Publications

Abstract

Preterm neonates present multiple challenges due to organ immaturity.Cardiovascular:Patent ductus arteriosus (PDA) is common in lower gestational ages and may cause respiratory and circulatory complications. Treatment includes medical (ibuprofen, para-cetamol), surgical, or percutaneous approaches. Bradycardia is frequent and requires continuous monitoring.Digestive/Metabolic:Early enteral nutrition with fortified breast milk is preferred; parenteral nutrition is often required. Gastroesophageal reflux is usually benign. Preventing metabolic bone disease necessitates adequate calcium and phosphate intake. Jaundice is common; cholestasis often relates to parenteral nutrition.Infectious:Immune immaturity and invasive devices increase risks of early-onset (E.coli), nosocomial (CoNS), and fungal (Candida) infections. Diagnosis relies on blood cultures; treatment is empirical then targeted.Neurological:Common lesions include periventricular leukomalacia and intraventricular hemorrhage, with potential sequelae. Monitoring includes cranial ultrasound, EEG, MRI, and routine screening for hearing loss and retinopathy of prematurity.

No abstract available

Abstract

Preterm birth is defined as any birth occurring before 37 completed weeks of gestation (WG). It affects 9.9% of live births, representing 13.4 million births a year worldwide. In France, preterm birth rate is of 7.0%. The causes of preterm birth can be grouped into 3 main categories: infectious/inflammatory, vascular, and other. Risk factors, preventive measures, and impact on the child’s health depend of these causes. Risks of death and of neonatal complications are strongly associated with gestational age at birth. Other factors are also involved, such as birth weight (fetal growth restriction) or the administration of antenatal corticosteroids. In 2020 in France, survival rates were of 47% for children born alive at 24 WG, 80% at 26 WG, 92% at 28 WG and 97% at 31 WG.

Keywords: prematurity.

Abstract

Neonatal respiratory distress is one of the leading causes of hospitalization of preterm newborns in intensive care units. Regardless of the pathology, initial respiratory support is usually delivered nasally (non-invasive ventilation), with intubation now being much less common than in previous decades, even for the most extremely preterm babies.The most frequent respiratory pathology is respiratory distress syndrome (RDS) also termed hyaline membrane disease. It is prevented by antenatal corticosteroid therapy and very effectively treated by the administration of exogenous surfactant directly in the lungs. Apnea of prematurity can last for a long time and partly explains the need for prolonged hospitalization in intensive care units. The major risk is the progression toward bronchopulmonary dysplasia, a chronic respiratory disease of preterm babies which can have longer-term consequences. In the very long term, this pathology is likely to promote the development of adult chronic obstructive pulmonary disease

Abstract

Objective: To examine associations between a 5-min Apgar score < 7 and severe neonatal outcomes in very preterm (VPT) infants and how results are impacted by variations in assigning Apgar scores within an international context.

Design: Prospective observational population-based cohort study.

Setting: Eleven structurally and organisationally diverse countries across Europe.

Population: In total, 7900 liveborn VPT infants from the EPICE-SHIPS study.

Methods: Descriptive statistics, logistic regression, modified Poisson regression.

Main outcome measures: Associations between 5-min Apgar scores < 7 and adverse neonatal outcomes were estimated with adjustments for perinatal characteristics. We tested for interactions by country-level prevalence of an Apgar score < 7, grouped into low (14%-16%), medium (19%-22%) and high (28%-40%).

Results: 20.2% of infants had 5-min Apgar score < 7 with rates of 14%-40% across countries. A score < 7 increased risks of in-hospital mortality, intraventricular haemorrhage (IVH), cystic periventricular leukomalacia (cPVL), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and length of hospital stay (LHS), but not necrotising enterocolitis or late-onset infection (LOI). No interactions with country group were detected for mortality, cPVL and ROP, while associations with IVH, BPD and LHS were restricted to countries with lower prevalence of scores < 7.

Conclusions: Significant differences exist in the prevalence of low Apgar scores across countries. Their interactions with adverse outcomes demand caution when using the Apgar score in prognostic models for clinical care and research without local validation. More broadly, our findings emphasise the importance of accounting for country-specific effects in clinical assessment scores.

Abstract

Long-term outcomes of preterm children are one of the major challenges in neonatology. Neurodevelopmental disorders are common in these children. Severe motor, cognitive or neurosensory disorders mainly affect the most immature children. Minor difficulties are present in more than a third of children, whatever their gestational age. School integration is frequently affected, and recourse to developmental support is important. A combination of certain factors should alert caregivers to the risk of neurodevelopmental disorders. These include male gender, small for gestational age, high-grade intraventricular hemorrhage, cystic periventricular leukomalacia or bronchopulmonary dysplasia. Early identification of neurodevelopmental disorders makes it possible to provide support for children and their families and to take advantage of the cerebral plasticity of the developing brain.

Keywords: prematurity.

Abstract

Objective: Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in infants, whose neurodevelopmental consequences currently lack effective treatment. Since TBI is associated with neuroinflammation, modulation of the post-injury neuroinflammatory response is a promising strategy. Oxytocin is suggested to possess anti-inflammatory properties, and seems to play a role in clinical interventions that improve brain development in neonates. However, the underlying mechanisms remain unclear, as does its applicability to acute brain injury.

Methods: Here, we assess the effects of chemogenetic activation of oxytocinergic neurons on acute neuroinflammation and on long-term brain development after TBI in postnatal day 7 (P7) male mice. Immunohistochemistry, RNA sequencing, ex-vivo MRI-diffusion tensor imaging, in-vivo functional ultrasound imaging and behavioral assays are used for assessment. Oxytocinergic neurons were chemogenetically activated daily between P7 and P10.

Results: We show that chemogenetic activation of oxytocinergic neurons mitigates the acute neuroinflammatory response to TBI 24 h post-injury, where it reduces the expression of inflammation-related genes, and promotes brain repair and development gene pathways in microglia. In the long-term, early-life oxytocinergic neuron activation improves subcortical and cortical white matter damage after TBI, prevents hyperactivity and loss of social behavior, and restores TBI-induced alterations in resting-state functional connectivity of the isocortex. These effects were found 35 days after the last treatment session.

Conclusions: Our findings enhance the understanding of neuroinflammation modulation by oxytocin, reveal its long-term effects, and support intervention associated with endogenous oxytocin release as a promising neuroprotective strategy in pediatric TBI

No abstract available

Abstract

Objective: To assess the association between histological chorioamnionitis without maternal clinical symptoms and neurodevelopmental disabilities at age 5 years in children born very preterm.

Design: French national prospective population-based cohort study, EPIPAGE-2 (Etude épidémiologique sur les petits âges gestationnels).

Setting: All births from 22 to 34 weeks of gestational age in France in 2011 were eligible.

Population: Infants born alive between 24⁺⁰ and 31⁺⁶ weeks following preterm labour (PTL) or preterm premature rupture of membranes (PPROMs).

Exposure: Histological chorioamnionitis without maternal clinical symptoms, also called isolated histological chorioamnionitis, was defined as the presence of neutrophils in the chorionic plate, excluding clinical chorioamnionitis.

Main outcome measures: Neurodevelopmental disabilities, a composite outcome including cerebral palsy, developmental coordination disorders, sensory impairment, developmental cognitive deficiencies or behavioural difficulties. These assessments were comprehensive, standardised and conducted by trained neuropsychologists and paediatricians at age 5 years.

Results: Among 1296 children alive at 5 years of age, 486 (36.3%) were born in a context of isolated histological chorioamnionitis. Overall, 47% vs 33.6% of children exposed and not exposed to isolated histological chorioamnionitis had mild neurodevelopmental disabilities, and 13.8% vs 13.3% had moderate-to-severe neurodevelopmental disabilities. After multiple imputation and multivariable analysis, isolated histological chorioamnionitis was found not to be associated with the occurrence of mild or moderate-to-severe neurodevelopmental disabilities (adjusted OR: 1.0, 95% CI: 0.7 to 1.4 and 0.9, 0.6 to 1.2).

Conclusion: We did not find any association between isolated histological chorioamnionitis and neurodevelopmental disabilities at age 5 years in children born very preterm after PTL or PPROM.

Abstract

Objective: The objective is to investigate the prevalence of underweight and overweight and obesity (OWOB) and associated risk factors among 5-year-old children born very preterm (VPT).

Design: Multinational area-based cohort study of children born VPT.

Setting: 19 regions in 11 European countries.

Patients: Children born before 32 weeks of gestational age in 2011-2012 and followed up at 5 years of age.

Main outcome measures: Body mass index (BMI) at 5 years of age was classified into underweight and OWOB using International Obesity Task Force references, and associations with sociodemographic, perinatal and neonatal risk factors were assessed using multinomial logistic regression. Data came from medical records during the neonatal hospitalisation and parental questionnaires at 5 years of age. Models accounted for missing data and attrition by using multiple imputation by chained equations and inverse probability weighting.

Results: 27.6% of children were underweight and 10.8% were OWOB. Younger maternal age was associated with lower risks of underweight, while low maternal education, household unemployment and non-European maternal country of birth were associated with having OWOB. Fetal growth restriction, receiving postnatal steroids and bronchopulmonary dysplasia were associated with underweight, and fetal growth restriction, male sex and multiple birth were negatively associated with OWOB.

Conclusions: 38% of children born VPT had suboptimal BMI at 5 years, principally due to being underweight, with differing risk factors for underweight and OWOB. These results raise questions about underlying mechanisms and the growth trajectories and metabolic outcomes of underweight children, in light of high prevalence and association with clinical risk.