Neurodevelopmental regression (NDR) is a subtype of autism spectrum disorder (ASD) that manifests as loss of previously acquired developmental milestones. Early life dysregulation of nutritional metals and/or exposure to toxic metals have been associated with ASD, but the underlying biological mechanisms by which metals influence neurodevelopment remain unclear. We hypothesize that metals influences neurodevelopment through dysregulation of bioenergetics. Prenatal and early postnatal metal exposures were measured using validated tooth-matrix biomarkers in 27 ASD cases (13 with NDR) and 7 typically-developing (TD) controls. Mitochondrial respiration and glycolysis were measured in peripheral blood mononuclear cells using the Seahorse XF96. Children with ASD demonstrated lower prenatal and postnatal Copper (Cu) and prenatal Nickel concentrations and Copper-to-Zinc (Cu/Zn) ratio as compared with TD children. Children with ASD and NDR showed greater metal-related disruption of cellular bioenergetics than children with ASD without NDR. For children with ASD and NDR mitochondrial respiration decreased as prenatal Manganese concentration increased and increased as prenatal Zinc concentration increased; glycolysis decreased with increased exposure to prenatal Manganese and Lead and postnatal Manganese. For children with ASD without a history of NDR, glycolysis increased with increased postnatal exposure to Tin. Language and communication scores in children with ASD were positively related to prenatal Cu exposure and Cu/Zn ratio. This study suggests that prenatal nutritional metals may be important for neurodevelopment in children with ASD, and that exposure to toxic metals and differences in nutritional metal exposures is associated with dysregulation of cellular bioenergetics, particularly in the NDR subtype of ASD.

神经发育退缩（NDR）是自闭症谱系障碍（ASD）的一种亚型，表现为先前获得的发育里程碑的丧失。营养性金属的早期生命失调和/或暴露于有毒金属与ASD有关，但金属影响神经发育的潜在生物学机制仍不清楚。我们假设金属通过生物能学的失调影响神经发育。使用经验证的牙基质生物标记物对27例ASD病例（13例为NDR）和7例典型发育（TD）对照者进行了产前和产后早期金属暴露的测量。使用Seahorse XF96在外周血单个核细胞中测量线粒体呼吸和糖酵解。与TD儿童相比，患有ASD的儿童表现出较低的产前和产后铜（Cu）和产前镍浓度以及铜锌（Cu / Zn）比。与没有NDR的ASD儿童相比，患有ASD和NDR的儿童表现出更大的金属相关的细胞生物能学破坏。对于患有ASD和NDR的儿童，随着产前锰浓度的增加，线粒体呼吸减少；随着产前锌浓度的增加，线粒体呼吸增加。糖酵解随着产前锰和铅以及产后锰的暴露增加而降低。对于无NDR史的ASD儿童，糖酵解随着出生后锡摄入量的增加而增加。自闭症儿童的语言和交流得分与产前铜暴露和铜锌比呈正相关。