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

Usefulness of serum cystatin C to determine the dose of vancomycin in neonate

PurposeThe vancomycin dosage regimen is regularly modified according to the patient's glomerular filtration rate (GFR). In the present study, we aimed to assess the usefulness of serum cystatin C (Cys-C) concentration, compared with serum creatinine (SCr) concentration, for predicting vancomycin clearance (CLvcm) in neonates.MethodsWe retrospectively analyzed the laboratory data of 50 term neonates who were admitted to the neonatal intensive care unit and received intravenous vancomycin, and assessed the pharmacokinetic profiles. Creatinine clearance (CLcr) and GFR based on Cys-C (GFRcys-c) were estimated using the Schwartz and Larsson formulas, respectively.ResultsThe mean CLvcm (±standard deviation) was 74.52±31.17 L/hr, the volume of distribution of vancomycin was 0.67±0.14 L, and vancomycin half-life was 9.16±17.42 hours. The SCr was 0.46±0.25 mg/dL and serum Cys-C was 1.43±0.34 mg/L. The peak and trough concentrations of vancomycin were 24.65±14.84 and 8.10±5.35 mcg/mL, respectively. The calculated GFR based on serum creatinine concentration (GFR-Cr) and GFRcys-c were 70.2±9.45 and 63.6±30.18 mL/min, respectively. The correlation constant for CLvcm and the reciprocal of Cys-C (0.479, P=0.001) was significantly higher than that for CLvcm and the reciprocal of SCr (0.286, P=0.044). GFRcys-c was strongly correlated with CLvcm (P=0.001), and the correlation constant was significantly higher than that for CLvcm and CLcr (0.496, P=0.001). Linear regression analysis showed that only GFRcys-c was independently and positively correlated with CLvcm (F=41.9, P<0.001).ConclusionThe use of serum Cys-C as a marker of CLvcm could be beneficial for more reliable predictions of serum vancomycin concentrations, particularly in neonates

Dual bio-responsive gene delivery via reducible poly(amido amine) and survivin-inducible plasmid DNA

A bioreducible poly(amido amine) (SS-PAA) gene carrier, known as poly (amido-butanol) (pABOL), was used to transfect a variety of cancer and non-cancer cell lines. To obtain cancer-specific transgene expression for therapeutic efficiency in cancer treatment, we constructed survivin-inducible plasmid DNA expressing the soluble VEGF receptor, sFlt-1, downstream of the survivin promoter (pSUR-sFlt-1). Cancer-specific expression of sFlt-1 was observed in the mouse renal carcinoma (RENCA) cell line. pABOL enhanced the efficiency of gene delivery compared to traditional carriers used in the past. Thus, a dual bio-responsive gene delivery system was developed by using bioreducible p(ABOL) for enhanced intracellular gene delivery and survivin-inducible gene expression system (pSUR-sFlt-1 or pSUR-Luc reporter gene) that demonstrates increased gene expression in cancer that has advantages over current gene delivery system

A Case of Suspected Isotretinoin-Induced Malformation in a Baby of a Mother Who Became Pregnant One Month after Discontinuation of the Drug

Isotretinoin is a known human teratogen that can cause multiple malformations. At present, women who conceive one cycle after discontinuing isotretinoin are told that their teratogenic risk is not higher than baseline. We present a case of both ear malformation in a newborn whose mother had taken isotretinoin for 2 years until one month prior to the time when she became pregnant. We suggest that further studies of pharmacokinetics and malformation of isotreinoin are needed

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

Survival analysis of spinal muscular atrophy type I

PURPOSE: The life expectancy of patients with spinal muscular atrophy (SMA) type I is generally considered to be less than 2 years. Recently, with the introduction of proactive treatments, a longer survival and an improved survival rate have been reported. In this study, we analyzed the natural courses and survival statistics of SMA type I patients and compared the clinical characteristics of the patients based on their survival periods. METHODS: We reviewed the medical records of 14 pediatric patients diagnosed with SMA type I during a 9-year period. We examined the demographic and clinical characteristics of these patients, calculated their survival probabilities, and plotted survival curves as on the censoring date, January 1, 2010. We also compared the characteristics of the patients who died before the age of 24 months (early-death, ED group) and those who survived for 24 months or longer (long-survival, LS group). RESULTS: The mean survival time was 22.8+/-2.0 months. The survival probabilities at 6 months, 12 months, 18 months, 24 months, and 30 months were 92.9%, 92.9%, 76.0%, 76.0%, and 65.1%, respectively. Birth weight was the only factor that showed a statistically significant difference between the ED and LS groups (P=0.048). CONCLUSION: In this study, the survival probabilities at 2 years were far greater than expected. Because of the limited number of patients and information in this study, the contribution of improved supportive care on longer survival could not be clarified; this may be elucidated in larger cohort studiesope

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