ITGB2 (Integrin ß2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis.

ABSTRACT: Aberrant toll-like receptor (TLR) activation is central to necrotizing enterocolitis (NEC) pathogenesis. ß2 integrins regulate TLR signaling, and integrin ß2 (ITGB2) deficiency causes TLR hyperresponsiveness. To test the hypothesis that ITGB2 genetic variants modulate NEC susceptibility, we sequenced the exonic ITGB2 locus to compare the prevalence of deleterious variants among 221 preterm infants with and without NEC. ITGB2 variants were not associated with NEC in our entire cohort (NEC [9/56] versus controls [16/165], P = 0.19) or in extremely low birthweight infants (ELBW, controls [7.9%] versus NEC [18.2%]; P = 0.11) but were increased compared to the populace (4.5%, gnomad.broadinstitute.org). Combined annotation-dependent depletion -predicted deleterious ITGB2 variants increased proportionately with increasing NEC severity in ELBW infants (controls [6.7%] versus medical NEC [16.7%] versus surgical NEC [19%] (P = 0.03). Although ITGB2 variants were not associated with NEC in our preterm cohort, subgroup analysis showed a trend towards enrichment with NEC severity in ELBW infants.

Implementation of Updated Hearing Screen Guidelines in a Level IV NICU-A Quality Improvement Project.

Hearing loss is the most common congenital birth defect. In 2007, American Academy of Pediatrics updated the hearing screen guidelines to recommend hearing screen by 1 month of age, diagnostic evaluation by 3 months, and early interventions by 6 months. Early interventions have been shown to improve developmental outcome in children with hearing loss. Infants admitted to the neonatal intensive care unit (NICU) are at higher risk for hearing loss. For infants born before 34 weeks' gestation, there are no guidelines for initial hearing screen. Although auditory brain stem response can be reliably performed at 32 to 34 weeks, in most NICUs, they are screened prior to discharge per universal hearing screen guidelines. In high-risk infants, often with prolonged hospitalization, this leads to missed opportunity for early detection and implementation of early intervention services. Using quality improvement methodology, an updated hearing screen algorithm was developed and implemented in our level IV NICU along with an electronic medical record tool to improve the process of identifying infants meeting criteria for hearing screen.

Genetic predisposition to necrotizing enterocolitis in premature infants: Current knowledge, challenges, and future directions.

The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was initially informed by epidemiological data indicating differences in prevalence among different ethnic groups as well as concordance in twins. These early observations, together with major advances in genomic research, paved the way for studies that begin to reveal the contribution of genetics to NEC. Using the candidate gene or pathway approach, several potential pathogenic variants for NEC in premature infants have already been identified. More recently, genome-wide association studies and exome-sequencing based studies for NEC have been reported. These advances, however, are tempered by the lack of adequately powered replication cohorts to validate the accuracy of these discoveries. Despite many challenges, genetic research in NEC is expected to increase, providing new insights into its pathogenesis and bringing the promise of personalized care closer to reality. In this review we provide a summary of genetic studies in NEC along with defining the challenges and possible future approaches.

The Role of a Single Dose of Vancomycin in Reducing Clinical Sepsis in Premature Infants Prior to Removal of Peripherally Inserted Central Catheter: A Retrospective Study.

OBJECTIVE: Peripherally inserted central catheter (PICC) line removal is associated with bloodstream infections and clinical sepsis. We aim to investigate the role of a single prophylactic dose of vancomycin in decreasing the incidence of central line associated bloodstream infection associated with PICC removal. METHODS: A retrospective chart review of patients in the neonatal intensive care unit was conducted. Patients were divided into two study groups based on whether a single dose of vancomycin was administered (exposed) or not (nonexposed). The primary outcome measured was clinical sepsis with or without positive blood culture. RESULTS: The incidence of clinical sepsis in the exposed group was 7.3% compared with 6.3% in the nonexposed group (p-value: 0.7860). The incidence of culture-positive sepsis in the exposed group was 2.2% compared with 1.6% in the nonexposed group (p-value: 0.7673). The overall incidence of clinical and culture-positive sepsis in the subgroup with infants weighing <1,500 g and <32 weeks' gestational age was similar to the main study group. CONCLUSION: Our data do not support routine vancomycin prophylaxis prior to PICC line removal in premature infants to prevent sepsis associated with PICC removal. However, a large randomized controlled trial is further needed to delineate these results.

A Singleton Infant with Bilateral Renal Agenesis and Normal Pulmonary Function.

Bilateral renal agenesis leads to anhydramnios and other sequelae including pulmonary hypoplasia. There have been rare case reports of normal pulmonary function in the presence of bilateral renal agenesis in monoamniotic discordant twins, but this has never been reported in a singleton pregnancy. The few reported cases in twins have all been fatal in the neonatal period with no reported cases of survival beyond 2 months. We describe the first case of a singleton infant with bilateral renal agenesis who had normal pulmonary function and did well on peritoneal dialysis for 4 years while awaiting a renal transplant.

Use of Biphasic Continuous Positive Airway Pressure in Premature Infant with Cleft Lip-Cleft Palate.

Preterm infants (PIs) often require respiratory support due to surfactant deficiency. Early weaning from mechanical ventilation to noninvasive respiratory support decreases ventilation-associated irreversible lung damage. This wean is particularly challenging in PIs with cleft lip and cleft palate due to anatomical difficulties encountered in maintaining an adequate seal for positive pressure ventilation. PI with a cleft lip and palate often fail noninvasive respiratory support and require continued intubation and mechanical ventilation. We are presenting the first case report of a PI with cleft lip and palate who was managed by biphasic nasal continuous positive airway pressure.