Trends of Mortality, Time, and Causes of Death in Preterm Infants

( Ga Won Jeon ) 대한주산의학회 2019 Perinatology Vol.30 No.4

Objective: Although survival rate of preterm infants in Korea has increased in the past several decades, it seems to be stable recently. The objective of this study is to evaluate the mortality rate of preterm infants in a single center in Korea between 2009 and 2018. Methods: Preterm infants with gestational age (GA) <30 weeks who were admitted to Busan Paik Hospital (January 2009 to December 2018) were enrolled. Results: The overall mortality rate was 20.8%. Mortality rate decreased from 21.9% in 2009 to 9.2% in 2012. It then increased and reached a plateau at 20%. Mortality rate was 80.0% in those with GA of 22 weeks. It then decreased with increasing GA. It was 2.9% in those with GA of 29 weeks. The risk of death decreased by 0.573 times when GA increased by 1 week. Death immediately after birth was high in infants with GA of 22 weeks. It was rare in infants with GA ≥25 weeks. Death within 24 hours after birth was high in infants with GA ≤24 weeks who were delivered precipitately without appropriate perinatal support. Sepsis was the leading cause of all deaths. High grade intraventricular hemorrhage was the second common cause of death, especially in infants with GA ≤24 weeks. Conclusion: Mortality rate of preterm infants in this study did not decrease. Modifiable factors including delivery with appropriate supports of neonatal resuscitation team and sufficient maternal obstetric care, especially maternal infection control might reduce mortality, especially immediate postnatal death.

Granulocyte Colony Stimulating Factor Attenuates Hyperoxia-Induced Lung Injury by Down-Modulating Inflammatory Responses in Neonatal Rats

Ga Won Jeon,Won Soon Park,성동경,정유진,구수현,최서희,장윤실,신종범 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.1

Purpose: Granulocyte colony stimulating factor (G-CSF) has been known to increase neutrophil production and have anti-inflammatory properties, but the effect of G-CSF on pulmonary system is in controversy. We investigated whether G-CSF treatment could attenuate hyperoxia-induced lung injury, and whether this protective effect is mediated by the down-modulation of inflammatory responses in a neonatal rat model. Materials and Methods: Newborn Sprague-Dawley rats (Orient Co., Seoul, Korea) were subjected to 14 days of hyperoxia (90% oxygen) beginning within 10 h after birth. G-CSF (20 μg/kg) was administered intraperitoneally on the fourth, fifth, and sixth postnatal days. Results: This treatment significantly improved hyperoxia-induced reduction in body weight gain and lung pathology such as increased mean linear intercept, mean alveolar volume, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling positive cells. Hyperoxia-induced activation of nicotinamide adenine dinucleotide phosphate oxidase, which is responsible for superoxide anion production, as evidenced by upregulation and membrane translocation of p67^phox was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-β. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 was not significant. Conclusion: In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.

A Case of Asymptomatic, Localized, and Idiopathic Diffuse Alveolar Damage

Jeon, Young-Do,Hong, Christian,Joh, Joon-Sung,Jung, Ja-Young,Min, Ji-Won,Park, Seon-Young,Lee, Ga-Ram The Korean Academy of Tuberculosis and Respiratory 2012 Tuberculosis and Respiratory Diseases Vol.72 No.4

Diffuse alveolar damage (DAD) is a histological change in lung tissue, and is generally caused by an acute lung injury, which is characterized by bilateral and widespread damages. Localized DAD occurs very rarely. The causes for DAD are numerous, but the chief cause is acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia, in cases of idiopathic manifestation. The 82-year-old patient, in this case study, showed a DAD lesion in only 1 lobe. The patient was otherwise healthy, with no previous symptoms of DAD. He was admitted to our medical center owing to localized infiltration, observed on his chest radiograph. Laboratory studies showed no signs of infections. DAD was confirmed by a surgical lung biopsy. The patient received corticosteroid treatment and had gradually improved. We report the case of a patient with localized, idiopathic DAD that cannot be classified as acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia.

Hypoxia-inducible factor: role in cell survival in superoxide dismutase overexpressing mice after neonatal hypoxia-ischemia

Jeon, Ga Won,Sheldon, R. Ann,Ferriero, Donna M. The Korean Pediatric Society 2019 Clinical and Experimental Pediatrics (CEP) Vol.62 No.12

Background: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies. Purpose: HIF-1α deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit. Methods: On postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death. Results: HIF-1α protein expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1 overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1 overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death. Conclusion: HIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI.

Surfactant preparations for preterm infants with respiratory distress syndrome: past, present, and future

Jeon, Ga Won The Korean Pediatric Society 2019 Clinical and Experimental Pediatrics (CEP) Vol.62 No.5

Following the first successful trial of surfactant replacement therapy for preterm infants with respiratory distress syndrome (RDS) by Fujiwara in 1980, several animal-derived natural surfactants and synthetic surfactants have been developed. Synthetic surfactants were designed to overcome limitations of natural surfactants such as cost, immune reactions, and infections elicited by animal proteins contained in natural surfactants. However, first-generation synthetic surfactants that are protein-free have failed to prove their superiority over natural surfactants because they lack surfactant protein (SP). Lucinactant, a second-generation synthetic surfactant containing the SP-B analog, was better or at least as effective as the natural surfactant, suggesting that lucinactant could act an alternative to natural surfactants. Lucinactant was approved by the U. S. Food and Drug Administration in March 2012 as the fifth surfactant to treat neonatal RDS. CHF5633, a second-generation synthetic surfactant containing SP-B and SP-C analogs, was effective and safe in a human multicenter cohort study for preterm infants. Many comparative studies of natural surfactants used worldwide have reported different efficacies for different preparations. However, these differences are believed to due to site variations, not actual differences. The more important thing than the composition of the surfactant in improving outcome is the timing and mode of administration of the surfactant. Novel synthetic surfactants containing synthetic phospholipid incorporated with SP-B and SP-C analogs will potentially represent alternatives to natural surfactants in the future, while improvement of treatment modalities with less-invasive or noninvasive methods of surfactant administration will be the most important task to be resolved.

Respiratory support with heated humidified high flow nasal cannula in preterm infants

Jeon, Ga Won The Korean Pediatric Society 2016 Clinical and Experimental Pediatrics (CEP) Vol.59 No.10

The incidence of bronchopulmonary dysplasia (BPD) has not decreased over the last decade. The most important way to decrease BPD is by weaning the patient from the ventilator as soon as possible in order to reduce ventilator-induced lung injury that underlies BPD, and by using a noninvasive ventilator (NIV). Use of a heated, humidified, high flow nasal cannula (HHHFNC), which is the most recently introduced NIV mode for respiratory support in preterm infants, is rapidly increasing in many neonatal intensive care units due to the technical ease of use without sealing, and the attending physician's preference compared to other NIV modes. A number of studies have shown that nasal breakdown and neonatal complications were lower when using a HHHFNC than when using nasal continuous positive airway pressure (nCPAP), or nasal intermittent positive pressure ventilation. The rates of extubation failure during respiratory support were not different between patients who used HHHFNC and nCPAP. However, data from the use of HHHFNC as the initial respiratory support "after birth", particularly in extremely preterm infants, are lacking. Although the HHHFNC is efficacious and safe, large randomized controlled trials are needed before the HHHFNC can be considered an NIV standard, particularly for extremely preterm infants.

Antenatal Magnesium Sulfate Is Not Associated With Improved Long-Term Neurodevelopment and Growth in Very Low Birth Weight Infants

Jeon Ga Won,Ahn So Yoon,Kim Su Min,Yang Misun,Sung Se In,Sung Ji-Hee,Oh Soo-young,Roh Cheong-Rae,Choi Suk-Joo,Chang Yun Sil 대한의학회 2023 Journal of Korean medical science Vol.38 No.44

Background: Though antenatal magnesium sulfate (MgSO4) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. Methods: We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24–31 weeks. Results: Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18–24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. Conclusion: Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.

Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice

Ga-young Jung,Sae-Bom Won,Juhae Kim,Sookyoung Jeon,Anna Han,Young Hye Kwon 한국독성학회 2013 Toxicological Research Vol.29 No.1

Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.

Risk Factors and Neonatal Outcomes of Patent Ductus Arteriosus Ligation in Preterm Infants in a Single Center over 6 Years

( Ga Won Jeon ) 대한주산의학회 2020 Perinatology Vol.31 No.4

Objective: To determine the effects of patent ductus arteriosus (PDA) ligation, clinical characteristics of infants who need surgical ligation of PDA and risk factors of PDA ligation were evaluated. Methods: Preterm infants with gestational age (GA) <30 weeks presenting with hemodynamically significant ductus arteriosus (HSDA) were enrolled. HSDA was closed with ibuprofen (medical group, n=55) or surgical ligation (surgical group, n=57). Results: GA and birth weight were smaller in the surgical group (27.8±1.4 weeks in the medical group vs. 26.1±1.6 weeks in the surgical group, P<0.001; 959±241 g in the medical group vs. 815±193 g in the surgical group, P=0.001, respectively). There were no significant differences in gender, Apgar scores, antenatal steroids therapy, maternal gestational diabetes mellitus, pregnancy-induced hypertension, or chorioamnionitis between the two groups. In the surgical group, total duration of mechanical ventilation and duration of invasive ventilation were longer, although postnatal day of ductal closure was not delayed. Moderate to severe bronchopulmonary dysplasia, high-grade intraventricular hemorrhage (≥grade 3), retinopathy of prematurity (≥stage 2), necrotizing enterocolitis (≥stage 2), and mortality rate were also similar between the two groups. Low GA was a significant risk factor associated with surgical ligation of PDA (adjusted odds ratio 0.493, 95% confidence interval 0.366-0.666; P<0.001). Conclusion: Although surgical ligation of PDA is inevitable in certain cases with large shunt and severe respiratory failure, clinicians should weigh the benefit of ductal closure and complications associated with surgery.

Serial Short-Term Outcomes of Very-Low-Birth-Weight Infants in the Korean Neonatal Network From 2013 to 2020

Jeon Ga Won,Lee Jang Hoon,Oh Minkyung,Chang Yun Sil 대한의학회 2022 Journal of Korean medical science Vol.37 No.29

Background: We aimed to determine the current survival rate and short-term outcomes of very-low-birth-weight infants (VLBWIs) in Korea, as well as whether the survival rate and short-term outcomes have improved over time since 2013, which was when the Korean Neonatal Network (KNN) was launched. Methods: This study used data from the annual reports of the KNN from 2013 to 2020. A total of 16,351 VLBWIs born at gestational age (GA) ≥ 22 weeks between January 1, 2013, and December 31, 2020, and who were registered in the KNN were enrolled. Serial outcomes were analyzed according to era (2013–14, 2015–16, 2017–18, and 2019–20). Results: More mothers delivered by cesarean section, had diabetes or hypertension during their pregnancy, and received antenatal steroids when analyzed by era. Fewer infants were intubated at birth and had air leaks when analyzed by era. The overall survival rate of VLBWIs between 2013 and 2020 was 87%. The rate of respiratory distress syndrome was 77% and that of bronchopulmonary dysplasia was 32% between 2013 and 2020. The rates of intraventricular hemorrhage (grade ≥ 3), periventricular leukomalacia, and sepsis decreased over time. The survival rate of infants with a GA of 26 weeks has improved serially according to era. Conclusion: Since the launch of the KNN in 2013, the survival rates of infants with GA 26 weeks and short-term outcomes have improved, which implies a quality improvement in antenatal and delivery room care. Further studies on the long-term neurodevelopmental outcomes of these KNN registrants are warranted.