Remote ischaemic conditioning in necrotising enterocolitis: a phase I feasibility and safety study

OBJECTIVE: Remote ischaemic conditioning (RIC) improves the outcome of experimental necrotising enterocolitis (NEC) by preserving intestinal microcirculation. The feasibility and safety of RIC in preterm infants with NEC are unknown. The study aimed to assess the feasibility and safety of RIC in preterm infants with suspected or confirmed NEC. DESIGN: Phase I non-randomised pilot study conducted in three steps: step A to determine the safe duration of limb ischaemia (up to 4 min); step B to assess the safety of 4 repeated cycles of ischaemia-reperfusion at the maximum tolerated duration of ischaemia determined in step A; step C to assess the safety of applying 4 cycles of ischaemia-reperfusion on two consecutive days. SETTING: Level III neonatal intensive care unit, The Hospital for Sick Children (Toronto, Canada). PATIENTS: Fifteen preterm infants born between 22 and 33 weeks gestational age. INTERVENTION: Four cycles of ischaemia (varying duration) applied to the limb via a manual sphygmomanometer, followed by reperfusion (4 min) and rest (5 min), repeated on two consecutive days. OUTCOMES: The primary outcomes were (1) feasibility defined as RIC being performed as planned in the protocol, and (2) safety defined as perfusion returning to baseline within 4 min after cuff deflation. RESULTS: Four cycles/day of limb ischaemia (4 min) followed by reperfusion (4 min) and a 5 min gap, repeated on two consecutive days was feasible and safe in all neonates with suspected or confirmed NEC. CONCLUSIONS: This study is pivotal for designing a future randomised controlled trial to assess the efficacy of RIC in preterm infants with NEC

Mortality and significant neurosensory impairment in preterm infants: an international comparison

International audienceObjective To compare mortality and rates of significant neurosensory impairment (sNSI) at 18–36 months’ corrected age in infants born extremely preterm across three international cohorts. Design Retrospective analysis of prospectively collected neonatal and follow-up data. Setting Three 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). Patients Extremely preterm neonates of <28 weeks’ gestation in year 2011. Main outcome measures Primary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness. Results Overall, 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). Conclusions Composite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.Three 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)

Neonatal outcomes of extremely preterm twins by sex pairing: an international cohort study

Objective: Infant boys have worse outcomes than girls. In twins, the 'male disadvantage' has been reported to extend to female co-twins via a 'masculinising' effect. We studied the association between sex pairing and neonatal outcomes in extremely preterm twins. Design: Retrospective cohort study SETTING: Eleven countries participating in the International Network for Evaluating Outcomes of Neonates. Patients: Liveborn twins admitted at 23-29 weeks' gestation in 2007-2015. Main outcome measures: We examined in-hospital mortality, grades 3/4 intraventricular haemorrhage or cystic periventricular leukomalacia (IVH/PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment and a composite outcome (mortality or any of the outcomes above). Results: Among 20 924 twins, 38% were from male-male pairs, 32% were from female-female pairs and 30% were sex discordant. We had no information on chorionicity. Girls with a male co-twin had lower odds of mortality, IVH/PVL and the composite outcome than girl-girl pairs (reference group): adjusted OR (aOR) (95% CI) 0.79 (0.68 to 0.92), 0.83 (0.72 to 0.96) and 0.88 (0.79 to 0.98), respectively. Boys with a female co-twin also had lower odds of mortality: aOR 0.86 (0.74 to 0.99). Boys from male-male pairs had highest odds of BPD and composite outcome: aOR 1.38 (1.24 to 1.52) and 1.27 (1.16 to 1.39), respectively. Conclusions: Sex-related disparities in outcomes exist in extremely preterm twins, with girls having lower risks than boys and opposite-sex pairs having lower risks than same-sex pairs. Our results may help clinicians in assessing risk in this large segment of extremely preterm infants

Mortality and significant neurosensory impairment in preterm infants: an international comparison

Objective: To compare mortality and rates of significant neurosensory impairment (sNSI) at 18-36 months' corrected age in infants born extremely preterm across three international cohorts. Design: Retrospective analysis of prospectively collected neonatal and follow-up data. Setting: Three 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). Patients: Extremely preterm neonates of &lt;28 weeks' gestation in year 2011. Main outcome measures: Primary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness. Results: Overall, 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). Conclusions: Composite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.</p