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ObjectiveTo 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).SettingAll births from 22 to 34 weeks of gestational age in France in 2011 were eligible.PopulationInfants born alive between 24+0 and 31+6 weeks following preterm labour (PTL) or preterm premature rupture of membranes (PPROMs).ExposureHistological 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 measuresNeurodevelopmental 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.ResultsAmong 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).ConclusionWe 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.

ObjectiveTo compare mortality and rates of significant neurosensory impairment (sNSI) at 18–36 months’ corrected age in infants born extremely preterm across three international cohorts.DesignRetrospective analysis of prospectively collected neonatal and follow-up data.SettingThree population-based observational cohort studies: the Australian and New Zealand Neonatal Network (ANZNN), the Canadian Neonatal and Follow-up Networks (CNN/CNFUN) and the French cohort Etude (Epidémiologique sur les Petits Ages Gestationnels: EPIPAGE-2).PatientsExtremely preterm neonates of <28 weeks’ gestation in year 2011.Main outcome measuresPrimary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness.ResultsOverall, 3055 infants (ANZNN n=960, CNN/CNFUN n=1019, EPIPAGE-2 n=1076) were included in the study. Primary composite outcome rates were 21.3%, 20.6% and 28.4%; mortality rates were 18.7%, 17.4% and 26.3%; and rates of sNSI among survivors were 4.3%, 5.3% and 3.3% for ANZNN, CNN/CNFUN and EPIPAGE-2, respectively. Adjusted for gestational age and multiple births, EPIPAGE-2 had higher odds of composite outcome compared with ANZNN (OR 1.71, 95% CI 1.38 to 2.13) and CNN/CNFUN (OR 1.72, 95% CI 1.39 to 2.12). EPIPAGE-2 did have a trend of lower odds of sNDI but far short of compensating for the significant increase in mortality odds. These differences may be related to variations in perinatal approach and practices (and not to differences in infants’ baseline characteristics).ConclusionsComposite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.

We compared the effects of the early-acting growth factors (GF), Flt-3 ligand (FL), c-Kit ligand (KL), and leukemia inhibitory factor (LIF), and the late-acting GF, granulocyte-colony stimulating factor (G-CSF) and megakaryocyte growth and development factor (MGDF), added alone in human long-term marrow culture (LTMC). The GF were used in primary cultures of mononuclear cells (MNC) and in cocultures of CD34+ cells on murine preestablished MS-5 stromal layers. GF activity was assessed as nonadherent and adherent progenitor cell production and cobblestone area formation at week 5. In this system, only FL, KL, and MGDF significantly stimulated early stages of hematopoiesis, whereas only G-CSF stimulated the proliferation of mature progenitor cells within the granulo-monocyte lineage and no effect was observed with LIF. FL displayed the strongest activity, and MGDF was more efficient than KL, both in primary cultures of MNC and in cocultures of CD34+ cells. However, the stimulatory effects of these GF used alone were dependent on the presence of a stromal layer. These LTMC data emphasize the particular roles for FL and MGDF in the stimulation of primitive hematopoiesis.