Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Ampicillin and Gentamicin Treatment for Early Onset Neonatal Sepsis: When One Size Does Not Fit All.

Based on in vitro susceptibilities and the concern for emergence of resistance and long-term safety, ampicillin plus gentamicin remains the recommended antibiotic regimen for early onset neonatal sepsis. Our objective was to identify potential limitations of this regimen based on clinical and pathogen characteristics while minimizing risks associated with prolonged antibiotic exposure. We identified 43 gram-negative pathogens in 42 patients. Escherichia coli (E coli) occurred in 50% and Streptococcus agalactiae in 23.8% of patient. Ampicillin resistance was common, particularly in E coli (85.7%). Mortality was 23.8%, all due to E coli. We found that E coli is the most frequent pathogen and has a high mortality particularly in neonates < 1500 g; mortality is high with the current dosing strategy when E coli is resistant to ampicillin even when sensitive to gentamicin; resistance to gentamicin remains low but seems to be increasing while resistance to third-generation cephalosporins remains very low.

Lack of Evidence for Time or Dose Relationship between Antenatal Magnesium Sulfate and Intestinal Injury in Extremely Preterm Neonates.

BACKGROUND: Recent studies reported conflicting results on the relationship between antenatal magnesium sulfate (MgSO4) exposure and neonatal intestinal injury. Most studies have not assessed MgSO4 exposure quantitatively and none reported the exposure timing. OBJECTIVES: The aim of this work was to assess whether there is a temporal or dose-dependent relationship between antenatal MgSO4 exposure and intestinal injury in extremely preterm neonates. METHODS: A retrospective study was made of inborn neonates with gestational age ≤28 weeks and/or birth weights ≤1,000 g. Primary outcomes included necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), and/or death prior to discharge or in the first 2 weeks of life. Outcome comparisons were made based on the timing of MgSO4 exposure, within 7 days (Mg7D) or within 3 days (Mg3D) of birth. Total cumulative doses for the Mg3D group were also computed. RESULTS: A total of 302 neonates were included, 210 in the Mg7D group, out of whom 179 (85.2%) constituted the Mg3D group. There were no differences noted when comparing MgSO4 exposure timing and the likelihood of NEC, SIP, and/or death. This remained the same for subgroup analysis of neonates < 26 weeks' gestation. Each 10-g increase in MgSO4 cumulative dose correlated with a decrease in SIP/NEC/death by 18.9% prior to discharge and by 21.9% in the first 2 weeks of life. Small for gestational age (SGA) was a potential effect modifier by a likelihood ratio test with p = 0.07. CONCLUSIONS: Antenatal MgSO4 exposure in extremely preterm neonates was not associated with an increased risk of intestinal injury or death, and might have reduced these complications in a dose-dependent manner in our study. This protective effect was more noticeable in SGA neonates.

Three-hourly feeding intervals are associated with faster advancement in very preterm infants.

OBJECTIVE: To compare the effect of two-hourly (Q2H) vs. three-hourly (Q3H) feeding on time to achieve full enteral feeding, growth metrics and respiratory tolerance in very preterm infants with birth weight ≤ 1250 g. STUDY DESIGN: Retrospective study review of 18 months before and after a change in our feeding guideline from Q3H to Q2H feedings. RESULTS: 113 infants were included, 59 in Q3H and 54 in Q2H groups. Q2H infants required 10% more days to achieve full enteral feeding, however it was not statistically significant (P = 0.054). Q2H feeding was associated with 16% more central catheter days (P = 0.02) and 17% more parenteral nutrition days (P = 0.019). There were no differences in respiratory outcomes or growth metrics between the groups. CONCLUSION: Very preterm infants fed Q3H had less central catheter and parenteral nutrition days when compared to those fed Q2H, without significant differences in growth or respiratory outcomes.

Regulation of cytochrome P4501A1 expression by hyperoxia in human lung cell lines: Implications for hyperoxic lung injury.

Supplemental oxygen, used to treat pulmonary insufficiency in newborns, contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome P4501A enzymes are induced by hyperoxia in animal models, but their role in human systems is unknown. Here we investigated the molecular mechanisms of induction of CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were exposed to hyperoxia (95% O2) for 0-72 h, and CYP1A1 activities, apoprotein contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1 activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction assays showed attenuation of cell injury with the CYP1A1 inducer beta-naphthoflavone (BNF). Our results strongly suggest that hyperoxia transcriptionally activates CYP1A1 expression in human lung cell lines by AHR-dependent mechanisms, and that CYP1A1 induction is associated with decreased toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous AHR ligands could lead to novel interventions in the treatment of BPD.

Terminal deletion of chromosome 15q26.1: case report and brief literature review.

Terminal deletions of chromosome 15q are rare events, with only six cases previously described. Here we describe a seventh case of a terminal deletion of the long arm of chromosome 15, with the present case exhibiting clinical features not previously described.

Laryngeal lymphatic malformation in a newborn.

Stridor in a neonate evokes a series of prompt evaluations to determine the etiology. Common etiologies include inherent structural defects (such as laryngomalacia), vocal fold paralysis, acquired infectious etiologies, or extrinsic compressions. We report a neonate with a lymphatic malformation (lymphangioma) initially confined to the larynx that presented with stridor and progressive respiratory failure. Only seven other cases have been reported to present with lymphatic malformation confined solely to the larynx. There are several different modalities available to treat this condition, but recurrences are common. The presentation and management are discussed below. Physicians should be aware that stridor in a neonate can result from this unusual intrinsic obstruction of the larynx.