Short-term pulmonary and systemic effects of hydrocortisone initiated 7-14 days after birth in ventilated very preterm infants: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week. DESIGN: Randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. INTERVENTION: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models. RESULTS: Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH2O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure. CONCLUSIONS: Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR2768; https://www.trialregister.nl/trial/2640) and European Union Clinical Trials Register (EudraCT, 2010-023777-19).

Effect of systemic hydrocortisone in ventilated preterm infants on parent-reported behavioural outcomes at 2 years' corrected age: follow-up of a randomised clinical trial.

OBJECTIVE: To report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years' corrected age (CA). DESIGN: Randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. INTERVENTION: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: Parent-reported behavioural outcomes at 2 years' CA assessed with the Child Behavior Checklist (CBCL 1½-5). RESULTS: Parents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalising and externalising problems, respectively; these scores were not significantly different between groups (mean difference -1.52 (95% CI -4.00 to 0.96), -2.40 (95% CI -4.99 to 0.20) and -0.81 (95% CI -3.40 to 1.77), respectively). In the subscales, we found a significantly lower T-score for anxiety problems in the hydrocortisone group (mean difference -1.26, 95% CI -2.41 to -0.12). CONCLUSION: This study found high rates of behaviour problems at 2 years' CA following very preterm birth, but these problems were not associated with hydrocortisone treatment initiated between 7 and 14 days after birth in ventilated preterm infants. TRIAL REGISTRATION NUMBER: NTR2768; EudraCT 2010-023777-19.

Decreasing incidence and severity of cerebral palsy in prematurely born children.

OBJECTIVE: To examine incidence and severity of cerebral palsy (CP), and associated factors among preterm survivors (gestational age <34 weeks), admitted to a neonatal intensive care unit from 1990-2005. STUDY DESIGN: Eighteen antenatal, perinatal and postnatal factors were analyzed. The cohort was divided in four birth periods: 1990-1993 (n=661), 1994-1997 (n=726), 1998-2001 (n=723), and 2002-2005 (n=850). The Gross Motor Function Classification System was used as primary outcome measure (mean age: 32.9 ± 5.3 months). Logistic regression analyses were used. RESULTS: CP incidence decreased from 6.5% in period I, to 2.6%, 2.9% and 2.2% (P<.001) in period II-IV, respectively. Simultaneously, cystic periventricular leukomalacia (c-PVL) decreased from 3.3% in period I to 1.3% in period IV (P=.004). Within the total cohort (n=3287), c-PVL grade III decreased from 2.3% in period I to 0.2% in period IV (P=.003). The number of children with Gross Motor Function Classification System levels III-V decreased from period I to IV (P=.035). Independent risk factors for CP were c-PVL and severe intraventricular hemorrhage, whereas antenatal antibiotics, presence of an arterial line, Caesarean section, and gestational age were independent protective factors. CONCLUSION: CP incidence and severity decreased from 1990-1993 onward, which could be attributed to a reduction of 93% in severe c-PVL.

Development of Nationwide Recommendations to Support Prenatal Counseling in Extreme Prematurity.

OBJECTIVES: To develop a nationwide, evidence-based framework to support prenatal counseling in extreme prematurity, focusing on organization, decision-making, content, and style aspects. METHODS: A nationwide multicenter RAND-modified Delphi method study was performed between November 2016 and December 2017 in the Netherlands. Firstly, recommendations were extracted from literature and previous studies. Secondly, an expert panel (n = 21) with experienced parents, obstetricians, and neonatologists rated the recommendations on importance for inclusion in the framework. Thirdly, ratings were discussed in a consensus meeting. The final set of recommendations was approved and transformed into a framework. RESULTS: A total of 101 recommendations on organization, decision-making, content, and style were included in the framework, including tools to support personalization. The most important recommendations regarding organization were to have both parents involved in the counseling with both the neonatologist and obstetrician. The shared decision-making model was recommended for deciding between active support and comfort care. Main recommendations regarding content of conversation were explanation of treatment options, information on survival, risk of permanent consequences, impossibility to predict an individual course, possibility for multiple future decision moments, and a discussion on parental values and standards. It was considered important to avoid jargon, check understanding, and provide a summary. The expert panel, patient organization, and national professional associations (gynecology and pediatrics) approved the framework. CONCLUSIONS: A nationwide, evidence-based framework for prenatal counseling in extreme prematurity was developed. It contains recommendations and tools for personalization in the domains of organization, decision-making, content, and style of prenatal counseling.