Pharyngeal pressure due to high-flow nasal cannula devices in preterm infants.

BACKGROUND: In infants, a high-flow nasal cannula (HFNC) generates continuous positive pressure on the upper airway. This study aimed to evaluate the association between pharyngeal pressure and flow rate, and the association between pharyngeal pressure and bodyweight for two types of HFNC devices commonly used in preterm infants: the Optiflow Junior, hereafter "FP" (Fisher & Paykel, Auckland, New Zealand), and the Precision Flow, hereafter "VT" (Vapotherm, Exeter, NH, USA). METHODS: Pharyngeal pressure measurements were performed in 12 preterm infants who received HFNC support. Flow rates of 1 to 4 L/kg/min were studied. RESULTS: The median weight at the time of measurement was 1,290 g (range, 953-1,932 g). The FP was used in eight infants and the VT in four. In both of the groups, the flow rate and pharyngeal pressure appeared to be positively correlated except for the premature cannula in the FP group. At a flow rate of ≥2 L/kg/min, there was a positive correlation between the bodyweight and pharyngeal pressure in infants with premature and neonatal cannulas in the FP group. Conversely, at the same flow rate, there was a negative correlation between the bodyweight and pharyngeal pressure in infants with a SOLO cannula in the VT group. CONCLUSIONS: In preterm infants, the flow rate and pharyngeal pressure were positively correlated in many HFNC cannulas. However, the pharyngeal pressure and bodyweight appeared to be positively and negatively correlated in the FP and VT groups, respectively. Future studies with larger sample sizes should further investigate this issue.

A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by SMN1 gene deletion/mutation. The drug nusinersen modifies SMN2 mRNA splicing, increasing the production of the full-length SMN protein. Recent studies have demonstrated the beneficial effects of nusinersen in patients with SMA, particularly when treated in early infancy. Because nusinersen treatment can alter disease trajectory, there is a strong rationale for newborn screening. In the current study, we validated the accuracy of a new system for detecting SMN1 deletion (Japanese patent application No. 2017-196967, PCT/JP2018/37732) using dried blood spots (DBS) from 50 patients with genetically confirmed SMA and 50 controls. Our system consists of two steps: (1) targeted pre-amplification of SMN genes by direct polymerase chain reaction (PCR) and (2) detection of SMN1 deletion by real-time modified competitive oligonucleotide priming-PCR (mCOP-PCR) using the pre-amplified products. Compared with PCR analysis results of freshly collected blood samples, our system exhibited a sensitivity of 1.00 (95% confidence interval [CI] 0.96-1.00) and a specificity of 1.00 (95% CI 0.96-1.00). We also conducted a prospective SMA screening study using DBS from 4157 Japanese newborns. All DBS tested negative, and there were no screening failures. Our results indicate that the new system can be reliably used in SMA newborn screening.

Evaluation index for asymmetric ventricular size on brain magnetic resonance images in very low birth weight infants.

OBJECTIVE: Asymmetric ventriculomegaly is often evident on brain magnetic resonance imaging (MRI) in very low birth weight infants (VLBWI) and is interpreted as white matter injury. However, no evaluation index for asymmetric left-right and anterior-posterior ventricular sizes has been established. METHODS: In this retrospective multicenter cohort study, brain T2-weighted MRI was performed at term-equivalent ages in 294 VLBWI born between 2009 and 2011. The value of a lateral ventricular index (LVI) to evaluate asymmetric ventricular size, as well as the relationship between the LVI value and walking at a corrected age of 18 months was investigated. At the level of the foramen of Monro in a horizontal slice, asymmetry between the left and right sides and between the anterior and posterior horns was identified by the corrected width and was detected by a low concordance rate and κ statistic value. An LVI representing the sum of the widths of the four horns of the lateral ventricle corrected for cerebral diameter was devised. RESULTS: Asymmetric left-right and anterior-posterior ventricular sizes were confirmed. The LVI value was significantly higher in the non-walking VLBWI group (n = 39) than in the walking VLBWI group (n = 255; 18.2 vs. 15.8, p = 0.02). An LVI cut-off value of 21.5 was associated with non-walking. Multivariate analysis revealed that an LVI value >21.5 was an independent predictor of walking disability at the corrected age of 18 months (odds ratio 2.56, p = 0.008). CONCLUSIONS: The LVI value calculated via MRI may predict walking disability at a corrected age of 18 months in VLBWI.

Serum unbound bilirubin as a predictor for clinical kernicterus in extremely low birth weight infants at a late age in the neonatal intensive care unit.

BACKGROUND: This study aimed to evaluate peak serum total bilirubin (TB) and unbound bilirubin (UB) levels in preterm infants with clinical kernicterus (KI) who were diagnosed by clinical findings during infancy. DESIGN/SUBJECTS: For this multicenter retrospective study, 18 Japanese extremely low birth weight (ELBW) infants with clinical KI were included. Clinical KI was diagnosed based on the presence of motor developmental impairment with/without athetosis, and abnormal magnetic resonance imaging or brainstem auditory evoked potential findings during infancy. High and low TB or UB levels were defined as serum TB levels ⩾ and <15 mg/dL or serum UB levels ⩾ and <0.8 µg/dL, respectively. The clinical characteristics of KI preterm infants were analyzed. The proportion of infants with high or low serum TB levels and with high or low serum UB levels was then investigated. Sensitivity and specificity were calculated. RESULTS: In 18 KI infants, the median age when serum TB levels peaked was 28 days after birth. In eight KI infants with low serum TB levels, 88% of them had high serum UB levels. For comparison of the number of infants who had high or low serum TB and UB levels, the sensitivity was 90% and specificity was 13%. CONCLUSIONS: Serum TB and UB levels peak at a later age than expected. Chronic serum UB monitoring may be helpful for identifying ELBW infants at risk for developing KI, even when they do not have high serum TB levels.

Blood lysophosphatidylcholine (LPC) levels and characteristic molecular species in neonates: prolonged low blood LPC levels in very low birth weight infants.

Lysophosphatidylcholine (LPC) has various stimulatory effects on many types of immune cells. The purpose of our study was to characterize blood LPC levels and to determine the composition of LPC molecular species (LPCs) in the neonatal period. Thirty-six neonates were enrolled in this study and then grouped according to birth-weight as follows: non-very low birth weight (NVLBW); >or=1,500 g (n=17), and very low birth weight (VLBW); <1,500 g (n=19). Sixteen healthy normal adults were used as controls. Levels of total blood LPC and LPCs (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPC species) were measured using HPLC coupled with tandem mass spectrometry. Total blood LPC levels at birth in neonates in both groups (NVLBW and VLBW) were significantly lower than those of adult levels. In NVLBW infants, LPC levels reached adult levels at postnatal day 3 compared with VLBW infants, who attained adult levels after postnatal day 57 (around full-term). The composition of the LPCs was different not only between neonates and adults, but between NVLBW and VLBW infants. These findings may be associated with the difference of immunity among adults, NVLBW, and VLBW infants.

Quantification of lysophosphatidylcholines and phosphatidylcholines using liquid chromatography-tandem mass spectrometry in neonatal serum.

We established an improved method for quantification of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) molecular species in neonatal serum using high-performance liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). A multiple reaction monitoring (MRM) mode of positive ionization for MS/MS was used. The method involved purification of phospholipids by solid phase extraction (SPE) from a 20-microl minimum specimen of serum. The assayed values of authentic 16:0-LPC and 18:0-LPC showed a linear response, and our quantitative results showed high precision for the all species of PC and LPC. Then, we quantified PC and LPC in adult and neonatal serum and compared them. Day 0-1 neonatal serum 16:0-, 18:0-, 18:1-, 18:2-LPC levels were significantly lower than adult ones. All species LPC levels in the day 0-1 neonates were significantly lower than day 4-8 neonates. Day 0-1 neonatal serum 16:0/18:2-, 18:0/18:2-PC levels were significantly lower than adult ones. Our method is advantageous for precise assessments of the relationships between PCs/LPCs levels and neonatal infectious diseases.