Serum neurotrophins at birth correlate with respiratory and neurodevelopmental outcomes of premature infants

Abstract

Objective Preterm birth is a significant cause of infant morbidity and mortality, which are primarily the result of respiratory and neurodevelopmental complications. However, no objective biomarker is currently available to predict at birth the risk and severity of such complications. Thus, we sought to determine whether serum neurotrophins concentrations measured at birth correlate with risk for later development of bronchopulmonary dysplasia (BPD) and long‐term neurodevelopmental outcomes. Methods This study prospectively included 223 newborns admitted to neonatal intensive care units (NICU) and divided into three groups: (i) preterm infants who developed BPD; (ii) preterm infants who did not develop BPD; (iii) term infants. An exploratory cohort was enrolled in West Virginia, followed by a validation cohort recruited in four NICUs in Ohio. Specimens for serum and tracheal neurotrophins concentrations were collected within 48 h of admission. Infants requiring a fraction of inspired oxygen >0.21 for at least 28 days were diagnosed with BPD. Neurodevelopmental outcomes were extrapolated from Bayley Scales of Infant Development—Third Edition (BSID‐III) administered at the 24‐month follow‐up visit. Results Serum brain‐derived neurotrophic factor (BDNF) concentration at birth had significant negative correlation with later diagnosis of BPD (P = 0.011) and with duration of invasive ventilation and oxygen supplementation (P = 0.009 and 0.015, respectively). Serum nerve growth factor (NGF) concentration at birth had significant positive correlation with BSID‐III cognitive and language composite scores at 24 months (P < 0.001 and 0.010, respectively). Conclusions These data suggest that serum neurotrophins concentrations measured at birth provide prognostic information on subsequent respiratory and neurodevelopmental outcomes.

Neurotrophic Factor Levels in Preterm Infants: A Systematic Review and Meta-Analysis

“…However, we did not rule out the possibility that preterm newborns might also have altered expression and production of these NFs, since our meta-analyses were performed with a small number of studies, which highlights the under exploration of some NFs. Interestingly, in some of the reviewed studies, we found relevant clinical correlations between NGF levels and neurodevelopmental outcomes ( 25 , 29 ). Suggesting that these NFs should be further explored.…”

“…In addition to preterm and term comparisons performed in the meta-analyses, findings showing an association between NFs and clinical outcomes were reported in some studies ( Table 1 ). Simpson et al ( 29 ) found that lower levels of serum BDNF were significantly associated with a higher risk of bronchopulmonary dysplasia among preterm newborns. Furthermore, Dhobale et al ( 21 ) showed a positive correlation between BDNF levels and gestational weeks.…”

“…Furthermore, Dhobale et al ( 21 ) showed a positive correlation between BDNF levels and gestational weeks. Regarding NGF, Simpson et al ( 29 ) documented that the levels measured at birth had a highly significant positive correlation with language and cognitive outcomes at 24 months of life. Moreover, a positive association of NGF and baby systolic blood pressure was found by Sahay et al ( 25 ).…”

Cord serum brain-derived neurotrophic factor levels at birth associate with temperament outcomes at one year

“…This study is the first to our knowledge examining the relationship between cord serum BDNF levels at birth with BSID-III scores at 12–14 months. One previous study assessed the relationship between BSID-III scores and cord serum BDNF at 24 months and reported no association between serum BDNF levels at birth and BSID-III cognitive, language or motor scores ( Simpson et al, 2019 ). Perera et al (2015) identified a positive association between plasma BDNF from cord blood and BSID-III mental development index scores at 2 years; however this relationship disappeared by 3 years of age ( Perera et al, 2015 ).…”

Pediatric Pulmonology 2019 year in review: Neonatal pulmonology

“…In the seemingly never‐ending search for preventive treatments, Cuna et al 16 compared ventilated prematurely born patients who received dexamethasone between day 14 and day 28 with those who received treatment after 28 days and found that the earlier‐treated group had better outcomes. To better identify those prone to develop BPD, molecular markers of susceptibility, such as brain‐derived neurotrophic factor 17 are being studied since we know that genetic contribution to BPD is significant 15 . Using inbred congenic neonatal mice, Tiono et al 18 showed significant genetic strain‐dependent susceptibility to hyperoxia and strain‐dependent variation in antioxidant responses.…”