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<p>We aimed to identify cord blood metabolic measures associated with childhood-onset neurodevelopmental disorders (NDDs) and to examine whether they improve prediction beyond known early-life risk factors. In a prospective study of 858 children followed to a median age of 14.1 years (IQR 13.7–14.8), cord blood levels of 110 metabolic measures were assessed at birth and NDD diagnoses obtained from nationwide register. We identified 12 cord blood metabolic measures together explaining 5.0% of variance in any NDD, seven related to HDL synthesis, concentration and composition, one to concentration of lipoprotein particles, two to fatty acids and two to amino acids; their levels were 0.26–0.36(95%CI: −0.55, −0.06) standard deviations lower in the children who were later diagnosed with any NDD compared to the children with no mental disorders (p-value for overall model including all 12 metabolic measures &lt;0.0001). They were also associated with early-life risk factors of NDDs, and improved the prediction of any NDD over a model that included only sociodemographic, prenatal and birth-related early-life risk factors(AUC = 0.74,95% CI 0.69–0.79; R2 = 16.6%; p &lt; 0.0001 vs. AUC 0.71,95% CI, 0.66–0.76; R2 = 12.2%; p &lt; 0.0001; Likelihood Ratio Test [LRT] p = 0.04). The improvement was more modest when the model additionally included maternal polygenic risk scores for ADHD and ASD (AUC = 0.75,95% CI 0.70–0.80; R2 = 18.3%; p &lt; 0.0001 vs. AUC 0.72,95% CI, 0.67–0.78; R2 = 13.9%; p &lt; 0.0001; LRT p = 0.08). Cord blood metabolic measures predicted NDDs diagnosed from birth through adolescence and improved prediction beyond early-life risk factors, with smaller incremental value when maternal PRSs for ADHD and ASD were included.</p>

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Metabolomic alterations in cord blood improve the prediction of childhood-onset neurodevelopmental disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月25日

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  • Polina Girchenko,
  • Marius Lahti-Pulkkinen,
  • Chenyao Ni,
  • Jari Lahti,
  • Li Tian,
  • Aino Airikka,
  • Eero Kajantie,
  • Katri Räikkönen

摘要

We aimed to identify cord blood metabolic measures associated with childhood-onset neurodevelopmental disorders (NDDs) and to examine whether they improve prediction beyond known early-life risk factors. In a prospective study of 858 children followed to a median age of 14.1 years (IQR 13.7–14.8), cord blood levels of 110 metabolic measures were assessed at birth and NDD diagnoses obtained from nationwide register. We identified 12 cord blood metabolic measures together explaining 5.0% of variance in any NDD, seven related to HDL synthesis, concentration and composition, one to concentration of lipoprotein particles, two to fatty acids and two to amino acids; their levels were 0.26–0.36(95%CI: −0.55, −0.06) standard deviations lower in the children who were later diagnosed with any NDD compared to the children with no mental disorders (p-value for overall model including all 12 metabolic measures <0.0001). They were also associated with early-life risk factors of NDDs, and improved the prediction of any NDD over a model that included only sociodemographic, prenatal and birth-related early-life risk factors(AUC = 0.74,95% CI 0.69–0.79; R2 = 16.6%; p < 0.0001 vs. AUC 0.71,95% CI, 0.66–0.76; R2 = 12.2%; p < 0.0001; Likelihood Ratio Test [LRT] p = 0.04). The improvement was more modest when the model additionally included maternal polygenic risk scores for ADHD and ASD (AUC = 0.75,95% CI 0.70–0.80; R2 = 18.3%; p < 0.0001 vs. AUC 0.72,95% CI, 0.67–0.78; R2 = 13.9%; p < 0.0001; LRT p = 0.08). Cord blood metabolic measures predicted NDDs diagnosed from birth through adolescence and improved prediction beyond early-life risk factors, with smaller incremental value when maternal PRSs for ADHD and ASD were included.