Detection and analysis of plasma lncRNA, miRNA and mRNA profile in preterm birth with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is a cause of morbidity and mortality in preterm infants and is strongly associated with adverse neurological outcomes. The incidence of severe IVH (grade 3 or 4) has persisted despite the overall decline in IVH. IVH has been attributed to changes in cerebral blood flow to the immature germinal matrix microvasculature. The cascade of adverse events following IVH includes inflammation, white matter injury, and delayed oligodendrial maturation. In this study, we aimed to identify long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression in the peripheral blood of preterm infants with IVH compared to normal controls, resulting in the finding of novel biomarkers for IVH. We conducted transcriptome sequencing and small RNA sequencing for identifying differential expression of RNA in preterm infants with IVH. We identified differentially expressed 47 lncRNAs, 95 miRNAs, and 1,370 mRNAs in preterm infants with IVH compared to normal control. Particularly, lncRNA H19 exhibited significantly high expression in preterm infants with IVH. The functional analysis revealed that differentially expressed RNAs in preterm infants with IVH were associated with ferroptosis, heme metabolism, and immune response such as lymphocyte activation and interferon response. In conclusion, these results demonstrate the potential of lncRNA, miRNA, mRNA as possible diagnostic and prognostic biomarkers for IVH.

Association between cortical thickness and cognitive ability in very preterm school-age children.

Very preterm children, born before 32 weeks of gestation, are at risk for impaired cognitive function, mediated by several risk factors. Cognitive impairment can be measured by various neurodevelopmental assessments and is closely associated with structural alterations of brain morphometry, such as cortical thickness. However, the association between structural alterations and high-order cognitive function remains unclear. This study aimed to investigate the neurodevelopmental associations between brain structural changes and cognitive abilities in very preterm and full-term children. Cortical thickness was assessed in 37 very preterm and 24 full-term children aged 6 years. Cortical thickness analysis of structural T1-weighted images was performed using Advanced Normalization Tools. Associations between cortical thickness and the Wechsler Intelligence Scale for Children were evaluated by regression analysis based on ordinary least square estimation. Compared with full-term children, very preterm children showed significant differences in cortical thickness, variously associated with cognitive abilities in several brain regions. Perceptual reasoning indices were broadly correlated with cortical thickness in very preterm and full-term children. These findings provide important insights into neurodevelopment and its association with cortical thickness, which may serve as a biomarker in predictive models for neurodevelopmental diagnosis of high-order cognitive function.

What Is the Optimal Digoxin Level? Challenging Case of Fetal Atrial Flutter Treatment in a Monochorionic Diamniotic Twin.

Background: Atrial flutter is an infrequent yet potentially fatal arrhythmia. Digoxin is the preferred first-line treatment for fetal atrial flutter due to its efficacy and favorable safety profile. The optimal digoxin serum target level for neonatal atrial flutter management remains uncertain, with the standard target level ranging from 1.0 to 2.0 ng/mL due to potential toxicity concerns above this threshold. Case Presentation: We present a case of atrial flutter in a fetus within a monochorionic diamniotic (MCDA) twin pregnancy that was successfully managed using a higher-than-standard target level of digoxin. A 34-year-old nulliparous woman was referred to our institution at 31 + 3 weeks of gestation due to fetal distress in an MCDA twin pregnancy. Fetal echocardiography revealed a ventricular rate of 214 bpm in twin A, while twin B exhibited no abnormal findings. Conclusions: Our case highlights a distinct correlation between the serum digoxin level and its impact on atrial flutter. A higher target serum level of digoxin may be necessary to achieve sinus conversion due to the unique maternal and fetal circulatory characteristics in MCDA pregnancies.

Prenatal Diagnosis of Fetal Obstructed Hemivagina and Ipsilateral Renal Agenesis (OHVIRA) Syndrome.

Background: Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome, also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome characterized by the triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Most cases of OHVIRA have been reported in adolescents or adults. Gartner duct cysts, including those manifesting as vaginal wall cysts, are also rare. Fetal OHVIRA syndrome and Gartner duct cysts are difficult to diagnose. Case Presentation: Here, the authors report a case of combined OHVIRA and Gartner duct cyst diagnosed prenatally by ultrasonography, along with a brief review of the relevant published reports. A 30-year-old nulliparous female was referred to our institution at 32 weeks' gestation for fetal right kidney agenesis. Detailed ultrasonographic examinations using 2D, 3D, and Doppler ultrasounds revealed hydrocolpometra, and uterus didelphys, with a normal anus and right kidney agenesis. Conclusions: When encountering female fetuses with ipsilateral renal agenesis or vaginal cysts, clinicians should be aware of OHVIRA syndrome and Gartner duct cysts and perform systematic ultrasonographic examinations for other genitourinary anomalies.

Altered functional connectivity in children born very preterm at school age.

Children born very preterm are at significant risk of neurodevelopmental impairment. This study sought to identify differences in cognitive function in children born very preterm compared to term-born controls and investigate alteration in white matter microstructure and functional connectivity (FC) based on tract-based spatial statistics (TBSS) and resting-state functional MRI, respectively. At 6 years of age, 36 children born very preterm (< 32 weeks' gestation) without major neurological disabilities and 26 term-born controls were tested using the Wechsler Intelligence Scale for Children, 4th edition, and Child Behavior Checklist. Whole-brain deterministic tractography and FC measurements were performed in both groups. The very preterm group had significantly lower intelligence scores than the term-born controls. The TBSS revealed no significant differences between the two groups, whereas FC was significantly increased between the frontoparietal network and the language network and was significantly decreased between the right salience network nodes in the very preterm group. The altered FC patterns between specific regions of the higher-order networks may reflect underlying deficits in the functional network architecture associated with cognitive function. Further studies are needed to demonstrate a direct connection between FC in these regions and cognitive function.

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report.

BACKGROUND: Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. CASE PRESENTATION: A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 µg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. CONCLUSION: Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae.

Neurodevelopmental Outcomes at 18-24 Months of Corrected Age in Very Low Birth Weight Infants with Late-onset Sepsis.

BACKGROUND: Preterm infants are prone to sepsis owing to their immature innate immunity and prolonged hospitalization. We aimed to evaluate the association between late-onset sepsis (LOS) during hospitalization and neurodevelopmental delay at 18-24 months of corrected age in very low birth weight infants (VLBWIs), and to ascertain this association when adjusted for perinatal risk factors. METHODS: This is a population-based study of VLBWIs born at 23-32 weeks of gestation between January 2014 and December 2017 who were enrolled in the Korean Neonatal Network. Bayley scales of infant development were evaluated at 18-24 months of corrected age in 2,098 infants. To test for LOS as a risk factor for neurodevelopmental delay, multiple logistic regression was used and adjusted for parental education status and clinical variables. RESULTS: Blood culture positive LOS was identified in 419 (20.0%) infants. Cognitive and motor delays were found in 392 (18.7%) and 347 (16.5%) infants, respectively. When multivariate analysis was performed, LOS had a significant association with cognitive delay (odds ratio, 1.48; 95% confidence interval, 1.02-2.16), but no association with motor delay in VLBWIs. Both delays were significantly more frequent in cases of intraventricular hemorrhage (IVH) ≥ grade 3, periventricular leukomalacia (PVL), and intrauterine growth restriction (IUGR) and duration of mechanical ventilation. Male sex and necrotizing enterocolitis ≥ grade 2 had an effect on motor delay, whereas paternal college graduation affected cognitive delay. CONCLUSION: In VLBWIs with LOS, there is a heightened risk of cognitive delays at 18-24 months of corrected age. Brain injury, such as severe IVH and PVL, duration of mechanical ventilation, and IUGR, were also associated with cognitive and motor delays.

The Prediction of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants through Clinical Indicators within 1 Hour of Delivery.

BACKGROUND: Despite the advances in neonatology, the incidence of bronchopulmonary dysplasia (BPD) is increasing. It is important to prevent the development of BPD in the first place. The online BPD outcome estimator from National Institute of Children Health and Human Development and Neonatal Research Network is available. However, it is not applicable for Asians. Moreover, limits are set for birth weight and gestational weeks excluding those who may still have BPD. The aim of this study was to develop a prediction model for BPD using first hour perinatal and neonatal factors in Korean very low birth weight infants (VLBWIs). METHODS: Data were collected for 8,022 VLBWIs with gestational age (GA) ≥ 22 weeks who were born between January 1, 2013 and December 31, 2016, and admitted to the neonatal intensive care units of the KNN. Multiple logistic regression models reanalyzed by stepwise selection with significant clinical indicators for BPD. PROC package was used to calculate the area under curve (AUC) and corresponding 95% confidence intervals. Moreover, it was used to search the best cut-off value. External validation was performed with the 2017 Korean neonatal network (KNN) data. RESULTS: After all missing data were excluded, 4,600 VLBWIs were included in the training dataset of the prediction model. Predictability of presence of BPD was 90.8% and prediction P value cut off was 0.550. Five-minute Apgar score, birth weight, GA, sex, surfactant use were significant indicators. Predictability of severe BPD was 81.5% and prediction P value cut off was 0.160. Five-minute Apgar score, birth weight, maternal PIH, chronic maternal hypertension, GA, sex, respiratory distress syndrome, need of resuscitation at birth were significant indicators. After external validation, sensitivity and specificity did not change significantly. CONCLUSION: From this study, high predictability was obtained using clinical parameters obtained within one hour of life. P value for prediction of each grade of BPD and equation for calculation was presented. It can be helpful for the early prediction of BPD in Korean VLBWI. This study will contribute to the prediction of BPD in Asians especially Korean VLBWIs, not currently included in the NICHD BPD online BPD predictor. In addition, the predictive power may be continuously increased with the cumulative data of KNN.

The Clinical Usefulness of Predictive Models for Preterm Birth with Potential Benefits: A KOrean Preterm collaboratE Network (KOPEN) Registry-Linked Data-Based Cohort Study.

Background: Preterm birth is strongly associated with increasing mortality, incidence of disability, intensity of neonatal care required, and consequent costs. We examined the clinical utility of the potential preterm birth risk factors from admitted pregnant women with symptomatic preterm labor and developed prediction models to obtain information for prolonging pregnancies. Methods: This retrospective study included pregnant women registered with the KOrean Preterm collaboratE Network (KOPEN) who had symptomatic preterm labor, between 16 and 34 gestational weeks, in a tertiary care center from March to November 2016. Demographics, obstetric and medical histories, and basic laboratory test results obtained at admission were evaluated. The preterm birth probability was assessed using a nomogram and decision tree according to birth gestational age: early preterm, before 32 weeks; late preterm, between 32 and 37 weeks; and term, after 37 weeks. Results: Of 879 registered pregnant women, 727 who gave birth at a designated institute were analyzed. The rates of early preterm, late preterm, and term births were 18.16%, 44.02%, and 37.83%, respectively. With the developed nomogram, the concordance index for early and late preterm births was 0.824 (95% CI: 0.785-0.864) and 0.717 (95% CI: 0.675-0.759) respectively. Preterm birth was significantly more likely among women with multiple pregnancy and had water leakage due to premature rupture of membrane. The prediction rate for preterm birth based on decision tree analysis was 86.9% for early preterm and 73.9% for late preterm; the most important nodes are watery leakage for early preterm birth and multiple pregnancy for late preterm birth. Conclusion: This study aims to develop an individual overall probability of preterm birth based on specific risk factors at critical gestational times of preterm birth using a range of clinical variables recorded at the initial hospital admission. Therefore, these models may be useful for clinicians and patients in clinical decision-making and for hospitalization or lifestyle coaching in an outpatient setting.

Influence of anti-tumor necrosis factor-alpha therapy to pregnant inflammatory bowel disease women and their children's immunity.

BACKGROUND/AIMS: The onset of inflammatory bowel disease (IBD) usually occurs at young age, and therefore, women IBD patients experience pregnancy during their disease progression. Recently, the use of anti-tumor necrosis factor-α (anti-TNF-α) has been rapidly increasing. The aim of this study was to evaluate pregnancy related outcomes in women with IBD who were treated with anti-TNF-α during pregnancy and immunity of their children. METHODS: Korean women with IBD who had been treated with anti-TNF-α during pregnancy had been enrolled. Medical records were reviewed and a survey was performed for each patient. For the patients who agreed on additional examination for their children, children's growth, medical history and antibody to hepatitis B surface antigen (anti-HBs) titer were checked. RESULTS: All 18 patients had been diagnosed with Crohn's disease. There was not any case of preterm delivery, low birth-weight infant, congenital anomaly, nor stillbirth. All 12 children had followed the regular vaccination schedule for hepatitis B and 4 of them showed negative results for anti-HBs. After the 1 booster vaccination, all children demonstrated seroconversion. Regarding live vaccines, 4 children had bacillus Calmette-Guerin and 4 had rotavirus vaccine before 6 months, without any specific side effects. CONCLUSIONS: This was the first study of immunity of the children born from IBD women who had been treated with anti-TNF-α medication during their pregnancy. IBD women had comparable pregnancy outcomes with the general women population, suggesting that the disease activity rather than the administered medication would be more important in healthy pregnancy. Considering the history of vaccination and anti-HBs titers, immunity seems to be intact in the children.

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.

Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.

Paternal involvement and early infant neurodevelopment: the mediation role of maternal parenting stress.

BACKGROUND: Father-child interactions are associated with improved developmental outcomes among infants. However, to the best of our knowledge, no study has addressed the effects of paternal involvement on the neurodevelopment of infants who are less than 6 months of age, and no study has reported how maternal parenting stress mediates the relationship between paternal involvement and infant neurodevelopment during early infancy. This study investigates the direct and indirect relationship between paternal involvement and infant neurodevelopment at 3-4 months of age. The indirect relationship was assessed through the mediating factor of maternal parenting stress. METHODS: The participants were recruited through the Sesalmaul Research Center's website from April to June 2014. The final data included 255 mothers and their healthy infants, who were aged 3-4 months. The mothers reported paternal involvement and maternal parenting stress by using Korean Parenting Alliance Inventory (K-PAI) and Parenting Stress Index (PSI), respectively. Experts visited the participants' homes to observe infant neurodevelopment, and completed a developmental examination using Korean version of the Ages and Stages Questionnaire II (K-ASQ II). A hierarchical multiple regression analysis was used for data analysis. RESULTS: Infants' mean ages were 106 days and girls accounted for 46.3%. The mean total scores (reference range) of the K-PAI, PSI, and the K-ASQ II were 55.5 (17-68), 45.8 (25-100), and 243.2 (0-300), respectively. Paternal involvement had a positive relationship with K-ASQ II scores (ß = 0.29, p < 0.001) at 3-4 months of age, whereas maternal parenting stress was negatively related with K-ASQ II scores (ß = -0.32, p < 0.001). Maternal parenting stress mediated the relationship between paternal involvement and early infant neurodevelopment (Z = 3.24, p < 0.001). A hierarchical multiple regression analysis showed that paternal involvement reduced maternal parenting stress (ß = -0.25, p < 0.001), which led to positive infant outcomes (ß = 0.23, p < 0.001). CONCLUSIONS: Paternal involvement is significantly associated with infant neurodevelopment during early infancy, and maternal parenting stress partially mediates that association. This result emphasizes the importance of fathers' involvement and mothers' parenting stress on early infant neurodevelopment.

Cerebellar Development in Preterm Infants at Term-Equivalent Age Is Impaired after Low-Grade Intraventricular Hemorrhage.

OBJECTIVES: To investigate cerebellar development in preterm infants at term-equivalent age compared with healthy full-term infants and to examine the effect of a low-grade intraventricular hemorrhage (IVH) on cerebellar development. STUDY DESIGN: This study used 3T magnetic resonance and diffusion tensor imaging (DTI) at 36-41 weeks' postmenstrual age (PMA) in 72 preterm infants without severe brain injury and 16 full-term infants. Cerebellar volumes and DTI parameters of the cerebellar peduncles including fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity, and radial diffusivities were measured. Clinical variables that may affect brain development were collected. RESULTS: Compared with full-term infants, preterm infants showed smaller cerebellar volumes and a lower FA, greater ADC, and increased radial diffusivities in the cerebellar peduncles (all P < .05). This cerebellar impairment was associated significantly with PMA and IVH grade 2 but was independent of gestational age at birth. When we adjusted for clinical variables, an IVH grade 2 was related with 1.73 cm(3) reduction in cerebellar volumes and altered DTI parameters in the cerebellar peduncles, including decreased FA and increased radial diffusivities in the superior cerebellar peduncle and increases in ADC, axial diffusivity, and radial diffusivities of the middle cerebellar peduncle (all P < .05). Cerebellar hemispheric volumes were associated with both ipsilateral and contralateral IVH grade 2. CONCLUSION: Preterm infants without severe brain abnormalities showed impaired cerebellar development at term-equivalent age after we controlled for PMA at the time of the scan, and this is associated with IVH grade 2. These findings suggest that even a low-grade IVH has potential harmful effects on cerebellar development.

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.

Comparison of gastric and other bowel perforations in preterm infants: a review of 20 years' experience in a single institution.

PURPOSE: In this study, we aimed to review the clinical presentation of preterm infants with gastrointestinal perforations and compare the clinical features of gastric perforation with other intestinal perforations. METHODS: The medical records of preterm neonates with pneumoperitoneum, admitted to the neonatal intensive care unit (NICU) between January 1994 and December 2013, were retrospectively reviewed. RESULTS: Twenty-one preterm infants underwent exploratory laparotomy to investigate the cause of the pneumoperitoneum. The sample consisted of five patients (23.8%) with gastric perforation and 16 patients (76.2%) with intestinal perforation. No statistical differences were found in the birth history and other perinatal factors between the two groups. Underlying necrotizing enterocolitis, bilious vomiting, and paralytic ileus preceding the perforation were statistically more common in the intestinal perforation group. All preterm infants with gastric perforation survived to discharge; however, six preterm infants with intestinal perforation expired during treatment in the NICU. In the gastric perforation group, sudden pneumoperitoneum was the most common finding, and the mean age at diagnosis was 4.4±1.7 days of life. The location and size of the perforations varied, and simple closure or partial gastrectomy was performed. CONCLUSION: Patients with gastric perforation did not have a common clinical finding preceding the perforation diagnosis. Although mortality in previous studies was high, all patients survived to discharge in the present study. When a preterm infant aged less than one week presents with sudden abdominal distension and pneumoperitoneum, gastric perforation should first be excluded. Prompt exploratory laparotomy will increase the survival rates of these infants.

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.

The relationship between eosinophilia and bronchopulmonary dysplasia in premature infants at less than 34 weeks' gestation.

PURPOSE: Eosinophilia is common in premature infants, and its incidence increases with a shorter gestation period. We investigated the clinical significance of eosinophilia in premature infants born at <34 weeks gestation. METHODS: We analyzed the medical records of premature infants born at <34 weeks gestation who were admitted to the neonatal intensive care unit at Ewha Womans University Mokdong Hospital between January 2003 and September 2010. Eosinophilia was defined as an eosinophil percentage of >3% of the total leukocytes. Perinatal parameters and clinical parameters were also analyzed. RESULTS: Of the 261 infants born at <34 weeks gestation, 22.4% demonstrated eosinophilia at birth. The eosinophil percentage peaked in the fourth postnatal week at 7.5%. The incidence of severe eosinophilia increased after birth up to the fourth postnatal week when 8.8% of all patients had severe eosinophilia. Severity of eosinophilia was positively correlated with a lower gestational age, birth weight, and Apgar score. Respiratory distress syndrome, bronchopulmonary dysplasia, nephrocalcinosis, intraventricular hemorrhage, and sepsis were associated with a higher eosinophil percentage. The eosinophil percentage was significantly higher in infants with bronchopulmonary dysplasia from the first postnatal week and the percentage was the highest in the fourth postnatal week, with the maximal difference being 4.1% (P<0.001). CONCLUSION: Eosinophilia is common in premature infants and reaches peak incidence and severity in the fourth postnatal week. The eosinophil percentage was significantly higher in bronchopulmonary dysplasia patients from the first postnatal week. Severe eosinophilia was significantly associated with the incidence of bronchopulmonary dysplasia even after adjusting for other variables.

Early aggressive nutrition enhances language development in very low-birthweight infants.

BACKGROUND: 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. METHODS: A total of 90 infants among 129 infants who survived to discharge were included and divided into two groups (early aggressive nutrition [n = 52] vs conventional nutrition [n = 38]). Clinical findings were compared between the two groups and daily protein and energy intakes were collected for the first 4 weeks of life. Multiple regression analyses tested the association between weekly protein or energy intakes and the result of each category of the Denver Developmental Screening Test II at 18 months' corrected age or weight gain. RESULTS: The early aggressive nutrition group had higher rates of normal language development and lower rates of growth failure (<10th percentile) at both 40 weeks' and 18 months' corrected age compared to the conventional nutrition group. After controlling for the confounding variables, higher first week protein and energy intakes each independently contributed to normal language development (odds ratio [95% confidence interval]; 9.4 [1.8-49.6] per 1 g/kg of protein increase and 1.7 [1.1-2.8] per 10 kcal/kg of energy increase). Higher first-week protein intake was associated with a higher weight at 40 weeks' corrected age (r = 0.41, P = 0.005). CONCLUSIONS: This study demonstrates the importance of the protein and energy intakes in VLBW infants in the first week of life not only for growth but also for better language development.