Objective Although many perinatal factors have been linked to adverse neurodevelopmental outcomes in very premature infants, much of the variation in outcome remains unexplained. The impact on brain development of one potential factor, exposure to stressors in the Neonatal Intensive Care Unit, has not yet been studied in a systematic, prospective manner. Methods In this prospective cohort study of infants born at <30 weeks gestation, nurses were trained in recording procedures and cares. These recordings were used to derive Neonatal Infant Stressor Scale scores, which were employed to measure exposure to stressors. Magnetic resonance imaging (brain metrics, diffusion, and functional magnetic resonance imaging) and neurobehavioral examinations at term equivalent postmenstrual age were used to assess cerebral structure and function. Simple and partial correlations corrected for confounders including immaturity and severity of illness were used to explore these relationships. Results Exposure to stressors was highly variable, both between infants and throughout a single infant’s hospital course. Exposure to a greater number of stressors was associated with decreased frontal and parietal brain width, altered diffusion measures and functional connectivity in the temporal lobes, and abnormalities in motor behavior on neurobehavioral examination. Interpretation Exposure to stressors in the Neonatal Intensive Care Unit is associated with regional alterations in brain structure and function. Further research into interventions that may decrease or mitigate exposure to stressors in the Neonatal Intensive Care Unit is warranted.

Objective To investigate differences in neurobehavior between preterm infants at term and full term infants, changes in neurobehavior between 34 weeks postmenstrual age (PMA) and term equivalent in the preterm infant, and relationships of neurobehavior to perinatal exposures. Study design In this prospective cohort study, 75 infants were tested at 34 weeks PMA and again at term using the NICU Network Neurobehavioral Scale (NNNS). Infants had an MRI at term equivalent. Regression was used to investigate differences in NNNS domains of function across time and in relation to perinatal exposures. Results At term equivalent, premature infants demonstrated altered behavior compared with full term infants with poorer orientation (p<.001), lower tolerance of handling (p<.001), lower self regulation (p<.001), poorer reflexes (p<.001), more stress (p<.001), hypertonicity (p<.001), hypotonia (p<.001), and more excitability (p=.007). Preterm infants, from 34 weeks PMA to term equivalent, demonstrated changes in motor functions with declining quality of movement (p=.006), increasing hypertonia (p<.001), decreasing hypotonia (p=.001) and changes in behavior with increasing arousal (p<.001), increasing excitability (p<.001), and decreasing lethargy (p<.001). Cerebral injury was associated with more excitability (p=.002). However, no associations between any of the perinatal exposures and developmental change from 34 weeks PMA to term equivalent were detected. Conclusion Preterm infants have altered neurobehavior in a broad number of domains at term equivalent. Cerebral injury alters neurobehavior but does not appear to impair early neurobehavioral change. Important neurobehavioral changes occur prior to term, and this provides an opportunity for interventions within the NICU.

Background Previous studies of very preterm (VPT) infants have shown a wide range of seizure prevalence and association with intraventricular hemorrhage (IVH), white matter injury (WMI) and death. However, the impact of seizures on neurodevelopment is not well known. We hypothesized that seizures in the first three days after VPT birth would be associated with increased radiographic brain injury and later neurodevelopmental risk. Methods For 72 hours after birth 95 VPT infants underwent aEEG monitoring. High and low seizure burdens were related to radiographic brain injury, death in the neonatal period and children’s Bayley III performance at 2 years corrected age in a subgroup of 59 infants. Results The overall incidence of seizures in this sample was 48%. High seizure burden was associated with increased risk of IVH on day 1; IVH, WMI and death on day 2 and high grade IVH on day 3. The presence of seizures on any day was associated with decreased language performance at age 2, even after controlling for family social risk. Conclusions Seizures during the first three days after birth are common and are associated with an increased risk of IVH, WMI and death. They were also associated with poorer early language development.

Aim Histological chorioamnionitis (HCA) is associated with preterm birth and adverse neonatal outcomes. We evaluated the rise in C‐reactive protein (CRP) in preterm infants as a predictor of HCA severity and outcomes. Methods Consecutive preterm infants, born January 2009 to January 2014 in the National Maternity Hospital, Dublin, under 32 weeks' gestation or <1.5 kg birthweight, were included. Histological chorioamnionitis was staged as maternal inflammatory response, foetal inflammatory response and non‐HCA. Results Preterm infants (n = 518) were included with a mean gestational age 28.5 ± 2.8 weeks, birthweight 1.1 ± 0.3 kg, and 53.5% were male. Histological chorioamnionitis was found in 25.4%. Histological chorioamnionitis was present in 93.7% when CRP > 5 mg/L, 65.2% when CRP 1‐5 mg/L and in 19.4% when CRP < 1 mg/L. When both the immature to total neutrophil (IT) ratio was >0.2 and the CRP > 1 mg/L the positive predictive value and negative predictive value for HCA were 92.5% and 84.9%, respectively. Histological chorioamnionitis was associated with more resuscitation and respiratory distress syndrome (both P < .001). A CRP > 10 mg/L was associated with a foetal inflammatory response and increased early‐onset sepsis. Conclusion Higher early CRP was a surrogate predictor of HCA and correlated with the severity of HCA. Higher CRP and HCA were associated with adverse early outcomes.

Aim To determine the associations between perinatal exposures, cerebral maturation on amplitude-integrated encephalography (aEEG) and outcome. Methods During this prospective cohort study, 136 infants ≤30 weeks estimated gestational age received four hours of aEEG at four time points (between the first two weeks of life and term equivalent age) during hospitalisation. Perinatal factors were documented. Associations between perinatal exposures and Burdjalov-scores were investigated. Neurodevelopmental outcome was assessed at the age of two. Results Immature cyclicity on the initial aEEG recording was associated with higher CRIB score (p=0.01), vaginal delivery (p= 0.02), male gender (p<0.01) and death (p=0.01). Perinatal factors associated with lower Burdjalov-scores included cerebral injury (p<0.01), sepsis (p<0.01), lower caffeine dose (p=0.006), prolonged mechanical ventilation (p=0.002) and death (p<0.01). Burdjalov-scores at 30 (β=2.62, p<0.01) and 34 weeks post-menstrual age (β=2.89, p=0.05) predicted motor scores. Conclusion aEEG measures of cyclicity and Burdjalov-scores in the first six weeks of life, with an emphasis on 30 and 34 weeks post-menstrual age, demonstrated associations with perinatal factors known to predict adverse neurodevelopmental outcome.