미숙아의 폐동맥고혈압: 흡입 일산화질소치료의 최신지견 및 제한점

전가원 대한주산의학회 2025 Perinatology Vol.36 No.1

Pulmonary hypertension is more common in preterm infants compared to term infants, and the incidence increases as gestational age decreases. In preterm infants, pulmonary hypertension is a risk factor that increases mortality. Inhaled nitric oxide (iNO) is an approved treatment for pulmonary hypertension in preterm infants in Korea. Since January 2021, iNO has been used for hypoxic respiratory failure associated with early acute persistent pulmonary hypertension of the newborn (PPHN) in preterm infants. Although studies suggest that iNO improves oxygenation and reduces mortality in preterm infants with pulmonary hypertension, there are concerns about its effectiveness and potential adverse effects. In addition, there are several challenges in administering iNO therapy to preterm infants in Korea that need to be addressed. The current therapeutic indications in Korea allow iNO therapy to be administered only if treatment is started within 14 days of life, so it cannot be used for late pulmonary hypertension. Additionally, iNO therapy requires meeting the criteria for hypoxic respiratory failure, which includes calculating the oxygenation index (OI) using PaO2 values obtained from arterial blood gas analysis (ABGA). To evaluate treatment response, PaO2 values from ABGA are also necessary. However, invasive arterial blood sampling is a particularly challenging procedure in preterm infants. Therefore, alternative criteria beyond OI are needed. Furthermore, echocardiographic findings are essential to determine the therapeutic indication for PPHN in iNO therapy. However, not all neonatal intensive care units have consistent access to echocardiography. These issues must be addressed and resolved through further research and evidence.

Pathophysiology, classification, and complications of common asymptomatic thrombocytosis in newborn infants

전가원 대한소아청소년과학회 2022 Clinical and Experimental Pediatrics (CEP) Vol.65 No.4

We frequently encounter newborn infants with thrombocytosis in the neonatal intensive care unit. However, neonatal thrombocytosis is not yet fully understood. Thrombocytosis is more frequently identified in newborns and young infants, notably more often in those younger than 2 years than in older children or adults. The production of megakaryocytes (megakaryopoiesis) and platelets (thrombopoiesis) is mainly regulated by thrombopoietin (TPO). Increased TPO levels during infection or inflammation can stimulate megakaryopoiesis, resulting in thrombopoiesis. TPO concentrations are higher in newborn infants than in adults. Levels increase after birth, peak on the second day after birth, and start decreasing at 1 month of age. Initial platelet counts at birth increase with gestational age. Thus, preterm infants have lower initial platelet counts at birth than late-preterm or term infants. Postnatal thrombocytosis is more frequently observed in preterm infants than in term infants. A high TPO concentration and low TPO receptor expression on platelets leading to elevated plasma-free TPO, increased sensitivity of megakaryocyte precursor cells to TPO, a decreased red blood cell count, and immaturity of platelet regulation are speculated to induce thrombocytosis in preterm infants. Thrombocytosis in newborn infants is considered a reactive process (secondary thrombocytosis) following infection, acute/chronic inflammation, or anemia. Thrombocytosis in newborn infants is benign, resolves spontaneously, and, unlike in adults, is rarely associated with hemorrhagic and thromboembolic complications.

Risk factors and screening timing for developmental dysplasia of the hip in preterm infants

전가원,Choo Hye Jung,Kwon Yong Uk 대한소아청소년과학회 2022 Clinical and Experimental Pediatrics (CEP) Vol.65 No.5

Background: The delayed diagnosis of developmental dysplasia of the hip (DDH) requires complex treatment and sometimes progresses to hip osteoarthritis. Purpose: This study aimed to evaluate the risk factors and screening time for DDH in preterm infants. Methods: A total of 155 preterm infants with a gestational age <32 weeks screened for DDH with ultrasonography were enrolled in this retrospective chart review. Results: The incidence of DDH was 6.45% (10 of 155). Gestational age, birth weight, sex ratio, and breech presentation did not differ significantly between infants treated for DDH (n=10) and nontreated infants (n=145) (gestational age, 29.2±1.4 weeks vs. 29.6±2.0 weeks, P=0.583; birth weight, 1,240±237 g vs. 1,295±335 g, P=0.607; female sex, 7 of 10 (70.0%) vs. 77 of 145 (53.1%), P=0.346; and breech presentation, 5 of 10 (50.0%) vs. 43 of 145 (29.7%), P=0.286, respectively). Performing the first ultrasonography earlier than 38 weeks of postmenstrual age (PMA) increased the risk of an abnormal finding by 3.76 times compared to performing it at ≥38 weeks of PMA. These abnormal findings on ultrasonography resolved spontaneously. Breech presentation increased the risk of minor abnormal findings on the first ultrasonography by 3.11 times versus nonbreech presentation and resolved spontaneously. DDH in preterm infants did not occur predominantly on the left side or in infants born with breech presentation. Conclusion: Performing ultrasonography screening earlier than 38 weeks of PMA caused unnecessary subsequent ultrasonography and overtreatment. Breech presentation was not a risk factor for DDH in preterm infants. However, breech presentation could increase the risk of minor abnormal findings at the 1st ultrasonography compared to nonbreech presentation, which resolved spontaneously. The etiology and risk factors for DDH in preterm infants are somewhat different from those for DDH in term infants.

Bisphenol A leaching from polycarbonate baby bottles into baby food causes potential health issues

전가원 대한소아청소년과학회 2022 Clinical and Experimental Pediatrics (CEP) Vol.65 No.9

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Clinical Application of Near-Infrared Spectroscopy in Neonates

전가원 대한신생아학회 2019 Neonatal medicine Vol.26 No.3

The incidence of cerebral palsy has not decreased despite advances in neonatal care. Preterm infants are at a high risk of cerebral palsy. Moreover, preterm infants might experience permanent neurological sequelae due to injury in the preterm brain. Although the etiology of preterm brain injury is not fully understood, preterm brain injury is strongly associated with abnormal cerebral perfusion and oxygenation. Monitoring systemic blood pressure or arterial oxygen saturation using pulse oximetry is not enough to guarantee proper cerebral perfusion or oxygenation. Early detection of improper cerebral perfusion can prevent irreversible cerebral damage. To decrease brain injury through the early detection of under-perfusion and deoxygenation, other diagnostic modalities are needed. Near-infrared spectroscopy can continuously and noninvasively monitor regional oxygen saturation (rSO2), which reflects the perfusion and oxygenation status of tissues at bedside. Near-infrared spectroscopy represents a balance between tissue oxygen supply and demand. Cerebral rSO2 monitoring has been used most frequently in neonatal cardiac surgery to monitor cerebral oxygenation and prevent hypoxic damage or shock. Recently, cerebral, renal, or splanchnic rSO2 in neonates is frequently monitored. The progression of a disease, brain injury, and death can be prevented by detecting changes in rSO2 values using near-infrared spectroscopy. In this article, the basic principles, usefulness, and applications of near-infrared spectroscopy in neonates are discussed.

Improved survival rate with decreased neurodevelopmentaldisability in extreme immaturity

전가원,김묘징,김성신,심재원,장윤실,박원순,이문향 대한소아청소년과학회 2007 Clinical and Experimental Pediatrics (CEP) Vol.50 No.11

Purpose : The aim of this study was to determine whether improved survival of extremely low birth weight infants (ELBWI) was associated with decreased neurodevelopmental disability later in life, and also to identify the factors influencing this disability. Methods : ELBWI admitted to the neonatal intensive care unit of Samsung Medical Center, survived, and followed up until the corrected age of 18 months were enrolled. They were divided into two groups according to admission time: period I (1994-1999, n=36) and period II (2000-2004, n=98). Clinical data were collected retrospectively from the medical records. Results : Survival rates increased from 60.0% to 74.7%, cerebral palsy rates decreased from 22.2% to 8.2% and catch-up growth rate increased from 25.0% to 51.0% during period I and II. Despite less gestational age and birth weight, ELBWI during period II had less periventricular leukomalacia (PVL), sepsis and bronchopulmonary dysplasia compared to period I. The highest risk factors for cerebral palsy were intraventricular hemorrhage (IVH) (≥Grade III), failure of catch-up growth and PVL. Conclusion : In summary, improved viability was associated with decreased neurodevelopmental disability in ELBWI. Improved neonatal care with resultant decrease in PVL and IVH, and better nutritional support seem to be primarily responsible for this improved outcome. 목 적 : 초극소저출생체중아의 생존율 향상에 따라 장기 신경발달 장애가 감소했는지 여부와 이들의 장기 신경발달의 예후 인자에 대해 알아보고자 하였다. 방 법 : 1994년 11월부터 2004년 7월까지 삼성서울병원 신생아중환자실에서 입원 치료 받은 초극소저출생체중아 중 교정나이 18개월에 외래에서 추적관찰이 가능하였던 134명을 대상으로 하였으며 외래 방문 시 진찰소견과 의무기록을 후향적으로 분석하였다. 대상 환아를 1994년 11월부터 1999년 12월까지인 제 I기와 2000년 1월부터 2004년 7월까지인 제 II기로 나누었으며 각각 36명과 98명이 해당되었다. 결 과 : 제 I기에 비하여 제 II기에 재태연령과 출생체중이 낮았지만 생존율은 향상되었으며(제 I기: 60.0%, 제 II기: 74.7%) 뇌성마비는 감소하였고(제 I기: 22.2%, 제 II기: 8.2%) 따라잡기 성장은 향상되었다(제 I기: 25.0%, 제 II기: 51.0%). 뇌실주위 백질연화증, 패혈증과 기관지폐 이형성증의 이환율은 제 II기에 감소하였다. 뇌성마비의 가장 큰 위험요인은 3도 이상의 고도 뇌실내출혈, 따라잡기 성장의 실패와 뇌실주위 백질연화증이었다. 결 론 : 초극소저출생체중아의 생존율 향상은 장기적인 예후의 향상과 관련되어 있으며 신생아 관리의 질향상과 관련된 뇌실주위 백질연화증의 감소, 고도 뇌실내출혈의 감소, 더 나은 영양공급이 장기적인 예후의 향상과 관련된 것으로 보인다.

Changes in the Incidence of Bronchopulmonary Dysplasia among Preterm Infants in a Single Center over 10 Years

전가원 대한신생아학회 2020 Neonatal medicine Vol.27 No.1

Purpose: Bronchopulmonary dysplasia (BPD) is one of the most fatal respiratory morbidities in preterm infants, causing adverse respiratory and neurodevelopmental outcomes. Despite advances in neonatal ventilator care, the incidence of BPD has been static or even increased. The purpose of this study was to evaluate the incidence of BPD in a single center over 10 years. Methods: Preterm infants with gestational age (GA) <30 weeks who were admitted to Inje University Busan Paik Hospital from January 2009 to December 2018 and survived 28 days or more were enrolled. The incidence of BPD according to year and GA and the risk factors of BPD were evaluated. Results: Among 629 infants, 521 infants who survived 28 days or more were enrolled (BPD group, n=252; non-BPD group, n=269). The incidence of BPD was 48.4%, with moderate to severe BPD accounting for 13.9%. In preterm infants with GA ≤25, 26 to 27, and 28 to 29 weeks, the incidences of BPD were 57.5%, 51.5%, and 14.6%, respectively, with moderate to severe BPD accounting for 23.8%, 10.5%, and 3.7%, respectively. The incidence of BPD decreased from 68% in 2009 to 34.3% in 2014. Subsequently, it increased. Surfactant re-dosing and patent ductus arteriosus were more frequent in the BPD group than in the non-BPD group. Conclusion: BPD did not decrease over the previous 10 years despite advances in neonatal care.

Identification of a De Novo Heterozygous Missense FLNB Mutation in Lethal Atelosteogenesis Type I by Exome Sequencing

전가원,이미나,정지미,홍승연,김영남,신종범,기창석 대한진단검사의학회 2014 Annals of Laboratory Medicine Vol.34 No.2

Background: Atelosteogenesis type I (AO-I) is a rare lethal skeletal dysplastic disorder characterized by severe short-limbed dwarfism and dislocated hips, knees, and elbows. AO-I is caused by mutations in the filamin B ( FLNB ) gene; however, several other genes can cause AO-like lethal skeletal dysplasias. Methods: In order to screen all possible genes associated with AO-like lethal skeletal dys- plasias simultaneously, we performed whole-exome sequencing in a female newborn hav- ing clinical features of AO-I. Results: Exome sequencing identified a novel missense variant (c.517G>A; p.Ala173Thr) in exon 2 of the FLNB gene in the patient. Sanger sequencing validated this variant, and genetic analysis of the patient’s parents suggested a de novo occurrence of the variant. Conclusions: This study shows that exome sequencing can be a useful tool for the identi- fication of causative mutations in lethal skeletal dysplasia patients.

A Comparison of AmBisome(R) to Amphotericin B for Treatment of Systemic Candidiasis in Very Low Birth Weight Infants

전가원,구수현,이장훈,황종희,김성신,이은경,장욱,장윤실,박원순 연세대학교의과대학 2007 Yonsei medical journal Vol.48 No.4

Purpose: Amphotericin B is considered the treatment of choice for systemic candidiasis, but adverse effects may limit its use. An alternative option for the treatment of candidiasis includes lipid preparations of amphotericin B. This study investigated the safety and efficacy of AmBisome(R), a lipid formulation of amphotericin B containing liposomal structures, for the treatment of systemic candidiasis in very low birth weight infants (VLBWI). Materials and Methods: Data from 26 VLBWI treated with AmBisome(R) in the study group (AmBisome group) from October 2003 to July 2006 were compared with data from 20 VLBWI treated with amphotericin B as a historical control (Amphotericin group). This study was a prospective, historical control, multi-center trial. Results: Candida spp. was isolated in 73% (19/26) of the cases for the AmBisome group and 90% (18/20) of the cases for the Amphotericin group. The fungal eradication rate and the time to eradication was 84% (16/19) and 9±8 days in the AmBisome group, and 89% (16/18) and 10±9 days in the Amphotericin group, respectively (p=0.680 vs p=0.712). The major adverse effects were lower in the AmBisome group (renal toxicity, 21% vs 55%, p=0.029; hepatotoxity, 25% vs 65%, p=0.014, AmBisome group vs Amphotericin group, respectively). There was no significant difference in mortality attributed to systemic candidiasis (12% in the AmBisome group, 10% in the Amphotericin group, p= 0.868). Conclusion: AmBisome(R) is effective and safe for treating systemic fungal infections in VLBWI. Amphotericin B is considered the treatment of choice for systemic candidiasis, but adverse effects may limit its use. An alternative option for the treatment of candidiasis includes lipid preparations of amphotericin B. This study investigated the safety and efficacy of AmBisome(R), a lipid formulation of amphotericin B containing liposomal structures, for the treatment of systemic candidiasis in very low birth weight infants (VLBWI). Materials and Methods: Data from 26 VLBWI treated with AmBisome(R) in the study group (AmBisome group) from October 2003 to July 2006 were compared with data from 20 VLBWI treated with amphotericin B as a historical control (Amphotericin group). This study was a prospective, historical control, multi-center trial. Results: Candida spp. was isolated in 73% (19/26) of the cases for the AmBisome group and 90% (18/20) of the cases for the Amphotericin group. The fungal eradication rate and the time to eradication was 84% (16/19) and 9±8 days in the AmBisome group, and 89% (16/18) and 10±9 days in the Amphotericin group, respectively (p=0.680 vs p=0.712). The major adverse effects were lower in the AmBisome group (renal toxicity, 21% vs 55%, p=0.029; hepatotoxity, 25% vs 65%, p=0.014, AmBisome group vs Amphotericin group, respectively). There was no significant difference in mortality attributed to systemic candidiasis (12% in the AmBisome group, 10% in the Amphotericin group, p= 0.868). Conclusion: AmBisome(R) is effective and safe for treating systemic fungal infections in VLBWI.

Long-Term Neuroprotective Effect and Safety of Antenatal Magnesium Sulfate on Preterm Infants

전가원 대한주산의학회 2023 Perinatology Vol.34 No.3

In 2010, the American College of Obstetricians and Gynecologists (ACOG) issued a Committee Opinion regarding the administration of antenatal magnesium sulfate (MgSO4) for fetal neuroprotection based on randomized controlled trials and meta-analyses. ACOG recommends the use of antenatal MgSO4 for fetal neuroprotection. Consequently, antenatal MgSO4 is administered to pregnant women with a gestational age of less than 32 weeks to provide fetal neuroprotection and reduce the risk of cerebral palsy and neurodevelopmental impairment. Since the use of antenatal MgSO4 for fetal neuroprotection, concerns about the safety of the fetus and newborn and doubts about the long-term neuroprotective effects of antenatal MgSO4 have been raised. There is still in controversies whether antenatal MgSO4 provides short-term and long-term neuroprotection, such as decreased substantial gross motor dysfunction, cerebral palsy and cognitive dysfunction. Furthermore, the fetal and neonatal adverse effects of antenatal MgSO4, such as decreased vascular tone, blood flow of the mesenteric artery, and intestinal motility are still controversial. Therefore, preclinical studies and rigorous multicenter large cohort studies are necessary to determine the neuroprotective effects and safety of antenatal MgSO4, as well as to determine the optimal dosage and duration of treatment. It is important to administer MgSO4 to pregnant women with caution, taking into consideration the potential impact on the fetus and newborn.