San-Nan Yang

B-Type Natriuretic Peptide Predicts Responses to Indomethacin in Premature Neonates with Patent Ductus Arteriosus

OBJECTIVES To determine whether B-type natriuretic peptide (BNP) predicts indomethacin responsiveness in premature neonates with patent ductus arteriosus (PDA). STUDY DESIGN Premature neonates receiving indomethacin for an echocardiograhically large (diameter>1.5 mm) and clinically significant PDA were prospectively studied. All neonates underwent paired echocardiography and BNP measurements at baseline and 24 hours after each dose of indomethacin. After treatment, neonates who responded (with closed or insignificant PDA) and neonates who did not respond (with persistent significant PDA requiring surgical ligation) were compared. RESULTS Thirty-one premature neonates (mean gestational age, 30 weeks) underwent 119 paired echocardiography and BNP determinations. Mean BNP levels (1286+/-986 pg/mL) associated with significant PDA (n=96) were higher than those associated with closed or insignificant PDA (n=23; 118+/-124 pg/mL; P<.001). Twenty-three neonates responded and 8 neonates did not respond to indomethacin. Mean baseline BNP levels were higher in neonates who were non-responders (2234+/-991 pg/mL) than neonates who were responders (983+/-814 pg/mL; P=.001). A baseline BNP level>1805 pg/mL had a sensitivity rate of 88% and a specificity rate of 87% for predicting indomethacin non-responsiveness (P=.003). CONCLUSIONS High baseline BNP levels predict poor responses to indomethacin and the need for surgery in premature neonates with PDA.

Parenteral nutrition-associated cholestasis in premature babies: risk factors and predictors.

BACKGROUND One of the most common complications in infants under parenteral nutrition treatment is parenteral nutrition-associated cholestasis (PNAC). The etiology of PNAC is thought to be multifactorial. The aims of this study were to evaluate the risk factors for PNAC in our neonatal intensive care unit and determine useful predictors. METHODS This study enrolled premature infants (gestational age <36 weeks) who were admitted to our neonatal intensive care unit and treated with parenteral nutrition infusion for at least 2 weeks between January 2004 and January 2007. Multiple possible risk factors were analyzed by a retrospective review study design. PNAC was defined as direct bilirubin greater than 1.5 mg/dL during parenteral nutrition. RESULTS A total of 62 premature infants with prolonged course of parenteral nutrition were eligible for this study; 11 (17.74%) of the infants developed PNAC. There were significant differences in terms of gestational age, birth body weight, duration of parenteral nutrition, septic episodes, and average energy intake during the 2nd and 3rd weeks of life between infants with cholestasis and those without cholestasis. Of these risk factors, the duration of parenteral nutrition was most significant after multivariate logistic regression analysis. CONCLUSION Young gestational age, low birth body weight, more sepsis episodes, and long duration of parenteral nutrition were significant risk factors for PNAC in our study. Low energy intake during the 2nd and 3rd weeks of life is a predictor for PNAC.

Assisted exercise improves bone strength in very low birthweight infants by bone quantitative ultrasound

Aim:  To evaluate whether assisted exercise could prevent the development of osteopenia of prematurity, we performed assisted exercise in the study group of very low birthweight (VLBW) premature infants.

Combined Noninvasive Ventilation and Mechanical In-Exsufflator in the Treatment of Pediatric Acute Neuromuscular Respiratory Failure

The present study aims to evaluate the efficacy and complications of combined noninvasive ventilation (NIV) and assisted coughing by mechanical in‐exsufflator (MIE) for acute respiratory failure (ARF) in children with neuromuscular disease (NMD).

Neonatal Isolation Enhances Anxiety-like Behavior Following Early-life Seizure in Rats

BACKGROUND Emerging evidence indicates that early adverse experiences result in the maladaptive development of the hypothalamic-pituitary-adrenal (HPA) axis and compromise the developing brain to subsequent neurological insults. Well known that mother-infant interaction plays an important role in early environment stimulation, neonatal isolation (NI) paradigm has been used as an early-life stress model in many relevant studies. Further, the effect of seizure on the developing brain is still not clarified despite more susceptibility to seizures of the developing brain. We had previously demonstrated that NI exacerbates cognitive deficit following early-life seizure. The aim of the current study was to investigate whether NI predisposes the brain to early-life seizure-induced long-term anxiety sequelae. METHODS Rats were assigned randomly to the following four groups: (1) normal rearing rats (NR); (2) NI rats that underwent daily separation from their dams from postnatal day 2 (P2) to P9; (3) NR rats suffering lithium-pilocarpine-induced status epilepticus (SE) at P10 (NR+SE); and (4) NI+SE rats. At P60, anxiety-related behavior was evaluated using elevated plus-maze (EPM) test. RESULTS SE induced in isolated rats rather than in NR rats produced a decrease in percentage of time spent in open arms, and all rats experiencing NI displayed reduced number of closed arm entries. CONCLUSION Repetitive brief NI exacerbates anxiety-related behavior in EPM test following early-life SE.

B-type natriuretic peptide inhibits angiotensin II-induced proliferation and migration of pulmonary arterial smooth muscle cells

Pulmonary vascular remodeling, characterized by disordered proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a pathognomonic feature of pulmonary arterial hypertension. Thus, pharmacologic strategy targeting on anti‐proliferation and anti‐migration of PASMCs may have therapeutic implications for PAH. Here we investigated the effects and underlying mechanisms of B‐type natriuretic peptide (BNP) on angiotensin II (Ang II)‐induced proliferation and migration of PASMCs. Proliferation and migration of PASMCs cultured from Wistar rats were induced by Ang II, with or without BNP treatment. In addition, potential underlying mechanisms including cell cycle progression, Ca2+ overload, reactive oxygen species (ROS) production, signal transduction of MAPK and Akt, and the cGMP/PKG pathway were examined. We found that BNP inhibited Ang II‐induced PASMCs proliferation and migration dose dependently. BNP could also arrest the cell cycle progression in the G0/G1‐phase. In addition, BNP attenuated intracellular calcium overload caused by Ang II. Moreover, Ang II‐induced ROS production was mitigated by BNP, with associated down‐regulation of NAD(P)H oxidase 1 (Nox1) and reduced mitochondrial ROS production. Finally, Ang II‐activated MAPKs and Akt were also counteracted by BNP. Of note, all these effects of BNP were abolished by a PKG inhibitor (Rp‐8‐Br‐PET‐cGMPS). In conclusion, BNP inhibits Ang II‐induced PASMCs proliferation and migration. These effects are potentially mediated by decreased calcium influx, reduced ROS production by Nox1 and mitochondria, and down‐regulation of MAPK and Akt signal transduction, through the cGMP/PKG pathway. Therefore, this study implicates that BNP may have a therapeutic role in pulmonary vascular remodeling. Pediatr Pulmonol. 2014; 49:734–744.

Bone status and associated factors measured by quantitative ultrasound in preterm and full-term newborn infants☆

BACKGROUND A clear understanding of the factors associated with bone status in newborn infants is essential for devising strategies for preventing osteoporotic fracture in future generations. OBJECTIVE The aims of this study were to perform bone speed of sound (SOS) to assess the status of the tibia in preterm and full-term newborns, and to evaluate factors associated with bone status at birth. STUDY DESIGNS Bone SOS was measured by quantitative ultrasonography on the left tibia in full-term and preterm newborn infants immediately after birth. A birth chart and maternal history were recorded. Univariate and multivariate analyses were performed to identify factors affecting bone SOS at birth. SUBJECTS The study analyzed 667 infants, including 370 males and 297 females, during study period. RESULTS Univariate analysis revealed that gender, gestational age (GA) and birth anthropometrics significantly affected tibial bone SOS at birth whereas maternal factors did not. Multivariate multiple regression analysis revealed that gender (male-to-female coefficient of 45.71 and 32.52 in premature and full-term infants, respectively), GA (coefficient of 32.55 and 31.27 in premature and full-term infants, respectively, for every 1-week increase), and birth weight (coefficient of -0.11 and -0.103 in premature and full-term infants, respectively, for every 1-gram increase) were important factors affecting tibial bone SOS in both preterm and full-term newborn infants at birth. CONCLUSIONS Male gender and advanced GA have a positive effect on increasing tibial bone SOS at birth, while birth weight had a negative effect on increasing tibial bone SOS. Tibial bone SOS is higher in small-for-gestational-age infants than in those of appropriate-for-gestational-age infants.

Neonatal intensive care unit-specific screening criteria for retinopathy of prematurity

This study investigated the incidence of retinopathy of prematurity (ROP) and its risk factors in a tertiary referral hospital in Taiwan to evaluate the applicability of the ROP screening guidelines published by the American Academy of Pediatrics, American Academy of Ophthalmology, and American Association for Pediatric Ophthalmology and Strabismus in 2006 (2006 guidelines). A pediatric ophthalmologist applied the 2006 guidelines to screen for ROP and to treat with laser photocoagulation in each case. We retrieved all records of premature infants referred for ROP screening at the hospital during 2004 to 2008. Univariate logistic regression analysis was applied firstly to identify factors correlating with stage 3 ROP or with laser treatment, and then those significant (p < 0.05) risk factors were analyzed by multivariate logistic regression. In the 138 male and 118 female premature infants in this study, mean gestation age was 30.8 ± 2.8 weeks, and mean birth weight was 1464.7 ± 434.2 g. The percentage of infants with ROP in at least one eye was 38.7%. Thirty two (12.5%) had ROP stage 3 or higher in at least one eye. Multivariate logistic regression analysis showed that the best predictors of type 1 pre‐threshold ROP (requiring laser treatment) were young gestational age, low birth weight and male gender. As medical care of extremely premature infants improves, timely identification and treatment of conditions such as ROP are essential. Although the incidence of ROP in this institute was comparable to that in developing countries and higher than that in developed countries, the 2006 guidelines originally developed for a United States population were still applicable. However, the 2006 guidelines should be modified for a Taiwan population by considering gender.

Neonatal seizures: dialogues between clinic and bench.

Neonatal seizures are common and often reflect a severe underlying neurologic dysfunction in neonates. Phenobarbital remains the mainstay of treatment of neonatal seizures, however, but it is ineffective in many patients and has adverse profiles in cognition. Furthermore, gamma-aminobutyric acid is excitatory early in brain development; therefore, treatment of neonatal seizures with phenobarbital must be cautious. In this review, we highlight the substantial progress that has been made in animal studies, and translate these results to the treatment of seizures in human neonates.

The characteristics of premature infants with transient corneal haze

Background The etiology of transient corneal haze in premature infants is not known and how it relates to clinical outcomes in premature infants is not clear. Objectives To study associated factors of transient corneal haze in premature infants. Methods We performed a retrospective study of 261 premature infants from retinopathy of prematurity (ROP) screening in the neonatal intensive care unit at a tertiary referral hospital. Characteristics of premature infants with and without corneal haze were analyzed by correlation tests, Chi-square tests, and logistic regressions were used for statistical analyses. Associations between corneal haze and birth weight (BW), gestational age at birth (GA), central corneal thickness, intraocular pressure, and other systemic and ophthalmic data were evaluated. Results The incidence of corneal haze was 13.4%. Lower BW, lower GA, packed red blood cells (RBC) transfusion, more days on oxygen, older maternal age, bronchopulmonary disease, and stage 3 ROP are associated with corneal haze. The severity of corneal haze decreased with infants’ postmenstrual age. Multivariate logistic regression analyses revealed that BW and maternal age are the most important predictors of corneal haze. Conclusion Low BW and older maternal age are the most important predictors of corneal haze in premature infants. Premature infants with corneal haze could carry more systemic and ocular morbidities. Hence they may require more clinical attention. Corneal haze is unlikely to hinder the treatment of ROP. However, it is possible that corneal haze could hinder the examination of ROP in some infants. If corneal haze does interfere with ROP screening, a closer, more conservative follow-up schedule with a senior ophthalmologist experienced in managing ROP is recommended.