Mitochondrial DNA mutations in extremely preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease affecting extremely preterm infants. While mitochondrial dysfunction has been investigated in various medical conditions, limited research has explored mitochondrial DNA (mtDNA) gene mutations, specifically in BPD. This study aimed to evaluate mitochondrial mtDNA gene mutations in extremely preterm infants with BPD. In this prospective observational study, we enrolled a cohort of extremely preterm infants diagnosed with BPD. Clinical data were collected to provide comprehensive patient profiles. Peripheral blood mononuclear cells were isolated from whole-blood samples obtained within a defined timeframe. Subsequently, mtDNA extraction and sequencing using next-generation sequencing technology were performed to identify mtDNA gene mutations. Among the cohort of ten extremely preterm infants with BPD, mtDNA sequencing revealed the presence of mutations in seven patients, resulting in a total of twenty-one point mutations. Notably, many of these mutations were identified in loci associated with critical components of the respiratory chain complexes, vital for proper mitochondrial function and cellular energy production. This pilot study provides evidence of mtDNA point mutations in a subset of extremely preterm infants with BPD. These findings suggest a potential association between mitochondrial dysfunction and the pathogenesis of BPD. Further extensive investigations are warranted to unravel the mechanisms underlying mtDNA mutations in BPD.

Pulmonary Artery Measurements as Postnatal Prognostic Tool in Right Congenital Diaphragmatic Hernia.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is a rare and often fatal congenital anomaly, primarily attributed to lung hypoplasia, which is associated with small branch pulmonary artery (PA). This study investigated whether postnatal PA measurements obtained through echocardiography are associated with mortality or the extracorporeal membrane oxygenation (ECMO) requirement in neonates with RCDH. METHODS: A retrospective study was conducted on neonates with RCDH born between 2008 and 2022. Echocardiography was performed on the day of birth. The diameter of the main PA (MPA) was measured at the maximal dimension, and the diameters of the left PA (LPA) and right PA (RPA) were measured at the bifurcation. The primary outcome was mortality or ECMO requirement. Parameters, including the LPA:MPA ratio, RPA:MPA ratio, Nakata index, McGoon ratio, and ejection fraction (EF), were analyzed and compared with the observed-to-expected lung-to-head ratio (o/e LHR), initial blood gas, and defect size as predictive values. RESULTS: Among 39 neonates with RCDH, 25 (64.1 %) survived without ECMO. The non-survivor or ECMO group exhibited lower o/e LHR, reduced EF, smaller LPA and RPA diameters, and larger MPA diameter than survivors. Lower LPA:MPA ratio, Nakata index, McGoon ratio, and higher initial PaCO2 were associated with adverse outcomes. Notably, the LPA:MPA ratio showed the highest predictive capability (area under the curve, 0.983; p < 0.001). CONCLUSION: The LPA:MPA ratio is a promising postnatal predictor of mortality or ECMO requirement in neonates with RCDH. Additionally, Nakata index, McGoon ratio, and initial PaCO2 are significantly correlated with outcomes. LEVEL OF EVIDENCE: This is a level III. TYPE OF STUDY: Prognostic study.

Outcomes at 18-24 Months of Infants with Birth Weight under 500 g Born in Korea during 2013-2017: A Nationwide Cohort Study.

INTRODUCTION: This study aimed to investigate the outcomes of infants at 18-24 months born in the Korean Neonatal Network with a birth weight <500 g. METHODS: The anthropometric and neurodevelopmental data of infants with a birth weight <500 g at a gestational age of ≥22 weeks who were registered in the Korean Neonatal Network 2013-2017 and followed up at a corrected age of 18-24 months were reviewed. Neurodevelopmental impairment was defined as the presence of any of the following: (1) cerebral palsy; (2) severe visual impairment; (3) hearing impairment; or (4) cognitive impairment. Cognitive impairment was defined as (1) a Bayley Scales of Infant Development-II Mental Development Index score <70; and (2) Bayley Scales of Infant and Toddler Development-III Cognitive and Language Composite scores <85. Cognitive testing was performed for infants with suspected problems upon clinician's referral to developmental specialists. RESULTS: At a median corrected age of 20 months, 26/52 (50%) of included infants had neurodevelopmental impairment. Cerebral palsy, severe visual impairment, wearing of glasses, hearing impairment, and cognitive impairment occurred in 22%, 0%, 8%, 5%, and 57% of the included infants, respectively. The proportions of infants with <2 standard deviations of weight, length, and head circumference were 54%, 52%, and 56%, respectively. The majority (70%) of infants were rehospitalized, and the most common cause was respiratory problems. CONCLUSION: Half of infants with a birth weight <500 g in Korea may exhibit neurodevelopmental impairment and growth retardation at a corrected age of 18-24 months. Multidisciplinary follow-up along with continuous rehabilitation will be needed to improve neurological and physical development in this special population.

Early echocardiographic pulmonary artery measurements as prognostic indicators in left congenital diaphragmatic hernia.

BACKGROUND: To predict whether the left pulmonary artery (LPA) to the main pulmonary artery (MPA) ratio measured by echocardiography in left congenital diaphragmatic hernia (CDH) was related to death or need for extracorporeal membrane oxygenation (ECMO). METHODS: This retrospective study analyzed neonates with left CDH born between 2018 and 2022 in a single tertiary medical institution. Echocardiography was performed immediately after birth. The diameter of the LPA was measured at the bifurcation, and the diameter of the MPA was measured at the maximal dimension during the systolic phase. The Nakata index, McGoon ratio, and ejection fraction (EF) were analyzed and compared with the LPA: MPA ratio as predictive values. RESULTS: Seventy-two neonates with left CDH were included, 19 (26.4%) died or needed ECMO, and 53 (73.6%) survived without ECMO. The lower observed/expected lung-to-head ratio, lower EF, lower LPA: MPA ratio, lower RPA: MPA ratio, lower Nakata index, and lower McGoon ratio were associated with death or need for ECMO. By multivariate analysis, lower LPA: MPA ratio, RPA: MPA ratio, and Nakata index were independent postnatal risk factors for death or need for ECMO. Among the measurements, the LPA: MPA ratio had the highest area under the curve (0.957) with a sensitivity of 84.2% and specificity of 96.3% at a cut-off value of 31.2%. CONCLUSION: In patients with left CDH, the LPA: MPA ratio measured by echocardiography could be used as an independent postnatal predictor of death or need for ECMO.

Case report: a premature infant with severe intrauterine growth restriction, adrenal insufficiency, and inflammatory diarrhea: a genetically confirmed case of MIRAGE syndrome.

Introduction: MIRAGE syndrome is a rare disease characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Herein, we report the case of a girl with MIRAGE syndrome who presented with adrenal insufficiency and chronic diarrhea. Case presentation: The patient was born at 29 + 6 weeks of gestational age with a birth weight of 656 g (<3p). Her height and head circumference were also <3p. At birth, she presented with respiratory distress, meconium staining, and pneumomediastinum, which were managed with high-frequency ventilation and empirical antibiotics. Physical examination showed generalized hyperpigmentation and normal female genitalia. A few days after birth, polyuria and hypotension developed, and laboratory findings revealed hypoglycemia, hyponatremia, and hyperkalemia. Plasma adrenocorticotropic hormone levels were elevated with low serum cortisol levels and high plasma renin activity, which were suggestive of adrenal insufficiency. Hydrocortisone and fludrocortisone were introduced and maintained, and hyperpigmentation attenuated with time. Both kidneys looked dysplastic, and adrenal glands could not be traced on abdominal ultrasound. From the early days of life, thrombocytopenia and anemia were detected, but not to life-threatening level and slowly recovered up to the normal range. Despite aggressive nutritional support, weight gain and growth spurt were severely retarded during the hospital stay. Additionally, after introducing enteral feeding, she experienced severe diarrhea and subsequent perineal skin rashes and ulcerations. Fecal calprotectin level was highly elevated; however, a small bowel biopsy resulted in non-specific submucosal congestion. The patient was diagnosed with MIRAGE syndrome with SAMD9 gene mutation. She was discharged with tube feeding and elemental formula feeding continued, but chronic diarrhea persisted. By the time of the last follow-up at 15 months of corrected age, she was fortunately not subjected to severe invasive infection and myelodysplastic syndrome. However, she was dependent on tube feeding and demonstrated a severe developmental delay equivalent to approximately 5-6 months of age. Conclusion: The early diagnosis of adrenal crisis and hormone replacement therapy can save the life of -patients with MIRAGE syndrome; however, chronic intractable diarrhea and growth and developmental delay continue to impede the patient's well-being.

Prevention of human milk-acquired cytomegalovirus infection in very-low-birth-weight infants.

BACKGROUND: The aim of the study was to determine the rate of cytomegalovirus virolactia in the human milk (HM) of mothers of VLBW infants, compare the CMV infection rates and the changes in CMV DNA viral load and nutrient profile among different HM preparation methods. METHODS: A prospective randomized controlled study was performed in infants with gestational age < 32 weeks or birth-weight < 1500 g admitted to neonatal intensive care unit of Asan Medical Center and Haeundae Paik Hospital who were given mother's own milk. Enrolled infants were randomized into three groups according to the HM preparation methods: freezing-thawing (FT), FT + low-temperature Holder pasteurization (FT + LP), and FT + high-temperature short-term pasteurization (FT + HP). Urine CMV culture and PCR were obtained at birth and at 4, 8, and 12 weeks. HM CMV culture and PCR were obtained at birth and at 3, 6, 9, and 12 weeks. Changes in macronutrients in HM was obtained at 4 ~ 6 weeks. RESULTS: Of 564 infants, 217 mothers (38.5%) produced CMV PCR positive milk. After exclusion, a total of 125 infants were randomized into the FT (n = 41), FT + LP (n = 42), and FT + HP (n = 42) groups, whose rate of HM-acquired CMV infection was 4.9% (n = 2), 9.5% (n = 4), and 2.4% (n = 1), respectively. Out of seven CMV infected infants, two infants fed with FT + LP HM developed CMV infection- associated symptoms. Ages at diagnoses were earlier (28.5 days after birth) and at younger post conceptional age (< 32 weeks) in comparison to infants with asymptomatic CMV infection. CMV DNA viral load significantly decreased after pasturizations, especially in FT + HP group. CONCLUSIONS: HM-acquired symptomatic CMV infection rate is low and its impact on clinical course was not serious in our VLBW infants. However, evidences showing poor neurodevelopmental outcome in later life, we need to generate a guideline to protect VLBW infant form HM transmitted CMV infection. Based on our small sized study, we did not find any superiority in pasteurizing HM with frequently used LP in comparison to frozen or HP HM. More research is needed to determine the method and duration of pasteurization to reduce the HM-acquired CMV infection.

Postnatal Imaging for Prediction of Outcome in Patients with Left-sided Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate associations between postnatal imaging features and outcome of left-sided congenital diaphragmatic hernia, as defined by overall survival and a requirement for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Newborns diagnosed prenatally with left-sided congenital diaphragmatic hernia between January 2013 and September 2021 were studied retrospectively. The esophageal deviation index was newly defined as the largest diameter from the midline to deviated gastric tube divided by the largest transverse diameter of the thoracic cavity on the radiograph. Regression analyses were performed to identify postnatal imaging features associated with overall survival and a requirement for ECMO. The predictive power (ie, area under the curve [AUC] of a time-dependent receiver operating characteristic curve) of prenatal, postnatal, and intraoperative findings for predicting survival were calculated. RESULTS: Ninety-seven patients (54 males; mean gestational age, 38.3 ± 1.9 weeks; mean birth weight, 2956.5 ± 540.0 g) were analyzed. The esophageal deviation index (adjusted hazard ratio [HR], moderate [≥0.19 to <0.24], 6.427 [P = .029]; severe [≥0.24], 33.007 [P < .001]) and right pneumothorax (adjusted HR, 8.763; P = .002) were associated with overall survival and with a requirement for ECMO. Liver herniation on postnatal ultrasound also was associated with overall survival (P < .001) and need for ECMO (P = .001). In addition, the AUC for prediction of 1-year survival from postnatal ultrasound was comparable with that of prenatally or intraoperatively detected liver herniation (0.93; 95% CI, 0.88-0.97). CONCLUSIONS: The esophageal deviation index, right pneumothorax, and liver herniation observed by postnatal imaging have prognostic value in patients with left-sided congenital diaphragmatic hernia.

Clinical characteristics of neonatal cholestasis in a tertiary hospital and the development of a novel prediction model for mortality.

BACKGROUND: Few studies have described the aetiologies of neonatal cholestasis, and the overall neonatal cholestasis-related mortality (NCM) rate is unclear. We investigated the aetiology and outcome of neonatal cholestasis in a tertiary hospital and developed an NCM prediction model for these patients. METHODS: Patients aged <100 days with serum direct bilirubin (DB) levels of >1.0 mg/dL were retrospectively screened. Diagnostic and laboratory data during the 8-week follow-up period after enrolment between 2005 and 2020 were extracted digitally, and medical charts were reviewed manually by clinicians. Logistic regression was used to derive a prediction model for the 1-year mortality outcome of neonatal cholestasis, and performance evaluation and external validation were conducted for the NCM prediction model. FINDINGS: We enrolled 4028 neonates with DB of >1.0 mg/dL at least once. Prematurity and birth injury (35.4%), complex heart anomalies (18.6%), liver diseases (11.4%), and gastrointestinal anomalies (9.2%) were the most common aetiologies; 398 (9.9%) patients died before one year of age. The peak value of DB was positively correlated to the 1-year mortality rate. In the multivariate analysis, simple laboratory indices, including platelet, prothrombin time, aspartate aminotransferase, albumin, direct bilirubin, creatinine, and C-reactive protein, were independent predictors of 1-year mortality outcome of complete-case subjects. Using these laboratory indices, a logistic regression-based NCM prediction model was constructed. It showed acceptable performances on discrimination (area under the curve, 0.916), calibration (slope, 1.04) and Brier scoring (0.072). The external validation of the sample (n = 920) from two other centres also revealed similar performance profiles of the NCM model. INTERPRETATION: Various aetiologies of neonatal cholestasis were identified in a tertiary hospital, resulting in unfavourable outcomes of a large proportion. The NCM prediction model may have the potential to help clinicians to be aware of high-risk neonatal cholestasis. FUNDING: Ministry of Health & Welfare, Republic of Korea.

Neonatal sepsis-causing bacterial pathogens and outcome of trends of their antimicrobial susceptibility a 20-year period at a neonatal intensive care unit.

BACKGROUND: Due to increases in the number of infants born with younger gestational age (GA) and lower birth weight, the incidence of neonatal sepsis is increasing. PURPOSE: We investigated the changes in the prevalence of bacterial pathogens, their antimicrobial susceptibility, and sepsis-related mortality during 20 years at a neonatal intensive care unit. METHODS: The study period was divided into two 10-year phases (1998-2007 vs. 2008-2017). Medical records were reviewed to gather data on demographics, causative microbial pathogens, incidence of multidrug-resistant organisms, antimicrobial susceptibility, and rates of sepsis-related mortality. RESULTS: In both study phases, the most common pathogens for neonatal sepsis were coagulase-negative Staphylococcus (CoNS) (28.6%) and Enterobacter cloacae (16.1%) for early-onset sepsis (EOS, ≤72 hours after birth) and CoNS (54.7%) and Staphylococcus aureus (12.9%) for late-onset sepsis (LOS, >72 hours after birth). CoNS and S. aureus showed 100% sensitivity to vancomycin in both phases. The susceptibility of S. aureus to oxacillin increased from 19.2% to 57.9% in phase II than phase I. K. pneumonia and E. cloacae showed increases in its susceptibility to gentamicin, cefotaxime and ceftriaxone in phase II than phase I. In both phases, the most common pathogens that caused sepsis-related death were K. pneumoniae (18.2%) and Pseudomonas aeruginosa (13.6%). Sepsis-related mortality rate was higher in infants with GA <37 weeks than those with GA over 37 weeks (P=0.016). In addition, the mortality rate of neonatal sepsis caused by gram-negative bacteria was significantly higher than that caused by gram-positive bacteria (P<0.001). CONCLUSIONS: CoNS was the most common pathogen for EOS and LOS. While we found significant changes in antimicrobial sensitivities over time. GA below 37 weeks and gram-negative organisms are associated with mortality rate.

Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center's experience.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement. METHODS: We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors. RESULTS: A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50. CONCLUSIONS: The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.

Survival and Morbidities in Infants with Birth Weight Less than 500 g: a Nationwide Cohort Study.

BACKGROUND: This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. METHODS: The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. RESULTS: The survival rate of the infants was 28%, with a median gestational age and BW of 243/7 weeks (range, 220/7-336/7) and 440 g (range, 220-499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400-499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups. Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III-IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69-291), and 53% required assistive devices at discharge. CONCLUSION: Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.

Stem cells for bronchopulmonary dysplasia in preterm infants: A randomized controlled phase II trial.

We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 107 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957.

Comparing Axillary and Rectal Temperature Measurements in Very Preterm Infants: A Prospective Observational Study.

PURPOSE: The agreement between axillary temperature (AT) and rectal temperature (RT) measurements has not been well established in preterm infants. Therefore, our study aimed to evaluate the agreement between AT and RT measurements in very preterm infants. METHODS: Preterm infants <32 weeks of gestational age were prospectively included. The infants' body temperature (BT) was measured twice a day from day 1 to day 6. A paired t-test and the Bland-Altman method were used to analyze the difference between the AT and RT. A linear regression model was used to explore the effects of environmental factors on the differences of BT between the axillary and rectal measurements and to calibrate the RT according to the AT. RESULTS: Eighty infants each underwent 6 paired axillary and rectal measurements. The gestational age varied from 22 to 31 weeks (mean 28 weeks). The birth weight varied from 302 to 1,770 g (mean 1,025 g). The AT was significantly lower than the RT. The difference between the RT and AT significantly increased with increasing RT. The AT and RT demonstrated poor agreement overall; however, the RT can be estimated using the AT with the following equation: RT = -4.033 + 1.116 × AT. Environmental factors, including the incubator temperature, incubator humidity, phototherapy, and application of invasive mechanical ventilation did not affect the differences between the AT and RT measurements. CONCLUSION: AT measurements cannot be interchangeably used with RT measurements in very preterm infants.

Functional and structural evaluation in the lungs of children with repaired congenital diaphragmatic hernia.

BACKGROUND: To evaluate the long-term functional and structural pulmonary development in children with repaired congenital diaphragmatic hernia (CDH) and to identify the associated perinatal-neonatal risk factors. METHODS: Children with repaired CDH through corrective surgery who were born at gestational age ≥ 35 weeks were included in this analysis. Those who were followed for at least 5 years were subjected to spirometry and chest computed tomography for evaluation of their functional and structural growth. Main bronchus diameters and lung volumes (total, left/right) were measured. According to total lung volume (TLV) relative to body surface area, children were grouped into TLV ≥ 50 group and TLV < 50 group and the associations with perinatal-neonatal factors were analyzed. RESULTS: Of the 28 children (mean age, 6.2 ± 0.2 years) with left-sided CDH, 7 (25%) had abnormal pulmonary function, of whom 6 (87%) showed restrictive patterns. All pulmonary functions except FEF25-75% were worse than those in matched healthy control group. Worse pulmonary function was significantly associated with small head and abdominal circumferences at birth. The mean TLV was 1339.1 ± 363.9 mL and LLV/TLV was 47.9 ± 2.5 mL. Children with abnormal pulmonary function were more likely to have smaller lung volumes. In multivariate analysis, abdominal circumference at birth was significantly associated with abnormal lung volume. CONCLUSIONS: A quarter of children with repaired CDH showed abnormal pulmonary function. Small abdominal circumference at birth was associated with abnormal pulmonary function and lower TLV. .

Extremely low birth weight infant surviving left congenital diaphragmatic hernia: a case report.

In this study, we present the case of a 900 g, male infant born at 27+5 weeks, who was placed on high frequency oscillatory ventilation (HFOV) until repair of a left congenital diaphragmatic hernia (CDH) at 39 days of life (DOL). To date, this is the smallest infant with repair of the left CDH reported in the literature. After birth, he passed the cardiopulmonary stabilization phase and successfully underwent delayed surgery; in the process, he received ventilator assistance through HFOV. He weighed 1,660 gm at the time of surgery. We performed the thoracoscopic primary closure of the diaphragmatic defect. He was extubated on post-operation day (POD) 7 and discharged from hospital on POD 36 with 0.1 L/min supplemental oxygen via nasal cannula. He is being followed for growth and development and there has been no recurrence at the surgical site at 24 months of corrected age. In this case, high mean airway pressure (MAP) was required based on the patient's weight to achieve adequate recruitment of the left lung, and the patient was diagnosed with mental developmental delay on Bayley Scales of Infant Development-II. Thus, we suggest that the postnatal course and long-term outcomes for extremely low birth weight (ELBW) and preterm infants with left CDH is different from that for full-term babies. Therefore, future research should focus on preterm infants with left CDH.

Perinatal outcome of fetuses with congenital high airway obstruction syndrome: a single-center experience.

OBJECTIVE: To report our experience with management of fetuses with congenital high airway obstruction syndrome (CHAOS). METHODS: We retrospectively reviewed the cases of fetuses who were prenatally diagnosed and postnatally confirmed with CHAOS between 2010 and 2019 at Asan Medical Center, Seoul, Korea. RESULTS: Of 13 fetuses prenatally diagnosed with CHAOS, 7 were lost to follow-up and 6 were postnatally confirmed as having CHAOS. All fetuses, except one were delivered via cesarean section with an ex utero intrapartum treatment (EXIT) procedure. Two patients had coexisting congenital heart diseases requiring several cardiac surgeries following birth. Both of these patients demonstrated developmental delay; however, the remaining 4 had a normal development except for expressive language. Two infants died of respiratory complications, and the remaining 4 were alive at the end of the follow-up period. All 4 live patients underwent tracheostomy with planned reconstruction surgery. Three children are now able to phonate, and 1 can maintain a conservation. CONCLUSION: The proper management of CHAOS using the EXIT procedure results in high survival and low hypoxemia-induced complication rates. Therefore, an accurate prenatal diagnosis is necessary for an appropriate perinatal management.

Morbidity and Mortality of Very Low Birth Weight Infants with Congenital Heart Disease.

BACKGROUND AND OBJECTIVES: This study aimed to provide morbidity and mortality information on very low birth weight (VLBW) infants with congenital heart disease (CHD-VLBWs). METHODS: The study used a 10-year cohort of VLBW infants from a single institution. CHD was classified according to International Classification of Diseases, Version 9, Clinical Modification. Mortality and neonatal outcomes were assessed by comparing the CHD-VLBWs with gestational age- and birth weight-matched controls. RESULTS: The prevalence of CHD-VLBWs was 7.5% (79/1,050), mean gestational age was 31.1±3.2 weeks, and mean birth weight was 1,126.2±268.3 g; 50.6% of the infants were small for the gestational age. The CHD-VLBWs more commonly had bronchopulmonary dysplasia (BPD), and the longer they were exposed to oxygen, the more frequently they developed BPD. Those with cyanotic heart disease developed severe BPD more frequently. Necrotizing enterocolitis (NEC) occurred frequently in the CHD-VLBWs and was not associated with their feeding patterns. CHD-VLBWs had a higher mortality rate; prematurity-related diseases were the leading cause of death before surgery, while heart-related problems were the leading cause of death after surgery. We found no significant difference in mortality from prematurity-related disease between the CHD-VLBWs and controls. In the subgroup analysis of CHD, the cyanotic CHD group had a higher incidence of BPD and higher mortality rate than the acyanotic CHD group. CONCLUSIONS: CHD-VLBWs showed higher BPD, NEC, and mortality rates than those without CHD. There was also a higher incidence of BPD and mortality in VLBW infants with cyanotic CHD than in those with acyanotic CHD.

Challenges of acute peritoneal dialysis in extremely-low-birth-weight infants: a retrospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) has been used occasionally in extremely-low-birth-weight (ELBW) infants with acute kidney injury (AKI). This study aimed to evaluate the clinical characteristics and outcomes of ELBW infants with AKI treated with PD. METHODS: In this retrospective cohort study, the medical records of ELBW infants with AKI, who underwent PD from January 2008 to February 2018, were reviewed. A PD catheter (7.5-9.0 Fr) or central venous catheter (4 Fr) was used for the peritoneal access. Treatment with PD solutions (2.5 or 4.25%) was started at 10 mL/kg, which was increased to 20-30 mL/kg for 60-120 min/cycle continuing for 24 h. RESULTS: Twelve ELBW infants (seven male and five female infants) were treated, and their mean (±SD) gestational age and birth weight were 27.2 (±3.3) weeks and 706.5 (±220.5) g, respectively. Two patients had severe perinatal asphyxia (5-min Apgar score ≤ 3). The most important indication for starting PD was AKI due to sepsis. The average (±SD) duration of PD was 9.4 (± 7.7) days. The potassium levels in the ELBW infants with hyperkalemia decreased from 6.8 to 5.0 mg/mL after 9.3 (± 4.4) days. The most common complication of PD was mechanical dysfunction of the catheters, such as dialysate leakage (75%). Two patients were successful weaned off PD. The mortality rate of the infants treated with PD was 91.7%. CONCLUSIONS: In this series, the mortality rate of ELBW infants with AKI treated with PD was relatively high because of their incompletely developed organ systems. Therefore, the use of PD should be carefully considered for the treatment of ELBW infants with AKI in terms of decisions regarding resuscitation.

Congenital Anomalies in Very-Low-Birth-Weight Infants: A Nationwide Cohort Study.

BACKGROUND: Management of newborn infants with congenital anomalies is challenging and requires a multidisciplinary approach. The prevalence of congenital anomalies in very-low-birth-weight infants (VLBWIs; birth weight <1,500 g) has been rarely reported. OBJECTIVES: The aim of this study was to investigate the epidemiology of congenital anomalies in VLBWIs and the association with early mortality and major morbidities. STUDY DESIGN: A prospective cohort study was performed using data collected from 70 centers registered in the Korean Neonatal Network. Data from the VLBWIs with major congenital anomalies (n = 289) and the controls (n = 867), selected by 1:3 frequency matching for gestational age, were compared. RESULTS: The overall prevalence of major congenital anomalies in VLBWIs was 34.9 per 1,000 live births (289/8,156). The top 2 ranked subgroups of congenital anomalies were the digestive system (31.7%) and congenital heart defects (27.7%), followed by chromosomal anomalies, genitourinary tract defect, central nervous system, other anomalies, undefined, and respiratory system. The group with congenital anomalies had a higher mortality (40.7%) than the control group (11.1%). Each subgroup of congenital anomalies, except for chromosomal anomalies, increased the risk of mortality, with the highest odds ratio associated with "other" anomalies, which includes hydrops fetalis and congenital diaphragmatic hernia. In the multivariate analysis, congenital anomaly was a risk factor for mortality, bronchopulmonary dysplasia, and severe-grade intraventricular hemorrhage. VLBWIs with congenital anomaly demonstrated impaired in-hospital growth as compared with the control group. CONCLUSION: Congenital anomaly increased the risk of in-hospital mortality and was associated with short-term neonatal morbidities in the VLBWIs.