Department of Nutrition, University of California, Davis.
Now with Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington.
JAMA Netw Open. 2024 May 1;7(5):e2413399. doi: 10.1001/jamanetworkopen.2024.13399.
Disturbances in maternal, placental, and fetal metabolism are associated with developmental outcomes. Associations of maternal, placental, and fetal metabolism with subsequent neurodevelopmental outcomes in the child are understudied.
To investigate the metabolic associations within the maternal-placental-fetal unit and subsequent neurodevelopmental outcomes in younger siblings of children with autism spectrum disorder (ASD).
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted within a subset of the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort. MARBLES is a prospective birth cohort of younger siblings of children with ASD assessed for neurodevelopmental outcomes at approximately age 36 months. Participants in MARBLES were recruited through the UC Davis MIND Institute. This subset of the MARBLES cohort included younger siblings born between 2009 and 2015. Maternal third trimester serum, placental tissue, and umbilical cord serum samples were collected from participants. Only pregnancies with at least 2 of these sample types were included in this analysis. Data analysis was conducted from March 1, 2023, to March 15, 2024.
Quantitative metabolomics analysis was conducted on maternal third trimester serum, as well as placental tissue and umbilical cord serum collected at delivery.
Using the Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning, outcomes were classified as ASD, other nontypical development (non-TD), and typical development (TD).
This analysis included 100 maternal serum samples, 141 placental samples, and 124 umbilical cord serum samples from 152 pregnancies (median [IQR] maternal age, 34.6 [30.8-38.3] years; median [IQR] gestational age, 39.0 [38.6-39.7] weeks; 87 [57.2%] male infants). There was no evidence that the maternal third trimester serum metabolome was significantly associated with the other metabolomes. The placental and cord serum metabolomes were highly correlated (first latent variate pair: R2 = 0.75; P < .001) and the variate scores for each tissue were significantly associated with reduced risk of non-TD (placenta: relative risk [RR], 0.13; 95% CI, 0.02-0.71; cord: RR, 0.13; 95% CI, 0.03-0.70) but not ASD (placenta: RR, 1.09; 95% CI, 0.42-2.81; cord: RR, 0.63; 95% CI, 0.23-1.73) compared with the TD reference group.
In this cohort study of children with high familial risk of ASD, placental and cord serum metabolism at delivery were highly correlated. Furthermore, placental and cord serum metabolic profiles were associated with risk of non-TD.
母体、胎盘和胎儿代谢的紊乱与发育结果有关。母体、胎盘和胎儿代谢与自闭症谱系障碍（ASD）儿童后续神经发育结果的相关性研究还很少。
研究母胎胎儿单位内的代谢相关性以及 ASD 儿童的年幼兄弟姐妹的后续神经发育结果。
设计、地点和参与者：这是一项队列研究，在 Markers of Autism Risk in Babies, Learning Early Signs（MARBLES）队列的一个亚组中进行。MARBLES 是一个前瞻性的 ASD 儿童的年幼兄弟姐妹的出生队列，在大约 36 个月时评估神经发育结果。MARBLES 的参与者是通过加州大学戴维斯分校的 MIND 研究所招募的。该 MARBLES 队列的这个亚组包括 2009 年至 2015 年期间出生的年幼兄弟姐妹。从参与者中收集了母体第三个三个月的血清、胎盘组织和脐带血清样本。只有至少有 2 种这种样本类型的妊娠才包括在本分析中。数据分析于 2023 年 3 月 1 日至 2024 年 3 月 15 日进行。
对母体第三个三个月的血清，以及在分娩时收集的胎盘组织和脐带血清进行定量代谢组学分析。
使用自闭症诊断观察时间表和穆伦早期学习量表，将结果分类为自闭症、其他非典型发育（非 TD）和典型发育（TD）。
本分析包括 152 例妊娠中的 100 例母体血清样本、141 例胎盘样本和 124 例脐带血清样本（中位数[IQR] 母体年龄，34.6[30.8-38.3]岁；中位数[IQR] 孕龄，39.0[38.6-39.7]周；87[57.2%]为男性婴儿）。没有证据表明母体第三个三个月的血清代谢组与其他代谢组有显著关联。胎盘和脐带血清代谢组高度相关（第一潜在变量对：R2=0.75；P<0.001），每个组织的变量评分与非 TD 的风险降低显著相关（胎盘：相对风险[RR]，0.13；95%置信区间，0.02-0.71；脐带：RR，0.13；95%置信区间，0.03-0.70），但与 TD 参考组相比，与自闭症的风险无关（胎盘：RR，1.09；95%置信区间，0.42-2.81；脐带：RR，0.63；95%置信区间，0.23-1.73）。
在这项针对 ASD 高家族风险儿童的队列研究中，分娩时的胎盘和脐带血清代谢物高度相关。此外，胎盘和脐带血清代谢谱与非 TD 风险相关。
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