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Background: To investigate postnatal growth patterns and their relationship with the neurodevelopment of preterm infants born small for gestational age (SGA). Methods: This retrospective cohort study analyzed 90 infants born SGA with a birthweight

Background Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment. Methods This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months. Results The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score − 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p p Conclusions Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.

Background: Despite advances in neonatal intensive care and surgical procedures, perinatal mortality rates for premature infants with congenital heart disease (CHD) remain relatively high.Purpose: We aimed to describe the outcomes of premature infants with critical CHD and identify the risk factors including the new modified version of the Risk Adjustment for Congenital Heart Surgery (M-RACHS) category associated with in-hospital mortality in a Korean tertiary center.Methods: This was a retrospective cohort study of premature infants with critical CHD admitted to the neonatal intensive care unit from January 2005 to December 2016.Results: A total of 78 premature infants were enrolled. The median gestational age (GA) at birth was 34.9 weeks (range, 26.7–36.9 weeks), and the median birth weight was 1.91 kg (range, 0.53–4.38 kg). Surgical or percutaneous intervention was performed in 68 patients with a median GA at birth of 34.7 weeks (range, 26.7–36.8 weeks) and a median birth weight of 1.92 kg (range, 0.53–4.38 kg). The in-hospital survival rate was 76.9% among all enrolled preterm infants and 86.8% among patients who received an intervention. Very low birth weight (VLBW), persistent pulmonary hypertension of the newborn (PPHN), bronchopulmonary dysplasia (BPD), and M-RACHS category 5 or higher (more complex CHD) were independently associated with in-hospital mortality. For the 68 premature infants undergoing cardiac interventions, independent risk factors for mortality were VLBW, BPD, and CHD complexity. Late preterm infant and age at intervention were not associated with patient survival.Conclusion: For premature infants with critical CHD, VLBW, PPHN, BPD, and M-RACHS category ≥5 were risk factors for mortality. A careful approach to surgical intervention and prenatal care should be taken according to CHD type and neonatal condition.

Growth charts are essential for monitoring the postnatal growth of preterm infants. The preterm postnatal follow-up study (PPFS) of the Intergrowth-21st Project provides new growth standards based on a longitudinal study. This study was conducted to investigate the prevalence of extrautrine growth restriction (EUGR) and the associated factors of EUGR in preterm infants, using the PPFS charts and the Fenton charts. Data of 1,356 infants with gestational age (GA) less than 28 weeks from the Korean Neonatal Network were analysed. The prevalence of small for gestational age (SGA) of weight and length was higher with the Intergrowth charts than with the Fenton charts. EUGR in weight and length was more prevalent when using the Fenton charts. Multivariate analysis showed that low GA, high birthweight z score, male, treated patent ductus arteriosus (PDA), necrotizing enterocolitis, intraventricular haemorrhage and duration of parenteral nutrition (PN) were associated with EUGR in weight by the Intergrowth charts. High birthweight z score, treated PDA and PN duration were associated with EUGR defined by the Fenton charts. Conclusion: Compared to the Fenton charts, SGA was more defined and EUGR was less prevalent in extremely low gestational infants, while EUGR defined by the Intergrowth charts categorized infants with adverse clinical courses more elaborately.What is Known:• Preterm infants are at risk of postnatal growth restriction (PGR), although optimal postnatal growth is important for the long-term outcomes.• Growth charts are essential tools to monitor the postnatal growth of preterm infants.What is New:• PGR of weight and length were less defined with the Intergrowth charts than the Fenton charts.• PGR defined by the Intergrowth preterm postnatal follow-up study (PPFS) chart categorized preterm infants with morbidities more elaborately than the Fenton charts. Electronic supplementary material The online version of this article (10.1007/s00431-020-03796-0) contains supplementary material, which is available to authorized users.

Background The risk of selenium deficiency increases for infants receiving long-term parenteral nutrition (PN). This study analyzed selenium deficiency in neonates and infants requiring long-term PN and evaluated the effect of intravenous (IV) selenium provision. Methods This study was a retrospective study of neonates and infants who were admitted to neonatal intensive care unit from January 2010 to December 2019, received PN for at least 2 weeks, and had their serum selenium concentration measured. Patients were divided into two groups depending on their serum selenium concentration, a deficient group (n = 55) and a non-deficient group (n = 47). Results Of the study subjects, 53.9% (55/102) were deficient in selenium. No difference in demographic and clinical characteristics existed between the two groups except for the incidence of bronchopulmonary dysplasia. A subgroup analysis was performed for patients who were supplemented with IV selenium and whose serum selenium concentrations were monitored (n = 29). The average dose of IV selenium administered to patients was 2.7 ± 1.0 μg/kg/day. The average initial serum selenium concentration was 36.5 ± 18.0 μg/L and the serum concentration significantly increased to 52.5 ± 19.1 μg/L after IV selenium administration (p Conclusions Selenium deficiency is common in neonates and infants receiving long-term PN. Serum selenium concentration increased proportionally as the IV selenium dose increased. Therefore, it is recommended to supply a proper dose of IV selenium depending on the degree of selenium deficiency. This article is protected by copyright. All rights reserved.

BACKGROUND The severity of bronchopulmonary dysplasia (BPD) is an important predictor of prognosis in preterm infants. However, the severity of BPD was determined mainly by the degree of oxygen supplementation and mode of respiratory support. OBJECTIVES This retrospective study aimed to examine the role of partial pressure of carbon dioxide (pCO2 ) in predicting rehospitalization among preterm infants with severe BPD without invasive ventilation at 36 weeks' postmenstrual age (PMA). METHODS We assessed preterm infants aged

Background Despite significant advances in neonatology, bronchopulmonary dysplasia (BPD) remains the most common cause of serious morbidity and mortality in premature infants. The aim of the present study was to determine associations between the respiratory severity score (RSS) with death or BPD in premature infants. Methods This was a retrospective study conducted between January 2010 and December 2014. We enrolled preterm infants with a gestational age of less than 28 weeks who were supported by mechanical ventilation for more than a week during the first 4 weeks of life. We collected the RSS scores on day of life 2, 7, 14, 21 and 28. The correlations between postnatal RSSs and death or severe BPD were analyzed using multivariate logistic regression. Results Of the 138 eligible infants, 66 infants (47.8%) either died or developed severe BPD. The RSS cut-off values for predicting severe BPD or death were 3.0 for postnatal day (PND) 14 with an odds ratio (OR) of 11.265 (p = 0.0006, 95% confidence interval (CI), 2.842 to 44.646), 3.6 for PND 21 with an OR of 15.162 (p = 0.0003, 95% CI, 3.467 to 66.316), and 3.24 for PND 28 with an OR of 10.713 (p = 0.0005, 95% CI, 2.825 to 40.630). Conclusion Strong correlations were observed between the RSSs on PND 14, 21, and 28 and death or subsequent severe BPD. The RSS could provide a simple estimate of severe BPD or death., Further research with a larger study population is necessary to validate the usefulness of the RSS for predicting severe BPD or death. Electronic supplementary material The online version of this article (10.1186/s12887-019-1492-9) contains supplementary material, which is available to authorized users.

Background Owing to advances in the critical care of premature infants with bronchopulmonary dysplasia (BPD), BPD-associated pulmonary hypertension (PH) is becoming a growing concern. However, only few investigations were available on neurodevelopmental outcomes in preterm infants with PH. Therefore, this study aimed to identify the impact of PH on growth and neurodevelopment at 18–24 months of corrected age (CA). Methods We retrospectively analyzed the medical records of 394 infants (aged

Although impaired neurodevelopment is strongly associated with severe brain injury, most preterm infants survive without severe brain injury. In this study, the association of impaired neurodevelopment and neonatal morbidities of preterm infants was assessed after excluding those with severe brain injury. This was a retrospective study of very low birthweight infants in a single tertiary center. After excluding infants with severe brain injury, the study population was categorized as infants without intraventricular hemorrhage (IVH) and with low-grade IVH. Neurodevelopmental outcomes at a corrected age (CA) of 18–24 months were evaluated using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III). Cerebral palsy (CP), hearing impairment and blindness were also assessed and compared. Of 240 infants, 25 (11.6%) infants had combined neurodevelopmental impairment (NDI). In the multivariate analysis for combined NDI, small for gestational age (SGA) (adjusted OR 6.820, 95% confidence intervals (CI) 1.770–26.307), moderate to severe bronchopulmonary dysplasia (BPD) (aOR 3.21, 95% CI 1.032–9.999) and severe retinopathy of prematurity (ROP) (aOR 5.669, 95% CI 1.132–28.396) were associated with combined NDI. Among neonatal morbidities, moderate to severe BPD and severe ROP were associated with adverse neurodevelopmental outcomes in preterm infants without severe brain injury.

Prematurity, size at birth, and postnatal growth are important factors that determine cardiometabolic and neurodevelopmental outcomes later in life. In the present study, we aimed to investigate the associations between the size at birth and growth velocity after birth with cardiometabolic and neurodevelopmental outcomes in preterm infants. Fifty-six preterm infants born at p = 0.036) and perceptional reasoning index (β = 0.456, p = 0.003) of K-WISC-IV were positively correlated with postnatal weight gain in the neonatal intensive care unit. Although cardiometabolic outcomes were comparable in preterm SGA and AGA infants, the growth velocity at different time periods resulted in different cardiometabolic and neurocognitive outcomes. Thus, ensuring an optimal growth velocity at early neonatal period could promote good neurocognitive outcomes, while adequate growth after 1 year could prevent adverse cardiometabolic outcomes in preterm infants.

Background School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. Methods A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used. Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. Results The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001). In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. Conclusion This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems were not different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight., Graphical Abstract

Background: Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that antenatal magnesium sulfate use is associated with favorable neurodevelopmental outcomes in preterm infants. However, there are concerns regarding the effects of antenatal magnesium sulfate on neonates, especially regarding gastrointestinal morbidities. This study aims to explore the effects of antenatal magnesium sulfate on intestinal morbidities requiring surgery in preterm infants. Methods: This was a retrospective cohort study of 181 preterm infants who were born at less than 28 weeks of gestational age. Subjects were categorized as infants exposed to antenatal magnesium sulfate and those not exposed to antenatal magnesium sulfate. Results: Antenatal magnesium sulfate was associated with a decreased risk of surgical conditions of the intestine (OR 0.393, 95% CI 0.170–0.905). The multivariate analysis showed that the duration of antenatal magnesium sulfate use was associated with surgical conditions of the intestine (adjusted OR 0.766, 95% CI 0.589–0.997). In the

Background: To investigate postnatal growth patterns and their relationship with neurodevelopment in preterm infants born small for gestational age (SGA).Methods: This study analyzed 90 infants born SGA with birth weight Results: Z-score of HC in SGA infants increased from birth to 40 weeks PMA. Failure of head growth catch-up to 10th percentile by 4 months CA and all three parameters by 9 months CA and onwards were associated with worse neurodevelopmental outcomes. Z-score changes in head growth between birth and 35 weeks PMA were significantly associated with neurodevelopmental outcome (p=0.006, adjusted odds ratio 6.964, 95% confidence interval: 1.763-27.506). Conclusions: Head growth during neonatal intensive care unit stay were associated with neurodevelopmental outcomes in preterm SGA infants. Preterm SGA infants are predicted to have optimal neurodevelopment at 18 months CA, if the head growth catch-up is achieved by 4 months CA and length and weight by 9 months CA.

The prevalence of pregnancy-induced hypertension (PIH) and preeclampsia (PE) are 5–10% and 2–4%, respectively. PIH might affect angiogenesis in preterm neonates, but its association with bronchopulmonary dysplasia (BPD) remains controversial. This study evaluated the association between PIH and BPD in very low-birth weight infants. We retrospectively analysed the maternal, perinatal, and neonatal data of preterm infants born before 30 weeks of gestation, selected from the nationwide registry of very low-birth weight infants, between January 2013 and December 2014. As a result, 1,624 infants without maternal PIH (gestational age: 27.3 ± 1.8 weeks) and 203 infants with maternal PIH (28.0 ± 1.4 weeks, p

Predicting developmental outcomes with growth measurement would be beneficial for primary healthcare or in developing countries with low medical resources. This study aimed to identify physical growth measures that indicate neurodevelopment in very preterm infants. Preterm infants, born at &lt, 32 weeks&rsquo, gestation or weighing &lt, 1500 g, were included. We calculated the changes in z-score of weight, length, and head circumference (HC) at different time points: birth, postmenstrual age (PMA) 35 weeks, and 4 and 18 months corrected age (CA). We examined the relationship between growth and Bayley-III scores using linear regression. Among 122 infants, HC at 4 months CA and HC growth between PMA 35 weeks and 4 months CA showed a positive correlation with Bayley-III scores in appropriate-for-gestational-age infants (AGAs). Weight and length increases between birth and 18 months CA were also associated with AGAs&rsquo, development. In small-for-gestational-age infants (SGAs), only birthweight&rsquo, s z-score was associated with improved neurodevelopmental outcomes. HC at 4 months CA was an important indicator of favorable neurodevelopmental outcomes, and head growth spurt between PMA 35 weeks and 4 months CA contributed to this benefit in preterm AGAs. The period and indices should be monitored differently for SGAs and AGAs.

Very low birth weight (VLBW) neonates experience various problems, including meconium-related ileus (MRI). This study investigated the risk factors of MRI and surgical MRI in VLBW infants. VLBW neonates admitted to the Neonatal Intensive Care Unit of Seoul National University Children’s Hospital from October 2002 to September 2016 were included in the study. The diagnostic criteria for MRI were a decreased frequency of defecation with intolerable feeding, vomiting, and increased gastric residue (>50%); meconium-filled bowel dilatation in an imaging study; and no evidence of necrotizing enteritis or spontaneous intestinal perforation. Medical MRIs and surgical MRIs were managed through conventional treatment and surgical intervention. Of 1543 neonates, 69 and 1474 were in the patient and control groups, respectively. The risk factors for MRI include low birth weight (BW), cesarean section delivery, fetal distress, maternal diabetes, maternal hypertension, and maternal steroid use. Low BW and fetal distress were independent risk factors for MRI. Compared to the medical MRI group (n = 44), the risk factors for surgical MRI (n = 25) included males, younger gestational age, low BW, and meconium located at the small bowel. Male gender and low BW were independent risk factors for surgical MRI. Low BW and fetal distress were independent risk factors for MRI and male gender and low BW were independent risk factors for surgical MRI. In VLBW neonates, careful attention to the risk factors for MRI could minimize or avoid surgical interventions.

Background The cognitive consequences and risk factors based long-term outcome of very-low-birth-weight (VLBW; < 1,500 g) infants in Korea has not been studied. The aim of this study was to determine the influence of perinatal and neonatal risk factors on the cognitive performance of VLBW children at 3 to 5 years of age. Methods We enrolled 88 VLBW infants without cystic periventricular leukomalacia for the assessment of their demographic data, cognitive performance, and development of cerebral palsy (CP) at 3 to 5 years of age. Cognitive performance was assessed using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence IV. Growth data were assessed with measurements of weight, height, and head circumference (HC) at the corrected ages of 6, 12, and 18 months, and 3 to 5 years of age. Results In the VLBW group, the full-scale intelligence quotient (FSIQ) was 96.1 ± 15.2 at the mean age of 4.5 years. The incidence rate of CP was 3.4%. Overall, 17% (15/88) of the VLBW children had a below-average FSIQ (< 85). We divided the VLBW children into the abnormal FSIQ group (< 85, n = 15) and the normal FSIQ group (≥ 85, n = 73). VLBW children with intrauterine growth retardation (IUGR) was associated with a below-average FSIQ at the mean age of 4.5 years (< 85, 8/15, 53.3% vs. ≥ 85, 5/73, 6.8%; P < 0.001). After controlling for associated clinical factors, IUGR in the VLBW children was found to be associated with an abnormal FSIQ at the mean age of 4.5 years (P = 0.025). The weight, height, and HC obtained for both groups showed that normal growth was maintained at the mean age of 4.5 years with no significant difference between abnormal and normal FSIQ groups. Conclusion Fifteen of 88 (17%) of the VLBW children had a below-average FSIQ (< 85). VLBW with IUGR is associated with poor cognitive outcomes at the mean age of 4.5 years., Graphical Abstract

Altered hemodynamics associated with twin to twin transfusion syndrome (TTTS) can be manifested in the fetal and neonatal heart. This study evaluated the association between cardiac manifestations immediately after birth and brain injury in preterm infants with TTTS. Medical records of preterm infants who were born at

To investigate whether the levels of angiogenic factors in cord blood are associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants with maternal preeclampsia.This retrospective cohort study included 199 singleton infants (gestational age 32 weeks), including the preeclampsia group (59 infants) with severe/moderate BPD (24 infants) or no/mild BPD (35 infants) and the no preeclampsia group (140 infants).The levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin, and placental growth factor (PlGF) in cord blood were measured and compared among the study groups.The soluble endoglin level and the ratio of (sFlt-1 + soluble endoglin) to PlGF were significantly higher in the preeclampsia group than in the no preeclampsia group (P .05). Among preterm infants with maternal preeclampsia, both of these parameters were also significantly higher in the severe/moderate BPD group than the no/mild BPD group (P .05). Receiver operator curve analysis revealed that increased cord blood soluble endoglin was predictive of severe or moderate BPD in preterm infants with maternal preeclampsia (area under the curve 0.73). Gestational age (adjusted odds ratio [OR] 0.25; P .001) and high soluble endoglin level in cord blood (3420 pg/mL) (adjusted OR 11.9; P = .006) were significant risk factors for the development of severe or moderate BPD in the preeclampsia group according to multivariate logistic regression analysis.Increased cord blood soluble endoglin is associated with the development of severe or moderate BPD in preterm infants with maternal preeclampsia.

Spontaneous intestinal perforation (SIP) and surgical necrotizing enterocolitis (NEC) are intestinal conditions requiring surgical intervention in preterm infants. We aimed to compare the head growth and neurodevelopment of preterm infants with SIP and surgical NEC. A retrospective single-center study was performed in preterm infants born at less than 32 weeks of gestation and who had undergone surgery for NEC or SIP. Data from the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) at 24 months of corrected age (CA) and the Korean Ages and Stages Questionnaire (K-ASQ) or Korean Developmental Screening Test (K-DST) at 36 months were collected. Among 82 eligible infants, 60 infants had surgical NEC, and 22 infants were diagnosed with SIP. Head growth was faster until CA 4 months in preterm infants with SIP than in those with surgical NEC. At 36 months, abnormal findings in the K-ASQ or K-DST were more prevalent in the NEC group than in the SIP group in the gross motor (48.2% vs. 0%, p = 0.015), fine motor (40.7% vs. 0%, p = 0.037), cognitive (55.6% vs. 12.5%, p = 0.047), and social domains (44.4% vs. 0%, p = 0.032). More studies evaluating the neurodevelopmental outcomes of preterm infants with surgical NEC and SIP are required.

OBJECTIVES The aim of the present study was to report possible improvements in ventilator variables associated with a transition from synchronized intermittent mandatory ventilation to neurally adjusted ventilatory assist in preterm infants with bronchopulmonary dysplasia who required a high level of mechanical ventilatory support in a single center. DESIGN Retrospective study. SETTING Neonatal ICU. PATIENTS Twenty-nine preterm infants with a median gestational age of 25.4 weeks (range, 23.4-30.3 wk) and a median birth weight of 680 g (range, 370-1,230 g) and who were supported with a mechanical ventilator for more than 4 weeks and had a respiratory severity score greater than four during conventional mechanical ventilation prior to conversion to neurally adjusted ventilatory assist. INTERVENTIONS Comparison of ventilatory variables, work of breathing, and blood gas values during conventional ventilation and at various time intervals after the change to neurally adjusted ventilatory assist. MEASUREMENTS AND MAIN RESULTS The values of various ventilatory variables and other measurements were obtained 1 hour before neurally adjusted ventilatory assist and 1, 4, 12, and 24 hours after conversion to neurally adjusted ventilatory assist. During neurally adjusted ventilatory assist, the peak inspiratory pressure (20.12 ± 2.93 vs 14.15 ± 3.55 cm H2O; p < 0.05), mean airway pressure (11.15 ± 1.29 vs 9.57 ± 1.27 cm H2O; p < 0.05), and work of breathing (0.86 ± 0.22 vs 0.46 ± 0.12 J/L; p < 0.05) were significantly decreased, and the blood gas values were significantly improved. Significantly lower FIO2 and improved oxygen saturation were observed during neurally adjusted ventilatory assist compared with conventional ventilation support. The RSS values decreased and sustained during neurally adjusted ventilatory assist (4.85 ± 1.63 vs 3.21 ± 1.01; p < 0.001). CONCLUSIONS The transition from synchronized intermittent mandatory ventilation to neurally adjusted ventilatory assist ventilation was associated with improvements in ventilator variables, oxygen saturation, and blood gas values in infants with bronchopulmonary dysplasia in a single center. This study suggests the possible clinical utility of neurally adjusted ventilatory assist as a weaning modality for bronchopulmonary dysplasia patients in the neonatal ICU.

BackgroundStress signals during sucking activity such as nasal flaring, head turning, and extraneous movements of the body have been attributed to incoordination of sucking, swallowing, and respiration (SSR) in premature infants. However, the association of uncoordinated sucking pattern with developmental outcomes has not yet been investigated. The aim of this study was to investigate whether uncoordinated sucking pattern during bottle-feeding in premature infants is associated with the developmental outcomes at 8–12 and 18–24 months of age (corrected for prematurity).MethodsWe retrospectively reviewed the medical records and video recordings for the Neonatal Oral-Motor Assessment Scale (NOMAS) of premature infants and divided them into two groups based on the presence or absence of incoordination. The Bayley-III cognition composite scores of the incoordination-positive and incoordination-negative group were compared at 8–12 and 18–24 months of age.ResultsSeventy premature infants exhibited a disorganized sucking pattern according to the NOMAS. The average Bayley-III cognition composite scores at 8–12 months of age were 92.5 ± 15.6 and 103.0 ± 11.3 for the incoordination-positive (n = 22) and incoordination-negative groups (n = 48), respectively (p = 0.002). The average Bayley-III cognition composite scores at 18–24 months were 90.0 ± 17.9 and 100.7 ± 11.5 for the incoordination-positive (n = 21) and incoordination-negative groups (n = 46), respectively (p = 0.005). A multiple linear regression analysis indicated that the presence of uncoordinated sucking pattern, grade 3 or 4 germinal matrix hemorrhage–intraventricular hemorrhage, and moderate to severe bronchopulmonary dysplasia were independently associated with cognitive development at 18–24 months of age.ConclusionsUncoordinated sucking pattern in premature infants was independently associated with a higher risk of abnormal developmental outcome in the cognitive domain of the Bayley-III at both 8–12 and 18–24 months. There may be a need for periodic follow-up and early intervention for developmental delay when incoordination of SSR that results in stress signals on the NOMAS is observed before 40 weeks postmenstrual age.

Costello syndrome (CS) is a rare genetic disorder characterized by distinctive facial appearance, cardiopulmonary complications, severe growth retardation, skin and skeletal defects, developmental delay, and tumor predisposition. CS is caused by heterozygous de novo mutations in the proto-oncogene HRAS, which is a component of the RAS/mitogen-activated protein kinase pathway. Herein, we reviewed the phenotypic and genetic features of 5 Korean patients who were genetically diagnosed with CS. Atrial tachycardia and polyhydramnios, which are important prenatal features for CS, were observed in 4 and 5 patients, respectively. The distinctive coarse facial appearances of the patients and presence of deep palmoplantar creases supported the clinical diagnosis of CS, which was confirmed by HRAS sequence analysis. Extremely poor postnatal growth was observed in all 5 patients. Further, all patients exhibited cardiac abnormalities; left ventricular hypertrophy and hypertrophic cardiomyopathy were observed in 3 patients. All 5 patients suffered from airway problems; 3 of them required intubation right after birth, and 2 of them received tracheostomy. One patient with a p.Gly12Ser mutation was diagnosed with retroperitoneal rhabdomyosarcoma alveolar type at the age of 5 years. Consistent with previous reports, both patients with p.Gly12Cys mutations died within the first year of life due to cardiopulmonary failure. Our study summarizes the characteristics of these 5 Korean patients with CS and, along with previous studies, provides clues for genotype-phenotype correlation in patients with CS.

Background Systemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α (TNF-α) plays important roles in systemic inflammation and local inflammation leading to apoptosis of premyelinating oligodendrocytes and white matter injury (WMI) in brain tissue. This study was conducted to investigate whether etanercept, a TNF-α antagonist, could attenuate systemic lipopolysaccharide (LPS)-induced WMI in the immature brain. Results We found that intraperitoneal LPS administration caused systemic and local inflammation in brain tissue. Subsequent etanercept treatment significantly attenuated LPS-induced inflammation in brain tissue as well as in systemic circulation. Intraperitoneal LPS also induced microgliosis and astrocytosis in the cingulum and etanercept treatment reduced LPS-induced microgliosis and astrocytosis. Additionally, systemic LPS-induced apoptosis of oligodendrocyte precursor cells was observed, which was lessened by etanercept treatment. The concentration of etanercept in the CSF was higher when it was administrated with LPS than when administrated with a vehicle. Conclusions It appears that etanercept reduce WMI in the neonatal rat brain via attenuation of systemic and local inflammation. This study provides preclinical data suggesting etanercept-mediated modulation of inflammation as a promising approach to reduce WMI caused by sepsis or necrotizing enterocolitis in preterm infants.

Background: White matter injury (WMI) is the most common form of brain injury in preterm infants. It could be induced by a systemic inflammatory response in preterm infants. Objectives: We hypothesized that surgical necrotizing enterocolitis (surgNEC) results in more severe WMI than spontaneous intestinal perforation (SIP) on brain magnetic resonance imaging (MRI) at term-equivalent age (TEA). Methods: The medical records of 33 preterm infants born at less than 32 weeks of gestation who underwent surgery due to either NEC or SIP were reviewed retrospectively. White matter abnormality (WMA) on brain MRI was scored according to the diagnosis of surgNEC or SIP. Results: Nine patients were diagnosed with SIP and 24 with surgNEC. The median (range) gestational age of the SIP and surgNEC groups was 26+6 (23+3-27+6) and 25+5 weeks (23+3-31+2), respectively (p = 0.454). There were no differences in 1- and 5-min Apgar scores, mode of delivery, use of antenatal steroids, histologic chorioamnionitis, or incidence of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) between the two groups. Males were more prevalent in the surgNEC group (75.0 vs. 33.3%, p = 0.044), and the incidence of sepsis was higher in the surgNEC group than in the SIP group (75.0 vs. 33.3%, p = 0.044). Multivariate regression showed that the difference in WMA scores between the two groups remained significant (estimated difference = 2.418; 95% CI 0.107-4.729). Conclusion: In preterm infants at less than 32 weeks of gestation, those with surgNEC showed more severe WMI than infants with SIP on brain MRI at TEA.

Several treatments have been proposed to shorten the time to the attainment of full oral feeding (FOF) for premature infants, but there are only a few evaluation methods useful in estimating predictors of this period. We investigated whether specific items within the disorganized sucking patterns described by the Neonatal Oral-Motor Assessment Scale (NOMAS) could estimate the time to FOF in preterm infants with feeding difficulty. Preterm infants diagnosed with a disorganized sucking pattern in the NOMAS evaluation before 50 weeks of postmenstrual age were included. Video recordings of at least 2 min of oral feeding were further analyzed retrospectively by two assessors and the premature infants who exhibited disorganized sucking patterns (n = 109) were divided into three clusters (clusters 2–4). The observational items compatible with disorganization in the original NOMAS were divided into three groups: cluster 2 (disorganized: arrhythmical), cluster 3 (disorganized: arrhythmical + unable to sustain), and cluster 4 (disorganized: arrhythmical + incoordination ± unable to sustain) and further divided into incoordination-positive (cluster 4) and incoordination-negative groups (clusters 2 and 3). Premature infants in the incoordination-positive group (cluster 4, which means stress signals) showed a median transition time of 22 days (range: 4–121 days) which was longer than that in the incoordination-negative group (median 6 days; range: 1–25 days). Univariate linear regression analysis revealed that the presence of incoordination among disorganized sucking patterns (NOMAS cluster 4 vs. clusters 2 and 3), birth weight, total parenteral nutrition (TPN) duration, non-invasive positive pressure ventilation duration, the presence of moderate to severe bronchopulmonary dysplasia, pulmonary hypertension, sepsis, small for gestational age (SGA), and necrotizing enterocolitis are associated with the transition time to FOF. In a multivariate linear regression analysis, the variables revealed to be associated with the transition time were TPN duration, SGA, and the presence of stress signals (incoordination-positive group) among disorganized sucking patterns. When selecting premature infants to be treated with swallowing therapy, it is reasonable to pay more attention to the incoordination-positive group described in the NOMAS, that is, premature infants with stress signals to shorten the time to attain FOF.

The critical need to emphasize preterm infant follow-up after neonatal intensive care unit (NICU) discharge assures early identification of and intervention for neurodevelopmental disability. The aims of this study were to observe the follow-up rates in high-risk follow-up clinics, and analyze factors associated with non-compliance to follow-up among very low birth weight (VLBW) infants. The data was prospectively collected for 3063 VLBW infants between January 2013 and December 2014 from 57 Korean neonatal network (KNN) centers at a corrected age of 18-24 months. Correlations among demographic data, clinical variables, and neonatal intensive care unit (NICU) volume (divided into 4 quartiles) with the occurrence of non-compliance were analyzed. The overall follow-up rate at the corrected age of 18-24 month was 65.4%. The follow-up rates were inversely related to birth weight and gestational age. Apgar score, hospital stay, maternal age, and maternal education were significantly different between the compliance and non-compliance groups. The follow-up rate was higher for mothers with chorioamnionitis, abnormal amniotic fluid, multiple pregnancy, and in vitro fertilization. Infants with respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus ligation, periventricular leukomalacia, and retinopathy of prematurity were more common in the compliance group. Follow-up rates showed significant differences according to NICU volume. Using multivariate logistic regression, high birth weight, low NICU volume, siblings, foreign maternal nationality and high 5 min APGAR scores were significant independent factors associated with the non-compliance of VLBW infants for follow-up at 18-24 months of age. This is the first nation-wide analysis of follow-up for VLBW infants in Korea. Understanding factors associated with failure of compliance could help improve the long-term follow-up rates and neurodevelopmental outcomes through early intervention.

Background The aim of this study was to observe long-term outcomes of very low birth weight infants (VLBWIs) born between 2013 and 2014 in Korea, especially focusing on neurodevelopmental outcomes. Methods The data were collected from Korean Neonatal Network (KNN) registry from 43 and 54 participating units in 2013 and 2014, respectively. A standardized electronic case report form containing 30 items related to long-term follow up was used after data validation. Results Of 2,660 VLBWI, the mean gestational age and birth weight were 291/7 ± 26/7 weeks and 1,093 ± 268 g in 2013 and 292/7 ± 26/7 weeks and 1,125 ± 261 g in 2014, respectively. The post-discharge mortality rate was 1.2%–1.5%. Weight < 50th percentile was 46.5% in 2013 and 66.1% in 2014. The overall prevalence of cerebral palsy among the follow up infants was 6.2% in 2013 and 6.6% in 2014. The Bayley Scales of Infant Developmental Outcomes version II showed 14%–25% of infants had developmental delay and 3%–8% of infants in Bayley version III. For the Korean developmental screening test for infants and children, the area “Further evaluation needed” was 5%–12%. Blindness in both eyes was reported to be 0.2%–0.3%. For hearing impairment, 0.8%–1.9% showed bilateral hearing loss. Almost 50% were readmitted to hospital with respiratory illness as a leading cause. Conclusion The overall prevalence of long-term outcomes was not largely different among the VLBWI born between 2013 and 2014. This study is the first large national data study of long-term outcomes., Graphical Abstract

BackgroundBronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is a well-known complication of prematurity; however, the additional impact of a left-to-right interatrial shunt on this condition remains poorly understood. The aim of the present study was to identify the significance of atrial left-to-right shunt lesions in PH infants with moderate or severe BPD.MethodsThe medical records of 383 preterm infants (gestational age of < 32 weeks) who were diagnosed with BPD between 2005 and 2013 were retrospectively reviewed. Baseline characteristics such as interatrial shunts and outcomes were compared between the infants who developed PH (n = 50) and infants who did not (n = 144). Infants with hemodynamically significant residual patent ductus arteriosus were excluded. Among the infants diagnosed with PH (n = 50), the outcomes were compared between the patients with (n = 21) and without atrial shunts (n = 29) at 36 weeks corrected postmenstrual age.ResultsFifty (15%) preterm infants with BPD were diagnosed with PH. The number of infants with a history of atrial shunt lesions was significantly higher in the PH group than in the non-PH group (42% vs. 15.3%, respectively). The adjusted odds ratio for PH in the atrial shunt group was 3.8 (95% confidence interval, 1.8–8.0), compared to PH-BPD infants without an atrial shunt.ConclusionThe presence of an atrial left-to-right shunt was associated with PH in preterm infants with moderate or severe BPD. Close follow up is needed for infants with interatrial shunts, and a more tailored prognostic evaluation and treatment are recommended.

Background We investigated changes in the admission patterns of neonatal intensive care units and the epidemiology of neonatal sepsis following the rapid expansion and improvements in neonatal intensive care. Methods Data on the admission of neonates with culture-proven sepsis between 1996 and 2013 (period I, 1996–2005; period II, 2006–2013) were collected retrospectively. Results The admission of extremely low-birthweight (ELBW) infants increased between periods I and II (11.1 vs 28.7 infants per 1000 live births, P < 0.001). The survival rate of the ELBW infants improved (57.5 vs 80.1%, P < 0.001), and duration of hospital stay increased (median, 64 vs 80 days, P = 0.001). The incidence of sepsis among all infants and ELBW infants increased (all infants, 5.9 vs 12.7 cases per 1000 live births; ELBW infants, 189.5 vs 290.1 cases per 1000 live births). In ELBW infants, the incidence of sepsis caused by coagulase-negative Staphylococcus (CONS), significantly increased during period II (8.8 vs 25.4%, P = 0.039). On multivariate analysis, central vascular catheters and prolonged hospitalization were independently associated with increased sepsis rate, particularly CONS in ELBW infants. Conclusions The inborn admission rate for ELBW infants has increased significantly and is accompanied by improved survival and longer hospital stay. The incidence of neonatal sepsis, particularly in ELBW infants, has also increased, and CONS has emerged as a major pathogen. Central vascular catheters and prolonged hospitalization could be independent risk factors for the increased sepsis rate, particularly sepsis due to CONS.

Late-onset hyponatremia (LOH), hyponatremia occurring after two weeks of age with the achievement of full feeding, is the result of a negative sodium balance caused by inadequate salt intake or excessive salt loss due to immature renal or intestinal function in preterm infants. The aims of our study were to identify the risk factors for LOH and its influence on neonatal outcomes. This was a retrospective cohort analysis of 161 preterm infants born before 34 weeks of gestation between June 2009 and December 2010 at Seoul National University Hospital. LOH was defined as a sodium level ≤ 132 mEq/L or 133-135 mEq/L with oral sodium supplementation. LOH occurred in 49 (30.4%) of the studied infants. A lower gestational age, a shorter duration of parenteral nutrition, the presence of respiratory distress syndrome, the use of furosemide, and feeding with breast milk were significant risk factors for LOH. In terms of neonatal outcomes, the infants with LOH had longer hospital stays and higher risks of bronchopulmonary dysplasia and retinopathy of prematurity requiring surgery. LOH lasting at least 7 days significantly increased moderate to severe bronchopulmonary dysplasia, periventricular leukomalacia, and extra-uterine growth retardation. LOH is commonly observed in preterm infants; it may be a risk factor for bronchopulmonary dysplasia and retinopathy of prematurity or a marker of illness severity.

OBJECTIVE: To determine the immunologic effects of oropharyngeal colostrum administration in extremely premature infants. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving 48 preterm infants born before 28 weeks’ gestation. Subjects received 0.2 mL of their mother’s colostrum or sterile water via oropharyngeal route every 3 hours for 3 days beginning at 48 to 96 hours of life. To measure concentrations of secretory immunoglobulin A, lactoferrin, and several immune substances, urine and saliva were obtained during the first 24 hours of life and at 8 and 15 days. Clinical data during hospitalization were collected. RESULTS: Urinary levels of secretory immunoglobulin A at 1 week (71.4 vs 26.5 ng/g creatinine, P = .04) and 2 weeks (233.8 vs 48.3 ng/g creatinine, P = .006), and lactoferrin at 1 week (3.5 vs 0.9 μg/g creatinine, P = .01) were significantly higher in colostrum group. Urine interleukin-1β level was significantly lower in colostrum group at 2 weeks (55.3 vs 91.8 μg/g creatinine, P = .01). Salivary transforming growth factor-β1 (39.2 vs 69.7 μg/mL, P = .03) and interleukin-8 (1.2 vs 4.9 ng/mL, P = .04) were significantly lower at 2 weeks in colostrum group. A significant reduction in the incidence of clinical sepsis was noted in colostrum group (50% vs 92%, P = .003). CONCLUSIONS: This study suggests that oropharyngeal administration of colostrum may decrease clinical sepsis, inhibit secretion of pro-inflammatory cytokines, and increase levels of circulating immune-protective factors in extremely premature infants. Larger studies to confirm these findings are warranted.

Objective: The objective of this study was to describe respiratory and neurodevelopmental outcomes in infants with severe bronchopulmonary dysplasia (BPD) who needed invasive ventilation until 36 weeks’ postmenstrual age (PMA). Methods: A retrospective observational single-center study was conducted in our hospital. Eighty preterm infants born between January 2007 and December 2016 with less than 28 weeks’ gestational age and classified as having severe BPD were included in the study. Patients with invasive ventilation at 36 weeks’ PMA (invasive group) were compared with those with noninvasive ventilation (noninvasive group) in terms of perinatal characteristics and postnatal outcomes. Results: Antenatal characteristics and basic patient characteristics were comparable between the two groups. Incidence of pulmonary hemorrhage (13.6 vs. 1.7%, P=0.061) and clinical sepsis (66.7 vs. 31.0%, P=0.004) was more in the invasive group. Invasive group had longer hospital stay (133.50± 104.52 vs. 114.00±24.71 days, P=0.031), higher rates of readmission due to respiratory problems before 12 months of corrected age (57.1 vs. 32.1%, P=0.045), higher rates of having a tracheostomy (22.7 vs. 1.7%, P=0.005), and higher rates of infants with respiratory support at a corrected age of 6 months (22.7 vs. 3.5%, P=0.016). Neurodevelopmental outcomes including Bayley Scales of Infant Development-III, cerebral palsy, hearing aid, blindness, and composite outcome of them revealed no differences between the two groups. Conclusion: Invasive ventilation until postmenstrual age of 36 weeks does not predict poorer neurodevelopmental outcomes in infants with severe BPD. However, the invasive group was more prone to develop respiratory problems after discharge.

Background There are concerns about the extent of impaired endocrine and exocrine pancreatic function and poor quality of life (QoL) after pancreatectomy, but there is little information from large prospective follow-up studies. Methods Consecutive patients undergoing pancreaticoduodenectomy or distal pancreatectomy between 2007 and 2011 were included. Relative bodyweight (RBW), triceps skinfold thickness (TSFT), serum protein, albumin, transferrin, fasting blood glucose, postprandial 2-h glucose (PP2), glycosylated haemoglobin A1c and stool elastase measurements, and European Organization for Research and Treatment of Cancer QLQ-C30 questionnaires were collected serially for 1 year. Results Some 136 patients undergoing pancreatic resection completed the study. RBW and TSFT recovered to over 90 per cent of the preoperative value by 12 months, whereas transferrin, albumin and protein had returned to preoperative levels by 3 months. Diabetes mellitus, impaired fasting glucose or raised PP2 was present in 42 of 76 patients at 6 months and 36 of 76 at 12 months. Although steatorrhoea and diarrhoea had mainly resolved by 3 months, stool elastase level decreased after operation and showed no recovery. Nutritional status, pancreatic endocrine function and QoL returned to preoperative levels in 63 (46·3 per cent), 72 (52·9 per cent) and 77 (56·6 per cent) of 136 patients within 6 months of pancreatectomy. Multivariable analysis revealed that age 60 years or more, operation type, chronic pancreatitis and malignant disease had a significant impact on nutritional index, pancreatic function and QoL. Conclusion About half of all patients can expect recovery from pancreatectomy after 6 months, but those with risk factors need more careful follow-up and supportive management.

Background: Meconium obstruction (MO) of prematurity can result in increased morbidity or mortality and prolonged hospitalization if not diagnosed and treated appropriately. Objectives: The aims of our study were to identify the incidence and risk factors associated with MO and to review the treatment outcomes. Methods: A retrospective analysis was undertaken of 101 extremely low birth weight infants (ELBWIs) who were born between January 1, 2007, and April 1, 2009, at Seoul National University Hospital. Prenatal and neonatal factors were compared between the MO and control groups. The treatment outcomes were also reviewed. Results: Twenty-two (22%) patients were diagnosed as having MO. Eighteen of these patients (82%) had prenatal risk factors for MO. Respiratory distress syndrome was more prevalent in the MO group than in the control group (p = 0.001). Overall, 17 of the 22 patients (77%) were relieved with medical treatment and the rest underwent ileostomy. The times to full enteral feeding did not differ between the medically treated group and the control group. However, the surgically treated group required more time to achieve full enteral feeding, and some patients had persistent gastrointestinal problems. Conclusion: MO is not a rare condition in ELBWIs, and the majority of ELBWIs have prenatal risk factors. Medical management was effective, and medically manageable cases had good prognoses for subsequent feeding, whereas some surgically managed cases had persistent gastrointestinal problems.

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) ('classic' BPD) and with minimal early lung disease ('atypical' BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1(st), 3(rd) and 7(th) day of life and measured the levels of leukotriene E(4) (LTE(4)) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3(rd) day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7(th) day were the independent risk factor for developing moderate/severe BPD. In 'classic' BPD, the 8-OHdG values on the 3(rd) day were higher than those of 'atypical' BPD. In 'atypical' BPD, the LTE(4) values on the 7(th) day were higher than the values in 'classic' BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in 'atypical' BPD.

McKusick-Kaufman syndrome (MKS) is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP). We report a case of a female child with MKS who was transferred to the neonatal intensive care unit of Seoul National University Children's Hospital on her 15th day of life for further evaluation and management of an abdominal cystic mass. She underwent abdominal sonography, magnetic resonance imaging, genitography and cystoscopy which confirmed HMC with a transverse vaginal septum. X-rays of the hand and foot showed bony fusion of the left third and fourth metacarpal bones, right fourth dysplastic metacarpal bone and phalanx, right PAP and hypoplastic left foot with left fourth and fifth dysplastic metatarsal bones. In addition, she had soft palate cleft, mild hydronephroses of both kidneys, hypoplastic right kidney with ectopic location and mild rotation, uterine didelphys with transverse vaginal septum and low-type imperforated anus. She was temporarily treated with ultrasound-guided transurethral aspiration of the HMC. Our patient with HMC and PAP was diagnosed with MKS because she has two typical abnormality of MKS and she has no definite complications of retinal disease, learning disability, obesity and renal failure that develop in Bardet-Biedl syndrome, but not in MKS until 33 months of age. Here, we describe a case of a Korean patient with MKS.

Background The pathogenesis of coarctation of the aorta (CoA) has not been clearly elucidated. It is hypothesized that CoA patients have abnormal extension of ductal tissue into the aorta which plays some pathogenic role. The aim of this study was to investigate the extension of ductal tissue into the aorta in CoA patients by comparative analysis of ductal and aortic tissue histopathology, smooth muscle cell (SMC) phenotypes and apoptosis. Methods Fifteen cases of surgically resected specimens including coarctation segment (CS), ductus arteriosus (DA) and transition zone (TZ) were histologically reviewed. SMC phenotypes were determined by immunohistochemistry for myosin heavy chain isoforms SM1, SM2, SMemb and α-smooth muscle actin. Apoptotic cell death was estimated by the TUNEL method. Results A considerable amount of ductal tissue was found in CS and TZ in all investigated cases. CS showed a histologic pattern similar to that of closing DA. CS showed the least differentiated SMC phenotype and TZ intima displayed SMC phenotype more similar to that of DA than that of the normal aorta. TUNEL-positive cell deaths were frequently found in the media of both CS and DA, but absent in TZ. Conclusions Abnormal extension of ductal tissue into the aorta in CoA patients was indicated by similar histology and shared apoptosis. SMC phenotypic modulation may be involved in the formation of CoA. Our results strongly support the hypothesis that abnormal extension of ductal tissue in the aorta plays a crucial role in the pathogenesis of CoA.

To determine if histologic chorioamnionitis (HC) in the presence of respiratory distress syndrome (RDS) augments adverse pulmonary outcomes in extremely low birth weight (ELBW) infants.We retrospectively identified 184 ELBW infants who were born at and admitted to the neonatal intensive care units between June 2005 and June 2009.The mean gestational age of the cases was 27 ± 2 weeks, and the mean birth weight was 791 ± 147 g. A total of 88% (161/184) of patients developed bronchopulmonary dysplasia (BPD). HC was observed in 71 of 238 infants (39%). When infants were divided on the basis of the presence or absence of HC and RDS, the incidence of moderate or severe BPD and duration of oxygen requirement were greater in the HC+RDS+ group than in the HC-RDS+ or HC+RDS- groups. The combination of prenatal (HC) and postnatal (RDS) injuries increased significantly the risk for BPD. In the multivariate analysis, the significant predictors of developing BPD were low gestational age (odds ratio (OR), 0.6; confidence interval (CI), 0.4 to 0.7) and exposure to both HC and RDS (OR, 4.7; CI, 1.1 to 20.2).The HC and RDS work synergistically to induce lung injury in ELBW infants. Chorioamnionitis may interact with RDS to further increase the risk of BPD, despite either HC or RDS could not show independent significant association with BPD.

Background and Objectives: With the increasing survival of preterm infants, pulmonary hypertension (PH) related to bronchopulmonary dysplasia (BPD) has become an important complication. The aim of this study was to investigate the characteristics and outcome of PH in preterm infants with BPD and to identify the risk factors for PH. Subjects and Methods: We reviewed the records of 116 preterm infants with BPD cared for at a single tertiary center between 2004 and 2008. Results: Twenty-nine (25%) infants had PH >2 months after birth. PH occurred initially at a median age of 65 days (range, 7-232 days). Severe BPD, a birth weight

Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia (HI)] or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20, 30, and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE.

To determine the validity of a repeat thyroid function test for preterm infants, and to investigate factors that influence thyroid function of preterm infants, thyroid functions of 105 infants born at32 weeks' gestational age were evaluated. Initial serum free thyroxine (fT4) and thyrotropin (TSH) levels were measured during the first 10 days of life, and repeated tests were performed more than 2 weeks apart. We analyzed the effects of gestational age, systemic diseases, and nutrition on the development of thyroid dysfunction. Thirty-one infants (30%) had low fT4 levels (0.7 ng/dL) in the absence of elevated TSH levels (7 microU/mL). Thirteen infants (12%) had hypothyroidism (fT40.7 ng/dL, TSHor=10 microU/mL) and mean age at diagnosis was 28+/-17 days. Twelve infants had moderately elevated TSH (TSH 10-30 microU/mL) with normal fT4 levels after 1 week of postnatal life. The history of undergone surgical procedure which needed iodine containing disinfectants was significantly frequent in the infant with hypothyroidism and transient TSH elevation. Repeated thyroid function tests are necessary for preterm infants, even though they initially show normal thyroid function, and are especially important for infants who have been exposed to excessive or insufficient levels of iodine.

Antenatal inflammation is a known risk factor of bronchopulmonary dysplasia. The authors hypothesized that lipopolysaccharide (LPS) administration amplifies hyperoxia-induced lung injury in neonatal rats. LPS (0.5 or 1.0 microg) or normal saline was injected into the amniotic sacs of pregnant rats at 20 d gestation (term 22.5 d). After birth, rats were exposed to 85% oxygen or room air for 1 or 2 wk. Morphometric analysis of lungs was performed on 14 d. One week of hyperoxia without LPS administration resulted in modest lung injury. LPS at 0.5 microg alone did not alter lung morphology, but amplified the effect of 1 wk of hyperoxia resulting in marked inhibition of alveolarization (airspaces were enlarged and alveolar surface areas further reduced). LPS at 1.0 microg independently induced modest lung injury and also amplified the effect of 1 wk of hyperoxia. However, this sensitizing effect of LPS was not observed in rats subjected to 2 wks of hyperoxia, which in itself caused extensive lung injury (possibly masking the effect of LPS). The authors concluded that intra-amniotic LPS sensitizes neonatal rat lungs, and thus, amplifies the hyperoxia-induced inhibition of alveolarization.

Maternal chorioamnionitis has been associated with abnormal lung development. We examined the effect of maternal chorioamnionitis on the expression of transforming growth factor-beta1 (TGF-beta1) in the lungs of preterm infants. A total of 63 preterm (or=34 weeks) infants who were intubated in the delivery room were prospectively enrolled. Their placentas were examined for the presence of chorioamnionitis. Bronchoalveolar lavage (BAL) fluid and cells were obtained shortly after birth. TGF-beta1 was measured in BAL fluid and TGF-beta1 mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR) in BAL cells. TGF-beta1 mRNA expression in BAL cells showed a positive correlation with gestational age (r=0.414, p=0.002). TGF-beta1 mRNA expression was significantly decreased in the presence of maternal chorioamnionitis (0.70+/-0.12 vs. 0.81+/-0.15, p=0.007). Adjustment for gestational age, birth weight, and delivery mode did not nullify the significance. TGF-beta1 mRNA expression was marginally significantly decreased in preterm infants who developed bronchopulmonary dysplasia (BPD) later (0.75+/-0.11 vs. 0.82+/-0.15, p=0.055). However, adjustment for gestational age, patent ductus arteriosus (PDA), and maternal chorioamnionitis nullified the significance. These results might be an indirect evidence that maternal chorioamnionitis may inhibit normal lung development of fetus.