Timing of antenatal corticosteroids and survival without neurologic disabilities at 5½ years in children born before 35 weeks of gestation.

BACKGROUND: The efficacy of antenatal corticosteroids for neonatal preterm complications wanes beyond 7 days after treatment. The neurodevelopmental effects of longer treatment-to-birth intervals have not been adequately evaluated. OBJECTIVE: This study aimed to assess the impact of antenatal corticosteroid timing on survival without moderate or severe neurologic disabilities at 5½ years. STUDY DESIGN: This was a secondary analysis of the EPIPAGE-2 study, a national population-based cohort (France) that recruited neonates in 2011 and followed them up at 5½ years (results first reported in 2021). Participants were children born alive between 24+0 and 34+6 weeks, with a complete corticosteroid course, delivery >48 hours after the first injection, and neither limitation of care decided before birth nor severe congenital malformation. The study included 2613 children, 2427 of whom were alive at 5½ years; 71.9% (1739/2427) had a neurologic assessment at this age; 1537 had a clinical examination (complete for 1532), and 202 were assessed with a postal questionnaire. Exposure was defined as the interval between the first injection of the last antenatal corticosteroid course and delivery in days, studied in 2 categories (days 3-7 and after day 7), in 4 categories (days 3-7, 8-14, 15-21, and after day 21), and continuously in days. The main outcome was survival at 5½ years without moderate/severe neurologic disabilities, defined as moderate/severe cerebral palsy, or unilateral or bilateral blindness or deafness, or Full-Scale Intelligence Quotient 2 standard deviations below the mean. A multivariate analysis with a generalized estimated equation logistic regression model assessed the statistical association between the main outcomes and the interval from the first corticosteroid injection of the last course to birth. Multivariate analyses were adjusted for potential confounders, defined with a directed acyclic graph: gestational age in days, number of corticosteroid courses, multiple pregnancy, and cause of prematurity in 5 categories. Because neurologic follow-up was complete in only 63.2% of cases (1532/2427), the analyses used imputed data. RESULTS: Among 2613 children, 186 died between birth and 5½ years. Overall survival was 96.6% (95% confidence interval, 95.9-97.0), and survival without moderate or severe neurologic disabilities was 86.0% (95% confidence interval, 84.7-87.0). Survival without moderate or severe neurologic disabilities was lower after day 7 (85.0%) than during the interval from day 3 to day 7 (87.0%) (adjusted odds ratio, 0.70; 95% confidence interval, 0.54-0.89). CONCLUSION: The association of a >7-day interval between antenatal corticosteroid administration and birth with a lower rate of survival without moderate or severe neurologic disabilities among children aged 5½ years emphasizes the importance of better targeting women at risk of preterm delivery to optimize the timing and thus benefits of treatment.

Tocolysis after preterm prelabor rupture of membranes and 5-year outcomes: a population-based cohort study.

BACKGROUND: The administration of tocolytics after preterm prelabor rupture of membranes remains a controversial practice. In theory, reducing uterine contractility should delay delivery and allow for optimal antenatal management, thereby reducing the risks for prematurity and adverse consequences over the life course. However, tocolysis may be associated with neonatal death or long-term adverse neurodevelopmental outcomes, mainly related to prolonged fetal exposure to intrauterine infection or inflammation. In a previous study, we showed that tocolysis administration was not associated with short-term benefits. There are currently no data available to evaluate the impact of tocolysis on neurodevelopmental outcomes in school-aged children born prematurely in this clinical setting. OBJECTIVE: This study aimed to investigate whether tocolysis administered after preterm prelabor rupture of membranes is associated with neurodevelopmental outcomes at 5.5 years of age. STUDY DESIGN: We used data from a prospective, population-based cohort study of preterm births recruited in 2011 (referred to as the EPIPAGE-2 study) and for whom the results of a comprehensive medical and neurodevelopmental assessment of the infant at age 5.5 years were available. We included pregnant individuals with preterm prelabor rupture of membranes at 24 to 32 weeks' gestation in singleton pregnancies with a live fetus at the time of rupture, birth at 24 to 34 weeks' gestation, and participation of the infant in an assessment at 5.5 years of age. Exposure was the administration of any tocolytic treatment after preterm prelabor rupture of membranes. The main outcome was survival without moderate to severe neurodevelopmental disabilities at 5.5 years of age. Secondary outcomes included survival without any neurodevelopmental disabilities, cerebral palsy, full-scale intelligence quotient, developmental coordination disorders, and behavioral difficulties. A propensity-score analysis was used to minimize the indication bias in the estimation of the treatment effect on outcomes. RESULTS: Overall, 596 of 803 pregnant individuals (73.4%) received tocolytics after preterm prelabor rupture of membranes. At the 5.5-year follow-up, 82.7% and 82.5% of the children in the tocolysis and no tocolysis groups, respectively, were alive without moderate to severe neurodevelopmental disabilities; 52.7% and 51.1%, respectively, were alive without any neurodevelopmental disabilities. After applying multiple imputations and inverse probability of treatment weighting, we found no association between the exposure to tocolytics and survival without moderate to severe neurodevelopmental disabilities (odds ratio, 0.93; 95% confidence interval, 0.55-1.60), survival without any neurodevelopmental disabilities (odds ratio, 1.02; 95% confidence interval, 0.65-1.61), or any of the other outcomes. CONCLUSION: There was no difference in the neurodevelopmental outcomes at age 5.5 years among children with and without antenatal exposure to tocolysis after preterm prelabor rupture of membranes. To date, the health benefits of tocolytics remain unproven, both in the short- and long-term.

Risk of preterm delivery after medically indicated termination of pregnancy with induced vaginal delivery: a case-control study.

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. Impact statementWhat 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.

Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study.

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.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

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 240/7 to 316/7 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.

Impact of history of myomectomy on preterm birth risk in women with a leiomyomatous uterus: a propensity score analysis.

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.

Association between gestational age and severe maternal morbidity and mortality of preterm cesarean delivery: a population-based cohort study.

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.

Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta.

The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians' understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.

Placenta percreta is associated with more frequent severe maternal morbidity than placenta accreta.

BACKGROUND: Abnormally invasive placentation is the leading cause of obstetric hysterectomy and can cause poor to disastrous maternal outcomes. Most previous studies of peripartum management and maternal morbidity have included variable proportions of severe and less severe cases. OBJECTIVE: The aim of this study was to compare maternal morbidity from placenta percreta and accreta. STUDY DESIGN: This retrospective study at a referral center in Paris includes all women with abnormally invasive placentation from 2003 through 2017. Placenta percreta and accreta were diagnosed histologically or clinically. When placenta percreta was suspected before birth, a conservative approach leaving the placenta in situ was proposed because of the intraoperative risk of cesarean delivery. When placenta accreta was suspected, parents were offered a choice of a conservative approach or an attempt to remove the placenta, to be followed in case of failure by hysterectomy. Maternal outcomes were compared between women with placenta percreta and those with placenta accreta/increta. The primary outcome measure was a composite criterion of severe acute maternal morbidity including at least 1 of the following: hysterectomy during cesarean delivery, delayed hysterectomy, transfusion of ≥10 U of packed red blood cells, septic shock, acute kidney injury, cardiovascular failure, maternal transfer to intensive care, or death. RESULTS: Of the 156 women included, 51 had placenta percreta and 105 placenta accreta. Abnormally invasive placentation was suspected antenatally nearly 4 times more frequently in the percreta than the accreta group (96.1% [49/51] vs 25.7% [27/105], P < .01). Among the 76 women with antenatally suspected abnormally invasive placentation (48.7%), the rate of antenatal decisions for conservative management was higher in the percreta than the accreta group (100% [49/49] vs 40.7% [11/27], P < .01). The composite maternal morbidity rate was significantly higher in the percreta than the accreta group (86.3% [44/51] vs 28/105 [26.7%], P < .001). A secondary analysis restricted to women with an abnormally invasive placentation diameter >6 cm showed similar results (86.0% [43/50) vs 48.7% [19/38), P < .01). The rate of hysterectomy during cesareans was significantly higher in the percreta than the accreta group (52.9% [27/51] vs 20.9% [22/105], P < .01) as was the total hysterectomy rate (43/51 [84.3%] vs 23.8% [25/105], P < .01). CONCLUSION: Severe maternal morbidity is much more frequent in women with placenta percreta than with placenta accreta, despite multidisciplinary planning, management in a referral center, and better antenatal suspicion.

Preterm premature rupture of membranes at 22-25 weeks' gestation: perinatal and 2-year outcomes within a national population-based study (EPIPAGE-2).

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.

Intraoperative adverse events associated with extremely preterm cesarean deliveries.

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.

Impact of Latency Duration on the Prognosis of Preterm Infants after Preterm Premature Rupture of Membranes at 24 to 32 Weeks' Gestation: A National Population-Based Cohort Study.

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.

Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.

BACKGROUND: Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage. OBJECTIVE: We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation. STUDY DESIGN: The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome. RESULTS: The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2-4.5), 3.3% (95% confidence interval, 2.7-3.9), 12.1% (95% confidence interval, 11.0-13.3), and 17.0% (95% confidence interval, 15.7-18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1-17.0) and 4.4 (95% confidence interval, 1.1-17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio, 3.4; 95% confidence interval, 1.1-10.2]). Premature rupture of membranes did not significantly increase the risk. CONCLUSION: Relationships between the causes of preterm birth and intraventricular hemorrhage were limited to specific and rare cases involving acute hypoxia-ischemia and/or inflammation. While the emergent nature of placental abruption would challenge any attempts to optimize management, the prenatal care offered during preterm labor could be improved.

Assessment of atropine-sufentanil-atracurium anaesthesia for endotracheal intubation: an observational study in very premature infants.

BACKGROUND: Premedication before neonatal intubation is heterogeneous and contentious. The combination of a short acting, rapid onset opioid with a muscle relaxant is considered suitable by many experts. The purpose of this study was to describe the tolerance and conditions of intubation following anaesthesia with atropine, sufentanil and atracurium in very premature infants. METHODS: Monocentric, prospective observational study in premature infants born before 32 weeks of gestational age, hospitalised in the NICU and requiring semi-urgent or elective intubation. Intubation conditions, heart rate, pulse oxymetry (SpO2), arterial blood pressure and transcutaneous PCO2 (TcPCO2) were collected in real time during 30 minutes following the first drug injection. Repeated physiological measurements were analysed using mixed linear models. RESULTS: Thirty five intubations were performed in 24 infants with a median post conceptional age of 27.6 weeks and a median weight of 850 g at the time of intubation. The first attempt was successful in 74% and was similar for junior (75%) and senior (74%) operators. The operator rated conditions as "excellent" or "good" in 94% of intubations. A persistent increase in TcPCO2 as compared to baseline was observed whereas other vital parameters showed no significant variations 5, 10, 15 and 30 minutes after the first drug injection. Eighteen (51%) desaturations (SpO2 less than or equal to 80% for more than 60 seconds) and 2 (6%) bradycardia (heart rate less than 100 bpm for more than 60 seconds) were observed. CONCLUSION: This drug combination offers satisfactory success rate for first attempt and intubation conditions for the operator without any significant change in heart rate and blood pressure for the patient. However it is associated with frequent desaturations and a possible persistent hypercapnia. SpO2 and PCO2 can be significantly modified during neonatal intubation and should be cautiously followed in this high-risk population.

Routine maneuvers in eutocic breech vaginal delivery at term: A prospective cohort study.

OBJECTIVE: To study neonatal and maternal outcomes associated with routine maneuvers in breech vaginal delivery at term. METHODS: This was a secondary analysis of the multicenter PREMODA observational prospective study in France and Belgium. We included women with vaginal breech delivery, excluding those who underwent maneuvers to resolve a dystocic delivery. Maternal data and characteristics of labor, in addition to neonatal and maternal outcomes, were recorded. We defined two groups according to mode of delivery; breech vaginal delivery with or without routine maneuvers, and we compared the variables between the groups. To assess the factors associated with adverse perinatal outcomes, a multivariate logistic regression with adjustment for confounders was performed. RESULTS: Of the 2502 women with planned vaginal deliveries, 1794 were delivered vaginally, 606 of whom were excluded from the study due to maneuvers performed for dystocia. A total of 25 other patients were excluded as a result of missing data. A total of 537 women were included in the routine maneuvers group and 626 women in the no maneuvers group. Adverse perinatal outcome was similar for the two groups (4.5% vs 5.0%, P = 0.65) and no neonatal deaths were reported. Third degree perineal tear and postpartum hemorrhage >1 L rates were comparable for the two groups. After adjustment, the factors associated with adverse perinatal outcomes were primiparity and birth weight <2500 g. CONCLUSION: Routine maneuvers were not associated with an increase in neonatal morbidity in our population.

Birth weight and head circumference discordance and outcome in preterms: results from the EPIPAGE-2 cohort.

OBJECTIVE: To determine whether the relative measurement of birth weight (BW) and head circumference (HC) in preterm infants is associated with neurological outcomes. METHODS: The EPIPAGE-2 Study included 3473 infants born before 32 weeks' gestation, classified based on their Z-score of BW and HC on the Fenton curves as concordant (≤1 SD apart) or discordant (>1 SD difference). We defined four mutually exclusive categories: discordant smaller BW (sBW) with BW-1SD and concordant small measurement (CsM) with BW and HC concordant and both ≤-1SD. Neurological outcomes at 5.5 years were evaluated with standard tests. RESULTS: 2592 (74.8%) preterm neonates were categorised as CM, 258 (7.4%) CsM, 378 (10.9%) sHC and 239 (6.9%) sBW. Compared with the CM children, those born with CsM had significantly higher risks of cognitive deficiency (adjusted OR (aOR) 1.3, 95% CI (1.0 to 2.0)), developmental coordination disorders (aOR 2.6 (1.5 to 4.4)) and need for special school services (aOR 2.3 (1.5 to 3.7)). Those born with sBW had significantly lower risk of cognitive deficiency (aOR 0.6 (0.4 to 0.9)) and the sHC group significantly higher risk of developmental coordination disorders (aOR 1.8 (1.0 to 3.2)). CONCLUSIONS: The relative discordance of these preterm infants' BW and HC was associated with their neurological outcomes. It merits further exploration as an indirect indicator of development. TRIAL REGISTRATION NUMBER: NCT03078439.

Preterm and term prelabour rupture of membranes: A review of timing and methods of labour induction.

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.

The cause of birth is associated with neonatal prognosis in late preterm singletons.

INTRODUCTION: Recent studies have shown that the cause of very preterm births may be related to neonatal morbidity and mortality. Even though these risks are lower among late preterm births, this group accounts for the vast majority of all preterm births. The objective of this study was to evaluate the relation of neonatal morbidity and mortality to the cause of late preterm birth. MATERIALS AND METHODS: This retrospective observational cohort study included all women who gave birth to liveborn singletons from 34 to 36 weeks+6 days of gestation in a French level III maternity hospital in the 5-year period 2013-2017. The causes of preterm delivery were divided into 6 mutually exclusive groups. The main outcome was a composite neonatal morbidity criterion, defined by at least one among the following criteria: neonatal respiratory distress, neurological complications, neonatal sepsis, severe necrotizing enterocolitis, and neonatal hypoglycemia. We analyzed the association between cause of preterm delivery and neonatal morbidity after adjustment for gestational age and antenatal corticosteroid therapy. The reference group was preterm labor, defined by spontaneous preterm labor with intact membranes. RESULTS: During the study period, there were a total of 27 110 births, including 1114 singleton births at 34 to 36 weeks of gestation + 6 days (4.1%). Among the 968 late preterm births included, the risk of neonatal morbidity in the group with preterm premature rupture of membranes (PPROM) was similar to that in the preterm labor (reference) group: adjusted odds ratio (aOR) 1.2 (95% CI, 0.8-1.8). All the other causes of late preterm birth were associated with a higher risk of neonatal morbidity than the reference group: aOR 2.0 [95% CI, 1.1-3.5] for hypertensive disorders without suspected fetal growth restriction (FGR) (9.1% of cases), aOR 2.4 [95% CI, 1.4-4.2] for hypertensive disorders with suspected FGR (8.9%), aOR 4.2 [95% CI, 2.2-8.0] for suspected FGR without hypertensive disorders (5.8%), and aOR 4.4 [95% CI, 2.2-8.8] for vaginal bleeding related to abnormal placental insertion (4.7%). CONCLUSION: Among infants born from 34 to 36 weeks + 6 days of gestation, PPROM and preterm labor had similar risks of neonatal morbidity, while the other causes were associated with a risk of neonatal morbidity at least twice that with preterm labor.

Carbetocin versus Oxytocin for the Prevention of Postpartum Hemorrhage in Cesarean Deliveries: A Retrospective Study of Two Consecutive Periods.

Objective The aim of the study is to investigate whether carbetocin prevents postpartum hemorrhage (PPH) more effectively than oxytocin Methods This historical retrospective single-center cohort study compares women who underwent cesarean deliveries during two periods. During period A, oxytocin was used as a 10-unit bolus immediately after delivery, with 20 units thereafter infused for 24 hours. During period B, carbetocin in a single 100-µg injection replaced this protocol. The main outcome was PPH, defined as a decline in hemoglobin of more than 2 g/dL after the cesarean. The analysis was performed on the overall population and then stratified by the timing of the cesareans (before or during labor). A logistic regression analysis was performed. Results This study included 1,796 women, 52% of whom had a cesarean before labor; 15% had a PPH. The crude PPH rate was lower in period B than in period A (13 vs. 17%, respectively, odds ratio 0.75, 95% confidence interval [CI]: 0.58-0.98). The difference was no longer significant in the multivariate analysis (adjusted odds ratio: 0.81, 95% CI 0.61-1.06). Results were similar when stratified by the timing of the cesareans (before or during labor). Conclusion Carbetocin is not superior to oxytocin in preventing PPH. However, it does provide the advantage of requiring a single injection.