13.4% aged ≥ 65 years), 2,161 (64.4%) had anti-S antibodies and 906 (27.0%) had anti-N antibodies. The total seroprevalence was 66.1% (95% credible interval (CrI): 64.1-68.0). We estimated that 29.9% (95% Crl: 28.0-31.9) of the population developed antibodies after infection; the rest having developed antibodies via vaccination. Seroprevalence estimates differed markedly across age groups, being lowest among children aged 0-5 years (20.8%; 95% Crl: 15.5-26.7) and highest among older adults aged ≥ 75 years (93.1%; 95% Crl: 89.6-96.0). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with higher educational level.ConclusionMost of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and to minimise spread among children.

Background: The pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants., Methods: 2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models., Results: 437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2-2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9-3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9-4.4)., Conclusion: Very preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor., Impact: Late-onset sepsis risk differs according to the cause of preterm birth. Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis. Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Migrant women have a higher risk of developing postpartum depressive symptoms (PPDS) than do native women. This study aimed to investigate the role of host-country language proficiency in this disparity. We analysed the data of 1475 migrant and 1415 native women who gave birth at a Portuguese public hospital between 2017 and 2019 and were participants in the baMBINO cohort study. Migrants' language proficiency was self-rated and comprised understanding, speaking, reading, and writing skills. PPDS were assessed using the Edinburgh Postnatal Depression Scale with a cut-off score of ≥10. Multivariable logistic regression models were fitted to estimate the association between language proficiency and PPDS. PPDS were experienced by 7.2% of native women and 12.4% among migrants ( p < 0.001). Increasing proportions of PPDS were observed among decreasing Portuguese proficiency levels; 11% among full, 13% among intermediate, and 18% among limited proficiency women ( p trend < 0.001). Full (aOR 1.63 (95% CI 1.21-2.19)), intermediate (aOR 1.68 (95% CI 1.16-2.42)), and limited (aOR 2.55 (95% CI 1.64-3.99)) language proficiencies were associated with increasingly higher odds of PPDS among migrant women, compared to native proficiency. Prevention measures should target migrant women at high risk of PPDS, namely those with limited language skills, and promote awareness, early detection, and help-seeking, in addition to facilitating communication in their perinatal healthcare encounters.

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., (© 2020 John Wiley & Sons Ltd.)

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., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Introduction: The objective of this study was to investigate the association between planned mode of delivery and neonatal outcomes with spontaneous very preterm birth among singletons in cephalic presentation., Material and Methods: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national, prospective, population-based cohort study of preterm infants. For this study, we included women with a singleton cephalic pregnancy and spontaneous preterm labor or preterm premature rupture of membranes at 24-31 weeks' gestation. The main exposure was the planned mode of delivery (ie planned vaginal delivery or planned cesarean delivery at the initiation of labor). The primary outcome was survival at discharge and secondary outcome survival at discharge without severe morbidity. Propensity scores were used to minimize indication bias in estimating the association., Results: The study population consisted of 1008 women: 206 (20.4%) had planned cesarean delivery and 802 (79.6%) planned vaginal delivery. In all, 723 (90.2%) finally had a vaginal delivery. Overall, 187 (92.0%) and 681 (87.0%) neonates in the planned cesarean delivery and planned vaginal delivery groups were discharged alive, and 156 (77.6%) and 590 (76.3%) were discharged alive without severe morbidity. After matching on propensity score, planned cesarean delivery was not associated with survival (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 0.48-2.28) or survival without severe morbidity (aOR 0.64, 95% CI 0.36-1.16)., Conclusions: Planned cesarean delivery for cephalic presentation at 24-31 weeks' gestation after preterm labor or preterm premature rupture of membranes does not improve neonatal outcomes., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Objective: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth., Study Design: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 24 0/7 to 31 6/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period., Results: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2.", Conclusions: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

After preterm premature rupture of membranes (PPROM), antibiotics and antenatal steroids are effective evidence-based interventions, but the use of tocolysis is controversial. We investigated whether a unit policy of tocolysis use after PPROM is associated with prolonged gestation and improved outcomes for very preterm infants in units that systematically use these other evidence-based treatments. From the prospective, observational, population-based EPICE cohort study (all very preterm births in 19 regions from 11 European countries, 2011-2012), we included 607 women with a singleton pregnancy and PPROM at 24-29 weeks' gestation, of whom 101, 195 and 311 were respectively managed in 17, 32 and 45 units with no-use, restricted and liberal tocolysis policies for PPROM. The association between unit policies and outcomes (early-onset sepsis, survival at discharge, survival at discharge without severe morbidity and survival at two years without gross motor impairment) was investigated using three-level random-intercept logistic regression models, showing no differences in neonatal or two-year outcomes by unit policy. Moreover, there was no association between unit policies and prolongation of gestation in a multilevel survival analysis. Compared to a unit policy of no-use of tocolysis after PPROM, a liberal or restricted policy is not associated with improved obstetric, neonatal or two-year outcomes.

In France, the frequency of premature rupture of the membranes (PROM) is 2%-3% before 37 weeks' gestation (level of evidence [LE] 2) and less than 1% before 34 weeks (LE2). Preterm delivery and intrauterine infection are the major complications of preterm PROM (PPROM) (LE2). Prolongation of the latency period is beneficial (LE2). Compared with other causes of preterm delivery, PPROM is associated with a clear excess risk of neonatal morbidity and mortality only in cases of intrauterine infection, which is linked to higher rates of in utero fetal death (LE3), early neonatal infection (LE2), and necrotizing enterocolitis (LE2). The diagnosis of PPROM is principally clinical (professional consensus). Tests to detect IGFBP-1 or PAMG-1 are recommended in cases of uncertainty (professional consensus). Hospitalization is recommended for women diagnosed with PPROM (professional consensus). Adequate evidence does not exist to support recommendations for or against initial tocolysis (Grade C). If tocolysis is prescribed, it should not continue longer than 48 h (Grade C). The administration of antenatal corticosteroids is recommended for fetuses with a gestational age less than 34 weeks (Grade A) and magnesium sulfate if delivery is imminent before 32 weeks (Grade A). The prescription of antibiotic prophylaxis at admission is recommended (Grade A) to reduce neonatal and maternal morbidity (LE1). Amoxicillin, third-generation cephalosporins, and erythromycin (professional consensus) can each be used individually or eythromycin and amoxicillin can be combined (professional consensus) for a period of 7 days (Grade C). Nonetheless, it is acceptable to stop antibiotic prophylaxis when the initial vaginal sample is negative (professional consensus). The following are not recommended for antibiotic prophylaxis: amoxicillin-clavulanic acid (professional consensus), aminoglycosides, glycopeptides, first- or second-generation cephalosporins, clindamycin, or metronidazole (professional consensus). Women who are clinically stable after at least 48 h of hospital monitoring can be managed at home (professional consensus). Monitoring should include checking for clinical and laboratory factors suggestive of intrauterine infection (professional consensus). No guidelines can be issued about the frequency of this monitoring (professional consensus). Adequate evidence does not exist to support a recommendation for or against the routine initiation of antibiotic therapy when the monitoring of an asymptomatic woman produces a single isolated positive result (e.g., elevated CRP, or hyperleukocytosis, or a positive vaginal sample) (professional consensus). In cases of intrauterine infection, the immediate intravenous administration (Grade B) of antibiotic therapy combining a beta-lactam with an aminoglycoside (Grade B) and early delivery of the child are both recommended (Grade A). Cesarean delivery of women with intrauterine infections is reserved for the standard obstetric indications (professional consensus). Expectant management is recommended for uncomplicated PROM before 37 weeks (Grade A), even when a sample is positive for Streptococcus B, as long as antibiotic prophylaxis begins at admission (professional consensus). Oxytocin and prostaglandins are two possible options for the induction of labor in women with PPROM (professional consensus)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cesarean delivery rates at extreme prematurity have regularly increased over the past years, and few previous studies have investigated severe maternal morbidity associated with extreme preterm cesarean delivery., Objective: The aim of this study was to evaluate whether gestational age <26 weeks of gestation (weeks) was associated with severe maternal morbidity and mortality (SMMM) of preterm cesarean deliveries in comparison with cesarean deliveries between 26 and 34 weeks., Materials and Methods: The Etude Epidémiologique sur les petits âges gestationnels (EPIPAGE) 2 is a national prospective population-based cohort study of preterm births in 2011. We included mothers with cesarean deliveries between 22 and 34 weeks, excluding those who had a cesarean delivery for the second twin only and those with pregnancy terminations. SMMM was analyzed as a composite endpoint defined as the occurrence of at least 1 of the following complications: severe postpartum hemorrhage defined by the use of a blood transfusion, intensive care unit admission, or death. To assess the association of gestational age <26 weeks and SMMM, we used multivariate logistic regression and a propensity score-matching approach., Results: Among 2525 women having preterm cesarean deliveries, 116 before 26 weeks and 2409 between 26 and 34 weeks, 407 (14.4%) presented with SMMM. The SMMM occurred in 31 mothers (26.7%) who were at gestational age <26 weeks vs 376 (14.2%) between 26 and 34 weeks (P < .001). Cluster multivariate logistic regression showed significant association of gestational age <26 weeks and SMMM (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.42-4.40) and propensity score-matching analysis was consistent with these results (aOR, 2.27; 95% CI, 1.31-3.93)., Conclusion: Obstetricians should know about the higher SMMM associated with cesarean deliveries before 26 weeks, integrate this knowledge into decisions regarding cesarean delivery, and be prepared to manage the associated complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To assess neonatal and 2-year outcomes for preterm twins born after planned vaginal delivery compared with planned cesarean delivery., Methods: Women with preterm cephalic first twins delivered after preterm labor or preterm prelabor rupture of membranes from 24 0/7 to 34 6/7 weeks of gestation, with both fetuses alive at the beginning of labor, were identified from the national prospective population-based Etude Epidémiologique sur les Petits Ages Gestationnels 2 cohort study. Planned vaginal delivery was defined as vaginal delivery or cesarean delivery performed during labor. Planned cesarean delivery was considered if performed during labor for the indication of preterm twins or before labor whatever the indication. A propensity score analysis was used to compare planned vaginal delivery and planned cesarean delivery. Outcomes analyzed separately for the first and second twins were survival at discharge, survival at discharge without severe morbidity, and survival at 2 years of corrected age without neurosensory impairment., Results: Among the 932 women with a twin pregnancy, 549 were excluded mainly as a result of the first twin in noncephalic presentation, cause of delivery other than preterm labor or preterm prelabor rupture of membranes, at least one twin died before labor, and gestational age at delivery less than 24 weeks of gestation. The planned vaginal delivery group included 276 women and the planned cesarean delivery group 107. For first and second twins, survival at discharge (97.7% vs 98.3% and 95.6% vs 97.1%, respectively), survival at discharge without severe morbidity (91.6% vs 88.8% and 90.3% vs 84.5%, respectively), and survival at 2 years of corrected age without neurosensory impairment (96.0% vs 95.4% and 92.9% vs 90.8%, respectively) did not differ significantly between the planned vaginal delivery and planned cesarean delivery groups. Propensity score analysis showed that planned cesarean delivery was not associated with improved outcomes with the caveat that the infrequency of death and disability limited the statistical power of the study to detect potentially clinically meaningful differences between planned modes of delivery., Conclusion: Planned cesarean delivery for women in preterm labor or with preterm prelabor rupture of membranes was not associated with improved neonatal outcomes or 2-year outcomes.

Objectives: To synthetize the available evidence regarding the incidence and risk factors of preterm premature rupture of membranes (PPROM). To describe the evolution of pregnancy, neonatal outcomes and the prognosis of infants born in a context of PPROM, according to the existence of an associated intrauterine infection and to the latency duration., Method: Consultation of the Medline database, from 1980 to February 2018., Results: PPROM before 37 and before 34 weeks' gestation occur in 2-3% and <1% of pregnancies, respectively (LE2). Although many risk factors are identified, few are modifiable, and the vast majority of patients have no risk factors (LE2). Consequently, individual prediction of the risk of PPROM and primary prevention measures have not been shown to be effective and are not recommended in clinical practice (Grade B). Most women give birth within the week following PPROM (LE2). The main complications of PPROM are prematurity, intrauterine infection and obstetric and maternal complications (LE2). Latency duration and the frequency of complications decrease with increasing gestational age at PPROM (LE2). Neonatal prognosis is largely conditioned by gestational age at birth, with no apparent over-risk of poor outcomes linked to PPROM compared to other causes of preterm birth (LE2). In contrast, intrauterine infection is associated with an increased risk of in utero fetal death (LE3), necrotizing enterocolitis (LE1) and early-onset sepsis (LE2). The association of intrauterine infection with neurological morbidity remains controversial. Prolongation of latency, from gestational age at PPROM, is beneficial for the child (LE2)., Conclusion: PPROM is a major cause of prematurity and short- and long-term mortality and morbidity. Antenatal care is an important issue for obstetric and pediatric teams, aiming to reduce complications and adverse consequences for both mother and child., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To determine management of women with preterm premature rupture of membranes (PPROM)., Methods: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines., Results: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus)., Conclusion: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A)., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Importance: No trials to date have demonstrated the benefits of tocolysis on death and/or neonatal morbidity in preterm infants; tocolytics may affect the fetal blood-brain barrier., Objectives: To assess the risks associated with tocolysis in women delivering prematurely as measured by death and/or intraventricular hemorrhage (IVH) in preterm infants and to compare the association of calcium channel blockers (CCBs) nifedipine and nicardipine hydrochloride vs atosiban used for tocolysis with death and/or IVH., Design, Settings, and Participants: The French 2011 EPIPAGE-2 (Enquête Épidémiologique sur les Petits Âges Gestationnels) cohort was limited to mothers admitted for preterm labor without fever, who delivered from 24 to 31 weeks of gestation from April 1 through December 31, 2011. Groups of preterm infants with vs without tocolytic exposure and groups with atosiban vs CCB exposure were compared. Data analysis was performed from June 7, 2014, through September 3, 2017., Exposures: Tocolytics., Main Outcomes and Measures: The primary outcome was a composite of death and/or IVH in preterm infants. Secondary outcomes included death, IVH, and a composite of death and/or grades III to IV IVH., Results: A total of 1127 mothers (mean [SD] age, 25.5 [6.0] years) experienced preterm labor and gave birth to 1343 preterm infants with a male to female ratio of 1.23 and mean (SD) gestational age of 27 (2.5) weeks. Of these, 789 mothers (70.0%) received tocolytics; 314 (39.8%) received only atosiban, and 118 (15.0%) received only a CCB. In the first analysis, the primary outcome (death and/or IVH) was not significantly different in preterm infants with vs without tocolytic exposure (183 of 363 [50.4%] vs 207 of 363 [57.0%]; relative risk [RR], 0.88; 95% CI, 0.77-1.01; P = .07). The secondary outcome (death and/or grades III-IV IVH) was significantly lower in preterm infants with vs without tocolytic exposure (92 of 363 [25.3%] vs 118 of 363 [32.5%]; RR, 0.78; 95% CI, 0.62-0.98; P = .03). Other outcomes did not differ significantly. In the secondary analysis, death and/or IVH was not significantly different in preterm infants with atosiban vs CCB exposure (96 of 214 [44.9%] vs 62 of 121 [51.2%]; RR, 0.88; 95% CI, 0.70-1.10; P = .26), nor was IVH (77 of 197 [39.1%] vs 48 of 106 [45.3%]; RR, 0.86; 95% CI, 0.66-1.13; P = .29)., Conclusions and Relevance: In this population-based study, findings suggest that tocolytics were associated with a reduction of death and severe IVH. Other studies are necessary to compare perinatal outcomes after use of atosiban vs CCBs.

Background: Most clinical guidelines state that with early preterm premature rupture of membranes, obstetric and pediatric teams must share a realistic and individualized appraisal of neonatal outcomes with parents and consider their wishes for all decisions. However, we currently lack reliable and relevant data, according to gestational age at rupture of membranes, to adequately counsel parents during pregnancy and to reflect on our policies of care at these extreme gestational ages., Objective: We sought to describe both perinatal and 2-year outcomes of preterm infants born after preterm premature rupture of membranes at 22-25 weeks' gestation., Study Design: EPIPAGE-2 is a French national prospective population-based cohort of preterm infants born in 546 maternity units in 2011. Inclusion criteria in this analysis were women diagnosed with preterm premature rupture of membranes at 22-25 weeks' gestation and singleton or twin gestations with fetus(es) alive at rupture of membranes. Latency duration, antenatal management, and outcomes (survival at discharge, survival at discharge without severe morbidity, and survival at 2 years' corrected age without cerebral palsy) were described and compared by gestational age at preterm premature rupture of membranes., Results: Among the 1435 women with a diagnosis of preterm premature rupture of membranes, 379 were at 22-25 weeks' gestation, with 427 fetuses (331 singletons and 96 twins). Median gestational age at preterm premature rupture of membranes and at birth were 24 (interquartile range 23-25) and 25 (24-27) weeks, respectively. For each gestational age at preterm premature rupture of membranes, nearly half of the fetuses were born within the week after the rupture of membranes. Among the 427 fetuses, 51.7% were survivors at discharge (14.1%, 39.5%, 66.8%, and 75.8% with preterm premature rupture of membranes at 22, 23, 24, and 25 weeks, respectively), 38.8% were survivors at discharge without severe morbidity, and 46.4% were survivors at 2 years without cerebral palsy, with wide variations by gestational age at preterm premature rupture of membranes. Survival at 2 years without cerebral palsy was low with preterm premature rupture of membranes at 22 and 23 weeks but reached approximately 60% and 70% with preterm premature rupture of membranes at 24 and 25 weeks., Conclusion: Preterm premature rupture of membranes at 22-25 weeks is associated with high incidence of mortality and morbidity, with wide variations by gestational age at preterm premature rupture of membranes. However, a nonnegligible proportion of children survive without severe morbidity both at discharge and at 2 years' corrected age., (Copyright © 2018 Elsevier Inc. All rights reserved.)

It is inherent to human logic that both doctors and patients want to suppress uterine contractions when a woman presents in threatened preterm labor. Tocolysis is widely applied in women with threatened preterm labor with a variety of drugs. According to literature, tocolysis is indicated to enable transfer to a tertiary center as well as to ensure the administration of corticosteroids for fetal maturation. There is international discrepancy in the content and the implementation of guidelines on preterm labor. Tocolysis is often maintained or repeated. Nevertheless, the benefit of prolonging pregnancy has not yet been proven, and it is not impossible that prolongation of the pregnancy in a potential hostile environment could harm the fetus. Here we reflect on the use of tocolysis, focusing on maintenance and repeated tocolysis, and compare international guidelines and practices to available evidence. Finally, we propose strategies to improve the evaluation and use of tocolytics, with potential implications for future research., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Survival rates of infants born before 25 weeks of gestation are low in France and have not improved over the past decade. Active perinatal care increases these infants' likelihood of survival., Objective: Our aim was to identify factors associated with active antenatal care, which is the first step of proactive perinatal care in extremely preterm births., Methods: The population included 1020 singleton births between 22 0/6 and 26 0/6 weeks of gestation enrolled in the Etude Epidémiologique sur les Petits Ages Gestationnels 2 study, a French national population-based cohort of very preterm infants born in 2011. The main outcome was 'active antenatal care' defined as the administration of either corticosteroids or magnesium sulfate or delivery by caesarean section for fetal rescue. A multivariable analysis was performed using a two-level multilevel model taking into account the maternity unit of delivery to estimate the adjusted ORs (aORs) of receiving active antenatal care associated with maternal, obstetric and place of birth characteristics., Results: Among the population of extremely preterm births, 42% received active antenatal care. After standardisation for gestational age, regional rates of active antenatal care varied between 22% (95% CI 5% to 38%) and 61% (95% CI 44% to 78%). Despite adjustment for individual and organisational characteristics, active antenatal care varied significantly between maternity units (p=0.03). Rates of active antenatal care increased with gestational age with an aOR of 6.46 (95% CI 3.40 to 12.27) and 10.09 (95% CI 5.26 to 19.36) for infants born at 25 and 26 weeks' gestation compared with those born at 24 weeks. No other individual characteristic was associated with active antenatal care., Conclusion: Even after standardisation for gestational age, active antenatal care in France for extremely preterm births varies widely with place of birth. The dependence of life and death decisions on place of birth raises serious ethical questions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate the association between histologic chorioamnionitis (HCA) and bronchopulmonary dysplasia (BPD) in very preterm infants, both in a general population and for those born after spontaneous preterm labor and after preterm premature rupture of membranes (pPROM)., Study Design: This study included 2513 live born singletons delivered at 24-31 weeks of gestation from a national prospective population-based cohort of preterm births; 1731 placenta reports were available. HCA was defined as neutrophil infiltrates in the amnion, chorion of the membranes, or chorionic plate, associated or not with funisitis. The main outcome measure was moderate or severe BPD. Analyses involved logistic regressions and multiple imputation for missing data., Results: The incidence of HCA was 28.4% overall: 38% in cases of preterm labor, 64% in cases of pPROM, and less than 5% in cases of vascular disorders. Overall, the risk of BPD after adjustment for gestational age, sex, and antenatal steroids was reduced for infants with HCA (HCA alone: aOR 0.6 [95% CI 0.4-0.9]; associated with funisitis: aOR 0.5 [95% CI 0.3-0.8]). This finding was explained by the high rate of BPD and low rate of chorioamnionitis among children with fetal growth restriction. HCA was not associated with BPD in the preterm labor (13.4% vs 8.5%; aOR 0.9; 95% CI 0.5-1.8) or in the pPROM group (12.9% vs 12.1%; aOR 0.6; 95% CI 0.3-1.3)., Conclusion: In homogeneous groups of infants born after preterm labor or pPROM, HCA is not associated with BPD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: There are conflicting results regarding tocolysis in cases of preterm premature rupture of membranes. Delaying delivery may reduce neonatal morbidity because of prematurity and allow for prenatal corticosteroids and, if necessary, in utero transfer. However, that may increase the risks of maternofetal infection and its adverse consequences., Objective: The objective of the study was to investigate whether tocolytic therapy in cases of preterm premature rupture of membranes is associated with improved neonatal or obstetric outcomes., Study Design: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national prospective, population-based cohort study of preterm births that occurred in 546 maternity units in 2011. Inclusion criteria in this analysis were women with preterm premature rupture of membranes at 24-32 weeks' gestation and singleton gestations. Outcomes were survival to discharge without severe morbidity, latency prolonged by ≥48 hours and histological chorioamnionitis. Uterine contractions at admission, individual and obstetric characteristics, and neonatal outcomes were compared by tocolytic treatment or not. Propensity scores and inverse probability of treatment weighting for each woman were used to minimize indication bias in estimating the association of tocolytic therapy with outcomes., Results: The study population consisted of 803 women; 596 (73.4%) received tocolysis. Women with and without tocolysis did not differ in neonatal survival without severe morbidity (86.7% vs 83.9%, P = .39), latency prolonged by ≥48 hours (75.1% vs 77.4%, P = .59), or histological chorioamnionitis (50.0% vs 47.6%, P = .73). After applying propensity scores and assigning inverse probability of treatment weighting, tocolysis was not associated with improved survival without severe morbidity as compared with no tocolysis (odds ratio, 1.01 [95% confidence interval, 0.94-1.09], latency prolonged by ≥48 hours (1.03 [95% confidence interval, 0.95-1.11]), or histological chorioamnionitis (1.03 [95% confidence interval, 0.92-1.17]). There was no association between the initial tocolytic drug used (oxytocin receptor antagonists or calcium-channel blockers vs no tocolysis) and the 3 outcomes. Sensitivity analyses of women with preterm premature rupture of membranes at 26-31 weeks' gestation, women who delivered at least 12 hours after rupture of membranes, women with direct admission after the rupture of membranes and the presence or absence of contractions gave similar results., Conclusion: Tocolysis in cases of preterm premature rupture of membranes is not associated with improved obstetric or neonatal outcomes; its clinical benefit remains unproven., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To describe the incidence of breech presentation at 22-34 weeks' gestation, estimate the incidence of cesarean section delivery by cause of prematurity, and assess the factors associated with caesarean delivery in preterm breech births with preterm labor or preterm premature rupture of membranes., Study Design: EPIPAGE 2 is a French national prospective population-based cohort study of preterm births that occurred in 546 maternity units in 2011. We estimated the overall incidence of breech presentation and the incidence of cesarean delivery by cause of prematurity. Among the 579 singletons with breech presentation born at 22-34 weeks in a context of spontaneous preterm labor or membrane rupture, multivariable logistic regression was used to assess the association between individual and institutional characteristics and caesarean delivery., Results: Among the 3660 singletons born at 22-34 weeks' gestation in the EPIPAGE 2 study, 20.1% (n=911) were breech presentation. Among these births, the rate of cesarean section was 99.6% with vascular pathologies, intrauterine growth retardation or placental abruption as compared with 60.1% with spontaneous preterm labor or membrane rupture. The main indication for caesarean delivery was gestational age associated with breech presentation (61.0%). Delivery mode varied by region of birth. Other characteristics associated with caesarean delivery were hospital status (public teaching, public non-teaching or private), clinical chorioamniotitis, hospital admission after labor onset, and gestational age., Conclusion: Breech presentation is common in preterm infants and is associated with widespread use of cesarean delivery with significant regional disparities that could reflect the lack of consensus and recommendations on the preferential mode of delivery. Other factors associated with caesarean delivery are the status of the maternity unit, clinical chorioamniotitis, admission after labor onset and gestational age., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the impact of latency duration on survival, survival without severe morbidity, and early-onset sepsis in infants born after preterm premature rupture of membranes (PPROM) at 24-32 weeks' gestation., Study Design: This study was based on the prospective national population-based Etude Épidémiologique sur les Petits Ȃges Gestationnels 2 cohort of preterm births and included 702 singletons delivered in France after PPROM at 24-32 weeks' gestation. Latency duration was defined as the time from spontaneous rupture of membranes to delivery, divided into 4 periods (12 hours to 2 days [reference], 3-7 days, 8-14 days, and >14 days). Multivariable logistic regression was used to assess the relationship between latency duration and survival, survival without severe morbidity at discharge, or early-onset sepsis., Results: Latency duration ranged from 12 hours to 2 days (18%), 3-7 days (38%), 8-14 days (24%), and >14 days (20%). Rates of survival, survival without severe morbidity, and early-onset sepsis were 93.5% (95% CI 91.8-94.8), 85.4% (82.4-87.9), and 3.4% (2.0-5.7), respectively. A crude association found between prolonged latency duration and improved survival disappeared on adjusting for gestational age at birth (aOR 1.0 [reference], 1.6 [95% CI 0.8-3.2], 1.2 [0.5-2.9], and 1.0 [0.3-3.2] for latency durations from 12 hours to 2 days, 3-7 days, 8-14 days, and >14 days, respectively). Prolonged latency duration was not associated with survival without severe morbidity or early-onset sepsis., Conclusion: For a given gestational age at birth, prolonged latency duration after PPROM does not worsen neonatal prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To define the management of preterm labor (MAP)., Method: The literature search was conducted using computer databases Medline and the Cochrane Library for a period from 1969 to March 2016., Results: Leukocytosis screening may be useful in case of hospitalization for Preterm labor (PTL). Its use is not routine (professional consensus). Screening for urinary tract infection by urine culture should be systematic and antibiotic treatment should be performed in cases of bacterial colonization or urinary tract infection for a period of 7 days (grade A). The vaginal swab is useful to detect a strep B and was prescribed antibiotics during labor if positive (grade A). Routine antibiotic therapy is not recommended in case of PTL (grade A). Prolonged hospitalization does not reduce the risk of preterm delivery (NP3) and is not recommended (grade B). Bed rest does not reduce the risk of PTL (NP3), increases the risk of thromboembolism (NP3), and is not recommended (grade C). After hospitalization for PTL, a regular visit by a caregiver at home may be helpful when patients belong to a precarious environment or are psychologically vulnerable (Professional consensus). The benefit of monitoring home uterine activity repeated in the aftermath of hospitalization for PTL is not shown (NP3). It is not recommended to follow-up uterine activity systematically after hospitalization for PTL (grade C)., Conclusion: The management of PTL should be individualized, include searching and treatment of infection and avoid prolonged hospitalization or bed rest., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the association of the cause of preterm birth on in-hospital mortality of preterm neonates born from 24 to 34 weeks of gestation., Methods: L'Etude épidémiologique sur les petits âges gestationnels (EPIPAGE)-2 is a prospective, nationwide, population-based cohort of very preterm births. After dividing causes of preterm birth into six mutually exclusive groups, we analyzed the association of each cause with in-hospital deaths of preterm neonates born alive with adjustment for organizational, maternal, and obstetric factors., Results: The analysis included 3,138 singleton live births from 24 to 34 weeks of gestation with a newborn in-hospital mortality rate of 5.0% (95% confidence interval 4.5-5.7). Preterm labor was the most frequent cause of preterm birth (n=1,293 [43.5%]) followed by preterm premature rupture of membranes (n=765 [23.9%]), hypertensive disorders without suspected fetal growth restriction (n=397 [12.7%]), hypertensive disorders with suspected fetal growth restriction (n=408 [10.9%]), placental abruption after an uncomplicated pregnancy (n=92 [3.0%]), and suspected fetal growth restriction without hypertensive disorders (n=183 [5.9%]). Neonates born because of suspected fetal growth restriction with or without hypertensive disorders (adjusted odds ratio [OR] 3.0 [1.9-4.7] and adjusted OR 2.3 [1.1-4.6], respectively) had higher adjusted risks of in-hospital death than those born after preterm labor. Risks of in-hospital mortality for preterm births caused by preterm premature rupture of membranes (adjusted OR 1.3 [0.9-1.9]), hypertensive disorders without fetal growth restriction (adjusted OR 0.7 [0.4-1.4]), or placental abruption (adjusted OR 1.6 [0.7-3.7]) were similar to those born after preterm labor., Conclusion: Among neonates born alive before 34 weeks of gestation, only those born because of suspected fetal growth restriction have a higher mortality risk than those born after preterm labor.

Objective: To compare neonatal morbidity and mortality rates in preterm singleton breech deliveries from 26(0/7) to 29(6/7) weeks of gestation in centers with a policy of either planned vaginal delivery (PVD) or planned cesarean delivery (PCD)., Study Design: Women with preterm singleton breech deliveries occurring after preterm labor or preterm premature rupture of membranes (pPROM) were identified from the databases of five perinatal centers and classified as PVD or PCD according to the center's management policy. The independent association between planned mode of delivery and the risk of neonatal hospital death or morbidity was tested and quantified with ORs through two-level multivariable logistic regression modeling., Results: Of 142 782 deliveries during the study period, 626 (0.4%) were singletons in breech presentation from 26(0/7) to 29(6/7) weeks of gestation: after exclusions, 130 were in the PVD group and 173 in the PCD group. Severe newborn morbidity was similar in the two groups. Newborn mortality was 12% in the PCD group and 16% in the PVD group. Three neonates (1.7%, 95% CI: 0.34-5.0) died from head entrapment after vaginal delivery in the PVD group. Nonetheless, the policy of PVD was not associated with increased risks of neonatal death (aOR: 1.01, 95% CI: 0.33-2.92) or severe morbidity., Conclusion: Risks of mortality and severe morbidity in preterm breech were not increased by a policy of vaginal delivery. Head entrapment leading to death is however possible in cases of vaginal delivery but its rarity should be balanced with the maternal consequences of early preterm cesarean delivery., (Copyright © 2015. Published by Elsevier Ireland Ltd.)