Comparative Effects of Bone Marrow-derived Versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a life-threatening condition in preterm infants with few effective therapies. Mesenchymal stem or stromal cells (MSCs) are a promising therapeutic strategy for BPD. The ideal MSC source for BPD prevention is however unknown. The objective of this study was to compare the regenerative effects of MSC obtained from bone marrow (BM) and umbilical cord tissue (UCT) in an experimental BPD model. In vitro, UCT-MSC demonstrated greater proliferation and expression of anti-inflammatory cytokines as compared to BM-MSC. Lung epithelial cells incubated with UCT-MSC conditioned media (CM) had better-wound healing following scratch injury. UCT-MSC CM and BM-MSC CM had similar pro-angiogenic effects on hyperoxia-exposed pulmonary microvascular endothelial cells. In vivo, newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P) 1 to 21 were given intra-tracheal (IT) BM or UCT-MSC (1 × 106 cells/50 µL), or placebo (PL) on P3. Hyperoxia PL-treated rats had marked alveolar simplification, reduced lung vascular density, pulmonary vascular remodeling, and lung inflammation. In contrast, administration of both BM-MSC and UCT-MSC significantly improved alveolar structure, lung angiogenesis, pulmonary vascular remodeling, and lung inflammation. UCT-MSC hyperoxia-exposed rats however had greater improvement in some morphometric measures of alveolarization and less lung macrophage infiltration as compared to the BM-MSC-treated group. Together, these findings suggest that BM-MSC and UCT-MSC have significant lung regenerative effects in experimental BPD but UCT-MSC suppresses lung macrophage infiltration and promotes lung epithelial cell healing to a greater degree.

Association Between Neonatal Seizures and Social-Emotional Development and Adaptive Behavior in Extremely Low Birth Weight Infants.

AIM: To evaluate social-emotional development and adaptive behavioral outcomes in a cohort of extremely low birth weight infants with a confirmed diagnosis of neonatal seizures. METHODS: This is a retrospective cohort study of preterm infants weighing ≤1000 g at birth, with a diagnosis of neonatal seizures, evaluated between 21 and 31 months of age using the Bayley Scales of Infant Development (Bayley-III) in a longitudinal neurodevelopmental follow-up program. Seizures were diagnosed using continuous video electroencephalography interpreted by a pediatric neurologist. RESULTS: Nineteen infants meeting criteria were included and were matched with 38 control subjects, without clinical signs of seizures, and similar baseline characteristics. Multivariate analysis revealed significantly lower social-emotional development (-14.8 points; P = .05) and adaptive behavior scores (-10.8 points; P < .01) on the Bayley III in children with seizures compared to controls without clinical signs of seizure.Interpretation: Seizures are associated with impaired adaptive behavior and social-emotional development in this cohort of extremely low birth weight infants. These results highlight the negative association between neonatal seizures and functional development.

Lack of response to treatment with levetiracetam in extreme preterm infants with seizures.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of monotherapy with levetiracetam (LEV) in achieving seizure cessation in a retrospective cohort of extreme preterm infants with seizures. STUDY DESIGN: Charts of infants with a diagnosis of neonatal seizures admitted to the NICU between 2013 and 2017 were reviewed. Seizures were diagnosed using continuous video electroencephalography. All infants were initially started on LEV and reached a dose of 80 mg/kg/day. Other ASMs were added to LEV if seizures continued after 2 days. Data on additional clinical variables were collected for each infant. RESULT: Sixty-one infants born <28 weeks of gestation met inclusion criteria. Seventy-four percent of patients did not respond to LEV monotherapy and required additional medications. CONCLUSIONS: LEV monotherapy stopped seizures in only a small portion of cases.

Cognitive impairment among extremely low birthweight preterm infants from 1980 to present day.

OBJECTIVE: To report cognitive outcomes of preterm infants evaluated in a single center between 1980 and 2015. STUDY DESIGN: Cognitive scores at a median age of 33 months were collected in preterm infants (birthweight ≤ 1000 g). Cognition was assessed using the Bayley Scales of Infant Development and the Stanford Binet Intelligence Scales. RESULTS: Six-hundred and two infants born between 1980 and 2015 were evaluated. Significant cognitive impairment for all infants decreased by 9.4% (p = 0.015) across the study period. For larger infants (birthweight ≥ 750 g), significant impairment decreased by 14.6% (p = 0.002). In smaller infants (birthweight < 750 g) no significant changes were observed in cognitive outcomes over the study period. CONCLUSIONS: Overall, long-term outcomes of ELBW infants in our cohort showed significant improvement since 1980. Significant impairment decreased in infants with BW ≥ 750 g; and, despite increased survival of smaller (BW < 750 g) and sicker infants, significant impairment in that subgroup did not worsen over time.

Changes in Urinary Tract Infection Hospitalizations Post 2011 Revised American Academy Pediatrics Guidelines.

BACKGROUND: Multiple randomized trials over the past 2 decades have supported oral antimicrobial treatment for urinary tract infection (UTI), and the 2011 revised American Academy Pediatrics guidelines on the management of UTI provide further support for outpatient management. It is unknown whether practice patterns have changed as a result of these developments. OBJECTIVE: To examine temporal trends in UTI hospitalizations between 1997 and 2012 as measured by the Kids' Inpatient Database. DESIGN AND METHODS: The Kid's Inpatient Database was used to analyze trends in UTI hospitalizations between 1997 and 2012. This triennial database is publicly available through the Agency for Healthcare Research and Quality. Hospitalization volume for clinical classification software principal diagnosis category 159 Urinary tract infection was examined for trends across years by age. Changes in length of stay and charges corrected for inflation were also examined. RESULTS: There were significantly fewer weighted UTI hospitalizations in 2012 compared with 1997 to 2009 (48 102 SE ± 1494 in 2009 vs 41 177 SE ± 1467 in 2012, P < .0001). The largest decrease was in 15- to 17-year-old (19.2%) and <1-year-old (18.6%) groups. The length of stay trended down consistently, but charges have increased despite correcting for consumer price index. CONCLUSIONS: Year 2012 represents the first significant decrease in national hospitalization rates for UTI since 1997, a trend that may be explained by the accumulating evidence supporting outpatient management in addition to recommendations from the 2011 American Academy of Pediatrics UTI guidelines.

Topiramate for Seizures in Preterm Infants and the Development of Necrotizing Enterocolitis.

Neonatal seizures represent a significant health burden on the term and preterm neonatal population and are linked to poor long-term neurodevelopmental outcomes. Currently, there are no US Food and Drug Administration-approved antiepileptic drugs for neonates, and authors of the medical literature have yet to reach a consensus on the most adequate approach to neonatal seizures. Topiramate is readily used in the adult and older pediatric population for the management of migraines and partial-onset seizures. Topiramate continues to gain favor among pediatric neurologists who often recommend this medication as a third-line treatment of neonatal seizures. We report our recent experience with 4 preterm neonates, born between 2015 and 2017, who developed radiographic signs of necrotizing enterocolitis after receiving topiramate for seizures. Each was given oral topiramate for the treatment of electrographic and clinical seizures and developed the subsequent diagnosis of necrotizing enterocolitis, with abdominal distention, hemoccult-positive stools, and radiographic signs of intestinal distention and pneumatosis. More research regarding the risk factors of topiramate use in premature infants is needed.