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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.

This study aims to describe the incidence of acute respiratory infections (ARI) during the first year in infants born before 32 weeks’ gestation, and to analyze and study the risk factors as well as factors associated with oxygen requirement among infants with an ARI, in the palivizumab era. This study included 2571 infants from a nationwide French population–based cohort (Epipage 2). ARI at 1-year corrected age was identified by parental questionnaires. Risk and severity factors included those already known, and detailed information about neonatal morbidities. ARI occurred in 52.2% (n = 1349) of infants. Oxygen therapy was used in 33.2% (n = 391) of infants with an ARI. Risk factors for AII were male sex, bronchopulmonary dysplasia, presence of siblings at home, and childcare in the community together with incomplete treatment palivizumab. Mechanical ventilation in the neonatal period, bronchopulmonary dysplasia, and discharge between October and March were associated with more frequent oxygen requirement. No other factors describing neonatal morbidities were associated with risk of ARI or oxygen requirement.Conclusion: ARIs are still very common during the first year of life of very preterm children, and oxygen therapy is frequently needed. Educational strategies are needed in all families with a very preterm infant.What is Known:• Acute respiratory infections (ARIs) are the first cause of rehospitalizations in preterm children, with bronchopulmonary dysplasia being the main risk factor.• Palivizumab prophylaxis has proven its effect against severe RSV infections, but it is not universal.What is New:• No factor describing neonatal morbidity, except BPD, was associated with ARI occurrence or severity.• BPD and discharge during RSV season were the only factors associated with O2requirement during ARI.

ObjectiveTo assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity.DesignSecondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment was performed at age 5–6 years. A 2:1 propensity score matching was used to control for the non-randomised assignment of doxapram treatment.SettingPopulation-based cohort study.PatientsAll children born before 32 weeks’ gestation alive at age 5–6 years.InterventionsBlind and standardised assessment by trained neuropsychologists and paediatricians at age 5–6 years.Main outcome measuresNeurodevelopmental outcomes at age 5–6 years assessed by trained paediatricians and neuropsychologists: cerebral palsy, developmental coordination disorders, IQ and behavioural difficulties. A composite criterion for overall neurodevelopmental disabilities was built.ResultsThe population consisted of 2950 children; 275 (8.6%) received doxapram. Median (IQR) gestational age was 29.4 (27.6–30.9) weeks. At age 5–6 years, complete neurodevelopmental assessment was available for 60.3% (1780 of 2950) of children and partial assessment for 10.6% (314 of 2950). In the initial sample, children receiving doxapram had evidence of greater clinical severity than those not treated. Doxapram treatment was associated with overall neurodevelopmental disabilities of any severity (OR 1.43, 95% CI 1.07 to 1.92, p=0.02). Eight hundred and twenty-one children were included in the 2:1 matched sample. In this sample, perinatal characteristics of both groups were similar and doxapram treatment was not associated with overall neurodevelopmental disabilities (OR 1.09, 95% CI 0.76 to 1.57, p=0.63).ConclusionsIn children born before 32 weeks’ gestation, doxapram treatment for apnoea of prematurity was not associated with neurodevelopmental disabilities.

Purpose: The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2 years’ corrected age (CA) in infants born before 32 weeks’ gestation (WG). Methods: We studied neurodevelopment at 2 years’ CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire. Results: At 2 years’ CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability ( p  < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2 years’ CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p  = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p  = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0–9.1) but not NEC as compared with controls. Conclusion : NEC and SIP significantly increased the risk of death or sensorimotor disability at 2 years’ CA. SIP was also associated with risk of developmental delay at 2 years’ CA.

To evaluate the consequences of bronchopulmonary dysplasia (BPD) on academic outcomes and healthcare use in adolescents born very preterm. This cohort study included 15-year-old adolescents born very preterm (< 32 weeks) between 2011 and 2013, with and without BPD, and controls born full term. Data regarding academic performance, current medical follow-up, and family characteristics were collected. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD. From the 1341 children included in the initial cohort, 985 adolescents were eligible and 351 included (55 preterms with a history of BPD, 249 without, and 47 controls). Among adolescents born very preterm, a history of BPD was associated with a higher risk to attend a school for children with special needs (p < 0.05) and to have repeated a grade (p = 0.01). It was also associated with an increased number of medical and paramedical consultations. A history of BPD was not associated with the parents' employment status, family structure, or the presence of younger siblings. This study highlights that a history of BPD is associated with poorer academic outcomes and high healthcare use in adolescence.

Before 26 weeks of gestational age, because extremely preterm infants (EPI) face a high risk of death or disability, management decisions may involve either active treatment or palliative care. Survival chances largely depend on the willingness of medical teams and parents to opt for active management. Variability of practices explains differences in survival between countries and regions, and interpersonal variability may also exist among caregivers within the same center. Our objective was to study the variability of management decisions and their determinants among caregivers in a French type 3 maternity hospital. All caregivers, obstetricians, pediatricians, and midwives, involved in the management of EPI in a type 3 perinatal center were surveyed using a self-administered questionnaire. Each respondent reported their personal thresholds for deciding on active management, defined as the unborn child's estimated likelihood of survival without severe neonatal morbidity. Median and interquartile ranges (IQR) of these thresholds were calculated and compared by respondent characteristics. 85 (75%) eligible professionals responded. The median threshold of survival without severe neonatal morbidity below which active management was deemed impossible was 15% (IQR 10-30%), while the median threshold above which active management could not be refused was 80% (IQR 70-90%). Wide IQRs indicated significant variability in individual thresholds. This variability appeared to be influenced by profession and gender but was not associated with factors such as having children, age, experience, or the personal estimates of the neonates' outcomes. Decision thresholds for active management of EPI, expressed in terms of survival without severe neonatal morbidity, vary significantly among professionals. The thresholds reported in our study were notably higher than those observed in other countries, which may help explain the lower rates of active management before 26 weeks in France. Recognizing these differences and comparing personal thresholds with peers could facilitate more consensus-based decision-making within teams.

ObjectiveThe objective is to evaluate changes in survival to discharge of liveborn infants less than 32 weeks’ gestational age (GA) in France, where the latest available data on very preterm survival at a national-level are from the EPIPAGE-2 (Etude épidémiologique sur les petits âges gestationnels) cohort in 2011.DesignPopulation-based cohort study.SettingMetropolitan France in 2011, 2015 and 2020.PatientsAll births between 22 and 31 weeks’ GA using the EPIPAGE-2 cohort study for the year 2011 and hospital discharge data linked to death certificates from the Système National des Données de Santé for the years 2015 and 2020.Main outcome measuresThe primary outcome was survival to hospital discharge among liveborn infants. Survival rates were compared using modified Poisson regression and adjusted for population characteristics (maternal age, multiple birth, sex, small for GA). Data on all births were examined to assess changes to the live birth rate.ResultsSurvival to discharge among live births increased at 23 and 24 weeks’ GA from 1% and 31% in 2011 to 8% and 37% in 2015 and to 31% and 47% in 2020, respectively. From 25 to 28 weeks’ GA, survival rates tended to increase, but differences were not significant, and survival rates were stable from 29 to 31 weeks GA. Results were similar after adjustment. The proportion of live births versus stillbirths increased from 22 to 24 weeks’ GA.ConclusionSurvival rates among live births improved between 2011 and 2020 from 23 to 28 weeks’ GA, with marked changes at 23 and 24 weeks’ GA.

ObjectiveWe aimed to study neurodevelopmental outcomes and healthcare utilisation at age 5–6 years in very preterm children with bronchopulmonary dysplasia (BPD).DesignProspective and national population-based study.SettingAll the neonatal units in 25 French regions (21 of the 22 metropolitan regions and 4 overseas regions).PatientsChildren born before 32 weeks’ gestation in 2011.InterventionsBlind, comprehensive and standardised assessment by trained neuropsychologists and paediatricians at age 5–6 years.Main outcome measuresOverall neurodevelopmental disabilities, behavioural difficulties, developmental coordination disorders, full-scale IQ, cerebral palsy, social interaction disorders, rehospitalisation in the previous 12 months and detailed developmental support.ResultsOf the 3186 children included, 413 (11.7%) had BPD. The median gestational age of children with BPD was 27 weeks (IQR 26.0–28.0) and without BPD was 30 weeks (28.0–31.0). At age 5–6 years, 3150 children were alive; 1914 (60.8%) had a complete assessment. BPD was strongly associated with mild, moderate and severe overall neurodevelopmental disabilities (OR 1.49, 95% CI 1.05 to 2.20; 2.20, 1.41 to 3.42 and 2.71, 1.67 to 4.40). BPD was associated with developmental coordination disorders, behavioural difficulties, lower IQ score as well as rehospitalisation in the last 12 months and developmental support. The association between BPD and cerebral palsy was statistically significant before adjustment but not in adjusted analyses.ConclusionsBPD was strongly and independently associated with many neurodevelopmental disabilities. Improving medical and neurodevelopmental management of BPD in very preterm children should be a priority to reduce its long-term consequences.

Small for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population. Retrospective single-center cohort study including 141 neonates born between 24 and 30 weeks' gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Bronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2-15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9-11.3]). Small for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia. CNIL no. 1747084.

Deep learning, a subset of artificial intelligence, has gained attention in recent years for its ability to achieve human level performance in medical image analysis. As deep learning is increasingly being studied in medical image analysis, it is essential that clinicians are familiar with its underlying principles, strengths, and possible pitfalls in their evaluation. This article aims to clarify deep learning techniques applied in medical image analysis and to help frontline clinicians understand how to read and appraise studies about this new and rapidly advancing technology. While image analysis using deep learning has the potential to enhance the diagnosis of various medical conditions, clinicians, policy makers, and patients should exercise caution when evaluating the available evidence.