{"title":"极低出生体重儿的氢化可的松总剂量与学龄前的神经发育。","authors":"Akinobu Taniguchi, Basile Chrétien, Takashi Maeda, Kazuto Ueda, Ryosuke Miura, Ryuichi Tanaka, Toshihiko Suzuki, Yukako Muramatsu, Erina Kataoka, Eiko Kato, Hikaru Yamamoto, Koji Takemoto, Miharu Ito, Seiji Hayashi, Yuichiro Sugiyama, Kazuki Nishida, Yoshiaki Sato","doi":"10.1038/s41390-025-04426-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>An association between total hydrocortisone (HC) dosage in infants with extremely low birth weight (ELBW) and subsequent neurodevelopmental outcomes up to school age remains unclear.</p><p><strong>Method: </strong>We conducted a retrospective longitudinal cohort study across eight centers in Japan, including ELBW infants born between 2015 and 2017. We investigated the association between total HC dosage administered up to 36 weeks postmenstrual age and neurodevelopmental outcomes to school age.</p><p><strong>Results: </strong>Linear mixed model analysis showed a significant association between higher HC dosage and lower developmental and intelligence quotient (DQ/IQ) scores. This trend persisted at 6 years of age, suggesting a sustained effect of HC on cognitive outcomes. For every 10 mg increase in HC dosage, IQ scores decreased by 2.82 points (95% CI: -3.89 to -1.06, p = 0.001). The interaction term between HC dosage and time was not statistically significant (0.10, 95% CI: -0.18 to 0.37, p = 0.481), suggesting the association of HC dosage on DQ/IQ did not vary substantially throughout the study period.</p><p><strong>Conclusions: </strong>We found a relationship between total neonatal HC dosage in ELBW infants and DQ/IQ scores over time that persisted at school age. Clinicians should be aware of this potential dose-dependent effect on neurodevelopmental outcomes.</p><p><strong>Impact: </strong>As neonatal dexamethasone administration is known to affect neurodevelopment outcomes, hydrocortisone (HC) is considered an alternative to dexamethasone as a glucocorticoid treatment. In infants with extremely low birth weight (ELBW), a relationship has been noted between total HC dosage and neurodevelopment in early childhood. We confirmed the association between total HC dosage in infants with ELBW and poor developmental and intelligence quotients to school age. Although HC is commonly used in the management of ELBW infants, clinicians should be aware of its potential dose-dependent effects on neurodevelopmental outcomes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Total hydrocortisone dosage in extremely low birth weight infants and neurodevelopment up to school age.\",\"authors\":\"Akinobu Taniguchi, Basile Chrétien, Takashi Maeda, Kazuto Ueda, Ryosuke Miura, Ryuichi Tanaka, Toshihiko Suzuki, Yukako Muramatsu, Erina Kataoka, Eiko Kato, Hikaru Yamamoto, Koji Takemoto, Miharu Ito, Seiji Hayashi, Yuichiro Sugiyama, Kazuki Nishida, Yoshiaki Sato\",\"doi\":\"10.1038/s41390-025-04426-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>An association between total hydrocortisone (HC) dosage in infants with extremely low birth weight (ELBW) and subsequent neurodevelopmental outcomes up to school age remains unclear.</p><p><strong>Method: </strong>We conducted a retrospective longitudinal cohort study across eight centers in Japan, including ELBW infants born between 2015 and 2017. We investigated the association between total HC dosage administered up to 36 weeks postmenstrual age and neurodevelopmental outcomes to school age.</p><p><strong>Results: </strong>Linear mixed model analysis showed a significant association between higher HC dosage and lower developmental and intelligence quotient (DQ/IQ) scores. This trend persisted at 6 years of age, suggesting a sustained effect of HC on cognitive outcomes. For every 10 mg increase in HC dosage, IQ scores decreased by 2.82 points (95% CI: -3.89 to -1.06, p = 0.001). The interaction term between HC dosage and time was not statistically significant (0.10, 95% CI: -0.18 to 0.37, p = 0.481), suggesting the association of HC dosage on DQ/IQ did not vary substantially throughout the study period.</p><p><strong>Conclusions: </strong>We found a relationship between total neonatal HC dosage in ELBW infants and DQ/IQ scores over time that persisted at school age. Clinicians should be aware of this potential dose-dependent effect on neurodevelopmental outcomes.</p><p><strong>Impact: </strong>As neonatal dexamethasone administration is known to affect neurodevelopment outcomes, hydrocortisone (HC) is considered an alternative to dexamethasone as a glucocorticoid treatment. In infants with extremely low birth weight (ELBW), a relationship has been noted between total HC dosage and neurodevelopment in early childhood. We confirmed the association between total HC dosage in infants with ELBW and poor developmental and intelligence quotients to school age. Although HC is commonly used in the management of ELBW infants, clinicians should be aware of its potential dose-dependent effects on neurodevelopmental outcomes.</p>\",\"PeriodicalId\":19829,\"journal\":{\"name\":\"Pediatric Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41390-025-04426-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41390-025-04426-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
摘要
背景：极低出生体重（ELBW）婴儿氢化可的松（HC）总剂量与随后直至学龄的神经发育结局之间的关系尚不清楚。方法：我们在日本的8个中心进行了一项回顾性纵向队列研究，包括2015年至2017年出生的低体重婴儿。我们调查了经后36周的HC总剂量与学龄期神经发育结果之间的关系。结果：线性混合模型分析显示，高HC剂量与低DQ/IQ得分有显著相关。这种趋势持续到6岁，表明HC对认知结果的持续影响。HC剂量每增加10mg，智商分数下降2.82分（95% CI: -3.89 ~ -1.06, p = 0.001）。HC剂量与时间的交互项无统计学意义（0.10,95% CI: -0.18 ~ 0.37, p = 0.481），说明HC剂量对DQ/IQ的相关性在整个研究期间没有显著变化。结论：我们发现ELBW婴儿的新生儿HC总剂量与DQ/IQ分数之间的关系在学龄期持续存在。临床医生应该意识到这种潜在的剂量依赖性对神经发育结果的影响。影响：由于已知新生儿地塞米松给药会影响神经发育结果，氢化可的松（HC）被认为是地塞米松糖皮质激素治疗的替代方案。在极低出生体重（ELBW）婴儿中，已注意到HC总剂量与儿童早期神经发育之间的关系。我们证实了ELBW婴儿的总HC剂量与发育不良和学龄期智商之间的关联。虽然HC通常用于治疗ELBW婴儿，但临床医生应该意识到其对神经发育结果的潜在剂量依赖性作用。
Total hydrocortisone dosage in extremely low birth weight infants and neurodevelopment up to school age.
Background: An association between total hydrocortisone (HC) dosage in infants with extremely low birth weight (ELBW) and subsequent neurodevelopmental outcomes up to school age remains unclear.
Method: We conducted a retrospective longitudinal cohort study across eight centers in Japan, including ELBW infants born between 2015 and 2017. We investigated the association between total HC dosage administered up to 36 weeks postmenstrual age and neurodevelopmental outcomes to school age.
Results: Linear mixed model analysis showed a significant association between higher HC dosage and lower developmental and intelligence quotient (DQ/IQ) scores. This trend persisted at 6 years of age, suggesting a sustained effect of HC on cognitive outcomes. For every 10 mg increase in HC dosage, IQ scores decreased by 2.82 points (95% CI: -3.89 to -1.06, p = 0.001). The interaction term between HC dosage and time was not statistically significant (0.10, 95% CI: -0.18 to 0.37, p = 0.481), suggesting the association of HC dosage on DQ/IQ did not vary substantially throughout the study period.
Conclusions: We found a relationship between total neonatal HC dosage in ELBW infants and DQ/IQ scores over time that persisted at school age. Clinicians should be aware of this potential dose-dependent effect on neurodevelopmental outcomes.
Impact: As neonatal dexamethasone administration is known to affect neurodevelopment outcomes, hydrocortisone (HC) is considered an alternative to dexamethasone as a glucocorticoid treatment. In infants with extremely low birth weight (ELBW), a relationship has been noted between total HC dosage and neurodevelopment in early childhood. We confirmed the association between total HC dosage in infants with ELBW and poor developmental and intelligence quotients to school age. Although HC is commonly used in the management of ELBW infants, clinicians should be aware of its potential dose-dependent effects on neurodevelopmental outcomes.
期刊介绍：
Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of children''s diseases and
disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques
relevant to developmental biology and medicine are acceptable, as are translational human studies
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