Improving Brain Myelination with Iron (Fe) Supplementation in Term Infants with Perinatal Latent Iron Deficiency: A Double-Blind, Randomized, Placebo-Controlled Trial

通过补充铁 (Fe) 改善围产期潜在铁缺乏症足月婴儿的脑髓鞘形成：一项双盲、随机、安慰剂对照试验

• 批准号: 10247643
• 负责人: SANJIV B AMIN
• 金额: --
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247643
• 关键词: 2 year old; Academy; Acute; Address; Adult; Adverse event; Affect; American; Applications Grants; Auditory; Birth; Brain; Brain Stem; Caring; Child; Childhood; Clinical Research; Clinical Trials; Collaborations; Constipation; Copper; Database Management Systems; Developed Countries; Developing Countries; Development; Diabetes Mellitus; Diarrhea; Disabled Children; Dose; Double-Blind Method; Early identification; Education; Emotional Stress; Evaluation; Ferritin; Financial Hardship; Fostering; Funding; Future; Grant; Growth; Head circumference; Health; Health Care Costs; Hospitals; Human; Hypertension; Icterus; Impairment; India; Infant; Infection; Institution; Intake; Investigational Drugs; Iron; Iron Overload; Iron deficiency anemia; Isoprostanes; Joints; Laboratories; Language; Lead; Length; Life; Longevity; Measurement; Medical; Medical center; Mentors; Monitor; Mothers; Neonatal; Nervous system structure; Neural Conduction; Neurodevelopmental Disability; Neurodevelopmental Impairment; Neurologic; Neurological outcome; Nutrient; Nutrition Disorders; Oral; Outcome; Oxidative Stress; Parents; Pediatrics; Perinatal; Phase; Phase III Clinical Trials; Pilot Projects; Placebos; Policies; Populations at Risk; Pregnancy; Prevalence; Prevention; Problem behavior; Publishing; Randomized; Randomized Clinical Trials; Research; Research Personnel; Resources; Safety; Savings; Secondary Schools; Serum; Services; Special Education; Supplementation; Testing; Therapeutic; Therapeutic Uses; Time Management; Tissues; Toxic effect; Training; United States National Institutes of Health; Universities; Vomiting; Weight; Zinc; ancillary care; base; brain abnormalities; cohort; cost; critical period; design; disability; dosage; double-blind placebo controlled trial; early childhood; efficacy clinical trial; efficacy evaluation; expectation; experience; follow-up; global health; high risk; improved; indexing; infancy; iron deficiency; iron supplementation; maternal diabetes; maternal hypertension; myelination; neonatal period; neonate; neurodevelopment; neurophysiology; novel strategies; perinatal period; placebo group; postnatal; postnatal period; prevent; randomized placebo controlled trial; relating to nervous system; response; skills; social; therapy development; tool; urinary

This project is designed to further develop and strengthen collaborative research on perinatal and neonatal factors associated with neurological impairments in children. The project will be conducted at Sir Ganga Ram Hospital, Delhi, India, working in conjunction with the University of Rochester Medical Center, Rochester, NY. This collaboration was initiated in 2010 with support from an NIH-ICMR funded R03 grant to study jaundice- associated auditory toxicity in infants. The collaboration was strengthened further by our pilot study in term infants, which demonstrated that perinatal latent iron deficiency (P-LID) is associated with abnormal auditory neural myelination (ANM). We now propose a more extensive R01 grant proposal leveraging our joint resources and prior successful collaborations to further develop the capabilities of our Indian collaborators. We will conduct a double-blind randomized clinical trial (DBRCT) and evaluate the efficacy and safety of iron supplementation to improve ANM in term infants with P-LID. Abnormal ANM during the neonatal period has been associated with negative neurodevelopmental outcomes during early childhood. Worldwide, iron deficiency (ID) is the most common preventable nutritional disorder that contributes to abnormal neurological outcome across the life span. Iron is essential for brain myelination which peaks during the perinatal period (2 months before and after birth at term gestation). Currently, the American Academy of Pediatrics recommends that term infants not receive any iron supplementation during the first 4 months of life. However, P-LID (serum ferritin < 76 ng/mL) is common at birth among term infants born to mothers with hypertension, diabetes, or ID anemia during pregnancy. In India, maternal ID during pregnancy and P-LID among term infants are extremely common. P-LID during the critical period of peak brain myelination in neonates has been associated with acute and long-lasting abnormal brain development. These neurodevelopmental disabilities result not only in poor life expectations, but billions of dollars in annual costs globally to provide affected children with care and special education. Therefore, early identification of P-LID and optimal iron supplementation during the critical postnatal period of brain maturation may help to improve brain myelination and prevent neurodevelopmental disabilities. The primary objective of this DBRCT is to determine if oral iron supplementation of 2 or 4 mg/kg/day for 2 months, compared to placebo, will be safe and improve ANM, as evaluated by auditory brainstem evoked response, in 255 term infants with P-LID (165 in India & 90 in the US). In carrying out this DBRCT, we will develop a Center of Excellence in Clinical Research in New Delhi, India, through education, mentoring and high quality research experiences. In the long- term, we aim to determine if improving myelination with iron supplementation will enhance long-term neurodevelopmental outcomes in term infants. Building sustainable research capacity in India to support future collaborative DBRCT that address nervous system impairment during early infancy and childhood will ultimately lead to development of treatment and prevention policies that can be implemented globally.

该项目旨在进一步发展和加强关于围产期和新生儿的合作研究。 与儿童神经损伤相关的因素。该项目将在Sir Ganga Ram进行 医院，德里，印度，与罗切斯特大学医学中心，罗切斯特，纽约合作。 这项合作始于2010年，得到了NIH-ICMR资助的R 03赠款的支持，用于研究黄疸- 相关的听觉毒性。我们的试验研究进一步加强了合作， 婴儿，这表明，围产期潜伏性缺铁（P-LID）与异常的听觉 神经髓鞘形成（ANM）。我们现在提出一个更广泛的R 01赠款提案，利用我们的联合资源 以及之前成功的合作，以进一步发展我们印度合作者的能力。我们会进行 一项双盲随机临床试验（DBRCT），评估补铁对 改善足月P-LID婴儿ANM新生儿期异常ANM与 儿童早期的神经发育不良。在世界范围内，缺铁（ID）是最常见的 一种常见的可预防的营养失调，导致终生神经系统异常。 铁对于脑髓鞘形成是必不可少的，其在围产期（出生前和出生后2个月， 足月妊娠）。目前，美国儿科学会建议足月婴儿不接受任何 在生命的前4个月补充铁。然而，P-LID（血清铁蛋白< 76 ng/mL）在以下情况下是常见的： 妊娠期间患有高血压、糖尿病或ID贫血的母亲所生的足月儿。在印度， 怀孕期间的孕产妇ID和足月婴儿中的P-LID非常常见。关键期间的P-LID 新生儿脑髓鞘形成高峰期与急性和长期的脑异常有关 发展这些神经发育障碍不仅导致预期寿命不高， 在全球范围内，每年花费200万美元，为受影响的儿童提供护理和特殊教育。因此早期 出生后脑成熟关键期P-LID和最佳铁补充的鉴定 可能有助于改善大脑髓鞘形成和预防神经发育障碍。这项工作的主要目的是 DBRCT旨在确定与安慰剂相比，2或4 mg/kg/天口服补铁2个月是否会 在255例患有P-LID的足月儿中，通过听觉脑干诱发反应评估， (165在印度和90在美国）。在开展DBRCT的过程中，我们将建立一个临床卓越中心， 在印度新德里进行研究，通过教育，指导和高质量的研究经验。在漫长的- 长期而言，我们的目标是确定通过补充铁来改善髓鞘形成是否会增强长期的 足月儿的神经发育结果。在印度建立可持续的研究能力，以支持未来 合作的DBRAT最终将解决婴儿早期和儿童时期的神经系统损伤问题， 导致制定可在全球实施的治疗和预防政策。