; for the Effective Perinatal Intensive Care in Europe (EPICE) Research Group 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.

Near-infrared spectrophotometry (NIRS) potentially provides a tool for noninvasive tissue oxygenation and blood volume monitoring. Cerebral monitoring could be useful in the prevention of hypoxic ischemic brain injury in newborns. This study sought to validate such NIRS measurements in normoventilated, hypocapnic, and hypoxemic states in the brain of newborn piglets vs. arterial (SaO2) and sagittal sinus blood hemoglobin saturation (SssO2) and blood volume measurements with 99mTc-labeled erythrocytes. NIRS measurements of cerebral blood volume (CBV) were performed with both oxyhemoglobin and indocyanine green as tracers, and changes in CBV were monitored by following the change in the concentration of total hemoglobin (i.e., oxyhemoglobin + deoxyhemoglobin). NIRS CBV measurements did not correlate well with the radioactive measurements. NIRS measurements of oxygenation, however, correlated well with a weighted mean value of SaO2 and SssO2 (r = 0.90; P < 0.0001). Multiple linear regression of the oxygenation index (i.e., oxyhemoglobin - deoxyhemoglobin) on SaO2 and SssO2 suggested that NIRS sees hemoglobin in tissue in a venous-to-arterial ratio of 2:1. Therefore, in this study, NIRS reliably monitored changes in cerebral tissue oxygenation but not in CBV.

No abstract

Disturbances in cerebral blood flow (CBF) are a major factor in the etiology and pathogenesis of cerebral damage in the neonate. As most animals are more mature at birth than man, extrapolation from animal studies to the human is questionable. Therefore, we have measured regional CBF (rCBF) in preterm infants. rCBF flow was measured in 12 normotensive and normoxic preterm infants [mean birth weight 915 g (range 550 to 2680 g), mean gestational age 27.7 wk (25 to 32 wk)]. All infants had a normal cerebral ultrasound examination. rCBF was measured using a mobile brain dedicated fast-rotating four-head multidetector system specially designed for neonatal studies. The tracer was 99mTc-labeled D,L-hexamethylpropylenamine oxime in a dose of 4 Mbq/kg. rCBF of the subcortical white matter was 0.53 (0.48-0.58) of the global CBF. After correction for scattered radiation, the estimate of rCBF to the white matter was reduced to 0.39 (0.36-0.42). The flow to the basal ganglia was 2.33 (2.08-2.59) times the global CBF. After correction for partial volume effect, the cortical flow was higher than the flow to the basal ganglia and highest in the frontotemporal cortex (motor cortex). The flow to the cerebellum was of the same magnitude as the flow to the basal ganglia, but with a significantly higher variation. rCBF in 12 preterm infants showed a flow distribution similar to flow in other newborn mammals. The gray-white matter contrast, however, was greater. This new information, combined with existing data showing low global CBF, suggests that blood flow to the white matter in the preterm human neonate is extremely low.

No consensus exists in Europe about size or other criteria for NICUs. A better understanding of the characteristics associated with high-quality neonatal care is needed, given the high proportion of very preterm infants who are cared for in units that are considered small or less specialized by many recommendations.

for the Effective Perinatal Intensive Care in Europe (EPICE) Research Group 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 PARTICIPANTSThe 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 MEASURESThree 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. RESULTSOf 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.

on behalf of the EPICE Cohort abstract BACKGROUND AND OBJECTIVE: Stillbirth and in-hospital mortality rates associated with very preterm births (VPT) vary widely across Europe. International comparisons are complicated by a lack of standardized data collection and differences in definitions, registration, and reporting. This study aims to determine what proportion of the variation in stillbirth and in-hospital VPT mortality rates persists after adjusting for population demographics, case-mix, and timing of death.

Key Points Question How was the whole range of gestational age at birth associated with socioeconomic outcomes in adulthood (education, personal income, and primary source of income)? Findings In this cohort study including 228 030 singletons, lower gestational age (<39 weeks of gestation) was associated with lower odds of high educational level and high personal income and increased odds of receiving disability pension and cash welfare benefits compared with individuals born at 40 weeks of gestation. Meaning These findings suggest that lower gestational age even within the term range may have implications for long-term opportunities and well-being as measured by socioeconomic outcomes in adulthood.