So-Yeon Shim

Induction of Early Meconium Evacuation Promotes Feeding Tolerance in Very Low Birth Weight Infants

Background: A delay in reaching full enteral feeding is linked to poorer outcome in preterm neonates. Meconium retention has been viewed as a cause of bowel dysfunction in very low birth weight infants (VLBWI). Thus, adequate evacuation of meconium could help to promote feeding tolerance. Objectives: Our goal was to determine the effect of the induction of early meconium evacuation on feeding tolerance in VLBWI. Methods: An observational study involving two subsequent periods was performed in inborn infants with birth weights of <1,500 g, before (control) and after (study) the induction of early meconium evacuation by routine glycerin enema. The total duration of these periods was from January 2003 to December 2005. To evaluate feeding tolerance, we measured time to achieve full enteral feeding. Complications such as sepsis and necrotizing enterocolitis were compared. Results: The study group achieved full enteral feeding significantly faster than the control group (hazard ratio (HR) = 2.9; 95% confidence interval (CI) = 1.8–4.8), and this effect was more definite in infants with a birth weight of <1,000 g (HR = 4.6; 95% CI = 1.9–11.1). The study group passed first meconium faster than the control group (median = 1.4 vs. 3.7 days; p < 0.001). Sepsis, especially as determined by positive culture in central venouscatheter, was significantly reduced in the study group (7.7 vs. 27.8%; p = 0.02). Conclusions: The induction of early meconium evacuation had a significantly positive effect on feeding tolerance and sepsis prevention in VLBWI.

Oxidative stress and the antioxidant enzyme system in the developing brain

Preterm infants are vulnerable to the oxidative stress due to the production of large amounts of free radicals, antioxidant system insufficiency, and immature oligodendroglial cells. Reactive oxygen species (ROS) play a pivotal role in the development of periventricular leukomalacia. The three most common ROS are superoxide (O2•-), hydroxyl radical (OH•), and hydrogen peroxide (H2O2). Under normal physiological conditions, a balance is maintained between the production of ROS and the capacity of the antioxidant enzyme system. However, if this balance breaks down, ROS can exert toxic effects. Superoxide dismutase, glutathione peroxidase, and catalase are considered the classical antioxidant enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx), is also an important scavenger of free radicals. Prdx1 expression is induced at birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is consistent with the classical antioxidant enzymes. Several antioxidant substances have been studied as potential therapeutic agents; however, further preclinical and clinical studies are required before allowing clinical application.

Altered Microstructure of White Matter Except the Corpus Callosum Is Independent of Prematurity

Background: Diffusion tensor imaging (DTI) reflects the maturation of the brain microstructure. Although preterm infants are at significant risk for altered brain microstructure, it remains unclear whether this is affected by prematurity itself or other clinical factors. Objectives: To investigate DTI parameters in preterm infants at a term-equivalent age (TEA) compared with healthy term infants and to assess the associations between DTI parameters and clinical factors that may affect brain development. Methods: We studied 34 preterm infants without apparent brain lesions and 12 healthy term infants using tract-based spatial statistics. Region-of-interest analysis was performed in the posterior and anterior limbs of the internal capsule (PLIC and ALIC), corpus callosum (CC), optic radiation, and cerebral peduncle. Results: Preterm infants had significantly decreased fractional anisotropy (FA) in nearly the entire white matter (WM) compared with term infants (p < 0.01). Multiple regression analysis showed that FA in the PLIC, ALIC, optic radiation, and cerebral peduncle were positively associated with postmenstrual age (PMA) at imaging and that the apparent diffusion coefficient was negatively associated with PMA. Only FA in the CC was positively correlated with gestational age. Chronic lung disease (CLD) and postnatal infection were associated with decreased FA in the CC and PLIC, respectively. Conclusions: Preterm infants at TEA showed an altered microstructure of the WM compared with healthy term infants. The altered microstructure of the measured WM except the CC was independent of the degree of prematurity. Chronic lung disease and postnatal infection are related to localized WM alterations.

Cord Blood KL-6, a Specific Lung Injury Marker, Correlates with the Subsequent Development and Severity of Atypical Bronchopulmonary Dysplasia

Background: A considerable number of preterm infants may have been exposed to inflammation in utero and may be born with an inflamed lung. Objectives: To determine the impact of antenatal lung injury and inflammatory response on the pathogenesis of bronchopulmonary dysplasia (BPD) according to its clinical pattern, using KL-6 (as a lung injury marker) and C-reactive protein (CRP) (as a marker of inflammatory response). Methods: In this case-control study, a total of 74 infants (<32 weeks of gestation) including BPD with minimal early lung disease (‘atypical’; 21 infants), BPD with significant early lung disease (‘classic’; 29 infants) and the non-BPD (24 infants) groups underwent KL-6 and CRP in cord blood determinations. Results: The cord plasma KL-6 levels were significantly higher in the atypical and the total BPD groups than in the non-BPD group (median = 60.9 vs. 34.5 U/ml, p = 0.031; 43.5 vs. 34.5 U/ml, p = 0.02). However, the cord plasma CRP levels were not significantly different among the study groups. The cord plasma KL-6 levels in patients with atypical BPD were significantly higher in infants with moderate or severe BPD than in infants with mild BPD (median = 88.3 vs. 41.5 U/ml, p = 0.041) and were found to be significantly correlated with the duration of oxygen therapy (r = 0.502, p = 0.024). Conclusions: The present study shows that cord plasma KL-6, a specific lung injury marker, is increased and objectively reflects disease severity in atypical BPD.

Respiratory viruses in neonates hospitalized with acute lower respiratory tract infections

The burden of respiratory syncytial virus (RSV) in neonates has not been clearly studied. The aims of this study were to determine the overall distribution of respiratory viruses in neonates hospitalized with acute lower respiratory tract infectiosns (ALRI) and to describe the clinical characteristics of RSV infections in these neonates.

Intraventricular Hemorrhage and Post Hemorrhagic Hydrocephalus among Very-Low-Birth-Weight Infants in Korea

Here, we aimed to evaluate the incidence and mortality of intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) among very-low-birth-weight (VLBW) infants in Korea and assess the associated factors of PHH. This cohort study used prospectively collected data from the Korean Neonatal Network (KNN). Among 2,386 VLBW infants in the KNN database born between January 2013 and June 2014, 63 infants who died without brain ultrasonography results were excluded. Maternal demographics and neonatal clinical characteristics were assessed. The overall incidence of IVH in all the VLBW infants was 42.2% (987 of 2,323), while those of IVH grade 1, 2, 3, and 4 were 25.1%, 7.0%, 4.8%, and 5.5%, respectively. The incidence and severity of IVH showed a negatively correlating trend with gestational age and birth weight. PHH developed in 0%, 3.5%, 36.1%, and 63.8% of the surviving infants with IVH grades 1, 2, 3, and 4, respectively. Overall, in the VLBW infants, the IVH-associated mortality rate was 1.0% (24/2,323). Only IVH grade severity was proven to be an associated with PHH development in infants with IVH grades 3-4. This is the first Korean national report of IVH and PHH incidences in VLBW infants. Further risk factor analyses or quality improvement studies to reduce IVH are warranted.

Serial Diffusion Tensor Images during Infancy and Their Relationship to Neuromotor Outcomes in Preterm Infants

Background: Even preterm infants with normal magnetic resonance imaging (MRI) results are at greater risk for neuromotor dysfunction. Objectives: Our aim was to compare serial diffusion tensor imaging (DTI) data from preterm infants without apparent brain abnormalities on magnetic resonance imaging with those from term controls and to investigate the white matter (WM) region associated with neuromotor outcomes. Methods: We obtained serial DTIs from 21 preterm infants at term-equivalent age (TEA) and 1 year of corrected age. As controls, 15 term neonates and 20 newly recruited term infants aged 1 year underwent DTI. Preterm and term infants at 1 year of age were assessed with the Bayley Scales of Infant Development, second edition. Tract-based spatial statistics and regions of interest were used for analysis. Results: At TEA, the entire WM development was delayed in the preterm infants compared with the term controls, but at 1 year of age, the WM development, except for that of the corpus callosum (CC), had reached the development level of the term controls. The psychomotor developmental index was positively correlated with the fractional anisotropy (FA) in the CC (particularly in the body and splenium) at 1 year of age after correcting for gestational age, chronic lung disease, and postnatal infection. Conclusions: The CC of the preterm infants was consistently underdeveloped compared with that of the term controls. The FA in the CC, particularly in the body and splenium at 1 year of age, well reflected the degree of motor function in infants without apparent brain abnormalities.

Expression of peroxiredoxin 1, 2, and 6 in the rat brain during perinatal development and in response to dexamethasone

Peroxiredoxins (Prdx), a family of antioxidant proteins, have important defensive roles in the degenerative brain diseases and neuronal cell death in adult subjects. However, little is known in the neonatal brain. Here, we studied the developmental expression of Prdxs and their response to dexamethasone in the perinatal rat brain. Prdx 1 expression increased during late gestations and peaked at postnatal-day 1, when its expression gradually decreased. Prdx 2 expression remained largely unchanged. Prdx 6 expression continually increased as growing. Using immunohistochemistry, each Prdx showed a strong expression in the cerebral cortex and hippocampus. Prdx 1 was strongly expressed in the corpus callosum. The dexamethasone injection increased the expression of Prdx 6. In conclusion, we reveal for the first time that Prdx 1, 2 and 6 are found in abundance in the perinatal rat brain and are differentially expressed during development. The expression of Prdx 6 was affected by dexamethasone treatment.

Early aggressive nutrition enhances language development in very low‐birthweight infants

Inadequate nutrition in very‐low‐birthweight (VLBW) infants is known to be associated with growth failure and poor neurological outcomes. We aimed to investigate the association of early aggressive protein and energy intakes with weight gain and 18‐month neurodevelopmental outcomes in VLBW infants.

Gestational age-specific sex difference in mortality and morbidities of preterm infants: A nationwide study

This study aims to determine whether male sex has adverse effect on mortality and morbidities in very low birth weight infants (VLBWI) <30 weeks of gestation and to ascertain this sex effect, stratified by gestational age, adjusting for perinatal risk factors. This is a population-based study from Korean Neonatal Network for VLBWI born at 23+0 and 29+6 weeks of gestation between January 2013 and December 2014. The primary outcome was gestation-specific sex difference in the occurrence of mortality, combined morbidities, and individual morbidity. A total of 2228 VLBWI were enrolled (males, 51.7%). Mortality was not different between sexes. The risk of bronchopulmonary dysplasia and combined morbidities was significantly higher in males ≤25 weeks of gestation (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.35–3.20 and OR 2.00, CI 1.19–3.39, respectively). Males had a significantly higher incidence of periventricular leukomalacia at 23 and 29 weeks of gestation. The risk of severe retinopathy of prematurity was higher in females >25 weeks of gestation. Although both sexes have similar risk for mortality, male sex remains an independent risk for major morbidities, especially at ≤25 weeks of gestation. The risk of each outcome for males has a specific pattern with increasing gestational age.