The impact of a quality improvement effort in reducing admission hypothermia in preterm infants following delivery

Purpose Hypothermia at admission is associated with increased mortality and morbidity in preterm infants. We performed a quality improvement (QI) effort to determine the impact of a decrease in admission hypothermia in preterm infants. Methods The study enrolled very low birth weight (VLBW) infants born at Gangnam Severance Hospital between January 2013 and December 2016. This multidisciplinary QI effort included the use of occlusive wraps, warm blankets, and caps; the delivery room temperature was maintained above 23.0˚C, and a check-list was used for feedback. Results Among 259 preterm infants, the incidence of hypothermia (defined as body temperature <36.0˚C) decreased significantly from 68% to 41%, and the mean body temperature on neonatal intensive care unit admission increased significantly from 35.5˚C to 36.0˚C. In subgroup analysis of VLBW infants, admission hypothermia and neonatal outcomes were compared between the pre-QI (n=55) and post-QI groups (n=75). Body temperature on admission increased significantly from 35.4˚C to 35.9˚C and the number of infants with hypothermia decreased significantly from 71% to 45%. There were no cases of neonatal hyperthermia. The incidence of pulmonary hemorrhage was significantly decreased (P=0.017). Interaction analysis showed that birth weight and gestational age were not correlated with hypothermia following implementation of the protocol. Conclusion Our study demonstrated a significant reduction in admission hypothermia following the introduction of a standardized protocol in our QI effort. This resulted in an effective reduction in the incidence of massive pulmonary hemorrhage

Postdischarge growth assessment in very low birth weight infants

PurposeThe goal of nutritional support for very-low-birth-weight (VLBW) infants from birth to term is to match the in utero growth rates; however, this is rarely achieved.MethodsWe evaluated postdischarge growth patterns and growth failure in 81 Korean VLBW infants through a retrospective study. Weight and height were measured and calculated based on age percentile distribution every 3 months until age 24 months. Growth failure was defined as weight and height below the 10th percentile at 24 months. For the subgroup analysis, small-for-gestational age (SGA) and extremely low birth weight (ELBW) infants were evaluated. The growth patterns based on the Korean, World Health Organization (WHO), or Centers for Disease Control and Prevention (CDC) standard were serially compared over time.ResultsAt postconception age (PCA) 40 weeks, 47 (58%) and 45 infants (55%) showed growth failure in terms of weight and height, respectively. At PCA 24 months, 20 infants (24%) showed growth failure for weight and 14 (18%) for height. Growth failure rates were higher for the SGA infants than for the appropriate-weight-for-gestational age infants at PCA 24 months (P=0.045 for weight and P=0.038 for height). Growth failure rates were higher for the ELBW infants than for the non-ELBW infants at PCA 24 months (P<0.001 for weight and P=0.003 for height). Significant differences were found among the WHO, CDC, and Korean standards (P<0.001).ConclusionAdvancements in neonatal care have improved the catch-up growth of VLBW infants, but this is insufficient. Careful observation and aggressive interventions, especially in SGA and ELBW infants, are needed

Successful pleurodesis with OK-432 in preterm infants with persistent pleural effusion

OK-432 (picibanil) is an inactivated preparation of Streptococcus pyogenes that causes pleurodesis by inducing a strong inflammatory response. Intrapleural instillation of OK-432 has recently been used to successfully treat neonatal and fetal chylothorax. Here we report a trial of intrapleural instillation of OK-432 in two preterm infants who were born with hydrops fetalis and massive bilateral pleural effusion. Both cases showed persistent pleural effusion, refractory to conservative treatment, up to postnatal days 26 and 46, respectively. An average of 80 to 140 mL of pleural fluid was drained daily. In case 1, the infant was treated with OK-432 during the fetal period at gestation 28 weeks and 4 days of gestation, but showed recurrence of pleural effusion and progressed into hydrops. Within two to three days after OK-432 injection, the amount of pleural fluid drainage was dramatically decreased and there was no reaccumulation. We did not observe any side effects related to OK-432 injection. We suggest that OK-432 should be considered as a therapeutic option in infants who have persistent pleural effusion for more than four weeks, with the expectation of the early removal of the chest tube and a good outcome

Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures

PurposeThe aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM.MethodsA retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day.ResultsSeventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults.ConclusionLEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring

X-linked Myotubular Myopathy in a Family with Two Infant Siblings: A Case with MTM1 Mutation

X-linked myotubular myopathy (XLMTM) is a rare congenital muscle disorder, caused by mutations in the MTM1 gene. Affected male infants present severe hypotonia, and generalized muscle weakness, and the disorder is most often complicated by respiratory failure. Herein, we describe a family with 2 infants with XLMTM which was diagnosed by gene analysis and muscle biopsy. In both cases, histological findings of muscle showed severely hypoplastic muscle fibers with centrally placed nuclei. From the family gene analysis, the Arg486STOP mutation in the MTM1 gene was confirmed

Effect of severe neonatal morbidities on long term outcome in extremely low birthweight infants

PurposeTo assess the validity of individual and combined prognostic effects of severe bronchopulmonary dysplasia (BPD), brain injury, retinopathy of prematurity (ROP), and parenteral nutrition associated cholestasis (PNAC).MethodsWe retrospectively analyzed the medical records of 80 extremely low birthweight (ELBW) infants admitted to the neonatal intensive care unit (NICU) of the Severance Children's Hospital, and who survived to a postmenstrual age of 36 weeks. We analyzed the relationship between 4 neonatal morbidities (severe BPD, severe brain injury, severe ROP, and severe PNAC) and poor outcome. Poor outcome indicated death after a postmenstrual age of 36 weeks or survival with neurosensory impairment (cerebral palsy, delayed development, hearing loss, or blindness) between 18 and 24 months of corrected age.ResultsEach neonatal morbidity correlated with poor outcome on univariate analysis. Multiple logistic regression analysis revealed that the odds ratios (OR) were 4.9 (95% confidence interval [CI], 1.0-22.6; P=0.044) for severe BPD, 13.2 (3.0-57.3; P<.001) for severe brain injury, 5.3 (1.6-18.1; P=0.007) for severe ROP, and 3.4 (0.5-22.7; P=0.215) for severe PNAC. Severe BPD, brain injury, and ROP were significantly correlated with poor outcome, but not severe PNAC. By increasing the morbidity count, the rate of poor outcome was significantly increased (OR 5.2; 95% CI, 2.2-11.9; P<.001). In infants free of the above-mentioned morbidities, the rate of poor outcome was 9%, while the corresponding rates in infants with 1, 2, and more than 3 neonatal morbidities were 46%, 69%, and 100%, respectively.ConclusionIn ELBW infants 3 common neonatal mornidifies, severe BPD, brain injury and ROP, strongly predicts the risk of poor outcome

A Highly Entangled Polymeric Nanoconstruct Assembled by siRNA and its Reduction-Triggered siRNA Release for Gene Silencing

A nanoconstruct (NC) is developed from a biocompatible natural polymer and siRNA conjugates to deliver small interfering RNA (siRNA) target-specifically without cationic condensation reagents. This study reports a novel siRNA-mediated cross-linked NC produced by hybridizing two complementary single-stranded siRNAs that are conjugated to the polymer dextran via a disulfide linkage. The reducible disulfide bond between the siRNA and polymer allow siRNA release from the NC in the reducible cytoplasmic region after the NC enters the cell. In addition, when the NC contains the prostate-carcinoma-binding peptide aptamer DUP-1, it can selectively deliver siRNA into prostate cancer cells of the PC-3 lines; thus, the newly formulated NC has reduced the cytotoxicity and improved the efficacy of target-specific siRNA delivery. Moreover, this new concept of NCs using biocompatible siRNA and a neutral polymer may provide insightful knowledge for future directions for designing NCs for stimuli-responsive and advanced target-specific siRNA delivery.X1124sciescopu