Parenti Mariana, Schmidt Rebecca J, Tancredi Daniel J, Miller Meghan, Hertz-Picciotto Irva, Walker Cheryl K, Slupsky Carolyn M
Department of Nutrition, University of California, Davis, CA, United States.
Department of Public Health Sciences, University of California, Davis, CA, United States; MIND Institute, University of California, Davis, CA, United States.
J Nutr. 2025 Jul;155(7):2185-2194. doi: 10.1016/j.tjnut.2025.05.016. Epub 2025 May 23.
The first month of pregnancy is a key time in early developmental programming. Prenatal vitamin/mineral supplement use during the first month of pregnancy (PNVmo1) was associated with reduced risk of autism spectrum disorder (ASD) in the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort.
We aimed to evaluate the associations between PNVmo1, the placental and umbilical cord serum metabolomes, and the child's later neurodevelopmental outcome in the MARBLES pregnancy cohort.
Placental (n = 78) and umbilical cord serum (n = 132) metabolomes were investigated using H nuclear magnetic resonance spectroscopy. PNVmo1 was determined by self-report. At 36 mo of age, child neurodevelopmental outcomes were classified by MARBLES clinicians into 3 groups: typically developing (TD), ASD, or nontypically developing (Non-TD) but not ASD, which was dominated by developmental delays and/or elevated autism symptoms but not meeting ASD criteria.
After adjustment for covariates, permutational multivariate analysis of variance revealed that PNVmo1 was significantly (P < 0.05) associated with the placental and umbilical cord serum metabolomes. In the placenta, higher concentrations of amino acids were observed in the PNVmo1 group (false discovery rate <0.1). After adjustment for PNVmo1 and other covariates, permutational multivariate analysis of variance revealed a significant association (P < 0.05) between the placental metabolome and Non-TD outcome status. No associations were observed in the analyses of umbilical cord serum metabolism or with ASD outcome. We tested for but did not find evidence that the placental metabolome explained the relationship between PNVmo1 and Non-TD outcome in an exploratory mediation analysis.
These findings suggest that the placental metabolome could be sensitive to nutrient supplementation during the earliest stages of pregnancy.
怀孕的第一个月是早期发育编程的关键时期。在“婴儿自闭症风险标志物:早期学习迹象”(MARBLES)队列研究中,孕期第一个月使用产前维生素/矿物质补充剂(PNVmo1)与自闭症谱系障碍(ASD)风险降低有关。
我们旨在评估MARBLES怀孕队列中PNVmo1、胎盘和脐带血清代谢组与儿童后期神经发育结局之间的关联。
使用氢核磁共振波谱法研究胎盘(n = 78)和脐带血清(n = 132)的代谢组。PNVmo1通过自我报告确定。在36个月大时,MARBLES临床医生将儿童神经发育结局分为3组:典型发育(TD)、ASD或非典型发育(非TD)但非ASD,后者主要表现为发育迟缓或自闭症症状加重,但未达到ASD标准。
在对协变量进行调整后,置换多变量方差分析显示PNVmo1与胎盘和脐带血清代谢组显著相关(P < 0.05)。在胎盘中,PNVmo1组中氨基酸浓度较高(错误发现率<0.1)。在对PNVmo1和其他协变量进行调整后,置换多变量方差分析显示胎盘代谢组与非TD结局状态之间存在显著关联(P < 0.05)。在脐带血清代谢分析或与ASD结局的分析中未观察到关联。在探索性中介分析中,我们进行了检验但未找到证据表明胎盘代谢组解释了PNVmo1与非TD结局之间的关系。
这些发现表明,胎盘代谢组可能对怀孕最早阶段的营养补充敏感。