Hara, Kaori

写真a

Affiliation

School of Medicine, Department of Pediatrics ( Shinanomachi )

Position

Researcher (Non-tenured) / Project Researcher(Non-tenured)

Career 【 Display / hide

  • 2015.04
    -
    Present

    慶應義塾大学医学部小児科学教室, 助教

Academic Background 【 Display / hide

  • 2002.04
    -
    2008.03

    Keio Univercity, medicine

    University, Graduated

  • 2018.04
    -
    2022.03

    Keio University, 医学部, 医学研究科博士課程

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Coursework, 2022.03

Licenses and Qualifications 【 Display / hide

  • 小児科専門医, 2013.10

  • 周産期(新生児)専門医, 2016.12

 

Research Areas 【 Display / hide

  • Life Science / Genetics (ゲノムインプリンティング)

  • Life Science / Embryonic medicine and pediatrics

Research Keywords 【 Display / hide

  • インプリンティング異常症

  • ビタミンD

  • 新生児学

 

Papers 【 Display / hide

  • Bidirectional changes in serum 25-hydroxyvitamin D in newborns during the first four days of life: A longitudinal cohort study.

    Ikeda K, Hara-Isono K, Morisawa K, Abe K

    Clinical nutrition ESPEN    103289 2026.04

  • Weekly vitamin D supplementation during early infancy as a potential strategy to prevent vitamin D insufficiency: A two-center retrospective study

    Hara-Isono K., Morisawa K., Hida M., Iwamoto S., Ikeda K.

    Pediatrics and Neonatology 67 ( 2 ) 203 - 209 2026.03

    ISSN  18759572

     View Summary

    Background: For preventing Vitamin D (VD) insufficiency, several VD supplementation guidelines were established worldwide. In Japan, no nationwide guidelines for preventing VD insufficiency have been implemented, whereas guidelines for preventing vitamin K (VK) deficiency-related bleeding recommend weekly supplementation of VK. The aim of this study is to clarify whether weekly VD plus VK supplementation during the early neonatal period prevents VD insufficiency at one month of age.MethodsWe retrospectively analyzed serum 25-hydroxyvitamin D (25(OH)D) levels of 555 one-month-old infants born between 2017 and 2023. Infants were classified into the control group (not supplemented), weekly group (1000 IU/week), and daily group (240 IU/day). We compared serum 25(OH)D levels among the three groups. Multivariable logistic regression analyses adjusted for formula intake and BMI were performed to better estimate the effect of VD supplementation on the prevention of VD insufficiency.ResultsWe included 414, 55, and 86 infants in the control, weekly, and daily groups, respectively. All infants received weekly supplementation of VK. Serum 25(OH)D levels in the weekly and daily groups were higher than those in the control group (median (ng/mL): control 9.7 vs weekly 22.2, P < 0.001; control vs daily 23.0, P < 0.001). The frequencies of VD insufficiency were 370/414 (89.4 %), 11/55 (20.0 %), and 22/86 (25.6 %) in the control, weekly, and daily groups, respectively. Adjusted odds ratios of VD insufficiency compared to the control were 0.038 (95 % confidence intervals (95 %CI): 0.017, 0.085) and 0.036 (95 %CI: 0.019, 0.067) in the weekly and daily groups, respectively. No infant with VD excess was observed.ConclusionOur results demonstrated that combined weekly supplementation of VD and VK during early infancy can prevent VD insufficiency at one month of age without causing VD excess. This finding may provide evidence for the development of nationwide prophylaxis for VD insufficiency in regions lacking specific guidelines.

  • Effects of maternal commercial supplementation on 25-hydroxyvitamin D levels in newborns: a retrospective cohort study in a single center, Saitama, Japan, 2022–2023

    Morisawa K., Ikeda K., Hida M., Hara-Isono K.

    Endocrine Journal 73 ( 2 ) 243 - 249 2026

    ISSN  09188959

     View Summary

    Vitamin D (VD) insufficiency in pregnant women is a serious health problem worldwide. To prevent VD insufficiency during pregnancy, several guidelines recommend 600 IU/day VD for all pregnant women. In Japan, no national guidelines for preventing VD insufficiency have been implemented, and no study has evaluated adequate VD intake in pregnant women; however, the number of pregnant women taking commercial dietary supplements containing VD has increased in recent years. This study aimed to examine the effects of maternal commercial supplementation of VD on 25-hydroxyvitamin D (25(OH)D) levels in newborns. We retrospectively analyzed the serum 25(OH)D levels in 279 four-days-old newborns born at the Saitama City Hospital from 2022 to 2023. Newborns were classified into a supplement group (mothers who took VD-containing commercial supplements regularly throughout pregnancy; n = 103) and a non-supplement group (mothers who did not take any supplements during pregnancy; n = 176). The study findings revealed that serum 25(OH)D levels in newborns in the supplement group were higher than those in the non-supplement group (median [interquartile range]: supplement group 17.2 [14.6, 22.9] vs. non-supplement group 14.3 [11.6, 16.7], p < 0.001). In the supplement group, approximately 70% of newborns still showed VD insufficiency. Although the maternal use of VD-containing commercial supplements during pregnancy increased the serum 25(OH)D levels in newborns at four days of age, additional measures, such as VD supplementation for newborns, are needed to improve neonatal VD status.

  • Age-dependent discordance in chemiluminescent immunoassay-electrochemiluminescence immunoassay correlation for 25-hydroxyvitamin D measurement reveals methodological considerations for assessment in early infancy

    Ota M., Ikeda K., Morisawa K., Nakagawa T., Hida M., Hara-Isono K.

    Endocrine Journal 73 ( 4 ) 563 - 570 2026

    ISSN  09188959

     View Summary

    Vitamin D (VD) status is assessed by measuring serum 25-hydroxyvitamin D (25(OH)D) levels using immunoassays. In December 2024, a Japanese diagnostic laboratory transitioned from chemiluminescent immunoassay (CLIA: LIAISON<sup>®</sup> 25 OH Vitamin D Total Assay) to an electrochemiluminescent immunoassay (ECLIA: Elecsys<sup>®</sup> Vitamin D Total III assay). Although these methods yield comparable results in adults, it remains unclear whether this applies to children, particularly newborns and infants. This study aims to clarify the impact of transition from CLIA to ECLIA on 25(OH)D levels during early infancy. Serum 25(OH)D levels were measured in 84 infants under three months old (67 under four days old) using both CLIA and ECLIA. Correlation and agreement were assessed using Passing–Bablok regression and Bland–Altman analyses, respectively. The obtained regression equation was applied to 252 age- and sex-matched cases from 2,253 historical controls in the registry to evaluate changes in VD classification. The regression equation was Y<inf>ECLIA</inf> = 0.846X<inf>CLIA</inf> – 2.281 (τ = 0.53, p < 0.001). Bland–Altman analysis revealed a constant negative bias of –4.89 ± 3.53 ng/mL [–5.66, –4.12] (mean ± standard deviation [95% confidence interval]) for ECLIA versus CLIA. Reclassification revealed an increase in VD deficiency (25(OH)D < 12 ng/mL) from 27.8% to 61.9%, and VD insufficiency (25(OH)D < 20 ng/mL) from 75.4% to 91.7%. The transition from CLIA to ECLIA led to lower measured 25(OH)D levels in newborns and infants and increased VD deficiency and insufficiency diagnoses. Method-specific differences should be considered when evaluating VD status during early infancy, particularly in infants under four days.

  • Investigation of methylation profiles in Silver–Russell syndrome to explore episignatures

    Hara-Isono K., Inoue T., Nakamura A., Fuke T., Yamazawa K., Matsubara K., Fukami M., Ogata T., Kawai T., Kagami M.

    Clinical Epigenetics 17 ( 1 ) 184 2025.12

    ISSN  18687075

     View Summary

    Background: Episignatures are disease-specific, genome-wide DNA methylation patterns identified in more than 100 genetic syndromes caused by mutation of genes related to epigenetic modifiers. The utility of episignatures as a disease diagnostic tool has been demonstrated in recent years. However, studies evaluating episignatures in imprinting disorders (IDs) are very limited. We hypothesized that identifying episignatures in Silver–Russell syndrome (SRS), one of the representative IDs, could lead to the development of a new diagnostic tool for SRS. We investigated methylation profiles in patients with different molecular etiologies to clarify the presence or absence of DNA methylation episignatures in SRS. Results: We conducted genome-wide methylation analysis (GWMA) using the HumanMethylationEPIC array in 27 patients consisting of five groups based on molecular etiologies satisfying clinical diagnostic criteria: hypomethylation of H19-differentially methylated region (DMR) (n = 9), maternal uniparental disomy chromosome 7 (n = 11), IGF2 variant (n = 3), PLAG1 variant (n = 2), and deletions including KCNQ1OT1:TSS-DMR (n = 2). We compared the methylation levels of CpGs (β values) between each group and control group (94 pediatric samples) and extracted aberrantly methylated CpGs satisfying the following criteria: (1) Bonferroni-corrected p value < 0.05, and (2) the absolute value of ∆β (|∆β|), the difference between the average β value of each ID group and controls at each probe, was above 0.1. Based on the extracted aberrantly methylated CpGs, we examined (1) aberrantly methylated patterns, (2) aberrantly methylated regions, and 3) CpG-enriched genes and their functions, shared by multiple groups. Although several CpGs were commonly hypermethylated or hypomethylated in two of the five groups, the number of CpGs was too small to form characteristic methylation patterns. Several aberrantly methylated regions, including disease-responsible DMRs of SRS, were identified in each group, but no regions common in multiple groups were identified. Previously reported aberrantly methylated regions other than disease-responsible DMRs were not identified. In addition, we found no CpG-enriched genes or their functions common in multiple groups. Conclusions: GWMA in SRS patients with different molecular etiologies identified no characteristic episignatures. Only methylation changes of CpGs within disease-responsible DMRs, not genome-wide methylation changes, occur in some SRS etiologies.

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