PDF(Pubmed)
Abstract：
BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks\' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear.
METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks\' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months\' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability.
CONCLUSIONS: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results.
BACKGROUND: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.
METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks\' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months\' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability.
CONCLUSIONS: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results.
BACKGROUND: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.
摘要：
背景：维生素D是生命早期发育健康的肺和其他器官所必需的。大多数在妊娠28周之前出生的婴儿在出生时维生素D水平较低，并且在第一个月内摄入量有限。肠内补充维生素D廉价且广泛使用。极端早产儿的适当补充方案是有争议的，不同治疗方案对其血液水平和结局的影响尚不清楚.
方法：随机化，在美国一家大型学术中心进行的盲法有效性比较试验,以比较两种维生素D补充方案对妊娠<28周或出生体重<1000g的新生儿的影响.婴儿按出生体重分层，并在出生后96小时内随机分配，在出生后的前28天内进行常规补充（400IU/天，已确定的喂养）或增加补充（800IU/天，任何喂养）。我们假设，与安慰剂加常规剂量（400IU/天，建立喂养）相比，较高和早期的维生素D剂量（800IU/天，早期喂养）将大大增加25-羟基维生素D3的总水平，如1个月的最新技术，在月经后36周龄时减少呼吸支持（在预测后期不良结局的序数量表上），并改善或至少不恶化其他重要的次要结果。研究中的婴儿将在22-26个月的矫正年龄（〜2岁）进行随访，并进行盲认证的审查员评估神经发育结果。最少180名婴儿的样本量提供了>90％的能力来检测血清25-羟基维生素D3增加33％的后验概率>95％，以及>80％的能力通过使用中性先验概率的意向治疗贝叶斯分析来检测减少呼吸支持的相对风险降低20％的后验概率。
结论：我们的研究将有助于阐明补充维生素D及其相关血清代谢物与极早产儿临床结局的不确定关系。确认我们的假设将促使重新考虑极端早产儿使用的补充方案，并证明进行大型多中心研究以验证结果的普遍性。
背景：ClinicalTrials.govNCT05459298。2022年7月14日注册。
方法：随机化，在美国一家大型学术中心进行的盲法有效性比较试验,以比较两种维生素D补充方案对妊娠<28周或出生体重<1000g的新生儿的影响.婴儿按出生体重分层，并在出生后96小时内随机分配，在出生后的前28天内进行常规补充（400IU/天，已确定的喂养）或增加补充（800IU/天，任何喂养）。我们假设，与安慰剂加常规剂量（400IU/天，建立喂养）相比，较高和早期的维生素D剂量（800IU/天，早期喂养）将大大增加25-羟基维生素D3的总水平，如1个月的最新技术，在月经后36周龄时减少呼吸支持（在预测后期不良结局的序数量表上），并改善或至少不恶化其他重要的次要结果。研究中的婴儿将在22-26个月的矫正年龄（〜2岁）进行随访，并进行盲认证的审查员评估神经发育结果。最少180名婴儿的样本量提供了>90％的能力来检测血清25-羟基维生素D3增加33％的后验概率>95％，以及>80％的能力通过使用中性先验概率的意向治疗贝叶斯分析来检测减少呼吸支持的相对风险降低20％的后验概率。
结论：我们的研究将有助于阐明补充维生素D及其相关血清代谢物与极早产儿临床结局的不确定关系。确认我们的假设将促使重新考虑极端早产儿使用的补充方案，并证明进行大型多中心研究以验证结果的普遍性。
背景：ClinicalTrials.govNCT05459298。2022年7月14日注册。
