A recent study published in eBioMedicine investigated the relationship between the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), and the umbilical cord blood lipidome at the age of two.
The researchers also determined the relationship between prenatal and perinatal ASD and ADHD estimators, and the umbilical cord blood lipidome.
Profile of umbilical cord blood lipid correlation networks are associated with subsequent symptoms of Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder at age 2: a prospective birth cohort study
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Early risk factors such as pollutants and maternal inflammation impact neurological developmental disorders such as ASD and ADHD.
These disorders can lead to changes in serum lipids, which are crucial for neurological development and account for 50-60% of brain weight (dry). However, research on lipid metabolism and lipid profiles in early neurological developmental disorders is limited.
The Barwon Infant Study (BIS) reported that disrupted energy metabolism at 28 weeks of pregnancy is linked to ASD symptoms at the age of two and four, suggesting that lipid profiles may be crucial for ASD and ADHD.
About the Study
In this prospective birth cohort study, researchers used lipidomic analysis data from the BIS to examine the relationship between umbilical cord blood lipids and ASD and ADHD symptoms at the age of two.
They also investigated the relationship between prenatal and perinatal factors and ASD and ADHD, as well as the extent to which umbilical cord blood lipids mediate this relationship.
The BIS cohort of 1,074 mother-child dyads in Victoria, Australia analyzed infant blood lipids at birth using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS).
The researchers grouped lipids into lipid modules using weighted gene co-expression network analysis (WGCNA).
They conducted multivariate linear regressions to examine associations between the modules and ASD and ADHD symptoms after two years, considering the child’s age at assessment, birth gender, time to serum freeze, time in the freezer, and contamination with maternal cord blood.
The team performed a mediation analysis to assess the indirect effects of prenatal and perinatal factors increasing ASD and ADHD symptom risk through the modules.
The study recruited individuals from Barwon using prenatal sampling frames from July 2010 to July 2013. The researchers collected maternal blood at 28 weeks of pregnancy and cord blood at birth. Additionally, they collected infant venous blood and analyzed umbilical cord blood for contamination with maternal blood by analyzing methylation profiles of deoxyribonucleic acid (DNA).
The researchers measured lipid levels from maternal blood at 28 weeks of pregnancy, umbilical cord blood, and infant blood at six months, twelve months, and four years. They also assessed targeted metabolic profiles from maternal and umbilical cord blood, analyzing them using nuclear magnetic resonance (NMR).
The team evaluated ASD and ADHD-related symptoms in preschool children using the Child Behavior Checklist (CBCL) at the age of two and the Strengths and Difficulties Questionnaire P4-10 (SDQ) at the age of four. They determined prenatal factors from maternal questionnaires, clinical examinations, and prenatal records.
They validated perinatal factors with hospital data, including delivery mode, cesarean section (planned or emergency), duration of labor, gender and gestational age of the child at birth, Apgar scores at five minutes, and birth weight.
The acylcarnitine module was associated with ASD and ADHD symptoms at the age of two. Higher acylcarnitine levels at birth partially mediated risk factors for neurological developmental outcomes, including household income, maternal inflammation, and Apgar scores.
Other lipids in umbilical cord blood were also associated with ASD and ADHD symptoms. Nine lipid modules showed a significant association with increased ADHD symptom risk after two years, with four also significantly associated with increased ASD symptom risk after two years.
The lipid modules Blue-SMD(Hub), Turquoise-PE(Hub), and Cyan-AC showed the lowest p-values and the highest magnitude of association with ADHD symptom risk.
With a one standard deviation increase in the modules Cyan-AC, Turquoise-PE(Hub), and Blue-SMD(Hub), the estimated mean differences in ADHD symptoms after two years were 0.5 points, 0.4 points, and 0.3 points, respectively.
Higher Cyan-AC levels in umbilical cord blood partially mediated the relationship between lower household income during pregnancy and higher frequency of ADHD symptoms at the age of two.
Maternal NOPMS and NOPMS and GlycA at birth were associated with ADHD symptoms, but maternal GlycA was not. The umbilical cord blood lipid profile mediated the relationship between birth factors such as low Apgar score, birth GlycA, non-oxidative pyruvate metabolism at birth, and ADHD symptoms.
Acylcarnitines mediated the relationships between household income, maternal NOPMS, GlycA at birth, and ASD symptoms.
The study identified several pieces of evidence for causality, including consistent findings across the two-year CBCL and the four-year SDQ questionnaire subscales that acylcarnitines are associated with ASD and ADHD symptoms.
Overall, the study results demonstrated the relationship between umbilical cord blood lipidome and ASD and ADHD symptom risk at the age of two and four. Higher acylcarnitine levels in umbilical cord blood at birth were associated with prenatal and perinatal risk factors for ASD and ADHD symptoms in early life.
The findings underscore the importance of lipids at birth for the pathogenesis and prevention of ASD and ADHD.
Future research could include measurements of carnitine, short-, medium-, and very long-chain acylcarnitines, mitochondrial function, carnitine shuttle transport, and related metabolites to elucidate ASD and ADHD mechanisms in children.