TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats

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.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012R1A1A2044109 and 2017R1D1A1B03036383). The funding body played no role in the design and interpretation of the experiments

Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants

Background Various types of noninvasive respiratory modalities that lead to successful extubation in preterm infants have been explored. We aimed to compare noninvasive neurally adjusted ventilatory assist (NIV-NAVA) and nasal continuous positive airway pressure (NCPAP) for the postextubation stabilization of preterm infants. Methods This retrospective study was divided into two distinct periods, between July 2012 and June 2013 and between July 2013 and June 2014, because NIV-NAVA was applied beginning in July 2013. Preterm infants of less than 30 weeks GA who had been intubated with mechanical ventilation for longer than 24 h and were weaned to NCPAP or NIV-NAVA after extubation were enrolled. Ventilatory variables and extubation failure were compared after weaning to NCPAP or NIV-NAVA. Extubation failure was defined when infants were reintubated within 72 h of extubation. Results There were 14 infants who were weaned to NCPAP during Period I, and 2 infants and 16 infants were weaned to NCPAP and NIV-NAVA, respectively, during Period II. At the time of extubation, there were no differences in the respiratory severity score (NIV-NAVA 1.65 vs. NCPAP 1.95), oxygen saturation index (1.70 vs. 2.09) and steroid use before extubation. Several ventilation parameters at extubation, such as the mean airway pressure, positive end-expiratory pressure, peak inspiratory pressure, and FiO2, were similar between the two groups. SpO2 and pCO2 preceding extubation were comparable. Extubation failure within 72 h after extubation was observed in 6.3% of the NIV-NAVA group and 37.5% of the NCPAP group (P = 0.041). Conclusions The data in the present showed promising implications for using NIV-NAVA over NCPAP to facilitate extubation.This study was supported by a grant from the Seoul National University Hospital Research Fund (04–2015-0430) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03036383). The funders did not participate in the research, or in the preparation the manuscript

Factors associated with acute kidney injury among preterm infants administered vancomycin: a retrospective cohort study

Background Vancomycin (VCM) is a widely used antibiotic for the treatment of gram-positive microorganisms, with some nephrotoxic effects. Recent studies have suggested that piperacillin-tazobactam (TZP) aggravates VCM-induced nephrotoxicity in adults and adolescents. However, there is a lack of research investigating these effects in the newborn population. Therefore, this study investigates whether the concomitant use of TZP with VCM use increases the risk of acute kidney injury (AKI) and to explore the factors associated with AKI in preterm infants treated with VCM. Methods This retrospective study included preterm infants with birth weight < 1,500 g in a single tertiary center who were born between 2018 and 2021 and received VCM for a minimum of 3 days. AKI was defined as an increase in serum creatinine (SCr) of at least 0.3 mg/dL and an increase in SCr of at least 1.5 times baseline during and up to 1 week after discontinuation of VCM. The study population was categorized as those with or without concomitant use of TZP. Data on perinatal and postnatal factors associated with AKI were collected and analyzed. Results Of the 70 infants, 17 died before 7 postnatal days or antecedent AKI and were excluded, while among the remaining participants, 25 received VCM with TZP (VCM + TZP) and 28 VCM without TZP (VCM—TZP). Gestational age (GA) at birth (26.4 ± 2.8 weeks vs. 26.5 ± 2.6 weeks, p = 0.859) and birthweight (750.4 ± 232.2 g vs. 838.1 ± 268.7 g, p = 0.212) were comparable between the two groups. There were no significant differences in the incidence of AKI between groups. Multivariate analysis showed that GA (adjusted OR: 0.58, 95% CI: 0.35–0.98, p = 0.042), patent ductus arteriosus (PDA) (adjusted OR: 5.23, 95% CI: 0.67–41.05, p = 0.115), and necrotizing enterocolitis (NEC) (adjusted OR: 37.65, 95% CI: 3.08–459.96, p = 0.005) were associated with AKI in the study population. Conclusions In very low birthweight infants, concomitant use of TZP did not increase the risk of AKI during VCM administration. Instead, a lower GA, and NEC were associated with AKI in this population

A case of McKusick-Kaufman syndrome

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

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial

Background This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. Methods This exploratory randomized controlled trial enrolled infants born before 35weeks gestation with enterostomy. If the stomal output was ≥ 40mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. Results Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. Conclusions MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. Trial registration clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.This study was supported by Research Resettlement Fund for the new faculty of Seoul National University and Research Fund of Seoul National University Hospital (3020200170)

Neurodevelopmental Outcomes and Brain Volumetric Analysis of Low-Grade Intraventricular Hemorrhage

Purpose Extremely preterm infants are prone to brain injury and underdevelopment. Intraventricular hemorrhage (IVH) is the most common cause of brain injury and a significant risk factor for neurodevelopmental delay in preterm infants. Severe IVH is known to have a poor outcome; however, the outcomes of low-grade IVH remain controversial. This study aimed to evaluate neurodevelopmental outcomes and brain segmental volumes of preterm infants with low-grade IVH. Methods This retrospective cohort study included 109 extremely preterm infants who underwent term equivalent age-magnetic resonance imaging and neurodevelopmental evaluation at a corrected age of 18 to 24 months. We compared infants with and without low-grade IVH. Results Among the 109 extremely preterm infants, 25 had low-grade IVH and 84 had no IVH. There were no significant differences in the neurodevelopmental outcomes between the low-grade and no IVH groups. In multivariate analysis, low-grade IVH was associated with a smaller medullary volume (adjusted odds ratio, 0.575; 95% confidence interval, 0.346 to 0.957; P=0.034). Conclusion We found no significant differences in the neurodevelopmental outcomes of extremely preterm infants at a corrected age of 18 to 24 months between those with low-grade IVH and those without IVH. Low-grade IVH was associated with a smaller medullary volume

Factors associated with neurodevelopment in preterm infants with systematic inflammation

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 < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, 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 < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months. 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.This research was supported by the Basic Science Research Programme through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2012R1A1A2044109, 2017R1D1A1B03036383, and 2017R1D1A1B04030931) and supported by grant no 0420160450 from the SNUH Research Fun

Misdiagnosis of fetus-in-fetu as meconium peritonitis

Fetus-in-fetu (FIF) is a rare congenital condition in which a fetiform mass is detected in the host abdomen and also in other sites such as the intracranium, thorax, head, and neck. This condition has been rarely reported in the literature. Herein, we report the case of a fetus presenting with abdominal cystic mass and ascites and prenatally diagnosed as meconium pseudocyst. Explorative laparotomy revealed an irregular fetiform mass in the retroperitoneum within a fluid-filled cyst. The mass contained intestinal tract, liver, pancreas, and finger. Fetal abdominal cystic mass has been identified in a broad spectrum of diseases. However, as in our case, FIF is often overlooked during differential diagnosis. FIF should also be differentiated from other conditions associated with fetal abdominal masses

Association of uncoordinated sucking pattern with developmental outcome in premature infants: a retrospective analysis

Background Stress 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). Methods We 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. Results Seventy 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. Conclusions Uncoordinated 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