Essential Fatty Acid Deficiency as a modifiable determinant of cognitive dysfunction among 6-18-year-old Ugandan children of varying perinatal HIV status

必需脂肪酸缺乏是不同围产期 HIV 状况的 6-18 岁乌干达儿童认知功能障碍的可改变决定因素

• 批准号: 10741470
• 负责人: AMARA E EZEAMAMA
• 金额: $ 4.74万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10741470
• 关键词: 18 year old; Address; Adolescent; Affect; Age; Birth; Child; Child Development; Childhood; Cognition; Cognitive; Communities; Data; Development; Essential Fatty Acids; Exposure to; Feedback; Functional disorder; HIV; HIV therapy; Immune System Diseases; Impaired cognition; Infrastructure; Intervention; Intestines; Life; Link; Low Birth Weight Infant; Malnutrition; Measures; Medical Records; Metabolic; Minority; Morbidity - disease rate; Mother-to-child HIV transmission; Mothers; Neurocognitive; Neurosciences; Outcome; Parents; Perinatal; Persons; Pregnancy; Pregnant Women; Recording of previous events; Research; Risk; Risk Factors; School-Age Population; Supportive care; Training; Uganda; antiretroviral therapy; cohort; dysbiosis; executive function; follow-up; gut microbiome; host-microbe interactions; in utero; infancy; low and middle-income countries; neurocognitive disorder; neurotoxicity; nutrition; parent project; perinatal HIV; prevent; professor

PROJECT SUMMARY/ABSTRACT More than 1 in 3 children from low middle-income countries are at risk of neurocognitive disorder (ND) and/or significant scholastic problems due to high burden of infectious morbidity and malnutrition which contributes to immune dysfunction and disruption of normal host-microbe interactions in the gut (i.e., intestinal dysbiosis). While all children are at risk, the risk of neurocognitive dysfunction for perinatally HIV-infected (PHIV) and HIV-exposed uninfected (HEU) children is amplified by current and/or early life antiretroviral therapy (ART). ART for HIV-infected pregnant women effectively reduces the likelihood of mother-to-child transmission of HIV. This exposure, however, increases the likelihood of a range of risk factors for adverse neurodevelopmental outcomes such as low birth weight, metabolic problems, and neurotoxicity among children whose mothers received ART in pregnancy. Further, persons living with HIV and HEU children have different intestinal microbiomes compared to community controls. The extent to which interactions between nutritional deficiency, intestinal dysbiosis, and current ART or in utero/peripartum ART history among HIV-affected children creates a negative feedback loop that worsens ND, related outcomes relative to HIV unexposed uninfected (HUU) children is unknown. This gap in current understanding is addressed in this project. As part of completed and ongoing research, our team has established and maintained a large cohort of school-aged and adolescent (ages 6 to 18 years) PHIV (n=255), HEU (n=254) and HUU (n=257) children from Uganda. Most (49.7%) HIV exposed children in our existing cohort did not receive any peripartum ART to prevent HIV mother-to-child-transmission. The vast majority of those that received any peripartum intervention were exposed to sub-optimal IPA (34.8%) and a relative minority (15%) were exposed to combination ART through their mothers in the in utero/peripartum period. The parent project allows this team to follow the already established cohort for three more years, conduct annual assessment of cognition and repeated measures of nutrition, intestinal dysbiosis, and immune dysfunction. The data will be integrated with already available information to implement definitive analyses of relationships between change in neurocognitive outcomes over 36 months follow-up and perinatal HIV status, early ART status, and Essential Fatty Acid Deficiency. Overall Impact: By implementing this project, we will identify children who are at risk of worse developmental outcomes so that the available supportive care interventions can be directed to those in greatest need. Second, the predictors of neurocognitive risk evaluated are potentially modifiable, opening another avenue to intervene to ensure that all children are developmentally thriving in the long-term.

项目摘要/摘要 来自低收入国家的3个儿童中有1个以上有神经认知障碍的风险（ND） 和/或由于感染性发病率和营养不良的高负担而引起的重大学术问题，这 有助于免疫功能障碍和肠道中正常宿主 - 微生物相互作用的破坏（即肠道 营养不良）。虽然所有儿童都处于危险之中，但受HIV感染的神经认知功能障碍的风险 （pHIV）和艾滋病毒暴露的未感染（HEU）儿童被电流和/或早期生命抗逆转录病毒扩增 治疗（艺术）。艾滋病毒感染的孕妇的艺术有效地降低了母亲到孩子的可能性 艾滋病毒的传播。然而，这种暴露增加了不良风险因素的可能性 儿童的神经发育结果，例如低出生体重，代谢问题和神经毒性 他的母亲在怀孕时接受了艺术。此外，患有艾滋病毒和HEU孩子的人有不同 与社区对照相比，肠道微生物组。营养之间的相互作用程度 缺乏症，肠道营养不良，当前的艺术或子宫/围角膜史中受艾滋病毒影响的 儿童创建一个负面反馈循环，使ND恶化，相关结果与HIV暴露 未感染（HUU）儿童是未知的。该项目在当前理解中的这一差距得到了解决。 作为完成和正在进行的研究的一部分，我们的团队已经建立并维持了大量队列 学龄和青春期（6至18岁）pHIV（n = 255），heu（n = 254）和huu（n = 257）儿童 乌干达。大多数（49.7％）的艾滋病毒暴露在我们现有队列中 防止艾滋病毒母亲到儿童的传播。绝大多数接受了任何周围干预的人 暴露于亚最佳IPA（34.8％）和相对少数群体（15％）暴露于联合艺术中 通过其母亲在子宫/围栏时期。家长项目允许该团队遵循 已经建立了三年的队列，对认知进行年度评估并重复 营养，肠道营养不良和免疫功能障碍的度量。数据将与已集成 可用信息以实施神经认知变化之间关系的明确分析 在36个月的随访和围产期艾滋病毒状况，早期艺术状况和必需脂肪酸的结果中取得结果 不足。 总体影响：通过实施该项目，我们将确定有恶化风险的儿童 发展成果，以便可以将可用的支持护理干预措施直接针对 最需要。其次，评估的神经认知风险的预测因素可能会改变，开放 干预的另一种途径，以确保所有儿童在长期内发展蓬勃发展。