Hara, Kaori

写真a

Affiliation

School of Medicine, Department of Pediatrics (Shinanomachi)

Position

助教
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Career 【 Display / hide 】

  • 2015.04
    -
    Present

    慶應義塾大学医学部小児科学教室, 助教

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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

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Academic Degrees 【 Display / hide 】

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

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Licenses and Qualifications 【 Display / hide 】

  • 小児科専門医, 2013.10

  • 周産期（新生児）専門医, 2016.12

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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

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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

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Papers 【 Display / hide 】

  • Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes

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

    Clinical Epigenetics (Clinical Epigenetics)  15 ( 1 )  2023.12

    ISSN  18687075

    　View Summary

    Background: Our previous study suggested that assisted reproductive technology (ART) may be a possible risk factor for the development of epimutation-mediated imprinting disorders (epi-IDs) for mothers aged ≥ 30 years. However, whether ART or advanced parental age facilitates the development of uniparental disomy-mediated IDs (UPD-IDs) has not yet been investigated. Results: We enrolled 130 patients with aneuploid UPD-IDs including various IDs confirmed by molecular studies and obtained ART data of the general population and patients with epi-IDs from a robust nationwide database and our previous report, respectively. We compared the proportion of ART-conceived livebirths and maternal childbearing age between patients with UPD-IDs and the general population or patients with epi-IDs. The proportion of ART-conceived livebirths in patients with aneuploid UPD-IDs was consistent with that in the general population of maternal age ≥ 30 years and was lower than that in the patients with epi-IDs, although there was no significant difference. The maternal childbearing age of patients with aneuploid UPD-IDs was skewed to the increased ages with several cases exceeding the 97.5th percentile of maternal childbearing age of the general population and significantly higher than that of patients with epi-IDs (P < 0.001). In addition, we compared the proportion of ART-conceived livebirths and parental age at childbirth between patients with UPD-IDs caused by aneuploid oocytes (oUPD-IDs) and that by aneuploid sperm (sUPD-IDs). Almost all ART-conceived livebirths were identified in patients with oUPD-IDs, and both maternal age and paternal age at childbirth were significantly higher in patients with oUPD-IDs than in patients with sUPD-IDs. Because maternal age and paternal age were strongly correlated (rs = 0.637, P < 0.001), higher paternal age in oUPD-IDs was explained by the higher maternal age in this group. Conclusions: Different from the case of epi-IDs, ART itself is not likely to facilitate the development of aneuploid UPD-IDs. We demonstrated that advanced maternal age can be a risk factor for the development of aneuploid UPD-IDs, particularly oUPD-IDs.

  • Seasonal variation in vitamin D status of Japanese infants starts to emerge at 2 months of age: a retrospective cohort study

    Takahashi K., Arimitsu T., Hara-Isono K., Ikeda K.

    British Journal of Nutrition (British Journal of Nutrition)  129 ( 11 ) 1908 - 1915 2023.06

    ISSN  00071145

    　View Summary

    Vitamin D seasonality has been reported in adults and children, suggesting that sunlight exposure has effects on 25(OH)D production. While vitamin D deficiency among infants has received significant attention, little is known about the extent to which vitamin D status during early infancy is affected by sunlight exposure. Here, we retrospectively analysed serum 25(OH)D levels of 692 samples obtained from healthy infants aged 1-2 months born at Saitama City Hospital, Japan (latitude 35·9° North) between August 2017 and September 2021. Data regarding the frequency of outdoor activities, formula intake and BMI were also collected and analysed. Month-to-month comparisons of vitamin D levels revealed significant variation in 25(OH)D levels in breastfed infants starting at 2 months, with maximal and minimal levels in September and January, respectively. An outdoor activity score of 0 was most common at 1 month (83·9 %) and a score of 3 was most common at 2 months (81·2 %), suggesting an increased amount of sunlight exposure at 2 months. Multiple linear regression analysis revealed the amount of formula intake to be significantly associated with vitamin D status at both 1 (t = 17·96) and 2 months (t = 16·30). Our results comprise the first evidence that seasonal variation of vitamin D begins at 2 months among breastfed infants from East Asia, though dietary intake appears to be the major determinant of vitamin D status. These findings provide new insights into the influence of dietary and non-dietary factors on vitamin D status during early infancy.

  • Incidence and clinical risk factors of Bednar's aphthae in Japanese newborns

    Narukama R., Takahashi K., Arimitsu T., Hara-Isono K., Shimizu H., Ikeda K.

    Pediatrics International (Pediatrics International)  65 ( 1 )  2023.01

    ISSN  13288067

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    Background: The etiology of Bednar's aphthae remains unclear. Our aim was to investigate the incidence of, and factors associated with, Bednar's aphthae in a Japanese newborn cohort. Methods: A retrospective cross-sectional study was conducted on neonates discharged from the well-baby nursery at Saitama City Hospital, Japan. The principal investigator carefully examined each neonate's oral cavity, up to and including the pharynx, with a light-emitting diode (LED) headlight to determine the presence of Bednar's aphthae. Maternal and neonatal clinical characteristics were first compared between neonates with and those without Bednar's aphthae by univariate analysis. Variables with significant inter-group differences upon univariate analysis were entered into a multivariable logistic-regression model. Results: This study enrolled 1996 infants. We observed Bednar's aphthae in 9.3% of the Japanese newborn infants who were included. When restricted to infants who were born via vaginal delivery, 13.2% of them had aphthae. Multivariable logistic regression analysis identified vaginal delivery (odds ratio = 6.19, p < 0.0001) in Model 1, and vaginal delivery (odds ratio = 6.73, p < 0.0001) and birth weight (odds ratio = 0.9995, p = 0.034) in Model 2 as independent risk factors for the disease. Conclusion: This is the first report of the prevalence of Bednar's aphthae among Japanese neonates. Vaginal delivery was identified as the strongest risk factor. Although confounding between mode of delivery and mechanical stimuli associated with sucking was not found in this study, the findings pave the way for a better understanding of the etiology of Bednar's aphthae.

  • Frequency and clinical characteristics of distinct etiologies in patients with Silver-Russell syndrome diagnosed based on the Netchine-Harbison clinical scoring system

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

    Journal of Human Genetics (Journal of Human Genetics)  67 ( 10 ) 607 - 611 2022.10

    ISSN  14345161

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    Silver-Russel syndrome (SRS) is a representative imprinting disorder (ID) characterized by growth failure and diagnosed by clinical features. Recently, international consensus has recommended using the Netchine-Harbison clinical scoring system (NH-CSS) as clinical diagnostic criteria. Loss of methylation of H19/IGF2:intergenic differentially methylated region (H19LOM) and maternal uniparental disomy chromosome 7 (UPD(7)mat) are common etiologies of SRS; however, other IDs, pathogenic variants (PVs) of genes, and pathogenic copy number variants (PCNVs) have been reported in patients meeting NH-CSS. To clarify the frequency and clinical characteristics of each etiology, we conducted (epi)genetic analysis in 173 patients satisfying NH-CSS. H19LOM and UPD(7)mat were identified in 34.1%. PCNVs, other IDs, and PVs were in 15.0%. Patients with all six NH-CSS items were most frequently observed with H19LOM and UPD(7)mat. This study confirmed the suitability of NH-CSS as clinical diagnostic criteria, the (epi)genetic heterogeneity of SRS, and showed the necessity of further discussion regarding the “SRS spectrum”.

  • Pathogenic Copy Number and Sequence Variants in Children Born SGA With Short Stature Without Imprinting Disorders

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

    Journal of Clinical Endocrinology and Metabolism (Journal of Clinical Endocrinology and Metabolism)  107 ( 8 ) E3121 - E3133 2022.08

    ISSN  0021972X

    　View Summary

    Context: Children born small-for-gestational-age with short stature (SGA-SS) is associated with (epi)genetic defects, including imprinting disorders (IDs), pathogenic copy number variants (PCNVs), and pathogenic variants of genes involved in growth. However, comprehensive studies evaluating these 3 factors are very limited. Objective: To clarify the contribution of PCNVs and candidate pathogenic variants to SGA-SS. Design: Comprehensive molecular analyses consisting of methylation analysis, copy number analysis, and multigene sequencing. Methods: We enrolled 140 patients referred to us for genetic testing for SGA-SS. Among them, we excluded 42 patients meeting Netchine- Harbison clinical scoring system criteria for Silver-Russell syndrome and 4 patients with abnormal methylation levels of the IDs-related differentially methylated regions. Consequently, we conducted copy number analysis and multigene sequencing for 86 SGA-SS patients with sufficient sample volume. We also evaluated clinical phenotypes of patients with PCNVs or candidate pathogenic variants. Results: We identified 8 (9.3%) and 11 (12.8%) patients with PCNVs and candidate pathogenic variants, respectively. According to the American College of Medical Genetics standards and guidelines, 5 variants were classified as pathogenic and the remaining 6 variants were classified as variants of unknown significance. Genetic diagnosis was made in 12 patients. All patients with PCNVs or candidate pathogenic variants did not correspond perfectly to characteristic clinical features of each specific genetic cause. Conclusion: We clarified the contribution of PCNVs and pathogenic variants to SGA-SS without IDs. Comprehensive molecular analyses, including copy number analysis and multigene sequencing, should be considered for patients with unknown SGA-SS etiology.

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