Risk factors for very preterm delivery out of a level III maternity unit: The EPIPAGE-2 cohort study.

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.

Volume of Neonatal Care and Survival without Disability at 2 Years in Very Preterm Infants: Results of a French National Cohort Study.

OBJECTIVES: To investigate the relation between neonatal intensive care unit (NICU) volume and survival, and neuromotor and sensory disabilities at 2 years in very preterm infants. STUDY DESIGN: The EPIPAGE-2 (Etude Epidémiologique sur les Petits Âges Gestationnels-2) national prospective population-based cohort study was used to include 2447 babies born alive in 66 level III hospitals between 24 and 30 completed weeks of gestation in 2011. The outcome was survival without disabilities (levels 2-5 of the Gross Motor Function Classification System for cerebral palsy with or without unilateral or bilateral blindness or deafness). Units were grouped in quartiles according to volume, defined as the annual admissions of very preterm babies. Multivariate logistic regression analyses with population average models were used. RESULTS: Survival at discharge was lower in hospitals with lower volumes of neonatal activity (aOR 0.55, 95% CI 0.33-0.91). Survival without neuromotor and sensory disabilities at 2 years increased with hospital volume, from 75% to 80.7% in the highest volume units. After adjustment for gestational age, small for gestational age, sex, maternal age, infertility treatment, multiple pregnancy, principal cause of prematurity, parental socioeconomic status, and mother's country of birth, survival without neuromotor or sensory disabilities was significantly lower in hospitals with a lower volume of neonatal activity (aOR 0.60, 95% CI 0.38-0.95) than in the highest quartile hospitals. CONCLUSIONS: These results suggest that lower neonatal intensive care unit volume is associated with lower survival without an increase in disabilities at 2 years. These results could be useful to generate improvements of perinatal regionalization.

Cognitive Training for Visuospatial Processing in Children Aged 5½ to 6 Years Born Very Preterm With Working Memory Dysfunction: A Randomized Clinical Trial.

Importance: Compared with term-born peers, children born very preterm generally perform poorly in executive functions, particularly in working memory and inhibition. By taking advantage of neuroplasticity, computerized cognitive training of working memory in those children could improve visuospatial processing by boosting visual inhibition via working memory. Objective: To evaluate the long-term effect of cognitive working memory training on visuospatial processing in children aged 5½ to 6 years born very preterm who have working memory impairment. Design, Setting, and Participants: This multicenter (18 French university hospitals), open-label randomized clinical trial with 2 parallel groups (EPIREMED) was conducted from November 2016 to April 2018, with the last follow-up during August 2019. Eligible children from the EPIPAGE 2 cohort were aged 5½ to 6 years, were born between 24 and 34 weeks' gestation, and had a global intelligence quotient greater than 70 and a working memory index less than 85. Data were analyzed from February to December 2020. Intervention: Children were randomized 1:1 to standard care management and a working memory cognitive training program (Cogmed software) for 8 weeks (25 sessions) (intervention) or to standard management (control). Main Outcomes and Measures: The primary outcome was the visuospatial index score from the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition. Secondary outcomes were working memory, intellectual functioning, executive and attention processes, language skills, behavior, quality of life, and schooling. Neurobehavioral assessments were performed at inclusion and after finishing training at 6 months (intermeditate assessment; secondary outcomes) and at 16 months (final assessment; primary outcome). Results: There were 169 children randomized, with a mean (SD) age of 5 years 11 months (2 months); 91 (54%) were female. Of the participants, 84 were in the intervention group (57 of whom [68%] completed at least 15 cognitive training sessions) and 85 were in the control group. The posttraining visuospatial index score was not different between groups at a mean (SD) of 3.0 (1.8) months (difference, -0.6 points; 95% CI, -4.7 to 3.5 points) or 12.9 (2.6) months (difference, 0.1 points; 95% CI, -5.4 to 5.1 points). The working memory index score in the intervention group significantly improved from baseline at the intermediate time point (difference, 4.7 points; 95% CI, 1.2-8.1 points), but this improvement was not maintained at the final assessment. Conclusions and Relevance: This randomized clinical trial found no lasting effect of a cognitive training program on visuospatial processing in children aged 5½ to 6 years with working memory disorders who were born very preterm. The findings suggest that this training has limited long-term benefits for improving executive function. Transient benefits seemed to be associated with the developmental state of executive functions. Trial Registration: ClinicalTrials.gov Identifier: NCT02757794.

Hyperechoic congenital lung lesions in a non-selected population: from prenatal detection till perinatal management.

OBJECTIVE: To present longitudinal observations of hyperechoic lung lesions (HLL) in a non-selected population from the time of prenatal diagnosis by ultrasound (US) until postnatal surgery. METHODS: We conducted a retrospective study of all fetuses diagnosed with an HLL between 1990 and 2005 in our Fetal Medicine Unit. RESULTS: We observed 21 cases of HLL. Among the 17 fetuses with unilateral lesion, two cyst punctures were attempted on fetuses with signs of fetal compromise. Termination of pregnancy (TOP) was performed on seven fetuses. Fourteen fetuses were followed till birth. First Chest X-ray was abnormal in ten cases, while delayed CT scans revealed a lung lesion in 12 cases. Two neonates required emergency surgery and died post operatively. Surgery was successfully performed in all other cases (n = 10). Pathological examination revealed congenital high airway obstruction syndrome, CHAOS (n = 4), lower airway stenosis (n = 2), bronchogenic cyst (n = 1), congenital lobar emphysema (n = 1), and congenital cystic adenomatoid malformation, CCAM (n = 11) including two cases associated with a sequestration. CONCLUSION: HLL cover a wide spectrum of lung abnormalities of various severities. Post natal management should always include an early chest X-ray and CT scan to allow appropriate selection for surgery.

Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study.

IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. OBJECTIVES: To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.