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Introduction: Pregnant women with a fibrinogen level <2 g/L represent a high‐risk group that is associated with severe postpartum hemorrhage and other complications. Women who would qualify for fibrinogen therapy are not yet identified. Material and methods: A population‐based cross‐sectional study was conducted using the UK Obstetric Surveillance System between November 2017 and October 2018 in any UK hospital with a consultant‐led maternity unit. Any woman pregnant or immediately postpartum with a fibrinogen <2 g/L was included. Our aims were to determine the incidence of fibrinogen <2 g/L in pregnancy, and to describe its causes, management and outcomes. Results: Over the study period 124 women with fibrinogen <2 g/L were identified (1.7 per 10 000 maternities; 95% confidence interval 1.4–2.0 per 10 000 maternities). Less than 5% of cases of low fibrinogen were due to preexisting inherited dysfibrinogenemia or hypofibrinogenemia. Sixty percent of cases were due to postpartum hemorrhage caused by placental abruption, atony, or trauma. Amniotic fluid embolism and placental causes other than abruption (previa, accreta, retention) were associated with the highest estimated blood loss (median 4400 mL) and lowest levels of fibrinogen. Mortality was high with two maternal deaths due to massive postpartum hemorrhage, 27 stillbirths, and two neonatal deaths. Conclusions: Fibrinogen <2 g/L often, but not exclusively, affected women with postpartum hemorrhage due to placental abruption, atony, or trauma. Other more rare and catastrophic obstetrical events such as amniotic fluid embolism and placenta accreta also led to low levels of fibrinogen. Maternal and perinatal mortality was extremely high in our cohort. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a clinical prediction model for outcomes at 5 years of age for children born extremely preterm and receiving active perinatal management. Design: The EPIPAGE‐2 national prospective cohort. Setting: France, 2011. Population: Live‐born neonates between 24+0 and 26+6 weeks of gestation who received active perinatal management (i.e. birth in a tertiary‐level hospital, with antenatal steroids and resuscitation at birth). Methods: A prediction model using logistic modelling, including gestational age, small‐for gestational‐age (SGA) status and sex, was developed. Model performance was assessed through calibration and discrimination, with bootstrap internal validation. Main outcome measures: Survival without moderate or severe neurodevelopmental disability (NDD) at 5 years. Results: Among the 557 neonates included, 401 (72%) survived to 5 years, of which 59% survived without NDD (95% CI 54% to 63%). Predicted rates of survival without NDD ranged from 45% (95% CI 33% to 57%), to 56% (95% CI 49% to 64%) to 64% (95% CI 57% to 70%) for neonates born at 24, 25 and 26 weeks of gestation, respectively. Predicted rates of survival without NDD were 47% (95% CI 18% to 76%) and 62% (95% CI 49% to 76%) for SGA and non‐SGA children, respectively. The model showed good calibration (calibration slope 0.85, 95% CI 0.54 to 1.16; calibration‐in‐the‐large −0.0123, 95% CI −0.25 to 0.23) and modest discrimination (C‐index 0.59, 95% CI 0.53 to 0.65). Conclusions: A simple prediction model using three factors easily known antenatally may help doctors and families in their decision‐making for extremely preterm neonates receiving active perinatal management. [ABSTRACT FROM AUTHOR]

Aim: To describe the circumstances, causes and timing of death in extremely preterm infants. Methods: We included from the EPIPAGE‐2 study infants born at 24–26 weeks in 2011 admitted to neonatal intensive care units (NICU). Vital status and circumstances of death were used to define three groups of infants: alive at discharge, death with or without withholding or withdrawing life‐sustaining treatment (WWLST). The main cause of death was classified as respiratory disease, necrotizing enterocolitis, infection, central nervous system (CNS) injury, other or unknown. Results: Among 768 infants admitted to NICU, 224 died among which 89 died without WWLST and 135 with WWLST. The main causes of death were respiratory disease (38%), CNS injury (30%) and infection (12%). Among the infants who died with WWLST, CNS injury was the main cause of death (47%), whereas respiratory disease (56%) and infection (20%) were the main causes in case of death without WWLST. Half (51%) of all deaths occurred within the first 7 days of life, and 35% occurred within 8 and 28 days. Conclusion: The death of extremely preterm infants in NICU is a complex phenomenon in which the circumstances and causes of death are intertwined. [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: 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]

Aim: To estimate the incidence of diabetic ketoacidosis (DKA) among pregnant women, describe its clinical features, management and outcomes and identify the risk factors for the condition. Methods: A national population‐based case–control study was conducted in the UK using the UK Obstetric Surveillance System between April 2019 and September 2020 including all pregnant women with DKA irrespective of the level of blood glucose. The incidence rate of DKA in pregnancy was estimated. A case–control analysis limited to women with type 1 diabetes was performed comparing characteristics of women with DKA (cases) to those of women whose pregnancies were not complicated by DKA (controls). Results: In all, 82 women were identified with DKA in pregnancy; 6.3 per 100,000 maternities (95% CI: 5.0–7.9). No maternal deaths occurred, but perinatal mortality was 12/73 (16%) with 11 stillbirths and one neonatal death. DKA episodes mostly occurred in women with type 1 diabetes (85%) and in the 3rd trimester of pregnancy (71%). Episodes were mainly precipitated by infection (21%), vomiting (21%), steroid therapy (13%) and medication errors (10%). Fifteen percent of women had more than one episode of DKA during their pregnancy. Risk factors associated with DKA among women with type 1 diabetes identified through the case–control analysis were the woman and/or partner not being in a paid employment and having at least one microvascular complication of diabetes before pregnancy. Conclusion: DKA in pregnancy was associated with high perinatal mortality and was linked with factors related to socio‐economic deprivation, mental health problems and long‐term difficulties with glycaemic control. [ABSTRACT FROM AUTHOR]

Background: Regionalisation programmes aim to ensure that very preterm infants are born in level III units (inborn) through antenatal referral or transfer. Despite widespread knowledge about better survival without disability for inborn babies, 10%‐30% of women deliver outside these units (outborn). Objective: To investigate risk factors associated with outborn deliveries and to estimate the proportion that were probably or possibly avoidable. Methods: We used a national French population‐based cohort including 2205 women who delivered between 24 and 30+6 weeks in 2011. We examined risk factors for outborn delivery related to medical complications, antenatal care, sociodemographic characteristics and living far from a level III unit using multivariable binomial regression. Avoidable outborn deliveries were defined by pregnancy risk (obstetric history, antenatal hospitalisation) and time available for transfer. Results: 25.0% of women were initially booked in level III, 9.1% were referred, 49.8% were transferred, and 16.1% had outborn delivery. Risk factors for outborn delivery were gestational age <26 weeks (adjusted relative risk (aRR) 1.37, 95% confidence interval (CI) 1.13, 1.66), inadequate antenatal care (aRR 1.39, 95% CI 1.10, 1.81), placental abruption (aRR 1.66, 95% CI 1.27, 2.17), and increased distance to the closest level III unit ((aRR 2.79, 95% CI 2.00, 3.92) in the 4th versus 1st distance quartile). Among outborn deliveries, 16.7% were probably avoidable, and 25.6% possibly avoidable, which could increase the proportion of inborn deliveries between 85.9% and 92.9%. Avoidable outborn deliveries were mainly associated with gestational age, intrauterine growth restriction, preterm premature rupture of membranes, and haemorrhage, but not distance. Conclusions: Our study identified some modifiable risk factors for outborn delivery; however, when regionalised care relies heavily on antenatal transfer, as it does in France, only some outborn deliveries may be prevented. Earlier referral of high‐risk women will be needed to achieve full access to tertiary care. [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]

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

Introduction: Our main objective was to evaluate whether antenatal corticosteroids increase the risk of small head circumference in children born at term. Secondary objectives were to evaluate whether they increase the risk of small birthweight and birth length among those children.Material and Methods: A historical cohort included 275 270 live term born children between 2000 and 2013 in 175 French maternity units. The rate of head circumference below the 5th percentile among children born at term and exposed to antenatal corticosteroids was compared with that of two unexposed groups: those children born at term whose mothers had an episode of threatened preterm labor without corticosteroids and those whose mothers had neither threatened preterm labor nor corticosteroids. The association between this treatment and head circumference was evaluated by calculating adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs). The main outcome measure was a head circumference below the 5th percentile at birth, adjusted for sex, and gestational age according to the Pediatric, Obstetrics, and Gynecology Electronic Records Users Association (AUDIPOG) curves. Secondary outcomes were birthweight and birth length below the 5th percentile.Results: The rate of head circumference below the 5th percentile was 5.8% (n = 3388) among children exposed to antenatal corticosteroids and 4.3% (n = 7077) and 4.6% (n = 198 462), respectively, for the two unexposed groups. After adjustment, the risk of having a head circumference below the 5th percentile did not differ between the exposed group and the two control groups (aRR 1.28, 95% confidence interval [CI] 0.97-1.69] and aRR 0.91, 95% CI 0.74-1.13). We did not find an association between antenatal corticosteroids and the rate of birthweight below the 5th percentile. Children exposed to antenatal corticosteroids had a higher risk of a birth length below the 5th percentile when compared with those not exposed to threatened preterm labor or corticosteroids.Conclusions: We found no association between antenatal corticosteroids and increased risk of head circumference below the 5th percentile in children born at term. [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]

ABSTRACT Objective This study aimed to determine if screening for preeclampsia could be improved between 20 and 24 weeks of gestation by uterine artery Doppler (UAD), biomarkers and lipid-related markers. Method Women at high risk of preeclampsia according to obstetric and medical characteristics and history were prospectively enrolled. Transabdominal UAD, serum biomarkers (placenta growth factor (PlGF), soluble Fms-like tyrosine kinase-1 and sEndoglin) and lipid-related markers (total and high-density lipoprotein cholesterol, triglycerides and leptin) were prospectively collected between 20 and 24 weeks of gestation. The main endpoint was preeclampsia. UAD indices and biomarker levels were compared for the groups with and without preeclampsia. Multivariate analyses took into account the laboratory and ultrasound variables significantly associated with preeclampsia in the univariate analysis and age and nulliparity. Results The study at Tours University Hospital took place from March 2003 to February 2008 and included 235 women: 56 (23.8%) developed preeclampsia, 42 were severe (17.8%) and 14 occurred before 34 weeks of gestation (5.9%). The group with preeclampsia had a higher UAD pulsatility index ( p = 0.0003), more frequent bilateral notches ( p = .0001), lower PlGF levels (239.90 vs 302.00 pg/mL; p = 0.0015), and higher triglyceride (1.95 vs 1.70 mmol/l; p = 0.0068) and leptin levels (37.40 vs 22.55 ng/mL; p = < 0.001). No significant differences were observed for other markers. Screening for preeclampsia using these Doppler and laboratory findings produced an area under the curve of 0.795. Conclusion Second-trimester UAD findings, and PlGF, triglyceride and leptin levels could help to predict preeclampsia. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]