Aurélie Piedvache

Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort

Objectives To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity. Design Prospective multinational population based observational study. Setting 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. Participants 7336 infants born between 24+0 and 31+6 weeks’ gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission. Main outcome measures Combined use of four evidence based practices for infants born before 28 weeks’ gestation using an “all or none” approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. Results Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. Conclusions More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity.

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort

Importance Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.

Variation in term birthweight across European countries affects the prevalence of small for gestational age among very preterm infants.

This study assessed the prevalence of small for gestational age (SGA) among very preterm (VPT) infants using national and European intrauterine references.

Changes in management policies for extremely preterm births and neonatal outcomes from 2003 to 2012: two population‐based studies in ten European regions

To investigate changes in maternity and neonatal unit policies towards extremely preterm infants (EPTIs) between 2003 and 2012, and concurrent trends in their mortality and morbidity in ten European regions.

Use of magnesium sulfate before 32 weeks of gestation: a European population-based cohort study

Objectives The use of magnesium sulfate (MgSO4) in European obstetric units is unknown. We aimed to describe reported policies and actual use of MgSO4 in women delivering before 32 weeks of gestation by indication. Methods We used data from the European Perinatal Intensive Care in Europe (EPICE) population-based cohort study of births before 32 weeks of gestation in 19 regions in 11 European countries. Data were collected from April 2011 to September 2012 from medical records and questionnaires. The study population comprised 720 women with severe pre-eclampsia, eclampsia or HELLP and 3658 without pre-eclampsia delivering from 24 to 31 weeks of gestation in 119 maternity units with 20 or more very preterm deliveries per year. Results Among women with severe pre-eclampsia, eclampsia or HELLP, 255 (35.4%) received MgSO4 before delivery. 41% of units reported use of MgSO4 whenever possible for pre-eclampsia and administered MgSO4 more often than units reporting use sometimes. In women without pre-eclampsia, 95 (2.6%) received MgSO4. 9 units (7.6%) reported using MgSO4 for fetal neuroprotection whenever possible. In these units, the median rate of MgSO4 use for deliveries without severe pre-eclampsia, eclampsia and HELLP was 14.3%. Only 1 unit reported using MgSO4 as a first-line tocolytic. Among women without pre-eclampsia, MgSO4 use was not higher in women hospitalised before delivery for preterm labour. Conclusions Severe pre-eclampsia, eclampsia or HELLP are not treated with MgSO4 as frequently as evidence-based medicine recommends. MgSO4 is seldom used for fetal neuroprotection, and is no longer used for tocolysis. To continuously lower morbidity, greater attention to use of MgSO4 is needed.

Evidence-based neonatal unit practices and determinants of Postnatal corticosteroid-use in preterm births below 30 weeks ga in Europe. A population-based cohort study

Background Postnatal corticosteroids (PNC) were widely used to treat and prevent bronchopulmonary dysplasia in preterm infants until studies showed increased risk of cerebral palsy and neurodevelopmental impairment. We aimed to describe PNC use in Europe and evaluate the determinants of their use, including neonatal characteristics and adherence to evidence-based practices in neonatal intensive care units (NICUs). Methods 3917/4096 (95,6%) infants born between 24 and 29 weeks gestational age in 19 regions of 11 European countries of the EPICE cohort we included. We examined neonatal characteristics associated with PNC use. The cohort was divided by tertiles of probability of PNC use determined by logistic regression analysis. We also evaluated the impact of the neonatal unit’s reported adherence to European recommendations for respiratory management and a stated policy of reduced PNC use. Results PNC were prescribed for 545/3917 (13.9%) infants (regional range 3.1–49.4%) and for 29.7% of infants in the highest risk tertile (regional range 5.4–72.4%). After adjustment, independent predictors of PNC use were a low gestational age, small for gestational age, male sex, mechanical ventilation, use of non-steroidal anti-inflammatory drugs to treat persistent ductus arteriosus and region. A stated NICU policy reduced PNC use (odds ratio 0.29 [95% CI 0.17; 0.50]). Conclusion PNC are frequently used in Europe, but with wide regional variation that was unexplained by neonatal characteristics. Even for infants at highest risk for PNC use, some regions only rarely prescribed PNC. A stated policy of reduced PNC use was associated with observed practice and is recommended.

Wide variation in severe neonatal morbidity among very preterm infants in European regions

Objective To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates. Design Area-based cohort study of all births before 32 weeks of gestational age. Setting 16 regions in 11 European countries in 2011/2012. Patients Survivors to discharge from neonatal care (n=6422). Main outcome measures Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics. Results 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%–23.5%) and 13.8% including severe BPD (regional range 10.0%–23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%–18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50). Conclusion Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.

Cohort study from 11 European countries highlighted differences in the use and efficacy of hypothermia prevention strategies after very preterm birth

This study investigated the different strategies used in 11 European countries to prevent hypothermia, which continues to affect a large proportion of preterm births in the region.

Authors’ reply to Page and Rafi

We agree with Page and Rafi about the importance of identifying the key evidence based obstetric and neonatal interventions that can be monitored to assess quality of care for very preterm infants.1 2 As our study shows,3 evaluating the use and impact of four evidence based practices together sets higher standards and focuses attention on care processes. The EPICE (Effective Perinatal Intensive Care in Europe) project’s international dimension is a strength, as it reveals underuse of evidence based care in many health systems and cultures. But international …

PO-0749 Cpap Failure In Very Preterm Infants In European Regions With Different Respiratory Management Strategies: Results From The Epice Cohort

Background Many very preterm infants managed on early nasal continuous positive airway pressure (nCPAP) subsequently require intubation and ventilation and may suffer the consequences of delayed surfactant administration. We investigated risk factors for early nCPAP failure in European regions with diverse approaches to respiratory support. Methods The EPICE cohort included all births between 22+0 and 31+6 weeks of gestation in 19 European regions in 2011–2012. nCPAP failure was defined as mechanical ventilation in the first 72 h. Independent variables were gestational age, sex, multiple pregnancy, prenatal corticosteroids, pregnancy complications, small for gestational age (SGA), caesarean delivery, 5 min Apgar and region of birth. We classified regions into low (<35%), medium (35–55%) and high (≥55%) early nCPAP use. Time to CPAP failure was modelled using Cox models. Results Of 7566 infants admitted to neonatal care, 3360 (44%) received early CPAP with a range from 21% to 81% across regions; 22% of infants failed CPAP, with a regional range of 11% to 61%. Failure rates were 47% at <26 weeks, 29% at 26–29 weeks and 16% at 30–31 weeks. In adjusted models, low gestational age, male sex, SGA, Apgar <7, no prenatal steroids, and maternal hypertension were associated with failure. Regions with low and intermediary nCPAP use had higher failure rates (adjusted hazard ratio (aHR): 1.3 95% CI: 1.0–1.6 and aHR: 1.4 95% CI: 1.2–1.7, respectively) than high-use regions. Conclusions Perinatal factors identify infants likely to experience nCPAP failure. However, experience and training may also play an important role in effective nCPAP.