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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. [ABSTRACT FROM AUTHOR]

Background: To evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy.Methods: Retrospective cohort study including all women with a history of myomectomy (operated group) or uterine myomas during pregnancy (unoperated group) who delivered in a tertiary center between January, 2011 and December, 2017. The operated group included women who had a myomectomy history with or without myomas during the ongoing pregnancy. The unoperated group included women with uterine myoma(s) seen on at least one ultrasound during pregnancy without history of myomectomy. The primary outcome was preterm birth < 37 weeks, and the secondary outcome spontaneous preterm birth < 37 weeks. To control for confounding factors, a propensity score approach was used. Two sensitivity analysis were performed, one repeating the analysis using the propensity score after excluding operated women with persistent myomas and one using a classical multivariable logistic regression model.Results: The cohort included 576 women: 283 operated women and 293 unoperated women. The rate of preterm birth was similar in the two groups: 12.6% in the unoperated group and 12.0% in the operated group (p = 0.82). No difference in preterm birth risk was shown between unoperated and operated women in the cohort matched on the propensity score: OR 0.86; 95%CI [0.47-1.59]. These results were consistent for spontaneous preterm birth (OR 1.61; 95%CI [0.61-4.23]) and for the sensitivity analyses.Conclusion: In women with a leiomyomatous uterus, a history of myomectomy is not associated with a reduced preterm birth risk. [ABSTRACT FROM AUTHOR]

Objective: To compare the neurodevelopmental outcomes of preterm twins at 5½ years by chorionicity of pregnancy. Design: Prospective nationwide population‐based EPIPAGE2 (Etude Epidémiologique sur les Petits Âges Gestationnels) cohort study. Setting: A total of 546 maternity units in France, between March and December 2011. Population: A total of 1126 twins eligible for follow‐up at 5½ years. Methods: The association of chorionicity with outcomes was analysed using multivariate regression models. Main outcome measures: Survival at 5½ years with or without neurodevelopmental disabilities (comprising cerebral palsy, visual, hearing, cognitive deficiency, behavioural difficulties or developmental coordination disorders) were described and compared by chorionicity. Results: Among the 1126 twins eligible for follow‐up at 5½ years, 926 (82.2%) could be evaluated: 228 monochorionic (MC) and 698 dichorionic (DC). Based on chronicity and gestational age of birth, we found no significant differences for severe neonatal morbidity. The rates of moderate/severe neurobehavioral disabilities were similar in infants from DC pregnancies versus infants from MC pregnancies (OR 1.22, 95% CI 0.65–2.28). By gestational age and without twin–twin transfusion syndrome (TTTS), no difference according to chorionicity was found for all neurodevelopmental outcome measures. Conclusions: The neurodevelopmental outcomes among preterm twins at 5½ years is similar, irrespective of chorionicity. Linked article: This article is commented on by R. N. Brown, pp. 1059 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17527. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to identify factors associated with hypoxic-ischemic encephalopathy (HIE) among newborns with an umbilical pH < 7.00.Study Design: Case-control study during a four-year study period in a single academic tertiary-center, including all neonates ≥35 weeks with an umbilical pH < 7.00. Cases were neonates with HIE, regardless of Sarnat classification, and controls were neonates without signs of HIE. We used univariate and multivariate analysis to compare the maternal, obstetric, and neonatal characteristics of cases and controls.Results: Among 21,211 births, 179 neonates≥35 weeks (0.84%) had an umbilical pH < 7.00. One hundred and forty-seven(82.1%) newborns had severe asphyxia without HIE, 32(17.9%) had HIE and 21(11.7%) needed therapeutic hypothermia. Neonates with HIE were significantly more likely to have 5-minute Apgar score<7(75% versus 15.7% P < 0.01), together with a lower mean umbilical arterial pH (6.84 versus 6.95, P < 0.01) and lower mean base deficits (-17.0 versus -12.7, P < 0.01). Factors significantly associated with HIE were the mother being overweight(28.1% for cases versus 14.3% for controls, adjusted OR=4.6[1.4-15.2]) or obese(25.0% versus 13.6%, aOR=15.5[1.1-12.5]), smoking(18.7% versus 5.4%, aOR=5.8[1.6-21.2]), a sentinel event as cord prolaps or placenta abruption (34.4% versus 13.6%, aOR=2.7[1.1-7.2]), and decreased fetal heart rate variability(68.7% versus 44.2%, aOR=2.8[1.1-6.9]).Conclusion: Among neonates with an umbilical cord pH < 7.00, those with HIE had a more severe metabolic acidosis. Maternal factors associated with HIE among newborns with an umbilical pH < 7.00, were being overweight or obese, and smoking, and the associated obstetric factors were a sentinel event and decreased fetal heart rate variability. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: At the same time as survival is increasing among premature babies born before 26 weeks of gestation, the rates of cesarean deliveries before 26 weeks is also rising. Our purpose was to compare the frequency of intraoperative adverse events during cesarean deliveries in two gestational age groups: 24-25 weeks and 26-27 weeks.Material and Methods: This single-center retrospective cohort study included all women with cesarean deliveries performed before 28+0 weeks from 2007 through 2015. It compared the frequency of intraoperative adverse events between two groups: those at 24-25 weeks of gestation and at 26-27 weeks. Intraoperative adverse events were a classical incision, transplacental incision, difficulty in fetal extraction (explicitly mentioned in the surgical report), postpartum hemorrhage (≥500 mL of blood loss), and injury to internal organs. A composite outcome including at least one of these events enabled us to analyze the risk factors for intraoperative adverse events with univariate and multivariable analysis. Stratified analyses by the indication for the cesarean were performed.Results: We compared 74 cesarean deliveries at 24-25 weeks of gestation and 214 at 26-27 weeks. Intraoperative adverse events occurred at higher rates in the 24-25-week group (63.5 vs. 30.8%, p < 0.001). After adjustment for confounding factors, this group remained at significantly higher risk of intraoperative adverse events [adjusted odds ratio 5.04 (2.67-9.50)], even after stratification by indication for the cesarean.Conclusion: These results should help obstetricians and women making decisions about cesarean deliveries at these extremely low gestational ages. [ABSTRACT FROM AUTHOR]

We investigated whether nonsurgical termination of pregnancy after 14 weeks of gestation increases the risk of preterm delivery in a subsequent pregnancy. We conducted a two-centre retrospective case-control study. Patients who underwent non-surgical termination of pregnancy after 14 weeks of gestation between 2012 and 2015 and who gave birth after 14 weeks of gestation to a live-born singleton infant were included. Control patients were those who gave birth after 37 weeks of gestation (the same month as a case patient) and had a second delivery of a singleton foetus after 14 weeks of gestation. The primary outcome was preterm delivery during the second pregnancy period. We included 151 cases and 302 controls and observed 13 (8.6%) preterm births during the second pregnancy in the case group versus 8 (2.6%) (odds ratio: 3.62; 95% confidence interval: 1.40–8.65, p <.001) in the control group. This result remained significant after multivariate analysis. What is already known about this topic? Many studies have evaluated the association between first-trimester surgical or non-surgical termination of pregnancy and the risk of preterm birth in the subsequent pregnancy. However, no study has evaluated the association between second- or third-trimester non-surgical termination of pregnancy due to foetal disease and the risk of preterm birth in the subsequent pregnancy. A small number of studies have included a small proportion of patients who previously underwent non-surgical termination of pregnancy after 14 weeks of gestation and later experienced first-trimester termination during their second pregnancy. These studies focussed on the impact of the interpregnancy interval or pharmacological induction of labour on the risk of preterm delivery in the subsequent pregnancy. What did the results of this study add? This is the first study to specifically evaluate the association between second- and third-trimester non-surgical terminations of pregnancy and the risk of preterm birth in the subsequent pregnancy. When compared with term birth, nonsurgical termination of pregnancy was associated with the risk of spontaneous preterm birth and hospitalisation in the neonatal intensive care unit in the subsequent pregnancy. What are the implications of these findings for clinical practice and further research? Further studies are required to confirm our results, but information delivered to patients with a late termination of pregnancy and during their pregnancy follow-up for the subsequent pregnancy could be modified to provide this information. [ABSTRACT FROM AUTHOR]

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. Antibiotic prophylaxis after PPROM at 24–31 weeks: 3rd‐generation cephalosporins associated with improved neonatal outcomes. Antibiotic prophylaxis after PPROM at 24–31 weeks: 3rd‐generation cephalosporins associated with improved neonatal outcomes. [ABSTRACT FROM AUTHOR]

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. Mothers having caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression. Mothers having caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]