Ran Namgung

Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants☆☆☆★★★

Seasonal differences in newborn total body bone mineral content (TBBMC) have not been studied, particularly in relation to alterations in vitamin D status in winter. In vitamin D deficiency bone resorption may be high and bone mineralization low. Bone resorption may be assessed by serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) measures. Because vitamin D supplements throughout pregnancy are uncommon in Korea, we hypothesized that in Korean winter newborns, TBBMC is low and serum ICTP high from high bone resorption and low 25-hydroxyvitamin D (25-OHD) compared with those in summer newborns. Seventy-one Korean term infants were studied prospectively in summer (July through September, n = 37) versus winter (January through March, n = 34); TBBMC was measured before 3 days of age by dual-energy x-ray absorptiometry. Significant seasonal differences were found: winter newborns had 6% lower TBBMC (least squares means +/- SD; 86.7 +/- 7.7 gm vs 93.9 +/- 7.8 gm, p = 0.0002), lower cord serum 25-OHD (10.7 +/- 8 nm vs 30 +/- 15 nm, p = 0.0001) and 1,25-dihydroxyvitamin D, and higher ICTP (96.4 +/- 20.3 microg/L vs 74.8 +/- 24 microg/L, p = 0.0002) and calcium than summer newborns. TBBMC correlated with serum 25-OHD (r = 0.243, p = 0.047) and inversely with ICTP (r = -0.333, p = 0.008). We suggest that in Korea low maternal vitamin D status in winter results in marked reduction in newborn TBBMC.

Transient elastography and sonography for prediction of liver fibrosis in infants with biliary atresia.

The purpose of this study was to assess the diagnostic performance of transient elastography and sonography for noninvasive evaluation of liver fibrosis in infants with biliary atresia.

High Incidence of Rickets in Extremely Low Birth Weight Infants with Severe Parenteral Nutrition-Associated Cholestasis and Bronchopulmonary Dysplasia

Risk factors for rickets of prematurity have not been re-examined since introduction of high mineral formula, particularly in ELBW infants. We analyzed the incidence and the risk factors of rickets in extremely low birth weight (ELBW) infants. As a retrospective case-control study from 2004 to 2008, risk factors were analyzed in 24 patients with rickets versus 31 patients without. The frequency of rickets in ELBW infants was 24/55 (44%). Infants with rickets were diagnosed at 48.2 ± 16.1 days of age, and improved by 85.3 ± 25.3 days. By radiologic evaluation, 29% were grade 1 rickets, 58% grade 2 and 13% grade 3. In univariate analysis, infants with rickets had significantly higher incidence of patent ductus arteriosus, parenteral nutrition associated cholestasis (PNAC), severe PNAC and moderate/severe bronchopulmonary dysplasia (BPD). In multiple regression analysis, after adjustment for gestation and birth weight, rickets significantly correlated with severe PNAC and with moderate/severe BPD. Serum peak alkaline phosphatase levels were significantly elevated in rickets (P < 0.001). In ELBW infants, the incidence of rickets of prematurity remains high and the incidence of severe PNAC and moderate/severe BPD was significantly increased 18 and 3 times, respectively.

Usefulness of the delta neutrophil index for assessing neonatal sepsis

We investigated the significance of the calculated delta neutrophil index (DNI) as a diagnostic factor for neonatal sepsis.

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

Purpose To 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). Methods We retrospectively analyzed the medical records of 80 extremely low birthweight (ELBW) infants admitted to the neonatal intensive care unit (NICU) of the Severance Childrens 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. Results Each 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. Conclusion In ELBW infants 3 common neonatal mornidifies, severe BPD, brain injury and ROP, strongly predicts the risk of poor outcome.

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.

Imaging patterns of sonographic lenticulostriate vasculopathy and correlation with clinical and neurodevelopmental outcome

To evaluate the relationship between the imaging patterns of lenticulostriate vasculopathy (LSV) and clinical outcomes.

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 studies.

Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures

Background Phenobarbital (PB), commonly used as the preferred treatment for neonatal seizure, is a drug that requires careful dose adjustments based on therapeutic drug monitoring. It has been reported that PB metabolism was affected by cytochrome P450 (CYP)2C19 polymorphisms in adults requiring dose adjustment. Aim This study aimed to evaluate the effects of CYP2C19 genetic polymorphisms on PB pharmacokinetics (PK) in neonates and infants with seizures. Methods CYP2C19 (wild type: CYP2C19*1/*1, heterozygous extensive metabolisers: CYP2C19*1/*2, *1/*3 and poor metabolisers: CYP2C19*2/*2, *2/*3) genetic polymorphisms in 52 neonates and infants with seizures were analysed. PK parameters were compared based on genotypes. The NONMEM program was used for population PK modelling. Results No significant difference in PB clearance (CL), volume of distribution (Vd) and concentrations were shown among the CYP2C19 genotype groups. The results of PK modelling were as follows: Vd=3590 ×(body weight (BWT)/4)0.766 ×(AGE/2)0.283 and CL=32.6×(BWT/4)1.21. Conclusions PB PK parameters of neonates and infants with seizures were not significantly different among the groups with different CYP2C19 genotypes. The addition of CYP2C19 genotyping to PK models did not improve the dosing strategies in neonates and infants.

Positive Maternal C-Reactive Protein Predicts Neonatal Sepsis

Purpose To evaluate the diagnostic performance of maternal inflammatory marker: C-reactive protein (CRP) in predicting early onset neonatal sepsis (that occurring within 72 hours after birth). Materials and Methods 126 low birth weight newborns (gestation 32±3.2 wk, birth weight 1887±623 g) and their mothers were included. Neonates were divided into sepsis group (n=51) including both proven (positive blood culture) and suspected (negative blood culture but with more than 3 abnormal clinical signs), and controls (n=75). Mothers were subgrouped into CRP positive ≥1.22 mg/dL (n=48) and CRP negative <1.22 mg/dL (n=78) group, determined by Receiver Operating Characteristic curves, and odds ratio was calculated for neonatal sepsis according to maternal condition. Results Maternal CRP was significantly higher in neonatal sepsis group than in control (3.55±2.69 vs. 0.48±0.31 mg/dL, p=0.0001). Maternal CRP (cutoff value >1.22 mg/dL) had sensitivity 71% and specificity 84% for predicting neonatal sepsis. Maternal CRP positive group had more neonatal sepsis than CRP negative group (71% vs. 29%, p<0.001). Odds ratio of neonatal sepsis in maternal CRP positive group versus CRP negative group was 10.68 (95% confidence interval: 4.313-26.428, p<0.001). Conclusion The risk of early onset neonatal sepsis significantly increased in the case of positive maternal CRP (≥1.22 mg/dL). In newborn of CRP positive mother, the clinician may be alerted to earlier evaluation for possible neonatal infection prior to development of sepsis.