| 1. |
Naoki Egami, Masataka Ishimura, Masayuki Ochiai, Masako Ichiyama, Hirosuke Inoue, Souichi Suenobu, Toshiya Nishikubo, Keiji Nogami, Akira Ishiguro, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Shouichi Ohga, The clinical and genetic landscape of early-onset thrombophilia in Japan., Pediatric blood & cancer, 10.1002/pbc.30824, e30824, 2023.12, OBJECTIVES: To determine the optimal management for early-onset thrombophilia (EOT), the genetic and clinical features of protein C (PC)-, protein S (PS)-, or antithrombin (AT)-deficient patients of ≤20 years of age were studied in Japan. METHODS/RESULTS: Clinical and genetic information of all genetically diagnosed cases was collected through the prospective, retrospective study, and literature review. One-hundred-one patients had PC (n = 55), PS (n = 29), or AT deficiency (n = 18). One overlapping case had PC- and PS-monoallelic variant. Fifty-five PC-deficient patients (54%) had 26 monoallelic or 29 biallelic variant(s), and 29 (29%) PS-deficient patients had 20 monoallelic or nine biallelic variant(s). None of the patients had AT-biallelic variants. The frequent low-risk allele p.K193del (PC-Tottori) was found in five patients with monoallelic (19%) but not 29 with biallelic variant(s). The most common low-risk allele p.K196E (PS-Tokushima) was found in five with monoallelic (25%) and six with biallelic variant(s) (67%). One exceptional de novo PC variant was found in 32 families with EOT. Only five parents had a history of thromboembolism. Thrombosis concurrently developed in three mother-newborn pairs (two PC deficiency and one AT deficiency). The prospective cohort revealed the outcomes of 35 patients: three deaths with PC deficiency and 20 complication-free survivors. Neurological complications were more frequently found in patients with PC-biallelic variants than those with PC-, PS-, or AT-monoallelic variants (73% vs. 24%, p = .019). CONCLUSIONS: We demonstrate the need for elective screening for EOT targeting PC deficiency in Japan. Early prenatal diagnosis of PC deficiency in mother-infant pairs may prevent perinatal thrombosis in them.. |
| 2. |
Hirosuke Inoue, Masafumi Sanefuji, Yuri Sonoda, Masanobu Ogawa, Norio Hamada, Masayuki Shimono, Reiko Suga, Shoji F Nakayama, Yu Taniguchi, Koichi Kusuhara, Shouichi Ohga, Michihiro Kamijima, No association between prenatal lead exposure and neurodevelopment during early childhood in the Japan Environment and Children's Study., Scientific reports, 10.1038/s41598-022-19509-6, 12, 1, 15305-15305, 2022.09, Compared with the relatively well-investigated effects of childhood exposure to lead on neurocognitive deficits, those of prenatal exposure remain relatively inconclusive. We aimed to investigate the association between prenatal blood lead levels and neurodevelopmental delay during the first three years of life. From a prospective cohort of the Japan Environment and Children's Study, we analyzed a total of 80,759 children. The exposure factors were prenatal lead concentrations measured from maternal whole blood in the second/third trimesters and umbilical cord blood at birth. Neurodevelopment was assessed at 6, 12, 18, 24, 30, and 36 months old using a screening tool, the Ages and Stages Questionnaires, third edition (ASQ). The outcome measures were any suspected neurodevelopmental delay (sNDD) identified via the ASQ during the first (sNDD-1Y), second (sNDD-2Y), and third (sNDD-3Y) years of life. sNDD-1Y, 2Y, and 3Y were identified in 18.0%, 16.2%, and 17.2% of children, respectively. The geometric means of blood lead concentration in this study were much lower (0.62 μg/dL in maternal blood and 0.50 μg/dL in cord blood) than previously investigated levels. Multivariable regression models revealed that there were no associations between maternal blood lead and sNDD-1Y and 2Y and between cord blood lead and sNDD-1Y, 2Y, and 3Y. Although a higher maternal blood lead was associated with a reduced risk of sNDD-3Y (adjusted relative risk: 0.84, 95% confidence interval 0.75-0.94, per 1 increase in common logarithm of lead concentration), there were no dose-response relationships in the analysis using quintiles of lead concentrations. Using a large-scale data set, the present study demonstrated no convincing evidence for an inverse association between levels of prenatal blood lead and neurodevelopment in early childhood. Longitudinal measurements of prenatal and postnatal lead levels are needed to understand the relationship between lead exposure and neurocognitive development.. |
| 3. |
Yukari Kuroda, Toru Miyazaki, Nelson Hirokazu Tsuno, Hirosuke Inoue, Shouichi Ohga, Kazuo Irita, Sim, a new human platelet antigen located on glycoprotein IIIa, identified in a case of fetal-neonatal alloimmune thrombocytopenia in Japan., Transfusion, 10.1111/trf.17255, 63, 4, E17-E19, 2023.04. |
| 4. |
Reina Ogata, Kyoko Watanabe, Pin Fee Chong, Jun Okamoto, Yoshihiro Sakemi, Toshinori Nakashima, Takuro Ohno, Hiroyuki Nomiyama, Yuri Sonoda, Yuko Ichimiya, Hirosuke Inoue, Masayuki Ochiai, Hironori Yamashita, Yasunari Sakai, Shouichi Ohga, Divergent neurodevelopmental profiles of very-low-birth-weight infants., Pediatric research, 10.1038/s41390-023-02778-w, 2023.08, BACKGROUND: Advanced perinatal medicine has decreased the mortality rate of preterm infants. Long-term neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs) remain to be investigated. METHODS: Participants were 124 VLBWIs who had in-hospital birth from 2007 to 2015. Perinatal information, developmental or intelligence quotient (DQ/IQ), and neurological comorbidities at ages 3 and 6 years were analyzed. RESULTS: Fifty-eight (47%) VLBWIs received neurodevelopmental assessments at ages 3 and 6 years. Among them, 15 (26%) showed DQ/IQ |
| 5. |
Junko Fujiyoshi, Hirosuke Inoue, Toru Sawano, Yuichi Mushimoto, Yoshitomo Motomura, Kei Nishiyama, Noriyuki Kaku, Hazumu Nagata, Kenichiro Yamamura, Masataka Ishimura, Yuhki Koga, Masayuki Ochiai, Yasunari Sakai, Tatsuro Tajiri, Shouichi Ohga, Critical diseases in neonates after discharge home from birth hospital: A retrospective study from a tertiary hospital in Japan., Early human development, 10.1016/j.earlhumdev.2023.105869, 186, 105869-105869, 2023.09, INTRODUCTION: To establish actionable neonatal screening during the first month of life, we investigated critical diseases in seemingly healthy newborns discharged from birth hospitals. METHODS: This retrospective study enrolled previously healthy full-term infants who visited our hospital, a tertiary hospital in Japan, from home between 5 and 28 days after birth from 2009 to 2018. Infants with known perinatal or congenital diseases, positive newborn screening results, or accidental injuries were excluded. Data were collected from electronic medical records, including principal diagnosis, clinical details, and prognosis at 18 months of age. RESULTS: Ninety-seven (58 %) of 168 eligible neonates were admitted to the hospital, and 71 (42 %) were not. The median admission rate in patients with disease onset at ≤14 days after birth (80 %) was significantly higher than that in patients with disease onset at ≥15 days (42 %). Among 45 patients who received intensive medical care, 5 died and 10 developed neurodevelopmental sequelae. Four of 5 patients died by 100 days. Among 25 diseases treated in intensive care unit, 17 (68 %) diseases had a prevalence of |
| 6. |
Yoshihiro Sakemi, Toshinori Nakashima, Kyoko Watanabe, Masayuki Ochiai, Toru Sawano, Hirosuke Inoue, Kosuke Kawakami, Shuichi Isomura, Hironori Yamashita, Shouichi Ohga, Changing risk factors for postpartum depression in mothers admitted to a perinatal center., Pediatrics and neonatology, 10.1016/j.pedneo.2022.09.013, 64, 3, 319-326, 2023.05, BACKGROUND: The Edinburgh postnatal depression scale (EPDS) is commonly used in screening for major postpartum depression (PPD). We explored the clinical factors associated with score changes. METHODS: Mothers (n=1,287) who delivered a single live-born infant in Kokura Medical Center in Japan during 2018-2019 were analyzed. The EPDS-Japanese version was conducted at the first and fourth weeks after childbirth. Scores of ≥9 were considered to indicate an increased risk of PPD. RESULTS: The scores improved during the four-week period (5.03±0.12 to 3.79±0.10). Primiparity, Cesarean section (CS), and a low Apgar score were identified as initial risk factors, however, primiparity remained in the multivariate analysis (aOR 2.02, 95% CI 1.37-2.97). Age ≥35 years was associated with worsened scores (aOR 1.88, 95%CI 1.01-3.51), but CS improved (aOR 0.38, 95%CI 0.21-0.70). Primiparity, CS, and neonatal respiratory support were the initial risk factors, while infant anomaly was a late risk factor in mothers whose infants were admitted to the neonatal intensive care unit (NICU) (aOR 3.35, 95%CI 1.31-8.56). In mothers of infants with an NICU stay of ≥4 weeks, infant anomaly was associated with worsened scores (aOR 6.61, 95%CI 1.11-39.3), while respiratory support was associated with improved scores (aOR 0.09, 95%CI 0.01-0.65). Twenty-six mothrs with worsened scores received psychiatric support; three developed PPD. Two of the three were ≥35 years of age, neither of their infants had anomalies. CONCLUSION: Maternal aging and infant anomaly were risk factors for PPD. PPD occurred in mothers with worsened EPDS scores after mental care. Puerperants with worsening risk factors should be targeted to control PPD.. |
| 7. |
Makiko Kirino, Masayuki Ochiai, Masako Ichiyama, Hirosuke Inoue, Takeshi Kusuda, Tadamune Kinjo, Masataka Ishimura, Shouichi Ohga, Transient Hemi-Lower Limb Ischemia in the Newborn: Arterial Thrombosis or Persistent Sciatic Artery?, AJP Rep, 10.1055/s-0037-1598044, 7, 1, e13-e16, 2017.01. |
| 8. |
Atsushi Tanaka, Yoshiaki Sakaguchi, Hirosuke Inoue, Naoki Egami, Yuri Sonoda, Motoshi Sonoda, Masataka Ishimura, Masayuki Ochiai, Taeko Hotta, Takeshi Uchiumi, Yasunari Sakai, Shouichi Ohga, Stroke in a protein C-deficient infant after stem cell transplant for CHARGE syndrome., Pediatric blood & cancer, 10.1002/pbc.30047, 70, 4, e30047, 2023.04. |
| 9. |
Toru Sawano, Takuya Kondo, Go Ebihara, Kouji Nagata, Hirosuke Inoue, Junko Fujiyoshi, Masayuki Ochiai, Saki Kido, Yasuyuki Fujita, Yasunari Sakai, Kiyoko Kato, Tatsuro Tajiri, Shouichi Ohga, Lung to thorax transverse area ratio as a predictor of neurodevelopmental outcomes in fetuses with congenital diaphragmatic hernia., Early human development, 10.1016/j.earlhumdev.2022.105598, 170, 105598-105598, 2022.07, INTRODUCTION: Infants with congenital diaphragmatic hernia (CDH) are at risk of neurodevelopmental disabilities. This study aimed to investigate the association between lung to thorax transverse area ratio (LTR) and neurodevelopmental outcomes at 3 years of age in fetuses with CDH. METHODS: We performed a retrospective study of infants with prenatally diagnosed isolated left-sided CDH born in Kyushu University Hospital between 2008 and 2016. We examined the association between prenatal ultrasound findings including LTR and development quotient (DQ) at 36 to 42 months of chronological age. RESULTS: We identified 34 live-born fetuses with isolated left-sided CDH, of which 30 survived and four died before discharge. The median LTR in the survivors was higher than in the non-survivors (p |
| 10. |
Toshinori Nakashima, Hirosuke Inoue, Yoshihiro Sakemi, Hironori Yamashita, Effectiveness of umbilical culture for surveillance of methicillin-resistant Staphylococcus aureus among neonates admitted to neonatal intensive care units., Infection control and hospital epidemiology, 10.1017/ice.2022.150, 44, 6, 988-990, 2023.06, To compare the culture sensitivities of MRSA detection, we collected 988 paired umbilical and nasal cultures from screened neonates. MRSA positivity rates were 79.1% from umbilicus and 41.9% from nares (P = .01). The umbilicus was a more useful culture site than the nares for surveillance of MRSA among neonates upon admission.. |
| 11. |
Shoji Fukuoka, Kenichiro Yamamura, Hazumu Nagata, Daisuke Toyomura, Yusaku Nagatomo, Yoshimi Eguchi, Kiyoshi Uike, Yuichiro Hirata, Hirosuke Inoue, Masayuki Ochiai, Shouichi Ohga, Clinical outcomes of pulmonary agenesis: A systematic review of the literature., Pediatric pulmonology, 10.1002/ppul.26135, 57, 12, 3060-3068, 2022.12, INTRODUCTION: Pulmonary agenesis is a complete absence of the pulmonary parenchyma, airways, and vasculature unilaterally or bilaterally. Although bilateral cases are lethal, the outcome of unilateral cases remains not well described. We performed a comprehensive literature review to assess the clinical features of pulmonary agenesis. METHODS: Four database sources were searched on October 10, 2021 and two cases were included from our institution. Studies related to the clinical impact of comorbidity and intervention on the survival outcome in pulmonary agenesis were included for full-text review. RESULTS: We identified 259 patients-with right-sided (59%), left-sided (34%), and bilateral agenesis (7%)-among 195 articles and our two cases. Additional anomalies included cardiovascular (40%), skeletal (30%), gastrointestinal (20%), tracheal (20%: all stenoses), and genitourinary (14%) anomalies. Fifty-seven (24%) individuals in unilateral pulmonary agenesis had isolated disease. Outcomes related to survival were not uniformly reported, but the 2-year overall survival rate of unilateral agenesis was 62% and no subsequent death was reported until 13 years of age. The right-sided agenesis was more frequently associated with tracheal stenosis (27% vs. 11%, p = 0.003) than the left-sided disease. A multivariable analysis indicated that tracheal stenosis (hazard ratio [HR]: 2.2, 95% confidence interval [CI]: 1.3-4.1, p = 0.003) and gastrointestinal anomalies (HR: 2.0, 95% CI: 1.1-3.3, p = 0.010) were prognostic factors for mortality. CONCLUSIONS: The poor prognostic factors were tracheal stenosis, right agenesis, and gastrointestinal anomalies. Treatment for these comorbidities is a key point for improving the survival of unilateral pulmonary agenesis.. |
| 12. |
Shunsuke Yamamoto, Shingo Nakao, Hirosuke Inoue, Yuhki Koga, Kanako Kojima-Ishii, Yuichiro Semba, Takahiro Maeda, Koichi Akashi, Shouichi Ohga, A preterm newborn-onset juvenile myelomonocytic leukemia-like myeloproliferation with PTPN11 mutation., Pediatric blood & cancer, 10.1002/pbc.29915, 70, 2, e29915, 2023.02. |
| 13. |
Hirosuke Inoue, Yuka Matsunaga, Toru Sawano, Junko Fujiyoshi, Tadamune Kinjo, Masayuki Ochiai, Kouji Nagata, Toshiharu Matsuura, Tomoaki Taguchi, Shouichi Ohga, Survival outcomes of very low birth weight infants with trisomy 18., American journal of medical genetics. Part A, 10.1002/ajmg.a.62466, 185, 11, 3459-3465, 2021.11, Trisomy 18 (T18) is one of the most commonly diagnosed aneuploidies leading to poor survival outcome. However, little is known about the dual risk of T18 and very low birth weight (VLBW, weighing |
| 14. |
Mitsuru Arima, Hirosuke Inoue, Shintaro Nakao, Akiko Misumi, Maya Suzuki, Itsuka Matsushita, Shunsuke Araki, Chiemi Yamashiro, Kazumasa Takahashi, Masayuki Ochiai, Noriko Yoshida, Masayuki Hirose, Junji Kishimoto, Koji Todaka, Shunji Hasegawa, Kazuhiro Kimura, Koichi Kusuhara, Hiroyuki Kondo, Shouichi Ohga, Koh-Hei Sonoda, Study protocol for a multicentre, open-label, single-arm phase I/II trial to evaluate the safety and efficacy of ripasudil 0.4% eye drops for retinopathy of prematurity., BMJ open, 10.1136/bmjopen-2020-047003, 11, 7, e047003, 2021.07, INTRODUCTION: Retinopathy of prematurity (ROP) is a vascular proliferative disorder that occurs in preterm infants. Existing treatments are only indicated in severe ROP cases due to the high invasiveness and the potential risk of irreversible side effects. We previously elucidated that ripasudil, a selective inhibitor of the Rho-associated protein kinase, has the ability to inhibit abnormal retinal neovascularisation in animal models. In addition, ripasudil eye drops (Glanatec ophthalmic solution 0.4%) have been already used for the treatment of glaucoma. Since eye drop therapy is less invasive, early intervention for ROP is possible. The purpose of this phase I/II trial is to evaluate the safety and efficacy of ripasudil eye drops for preterm infants with ROP. METHODS AND ANALYSIS: This is a multicentre, open-label, single-arm phase I/II trial. To evaluate the safety and efficacy of ripasudil as much as possible, ripasudil will be administered to all enrolled preterm infants with zone I/II, stage 1, or worse ROP. The safety and efficacy of ripasudil in treated patients will be assessed in comparison to a historical control group. Because this is the first trial of ripasudil in preterm infants, a dose-escalation study (once daily for 1 week, then two times per day for 2 weeks) will be conducted in phase I. After obtaining approval from the independent data and safety monitoring board to continue the trial after the completion of phase I, phase II will be conducted. In phase II, ripasudil eye drops will be administered two times per day for 12 weeks. The primary endpoint in phase II is also safety. Efficacy and pharmacokinetics will be evaluated as secondary endpoints. ETHICS AND DISSEMINATION: This study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT04621136 and jRCT2071200047.. |
| 15. |
Takaaki Yamada, Chie Emoto, Tsuyoshi Fukuda, Yoshitomo Motomura, Hirosuke Inoue, Shouichi Ohga, Ichiro Ieiri, Optimal Teicoplanin Dosing Regimen in Neonates and Children Developed by Leveraging Real-World Clinical Information., Therapeutic drug monitoring, 10.1097/FTD.0000000000000930, 44, 3, 404-413, 2022.06, BACKGROUND: Teicoplanin is a glycopeptide antibiotic used for the treatment of methicillin-resistant Staphylococcus aureus infections. To ensure successful target attainment, therapeutic drug monitoring-informed dosage adjustment is recommended. However, it relies on the experience of the clinician and the frequency of drug measurements. This study aimed to design a new optimal dosing regimen of teicoplanin with a maintenance dosing strategy for neonates and children based on their physiological characteristics. METHODS: Data from teicoplanin-treated patients (n = 214) were collected from electronic medical records. Covariate analyses were performed using population pharmacokinetic (PK) modeling with 399 serum teicoplanin concentrations from 48 neonates and 166 children. Multiple PK simulations were conducted to explore optimal dosing regimens that would allow control of the trough concentration to the target of 15-30 mg/L quicker than the current standard regimen. RESULTS: Allometrically scaled body weight, postmenstrual age (PMA), renal function, and serum albumin were implemented as substantial covariates for teicoplanin clearance in a two-compartment PK model. Covariate analyses and comprehensive simulation assessments recommended the following modifications to the current regimen: 1) decreased dose for premature babies (PMA ≤ 28 weeks), 2) decreased dose for children with renal dysfunction, and 3) increased dose for children (0.5-11 years) with an estimated glomerular filtration rate of ≥90 mL/min/1.73 m2. CONCLUSIONS: This study leverages real-world clinical information and proposes new optimal dosing regimens for teicoplanin in neonates and children through PK modeling and simulation analyses, taking into account the age, including PMA, and renal function of patients.. |
| 16. |
Michiko Torio, Mariko Iwayama, Toru Sawano, Hirosuke Inoue, Masayuki Ochiai, Ryoji Taira, Kousuke Yonemoto, Yuko Ichimiya, Yuri Sonoda, Momoko Sasazuki, Yoshito Ishizaki, Masafumi Sanefuji, Kenichi Yamane, Hiroshi Yamashita, Hiroyuki Torisu, Ryutaro Kira, Toshiro Hara, Shigenobu Kanba, Yasunari Sakai, Shouichi Ohga, Neurodevelopmental Outcomes of High-Risk Preterm Infants: A Prospective Study in Japan., Neurology. Clinical practice, 10.1212/CPJ.0000000000000920, 11, 5, 398-405, 2021.10, OBJECTIVES: To determine the neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs, birth weight |
| 17. |
Naoki Egami, Masayuki Ochiai, Masako Ichiyama, Hirosuke Inoue, Motoshi Sonoda, Masataka Ishimura, Souichi Suenobu, Toshiya Nishikubo, Akira Ishiguro, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Shouichi Ohga, Clinical Impact of Heritable Thrombophilia on Neonatal-Onset Thromboembolism: A Nationwide Study in Japan., The Journal of pediatrics, 10.1016/j.jpeds.2021.07.001, 238, 259-267, 2021.11, OBJECTIVE: To clarify the incidence and genetic risk of neonatal-thromboembolism, we conducted a nationwide study exploring the impact of thrombophilia on neonatal-thromboembolism in Japan. STUDY DESIGN: A questionnaire survey was conducted for perinatal centers in Japan, focusing on the clinical expression, genotype, treatment, and outcome of patients who developed thromboembolism within 28 days of birth from 2014 to 2018. RESULTS: The estimated incidence of neonatal-thromboembolism was 0.39 cases per 10 000 live births. Intracranial lesions and purpura fulminans occurred in 66 and 5 of 77 patients, respectively. Fifty-eight (75.3%) infants presented within 3 days after birth. Four (5.2%) died, and 14 (18.2%) survived with disability. At the diagnosis, |
| 18. |
Nina Lenhartová, Masayuki Ochiai, Toru Sawano, Kazuaki Yasuoka, Junko Fujiyoshi, Hirosuke Inoue, Shouichi Ohga, Serum erythroferrone levels during the first month of life in premature infants., Journal of perinatology : official journal of the California Perinatal Association, 10.1038/s41372-021-01184-6, 42, 1, 97-102, 2022.01, OBJECTIVE: To examine erythroferrone (ERFE)-hepcidin iron regulation in premature infants under intensive care at risk of iron metabolic disorders. STUDY DESIGN: A retrospective cohort recruited 31 infants with a birth weight of |
| 19. |
Masafumi Sanefuji, Yuri Sonoda, Yoshiya Ito, Masanobu Ogawa, Vlad Tocan, Hirosuke Inoue, Masayuki Ochiai, Masayuki Shimono, Reiko Suga, Ayako Senju, Satoshi Honjo, Koichi Kusuhara, Shouichi Ohga, Physical growth and neurodevelopment during the first year of life: a cohort study of the Japan Environment and Children's Study., BMC pediatrics, 10.1186/s12887-021-02815-9, 21, 1, 360-360, 2021.08, BACKGROUND: The association between a slower physical growth and poorer neurodevelopment has been established in infants born preterm or small for gestational age. However, this association is inconsistent in term-born infants, and detailed investigations in infancy, when intervention is most beneficial for improving outcomes, are lacking. We therefore examined this association separately by sex during the first year of life in term-born infants. METHODS: Using data collected until children reached 12 months old in an ongoing prospective cohort of the Japan Environment and Children's Study, we analyzed 44,264 boys and 42,541 girls with singleton term-birth. The exposure variables were conditional variables that disentangle linear growth from weight gain relative to linear growth, calculated from the length and weight at birth and 4, 7 and 10 months old. Neurodevelopmental delay was identified using the Japanese-translated version of Ages & Stages Questionnaires, third edition. RESULTS: A reduced risk of neurodevelopmental delay at 6 months old was observed in children with a higher birth weight (adjusted relative risks [aRRs]: 0.91 and 0.93, 95 % confidence intervals [95 % CIs]: 0.87-0.96 and 0.88-0.98 in boys and girls, respectively) and increased linear growth between 0 and 4 months old (aRRs: 0.85 and 0.87, 95 % CIs: 0.82-0.88 and 0.83-0.91 in boys and girls, respectively). A reduced risk at 12 months was found in children with an increased linear growth between 0 and 4 months (aRRs: 0.92 and 0.90, 95 % CIs: 0.87-0.98 and 0.84-0.96 in boys and girls, respectively), boys with an increased relative weight gain between 0 and 4 months (aRR: 0.90, 95 % CI: 0.84-0.97), and girls with a higher birth weight (aRR: 0.89, 95 % CI: 0.83-0.96). CONCLUSIONS: These results suggest that a slow physical growth by four months old may be a predictor of neurodevelopmental delay during infancy.. |
| 20. |
Toshinori Nakashima, Hirosuke Inoue, Yoshihiro Sakemi, Masayuki Ochiai, Hironori Yamashita, Shouichi Ohga, Trends in Bronchopulmonary Dysplasia Among Extremely Preterm Infants in Japan, 2003-2016., The Journal of pediatrics, 10.1016/j.jpeds.2020.11.041, 230, 119-125, 2021.03, OBJECTIVE: To investigate recent trends in bronchopulmonary dysplasia (BPD) and its risk factors among extremely preterm infants. STUDY DESIGN: Demographic and clinical data were reviewed for 19 370 infants born at 22-27 weeks of gestation registered in the affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2016. We investigated the overall survival and prevalence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age and risk factors for developing BPD among the survivors. RESULTS: Among 19 370 infants, 2244 (11.6%) died by 36 weeks' postmenstrual age. The mortality rate decreased from 19.0% (99% CI, 15.7%-22.8%) in 2003 to 8.0% (99% CI, 6.2%-10.3%) in 2016. Among 17 126 survivors, BPD developed in 7792 (45.5%) infants, and its proportion significantly increased from 41.4% (99% CI, 36.5%-46.4%) in 2003 to 52.0% (99% CI, 48.2%-55.9%) in 2016. A multivariable analysis of the survivors showed a positive association of BPD with ≥4 weeks' supplemental oxygen or invasive ventilation, birth weight |
| 21. |
Ryoji Taira, Hirosuke Inoue, Toru Sawano, Junko Fujiyoshi, Yuko Ichimiya, Michiko Torio, Masafumi Sanefuji, Masayuki Ochiai, Yasunari Sakai, Shouichi Ohga, Management of apnea in infants with trisomy 18., Developmental medicine and child neurology, 10.1111/dmcn.14403, 62, 7, 874-878, 2020.07, This case series aimed to characterize the clinical features, management, and outcomes of apnea in infants with trisomy 18. Participants in this study were infants with trisomy 18 who were born alive and admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2018. Retrospective analysis was performed on clinical data recorded in our department. Twenty-seven infants with trisomy 18 were admitted to our hospital during the study period, of which 25 (nine males, 16 females) were enrolled as eligible participants in this study. Among them, 14 started presenting with apnea from median 3.5 days of age (range 0–47d). In these infants with apnea, eight received respiratory support of positive pressure ventilation (PPV). The 1-year survival rate of infants in the PPV group was higher than that of non-PPV-supported infants (5 out of 8 vs 0 out of 6 infants). Five PPV-supported infants received a diagnosis of epilepsy, which was controlled by antiepileptic drugs. Postnatal respiratory intervention provides better prognosis in infants with trisomy 18. Improved survival leads to accurate diagnosis and treatment of apneic events in association with epilepsy. What this paper adds: Respiratory support is effective against apnea in infants with trisomy 18. Intervention with ventilation provides a higher chance of prolonged survival. Improved survival leads to the accurate diagnosis and treatment of epilepsy-associated apnea.. |
| 22. |
Kazuaki Yasuoka, Hirosuke Inoue, N. Egami, Masayuki Ochiai, Koichi Tanaka, Toru Sawano, Hiroaki Kurata, Masako Ichiyama, J. Fujiyoshi, Yuki Matsushita, Yasunari Sakai, Shouichi Ohga, Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants, Journal of Pediatrics, 10.1016/j.jpeds.2019.05.033, 212, 117-123.e4, 2019.09, Objective: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants. Methods: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse. Results: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P |
| 23. |
Hiroaki Kurata, Masayuki Ochiai, Hirosuke Inoue, Takeshi Kusuda, Junko Fujiyoshi, Masako Ichiyama, Yoshifumi Wakata, Hidetoshi Takada, Inflammation in the neonatal period and intrauterine growth restriction aggravate bronchopulmonary dysplasia, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.11.007, 60, 5, 496-503, 2019.10, Background: To investigate the hematological features of infants with bronchopulmonary dysplasia (BPD) and their relationships with clinical severity. Methods: This prospective observational study enrolled 73 BPD patients from a total of 331 infants with a birth weight of |
| 24. |
Yuki Matsushita, Yasunari Sakai, Michiko Torio, Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Hiroaki Kurata, Junko Fujiyoshi, Masako Ichiyama, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan, Journal of Perinatology, 10.1038/s41372-019-0494-7, 39, 11, 1472-1479, 2019.11, Objective: To determine clinical features of very low birth weight infants (VLBWIs) who had developed epilepsy by age 3 years. Study design: Multicenter cohort study using the Neonatal Research Network of Japan database. We analyzed clinical variables of 8431 VLBWIs who had recorded data of neurological sequelae at age 3 years. Logistic regression identified the association between variables and development of epilepsy. Result: One hundred and forty-three (1.7%) infants developed epilepsy, 683 (8.1%) showed cerebral palsy (CP), and 1114 (13.2%) had psychomotor delay. Epilepsy was associated with history of sepsis [adjusted odds ratio (AOR) 3.23], severe intraventricular hemorrhage (IVH; AOR 5.13), and cystic periventricular leukomalacia (PVL; AOR 12.7). Severe IVH and cystic PVL were also frequently associated with CP and psychomotor delay. Conclusion: Severe IVH and cystic PVL are strongly associated with development of epilepsy, as well as other neurological sequelae, and are potential critical therapeutic targets.. |
| 25. |
Motoshi Sonoda, Masataka Ishimura, Katsuhide Eguchi, Akira Shiraishi, Shunsuke Kanno, Noriyuki Kaku, Hirosuke Inoue, Yoshitomo Motomura, Masayuki Ochiai, Yasunari Sakai, Manabu Nakayama, Osamu Ohara, Shouichi Ohga, Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis, International journal of hematology, 10.1007/s12185-019-02738-3, 111, 1, 131-136, 2020.01, Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 109/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH.. |
| 26. |
Mitsuru Arima, Masato Akiyama, Kohta Fujiwara, Yujiro Mori, Hirosuke Inoue, Eiko Seki, Takahito Nakama, Shoko Tsukamoto, Masayuki Ochiai, Shouichi Ohga, Koh-Hei Sonoda, Neurodevelopmental outcomes following intravitreal bevacizumab injection in Japanese preterm infants with type 1 retinopathy of prematurity., PloS one, 10.1371/journal.pone.0230678, 15, 3, e0230678, 2020.01, Purpose The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP). Methods In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis. Results Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03). Conclusions Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood.. |
| 27. |
Masayuki Ochiai, Hiroaki Kurata, Hirosuke Inoue, Masako Ichiyama, Junko Fujiyoshi, Shinichi Watabe, Takehiko Hiroma, Tomohiko Nakamura, Shouichi Ohga, Transcutaneous blood gas monitoring among neonatal intensive care units in Japan., Pediatrics international : official journal of the Japan Pediatric Society, 10.1111/ped.14107, 62, 2, 169-174, 2020.02, Background: This study aimed to investigate the utility of transcutaneous (tc) measurements of partial pressure of oxygen (tcPO2) and carbon dioxide (tcPCO2) monitoring in neonatal intensive care units (NICUs) in Japan. Methods: At the end of 2016,we sent a survey questionnaire on tc monitoring to all 106 NICUs registered with the Japanese Neonatologist Association. The questions included usage, subjects, methods, management, and the practical usefulness of tc monitoring. Results: The questionnaire was returned by 69 NICUs (65.1% of response rate). Seventeen institutions (24.6%) measured both tcPCO2 and tcPO2, and 42 (60.9%) measured tcPCO2 alone. Transcutaneous PCO2 or tcPO2 monitoring was applied for “pre-viable” infants born at 22–23 weeks’ gestational age (18.6% vs 23.5%), and infants of 2 and tcPO2 monitoring was started at birth in 49.2% and 70.6% of the newborn infants, respectively. The temperature of the sensor was set at 2 in 54.3% and >42°C for tcPO2 in 58.9% of NICUs. The accuracy for tcPO2 was rated as good in 35.3% or moderate in 64.7%, of institutions but or for tcPCO2 as 1.7% or 93.2%of institutions, respectively. Conclusion: Transcutaneous monitoring was widely, but limitedly, used for preterm infants. The lower temperature of the tcPCO2 sensor compared to that reported in other developed countries might compromise the accuracy but increase the feasibility of tc monitoring in Japan.. |
| 28. |
Hirosuke Inoue, Takayuki Hoshina, Tadamune Kinjo, Mitsumasa Saito, Koichi Kusuhara, Toshiro Hara, Toxic shock syndrome-like exanthematous disease in a 2-month-old infant, Pediatrics International, 10.1111/j.1442-200X.2010.03044.x, 52, 2, 2010.04. |
| 29. |
Hirosuke Inoue, Hidetoshi Takada, Takeshi Kusuda, Takako Goto, Masayuki Ochiai, Tadamune Kinjo, Jun Muneuchi, Yasushi Takahata, Naomi Takahashi, Tomohiro Morio, Kenjiro Kosaki, Toshiro Hara, Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism, European Journal of Pediatrics, 10.1007/s00431-009-1126-6, 169, 7, 839-844, 2010.07, It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months.. |
| 30. |
Yamamura Kenichiro, Muneuchi Jun, Uike Kiyoshi, Ikeda Kazuyuki, Inoue Hirosuke, Takahata Yasushi, Shiokawa Yuichi, Yoshikane Yukako, Makiyama Takeru, Horie Minoru, Hara Toshiro, A novel SCN5A mutation associated with the linker between III and IV domains of Na_v 1.5 in a neonate with fatal long QT syndrome, International Journal of Cardiology, 10.1016/j.ijcard.2009.04.023, 145, 1, 61-64, 2010.11. |
| 31. |
Hirosuke Inoue, K. Ihara, Masayuki Ochiai, Y. Takahata, H. Kohno, T. Hara, Congenital multiple pituitary hormone deficiency associated with hyperammonemia A case report with a short review of the literature, Journal of Perinatology, 10.1038/jp.2010.143, 31, 2, 146-148, 2011.02, We herein report a case study of a female newborn with multiple pituitary hormone deficiencies who presented with generalized seizures, hypoglycemia and hyperammonemia at 18 h after birth. In addition, we review the association of hyperammonemia in neonates with multiple pituitary hormone deficiencies reported in the previous literature. This unrecognized association should be taken into account for the early diagnosis and treatment of these patients.. |
| 32. |
Shunji Hikino, Shoichi Ohga, Tadamune Kinjo, Takeshi Kusuda, Masayuki Ochiai, Hirosuke Inoue, Satoshi Honjo, Kenji Ihara, Koichi Ohshima, Toshiro Hara, Tracheal aspirate gene expression in preterm newborns and development of bronchopulmonary dysplasia, Pediatrics International, 10.1111/j.1442-200X.2011.03510.x, 54, 2, 208-214, 2012.04, Background: Bronchopulmonary dysplasia (BPD) occurs in association with prenatal conditions predisposing infants to inflammation and remodeling of the premature lungs. Because of the lack of useful biomarkers for BPD, the gene expression of tracheal aspirate fluid (TAF) cells in premature infants was analyzed. Methods: Of 148 consecutive patients, 26 preterm infants (gestational age |
| 33. |
Junko Kitajima, Hirosuke Inoue, Shoichi Ohga, Tadamune Kinjo, Masayuki Ochiai, Takahisa Yoshida, Koichi Kusuhara, Toshiro Hara, Differential transmission and postnatal outcomes in triplets with intrauterine cytomegalovirus infection, Pediatric and Developmental Pathology, 10.2350/11-05-1034-CR.1, 15, 2, 151-155, 2012.07, We present a case of triplets with intrauterine cytomegalovirus (CMV) infection, each of whom showed differential transmission, placental pathology, and postnatal outcome. The first- and second-born infants were both vigorous and asymptomatic at birth, although the first-, but not the second-born, triplet had a high copy number of CMV DNA in the peripheral blood (1.2 × 103 copy/mL). The third-born triplet suffered from symptomatic CMV infection with a high viral load (6.0 × 106 copy/mL). The triamniotic-trichorionic placentas were not fused to each other. The histopathologic analysis showed that CMVpositive cells were frequently found in the decidua, villi, and amnion of the third-born triplet's placenta but were limited and scattered in the decidua or villi but not amnion of the other 2 placentas. The third-born triplet underwent ganciclovir therapy. None of the infants had physical or auditory problems at 4 years of age, whereas the third-born triplet had been diagnosed with an autistic disorder. This observation exemplifies the preventive roles of the individual placentas of triplets with regard to virus infection, thus suggesting that developing CMV disease largely depends on the placental function.. |
| 34. |
Tadamune Kinjo, Hirosuke Inoue, Takeshi Kusuda, Junko Fujiyoshi, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Yuhki Koga, Toshiro Hara, Shoichi Ohga, Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.09.005, 2018.01, Background: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. Methods: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into “progression group” (n = 7) that required any therapy and “spontaneous resolution group” (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. Results: Three patients developed leukemia during the study period (median, 1147 days; range, 33–3753). Three died of hepatic failure. All patients in the progression group were preterm birth 9
/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p |
| 35. |
Hirosuke Inoue, Masayuki Ochiai, Yasunari Sakai, Kazuaki Yasuoka, Koichi Tanaka, Masako Ichiyama, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shoichi Ohga, Neurodevelopmental outcomes in infants with birth weight ≤500 g at 3 years of age, Pediatrics, 10.1542/peds.2017-4286, 142, 6, 2018.12, OBJECTIVES: To determine neurodevelopmental outcomes at 3 years of age in children born with a birth weight (BW) of ≤500 g. METHODS: Infants who were born with a BW of ≤500 g from 2003 to 2012 in the Neonatal Research Network of Japan and survived to discharge from the NICU were eligible in this study. The study population consisted of 460 children (56.7% of 811 surviving infants) who were evaluated at 36 to 42 months of age. Neurodevelopmental impairment (NDI) was defined as having cerebral palsy, visual impairment, hearing impairment, or a developmental quotient score of |
| 36. |
Hiroaki Kurata, Masayuki Ochiai, Hirosuke Inoue, Masako Ichiyama, Kazuaki Yasuoka, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Yasunari Sakai, Shoichi Ohga, A nationwide survey on tracheostomy for very-low-birth-weight infants in Japan, Pediatric Pulmonology, 10.1002/ppul.24200, 54, 1, 53-60, 2019.01, Objectives: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan. Methods: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined. Results: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P |
| 37. |
Masako Ichiyama, Hirosuke Inoue, Masayuki Ochiai, masataka ishimura, Akira Shiraishi, Junko Fujiyoshi, Hironori Yamashita, Kazuo Sato, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Shoichi Ohga, Diagnostic challenge of the newborn patients with heritable protein C deficiency, Journal of Perinatology, 10.1038/s41372-018-0262-0, 39, 2, 212-219, 2019.02, Objective: The diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan. Study design: We determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry. Result: Physiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off |
| 38. |
Hirosuke Inoue, Jun Muneuchi, Takuro Ohno, Aiko Arikawa, Tatsuro Ishibashi, Toshiro Hara, Central retinal artery occlusion following transcatheter balloon aortic valvuloplasty in an adolescent with aortic valvular stenosis, Pediatric Cardiology, 10.1007/s00246-007-9181-0, 29, 4, 830-833, 2008.07, A 12-year-old girl with aortic valvular stenosis underwent transcatheter balloon aortic valvuloplasty (BAV) using a femoral artery approach. Anticoagulation with heparin during the procedure was used. The patient noted sudden onset of concentric constriction of the visual field in the right eye 40 min after BAV. Brain magnetic resonance imaging and cervical ultrasound revealed no abnormality. Funduscopic examination showed white swelling around the macular region, indicating ischemia, consistent with central retinal artery occlusion (CRAO). CRAO should be recognized as a rare and serious complication associated with BAV even among the pediatric population. This requires careful evaluation of anticoagulation during the left heart procedures.. |
| 39. |
Koichi Kusuhara, Takayuki Hoshina, Mitsumasa Saito, masataka ishimura, Hirosuke Inoue, Takahiko Horiuchi, Tetsuji Sato, Toshiro Hara, Successful treatment of a patient with tumor necrosis factor receptor-associated periodic syndrome using a half-dose of etanercept, Pediatrics International, 10.1111/j.1442-200X.2011.03525.x, 54, 4, 552-555, 2012.08, TNF receptor-associated periodic syndrome (TRAPS) is caused by mutations of TNFRSF1A gene and characterized by recurrent febrile episodes of prolonged duration and initial good response to steroids. Etanercept, a TNF blocker, has been used as a putative molecular-targeted agent for TRAPS, with some patients showing limited efficacy. Here, we report a patient with TRAPS who recovered from steroid dependency by etanercept and kept remission with a reduced dose of etanercept. The pathophysiology of TRAPS still remains to be elucidated and several hypotheses have been proposed. In the most recent hypothesis, the concerted action of wild-type and mutant TNF receptors plays an important role in provoking enhanced inflammation in TRAPS. The excellent response to etanercept in our patient suggested that there is heterogeneity in TRAPS patients in terms of the contribution of normal TNF signaling to autoinflammation.. |
| 40. |
Hirosuke Inoue, Shoichi Ohga, Takeshi Kusuda, Junko Kitajima, Tadamune Kinjo, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Toshiro Hara, Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants, Early Human Development, 10.1016/j.earlhumdev.2012.12.011, 89, 6, 425-429, 2013.06, Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease mostly occurring in preterm infants. The pathogenesis of BPD involves early inflammation and remodeling of the premature lung. Aim: To search for the novel predictive marker of BPD development, we studied serum levels of neutrophil gelatinase-associated lipocalin (NGAL), an innate immune mediator, in preterm infants. Methods: Serum NGAL concentrations at birth were measured by enzyme-linked immunosorbent assay. The reference levels were determined in 52 infants having no anomalies or inherited diseases. The levels and clinical variables were assessed in association with BPD. Results: Geometric means (95%CI) of serum NGAL levels at birth of infants having no underlying diseases were 32.4 (22.1-47.5), 58.6 (47.9-71.8), and 126.2 (99.0-168.7) ng/mL for <. and>. 36 gestational weeks (GW), respectively (p. <. these levels positively correlated with neutrophil or monocyte counts the median ngal ng and at birth of preterm infants gw who developed bpd were higher than those did not p="0.012)," respectively. in multivariable analysis for born less but had a significant association developing adjusted odds ratio p. conclusions: high serum could be an early sensitive marker because their physiologically low.. id="gencho_ronbuns10048779" class="qir_handle_link"> |
| 41. |
Arisa Fujiwara, Kotaro Fukushima, Hirosuke Inoue, Takeshi Takashima, Hiromasa Nakahara, Shoji Satoh, Masayuki Ochiai, Toshiro Hara, Mototsugu Shimokawa, Kiyoko Kato, Perinatal management of preterm premature ruptured membranes affects neonatal prognosis, Journal of Perinatal Medicine, 10.1515/jpm-2013-0192, 42, 4, 499-505, 2014.01, Aim: To determine the factors affecting neonatal prognosis in preterm premature rupture of membranes (PPROM). Method: We conducted a case-control study involving 92 women between the years 2000 and 2010 diagnosed with PPROM between 25 and 31 weeks' gestation, who received antenatal steroids, and delivered between 26 and 31 weeks' gestation; a retrospective cohort study was conducted based on the results. We used data from four tertiary centers and compared the frequencies of neonatal neurologic deficits and neonatal deaths. Results: There was a difference between the two groups; specifically, the ND group (n = 18) consisted of patients whose infants had neurologic deficits and/or neonatal deaths and the neurologically normal (NN) group (n = 74) included NN neonates amongst the patients who had expectant management (94% vs. 73%, respectively). Multivariable analysis revealed that expectant management was independently associated with an increased risk for neonatal neurologic deficits and neonatal deaths (odds ratio, 16.14). All neonates with poor prognosis in the expectantmanagement group delivered within 14 days after PPROM. Conclusions: Expectant management within 14 days after PPROM is associated with poor neonatal outcomes. Decisions regarding an expectant strategy should be made carefully. An immediate, planned delivery after steroid administration should be considered to improve neonatal prognosis in patients who have PPROM after 26 weeks' gestation.. |
| 42. |
Kazuhiro Okubo, Yasunari Sakai, Hirosuke Inoue, Satoshi Akamine, Yoshito Ishizaki, Yuki Matsushita, Masafumi Sanefuji, Hiroyuki Torisu, Kenji Ihara, Marco Sardiello, Toshiro Hara, Moyamoya disease susceptibility gene RNF213 links inflammatory and angiogenic signals in endothelial cells, Scientific Reports, 10.1038/srep13191, 5, 13191-13191, 2015.08, Moyamoya disease (MMD) is a cerebrovascular disorder characterized by occlusive lesions of the circle of Willis. To date, both environmental and genetic factors have been implicated for pathogenesis of MMD. Allelic variations in RNF213 are known to confer the risk of MMD; however, functional roles of RNF213 remain to be largely elusive. We herein report that pro-inflammatory cytokines, IFNG and TNFA, synergistically activated transcription of RNF213 both in vitro and in vivo. Using various chemical inhibitors, we found that AKT and PKR pathways contributed to the transcriptional activation of RNF213. Transcriptome-wide analysis and subsequent validation with quantitative PCR supported that endogenous expression of cell cycle-promoting genes were significantly decreased with knockdown of RNF213 in cultured endothelial cells. Consistently, these cells showed less proliferative and less angiogenic profiles. Chemical inhibitors for AKT (LY294002) and PKR (C16) disrupted their angiogenic potentials, suggesting that RNF213 and its upstream pathways cooperatively organize the process of angiogenesis. Furthermore, RNF213 down-regulated expressions of matrix metalloproteases in endothelial cells, but not in fibroblasts or other cell types. Altogether, our data illustrate that RNF213 plays unique roles in endothelial cells for proper gene expressions in response to inflammatory signals from environments.. |
| 43. |
Toshinori Nakashima, Hirosuke Inoue, Junko Fujiyoshi, Naoko Matsumoto, Longitudinal analysis of serum cystatin C for estimating the glomerular filtration rate in preterm infants, Pediatric Nephrology, 10.1007/s00467-015-3309-x, 31, 6, 983-989, 2016.01, Background: Cystatin C (Cys-C) is a more sensitive marker of renal function than creatinine (Cre) in pediatric and adult populations. However, the reference values of serum Cys-C for estimating glomerular filtration rates (eGFRs) in premature infants during the first year of life have not been sufficiently studied. Methods: In this prospective study, 481 blood samples were collected from 261 preterm infants with uncomplicated clinical courses during their first year of life. Infants were divided into three groups according to gestational age at birth: 27- 30 weeks, 31-33 weeks, and 34-36 weeks. Serum Cys-C and Cre levels were measured at 6-30 days, 3-5 months, 7- 9 months, and 12-14 months after birth and the eGFR was calculated using two previously published equations. Results: The median serum Cys-C levels were 1.776, 1.248, 1.037, and 0.960 mg/L at the first, second, third, and fourth measurement time-point, respectively, with the value significantly decreasing with age up to 12-14 months. Cys-C levels were independent of gestational age and gender. In contrast to Cys-C, serum Cre values declined rapidly up to 3-5 months, then remained constant up to 12-14 months. Using the Cys-C-based equation, the eGFR significantly increased with increasing age until approximately 1 year after birth; however, no such trend was noted using the equation based on Cys-C + Cre. Conclusions: Reference ranges for Cys-C in premature infants decline gradually over the first year after birth. Cys-C appears to be a more reliable marker than Cre for estimating GFR in preterm infants.. |
| 44. |
Masako Ichiyama, Shoichi Ohga, Masayuki Ochiai, Koichi Tanaka, Yuka Matsunaga, Takeshi Kusuda, Hirosuke Inoue, masataka ishimura, Tomohito Takimoto, Yui Koga, Taeko Hotta, Dongchon Kang, Toshiro Hara, Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism, Pediatric Research, 10.1038/pr.2015.180, 79, 1, 81-86, 2016.01, Background:The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation.Methods:We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis.Results:Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism.Conclusion:Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.. |
| 45. |
Hirosuke Inoue, Hisanori Nishio, Hidetoshi Takada, Yasunari Sakai, Etsuro Nanishi, Masayuki Ochiai, Mitsuho Onimaru, Si Jing Chen, Toshiro Matsui, Toshiro Hara, Activation of Nod1 signaling induces fetal growth restriction and death through fetal and maternal vasculopathy, Journal of Immunology, 10.4049/jimmunol.1500295, 196, 6, 2779-2787, 2016.03, Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface.. |
| 46. |
Satoshi Narumi, Naoko Amano, Tomohiro Ishii, Noriyuki Katsumata, Koji Muroya, Masanori Adachi, Katsuaki Toyoshima, Yukichi Tanaka, Ryuji Fukuzawa, Kenichi Miyako, Saori Kinjo, Shoichi Ohga, Kenji Ihara, Hirosuke Inoue, Tadamune Kinjo, Toshiro Hara, Miyuki Kohno, Shiro Yamada, Hironaka Urano, Yosuke Kitagawa, Koji Tsugawa, Asumi Higa, Masakazu Miyawaki, Takahiro Okutani, Zenro Kizaki, Hiroyuki Hamada, Minako Kihara, Kentaro Shiga, Tetsuya Yamaguchi, Manabu Kenmochi, Hiroyuki Kitajima, Maki Fukami, Atsushi Shimizu, Jun Kudoh, Shinsuke Shibata, Hideyuki Okano, Noriko Miyake, Naomichi Matsumoto, Tomonobu Hasegawa, SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7, Nature Genetics, 10.1038/ng.3569, 48, 7, 792-797, 2016.07, Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.. |
| 47. |
Masayuki Ochiai, Yuki Matsushita, Hirosuke Inoue, Takeshi Kusuda, Dongchon Kang, Kiyoshi Ichihara, Naoki Nakashima, Kenji Ihara, Shoichi Ohga, Toshiro Hara, Blood reference intervals for preterm low-birth-weight infants A multicenter cohort study in Japan, PLoS One, 10.1371/journal.pone.0161439, 11, 8, e0161439, 2016.08, Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDRBW and SDRGA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDRGA and SDRBW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine.. |
| 48. |
Masayuki Ochiai, Hiroaki Kurata, Hirosuke Inoue, Koichi Tanaka, Yuki Matsushita, Junko Fujiyoshi, Yoshifumi Wakata, Kiyoko Kato, Tomoaki Taguchi, Hidetoshi Takada, An Elevation of Serum Ferritin Level Might Increase Clinical Risk for the Persistence of Patent Ductus Arteriosus, Sepsis and Bronchopulmonary Dysplasia in Erythropoietin-Treated Very-Low-Birth-Weight Infants, Neonatology, 10.1159/000447991, 111, 1, 68-75, 2016.12, Background: The substantial risk of iron overload is not routinely monitored in most of the neonatal intensive care units (NICUs) in Japan; however, blood transfusion is an essential strategy for successfully treating preterm low-birth-weight infants. Objective: The aim of this study was to investigate the iron status and clinical features of infants with a birth weight of |
| 49. |
Kazuaki Yasuoka, Hirosuke Inoue, Koichi Tanaka, Junko Fujiyoshi, Yuki Matsushita, Masayuki Ochiai, Yuhki Koga, Toshiharu Matsuura, Tomoaki Taguchi, Shoichi Ohga, Successful liver transplantation for transient abnormal myelopoiesis-associated liver failure, Neonatology, 10.1159/000474930, 112, 2, 159-162, 2017.08, Infants with Down syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM occasionally involves liver fibrosis, which can be fatal. The management of liver disease in TAM has not yet been established and is mainly supportive. We report an infant with DS and TAM who developed end-stage liver failure. Liver dysfunction progressed even after blast cells disappeared from the circulation. He underwent a living-donor liver transplantation at 56 days of life without surgical complications. The explanted liver showed atrophy and severe fibrosis without leukemic cell infiltration. The posttransplant course was favorable with no hematological abnormality. He is doing well 8 months after transplantation. To the best of our knowledge, this report is the first showing that liver transplantation might be a treatment option for TAM-related liver failure.. |
| 50. |
Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Koichi Tanaka, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Shutaro Suga, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shoichi Ohga, Early Mortality and Morbidity in Infants with Birth Weight of 500 Grams or Less in Japan, Journal of Pediatrics, 10.1016/j.jpeds.2017.05.017, 190, 112-117.e3, 2017.11, Objective To assess the short-term prognosis of Japanese infants with a birth weight (BW) of ≤500 g. Study design Demographic and clinical data were reviewed for 1473 live born infants with a BW ≤500 g at gestational age ≥22 weeks who were treated in the 204 affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2012. Results Survival to hospital discharge occurred in 811 of 1473 infants (55%; 95% CI 53%-58%). The survival rates of BW ≤300 g, 301-400 g, and 401-500 g were 18% (95% CI 10%-31%), 41% (95% CI 36%-47%), and 60% (95% CI 57%-63%), respectively. In a multivariable Cox proportional hazards analysis, antenatal corticosteroid use (adjusted hazard ratio: 0.68; 95% CI 0.58-0.81; P <.01 cesarean delivery ci p advanced gestational age per week bw increase apgar score at minutes and no major congenital abnormalities were associated with survival to discharge. despite the improved rate over study period in least severe morbidity was present of survivors. conclusions improvements perinatal-neonatal medicine have but not morbidities infants a g japan.. id="gencho_ronbuns10048769" class="qir_handle_link"> |
| 51. |
Hirosuke Inoue, Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants., 10.1016/j.earlhumdev.2012.12.011., 89(6):425-9., 2013.06. |
| 52. |
Arisa Fujiwara, Hirosuke Inoue, Perinatal management of preterm premature ruptured membranes affects neonatal prognosis., 10.1515/jpm-2013-0192., 42(4):499-505. , 2014.07. |
| 53. |
大久保一宏, Hirosuke Inoue, Moyamoya disease susceptibility gene RNF213 links inflammatory and angiogenic signals in endothelial cells., Scientific reports, 10.1038/srep13191., 5, 13191-13191, 17;5:13191. , 2015.08, Moyamoya disease (MMD) is a cerebrovascular disorder characterized by occlusive lesions of the circle of Willis. To date, both environmental and genetic factors have been implicated for pathogenesis of MMD. Allelic variations in RNF213 are known to confer the risk of MMD; however, functional roles of RNF213 remain to be largely elusive. We herein report that pro-inflammatory cytokines, IFNG and TNFA, synergistically activated transcription of RNF213 both in vitro and in vivo. Using various chemical inhibitors, we found that AKT and PKR pathways contributed to the transcriptional activation of RNF213. Transcriptome-wide analysis and subsequent validation with quantitative PCR supported that endogenous expression of cell cycle-promoting genes were significantly decreased with knockdown of RNF213 in cultured endothelial cells. Consistently, these cells showed less proliferative and less angiogenic profiles. Chemical inhibitors for AKT (LY294002) and PKR (C16) disrupted their angiogenic potentials, suggesting that RNF213 and its upstream pathways cooperatively organize the process of angiogenesis. Furthermore, RNF213 down-regulated expressions of matrix metalloproteases in endothelial cells, but not in fibroblasts or other cell types. Altogether, our data illustrate that RNF213 plays unique roles in endothelial cells for proper gene expressions in response to inflammatory signals from environments.. |
| 54. |
Ichiyama Masako, Hirosuke Inoue, Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism., Pediatric research, 10.1038/pr.2015.180., 79, 1-1, 81-6, 79(1-1):81-6. , 2016.01, BACKGROUND: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation. METHODS: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis. RESULTS: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism. CONCLUSION: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.. |
| 55. |
Nakashima T, Hirosuke Inoue, Longitudinal analysis of serum cystatin C for estimating the glomerular filtration rate in preterm infants., 10.1007/s00467-015-3309-x., 31(6):983-9. , 2016.06. |
| 56. |
Hirosuke Inoue, Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy., 10.4049/jimmunol.1500295., 196(6):2779-87., 2016.05. |
| 57. |
Narumi S, Hirosuke Inoue, SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7., Nature genetics, 10.1038/ng.3569., 48, 7, 792-7, 48(7):792-7., 2016.07, Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.. |
| 58. |
Masayuki Ochiai, Hirosuke Inoue, An Elevation of Serum Ferritin Level Might Increase Clinical Risk for the Persistence of Patent Ductus Arteriosus, Sepsis and Bronchopulmonary Dysplasia in Erythropoietin-Treated Very-Low-Birth-Weight Infants., 111(1):68-75., 2017.01. |
| 59. |
Masayuki Ochiai, Hirosuke Inoue, Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan., PloS one, 10.1371/journal.pone.0161439, 11, 8, e0161439, 11(8):e0161439, 2016.08, Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDRBW and SDRGA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDRGA and SDRBW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine.. |
