Factors associated with neurodevelopment in preterm infants with systematic inflammation

Abstract

Background Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment. Methods This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months. Results The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score − 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months. Conclusions Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.

Impact of Early Nutrient Intake and First Year Growth on Neurodevelopment of Very Low Birth Weight Newborns

“…Survival of very low birth weight (VLBW) infants has increased over the last few decades; however, poor postnatal growth and suboptimal neurodevelopmental outcomes are common in this population compared to the infants born at term [1][2][3]. Preterm birth alters brain development and multiple factors have been shown to have an impact on neurological outcomes: preexisting conditions, size at birth [4], gestational age (GA) [5], nutrition and postnatal growth faltering [6], and comorbidities [7][8][9][10]. Preterm infants are born during a period of rapid fetal growth, requiring high nutrient intake to promote extrauterine growth.…”

Associations between early marriage and preterm delivery: Evidence from lowland Nepal

“…Meeting nutritional demands through enteral feeding after birth is constrained by the immaturity of the gut in preterm infants, meaning they are prone to poor growth and development in early life (Zozaya et al, 2019). Furthermore, preterm infants have an increased risk of being exposed to inflammation, either prenatally or postnatally, which impairs neurodevelopment (Cappelletti et al, 2016; Lee et al, 2021). Prematurity therefore has long‐term consequences on the health and cognitive development of individuals into adulthood (Kajantie et al, 2010; MacKay et al, 2010; Markopoulou et al, 2019).…”

Probiotic supplementation in neonates with congenital gastrointestinal surgical conditions: a pilot randomised controlled trial

“… 29 , 30 Studies in preterm infants have reported an association between postnatal growth restriction of the head circumference and adverse developmental outcomes. 31 – 33 Hence, it was reassuring that postnatal growth restriction for head circumference was less severe in the probiotic group in our RCT. Similar beneficial effects of probiotics on head circumference were observed in extremely low birth weight infants in recent RCTs.…”