Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

Vacy, Kristina; Thomson, Sarah; Moore, Archer; Eisner, Alex; Tanner, Sam; Pham, Cindy; Saffery, Richard; Mansell, Toby; Burgner, David; Collier, Fiona; Vuillermin, Peter; O’Hely, Martin; Boon, Wah Chin; Meikle, Peter; Burugupalli, Satvika; Ponsonby, Anne-Louise; Tang, Mimi L.K.; Gray, Lawrence; Ranganathan, Sarath; Sly, Peter; Mueller, Jochen; Dwyerm, Terry; Carlin, John

doi:10.1016/j.ebiom.2023.104949

Cited by 6 publications

(3 citation statements)

References 85 publications

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“… 51 ADHD symptoms have been associated with broader changes lipid metabolism across multiple lipid classes. 50 Thus, the placental and cord metabolic profiles reported here could be signs of altered cellular and lipid metabolism linked to impaired neurodevelopment that is detectable at birth.…”

Section: Discussionmentioning

confidence: 68%

“… 10 In an umbilical cord serum lipidomic analysis, circulating acylcarnitines were positively associated with symptoms of both ASD and ADHD at age 2 years. 50 There has been some work to suggest that higher plasma 3-OHB levels might correlate with decreased receptive language between 2 and 5 years in typically developing children. 51 ADHD symptoms have been associated with broader changes lipid metabolism across multiple lipid classes.…”

Section: Discussionmentioning

confidence: 99%

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Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

Parenti,

Schmidt,

Tancredi

et al. 2024

JAMA Netw Open

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ImportanceDisturbances 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresQuantitative metabolomics analysis was conducted on maternal third trimester serum, as well as placental tissue and umbilical cord serum collected at delivery.Main Outcomes and MeasuresUsing 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).ResultsThis 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 &lt; .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.Conclusions and RelevanceIn 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.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

Parenti,

Schmidt,

Tancredi

et al. 2024

JAMA Netw Open

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“…At this stage, 80 clinically relevant studies were identified for full-text review. Sequentially, 21 of these were excluded for various reasons: 6 studies which identified potentially predictive prenatal markers for ADHD [29][30][31][32][33][34]; 3 which comprised exclusively adult samples [35][36][37], as well as 1 study that included both children and adults without separately presenting differences between healthy children and those with ADHD [38]; 5 studies that did not measure the metabolites themselves [39][40][41][42][43]; 2 that were based on glycomic markers [44,45]; 2 for which the full text could not be obtained [46,47]; 1 study which compared ADHD children divided on the basis of inflammatory marker levels, with no control group [48]; and 1 study which had the full text available only in Catalan [49]. Additionally, through a thorough examination of these articles, as well as the identified reviews and meta-analyses, we identified 5 additional resources suitable for inclusion in the present review, resulting in a final number of 64 included studies.…”

Section: Methodsmentioning

confidence: 99%

Metabolomic Markers in Attention-Deficit/Hyperactivity Disorder (ADHD) among Children and Adolescents—A Systematic Review

Predescu,

Vaidean,

Rapciuc

et al. 2024

IJMS

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Attention-Deficit/Hyperactivity Disorder (ADHD), characterized by clinical diversity, poses diagnostic challenges often reliant on subjective assessments. Metabolomics presents an objective approach, seeking biomarkers for precise diagnosis and targeted interventions. This review synthesizes existing metabolomic insights into ADHD, aiming to reveal biological mechanisms and diagnostic potentials. A thorough PubMed and Web of Knowledge search identified studies exploring blood/urine metabolites in ADHD-diagnosed or psychometrically assessed children and adolescents. Synthesis revealed intricate links between ADHD and altered amino acid metabolism, neurotransmitter dysregulation (especially dopamine and serotonin), oxidative stress, and the kynurenine pathway impacting neurotransmitter homeostasis. Sleep disturbance markers, notably in melatonin metabolism, and stress-induced kynurenine pathway activation emerged. Distinct metabolic signatures, notably in the kynurenine pathway, show promise as potential diagnostic markers. Despite limitations like participant heterogeneity, this review underscores the significance of integrated therapeutic approaches targeting amino acid metabolism, neurotransmitters, and stress pathways. While guiding future research, this overview of the metabolomic findings in ADHD suggests directions for precision diagnostics and personalized ADHD interventions.

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Disrupted Prenatal Metabolism May Explain the Etiology of Suboptimal Neurodevelopment: A Focus on Phthalates and Micronutrients and their Relationship to Autism Spectrum Disorder

Parenti,

Slupsky

2024

Advances in Nutrition

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Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

Cited by 6 publications

References 85 publications

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

Metabolomic Markers in Attention-Deficit/Hyperactivity Disorder (ADHD) among Children and Adolescents—A Systematic Review

Disrupted Prenatal Metabolism May Explain the Etiology of Suboptimal Neurodevelopment: A Focus on Phthalates and Micronutrients and their Relationship to Autism Spectrum Disorder

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