Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates.

BACKGROUND: The aim of this study was to investigate the association between inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)) and sepsis severity (neonatal-Sequential-Organ-Failure-Assessment (nSOFA)) and neurodevelopmental outcomes at 2 years, among very preterm neonates. METHODS: Data on preterm neonates (gestational age <30 weeks) from 2016 until 2020 were reviewed. Outcomes of interest were NDI (no, mild, severe) and the motor and cognitive score on the Dutch-Bayley-Scales-of-Infant-and-Toddler-Development (Bayley-III-NL) assessed at the corrected age of 2 years. Logistic and linear regression analysis were used for categorical and continuous outcomes, respectively. All analyses were adjusted for gestational age, sex and birthweight-for-gestational-age SD-score. RESULTS: In total 410 patients were eligible for analysis. Maximum CRP concentrations were associated with lower motor and cognitive scores (effect estimate -0.03 points,(95% CI -0.07; -0.00) and -0.03 points,(95% CI -0.06; -0.004), respectively) and increased risk of severe NDI (odds ratio (OR) 1.01, (95% CI 1.00; 1.01)). High nSOFA scores (≥4) during sepsis episodes were associated with an increased risk of mild NDI (OR 2.01, (95% CI 1.34; 3.03)). There were no consistent associations between IL-6, PCT and the outcomes of interest. CONCLUSION: High CRP concentrations and sepsis severity in preterm neonates seem to be associated with neurodevelopmental outcomes in survivors at the age of 2 years. IMPACT STATEMENT: The level of inflammation and sepsis severity are associated with neurodevelopmental outcome in preterm neonates at 2 years of corrected age. Sepsis is a major health issue in preterm neonates and can lead to brain damage and impaired neurodevelopment. Biomarkers can be determined to assess the level of inflammation. However, the relation of inflammatory biomarkers with neurodevelopmental outcome is not known. The level of inflammation and sepsis severity are related to neurodevelopmental outcome in preterm neonates. Maximum CRP concentration and high nSOFA scores are associated with an increased risk of neurodevelopmental impairment in survivors at the corrected age of 2 years.

Necrotizing Enterocolitis in a Dutch Cohort of Very Preterm Infants: Prevalence, Mortality, and Long-Term Outcomes.

INTRODUCTION: To improve counseling of parents and to guide care strategies, we studied the disease course and outcomes of necrotizing enterocolitis (NEC) up to 2 years of corrected age (CA) from a multidisciplinary perspective. MATERIALS AND METHODS: This was a retrospective cohort study in preterm infants (birth weight < 1,500 g, gestational age < 32 weeks), diagnosed with NEC (Bell's stage ≥ II) from 2008 through 2020. Data on prevalence, mortality, surgery, intestinal failure (IF), growth, and neurodevelopment at 2-year follow-up were separately analyzed for medically and surgically treated children. RESULTS: Of 3,456 preterm infants, 200 (6%) were diagnosed with NEC, of whom 135 developed an indication for surgery within 7 days after the diagnosis; 28/135 died before surgery, and 37/107 died after an open-and-close procedure. An enterostomy was constructed in 62 patients and an end-to-end anastomosis in 15. The postoperative course was described for 77 patients, of whom 23 developed surgical complications (12/23 incisional hernias, 9/23 anastomotic strictures), 13/77 a short bowel, and 25/77 IF. Sixty-day survival after birth for medical NEC patients was 88% (hazard ratio [HR]: 0.698; p = 0.318), and for surgically treated NEC patients was 40% (HR: 3.729; p < 0.001). At 2-year follow-up, one patient received parenteral nutrition. Severe delay in weight for age, motor, and cognitive development was seen in 3, 6, and 2%, respectively. CONCLUSION: In this cohort, the mortality rate was high, especially in surgically treated NEC patients. The surgical complication rate is comparable to previous studies, but in surviving patients, persisting IF and severe delay in growth and neurodevelopment at 2 years CA were relatively rare.

Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents.

Background Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood. The main aim was to determine the maturation of different cardiac sympathetic-(SNS) and parasympathetic nervous system (PNS) activity parameters in healthy patients aged 0.5 to 20 years. A second aim was to determine potential sex differences. Methods and Results Five studies covering the 0.5- to 20-year age range provided impedance- and electrocardiography recordings from which heart rate, different PNS-parameters (eg, respiratory sinus arrhythmia) and an SNS-parameter (pre-ejection period) were collected. Age trends were computed in the mean values across 12 age-bins and in the age-specific variances. Age was associated with changes in mean and variance of all parameters. PNS-activity followed a cubic trend, with an exponential increase from infancy, a plateau phase during middle childhood, followed by a decrease to adolescence. SNS-activity showed a more linear trend, with a gradual decrease from infancy to adolescence. Boys had higher SNS-activity at ages 11 to 15 years, while PNS-activity was higher at 5 and 11 to 12 years with the plateau level reached earlier in girls. Interindividual variation was high at all ages. Variance was reasonably stable for SNS- and the log-transformed PNS-parameters. Conclusions Cardiac PNS- and SNS-activity in childhood follows different maturational trajectories. Whereas PNS-activity shows a cubic trend with a plateau phase during middle childhood, SNS-activity shows a linear decrease from 0.5 to 20 years. Despite the large samples used, clinical use of the sex-specific centile and percentile normative values is modest in view of the large individual differences, even within narrow age bands.

Infant autonomic nervous system response and recovery: Associations with maternal risk status and infant emotion regulation.

This study examined whether risk status and cumulative risk were associated with autonomic nervous system reactivity and recovery, and emotion regulation in infants. The sample included 121 6-month-old infants. Classification of risk status was based on World Health Organization criteria (e.g., presence of maternal psychopathology, substance use, and social adversity). Heart rate, parasympathetic respiratory sinus arrhythmia, and sympathetic preejection period were examined at baseline and across the still face paradigm. Infant emotion regulation was coded during the still face paradigm. Infants in the high-risk group showed increased heart rate, parasympathetic withdrawal, and sympathetic activation during recovery from the still face episode. Higher levels of cumulative risk were associated with increased sympathetic nervous system activation. Moreover, increased heart rate during recovery in the high-risk group was mediated by both parasympathetic and sympathetic activity, indicating mobilization of sympathetic resources when confronted with socioemotional challenge. Distinct indirect pathways were observed from maternal risk to infant emotion regulation during the still face paradigm through parasympathetic and sympathetic regulation. These findings underline the importance of specific measures of parasympathetic and sympathetic response and recovery, and indicate that maternal risk is associated with maladaptive regulation of stress early in life reflecting increased risk for later psychopathology.

Parental Perceptions of Aggressive Behavior in Preschoolers: Inhibitory Control Moderates the Association With Negative Emotionality.

Inhibitory control (IC) and negative emotionality (NE) are both linked to aggressive behavior, but their interplay has not yet been clarified. This study examines different NE × IC interaction models in relation to aggressive behavior in 855 preschoolers (aged 2-5 years) using parental questionnaires. Hierarchical regression analyses revealed that NE and IC predict aggression both directly and interactively. The highest aggression levels were reported in children with high NE and low IC. Interestingly, the protective effect of IC for aggressive behavior increases with rising levels of NE. Analyses focusing on physical aggression revealed a significant NE × IC interaction in boys aged 4-5 years only. These findings shed new light on potential compensatory mechanisms for aggressive behavior in developing children.

Prenatal reflective functioning in primiparous women with a high-risk profile.

The concept of maternal reflective functioning (RF) has been gaining increasing interest as a possible intermediate mechanism in associations between a wide range of psychosocial risk factors and poor child outcomes. The purpose of the present study was to determine which psychosocial risk factors are linked to prenatal RF in a high-risk (HR) group of primiparous women. Differences in prenatal RF between the HR group and a low-risk (LR) control group also were examined. The sample consisted of 162 women (M = 22.22 years, SD = 2.39; 83 classified as HR). RF was coded from the Pregnancy Interview (A. Slade, 2007a). Risk status was assessed by means of the Mini-International Neuropsychiatric Interview-plus (M.I.N.I.-plus; D.V. Sheehan et al., 1997) and several questionnaires. HR women demonstrated significantly lower RF quality than did the LR group. Regression analyses indicated that maternal education, size of social support network, and substance use during pregnancy were the strongest predictors of prenatal RF for the HR group. The results suggest that maternal RF potentially could be an important target for those prevention and intervention programs that aim to reduce adverse psychosocial development in offspring of HR mothers.

Relationship between the number of life events and memory capacity in children.

Stressful life events can result into declined memory performance at later age. One hypothesis suggests that stress affects the hippocampus, a brain area important for memory functioning. This study explored a potential relationship between the number of negative stressful life events and hippocampus-dependent declarative but not hippocampus-independent procedural memory performance in a community sample of 255 children, aged 6-12 years. The findings revealed that negative stressful life events were negatively related to verbal declarative memory, but not to nonverbal declarative and procedural memory. The memory impairments could not be accounted for by attention and sleep disturbances, and parenting characteristics as perceived by the child did not influence the vulnerability for the stress-related memory impairments. These findings provide further insight into the deleterious effects of negative stressful life events on learning in school-aged children.