3.5 | Possible effects of hair metabolic changes associated with DCDA-D twins on physical and neurocognitive development later in life
To further detect the altered metabolic activities in early life associated with poor later physical and neurocognitive development, we performed a correlation analysis between the predicted metabolic activity in the hair of DCDA-D twins and evaluation indices of physical and neurocognitive development in infants 2–3 years postpartum. There was no significant correlation between hair metabolic changes and physical development in infant 2-3 years (Figure 4C ). Fortunately, we found significantly positive correlations between the problem-solving domain and five metabolic pathways including cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, glutathione metabolism, nicotinate and nicotinamide metabolism, and pantothenate and CoA biosynthesis in DCDA-D twins (p<0.05) (Figure 4C ). Similarly, upregulated aminoacyl-tRNA biosynthesis also was associated with better fine motor and communication outcomes. Unexpectedly, no significant correlation was observed between the personal-social domain and altered metabolic pathways in our DCDA-D twins (Figure 4C ). In DCDA-D-S group, the correlation of problem solving and aminoacyl-tRNA biosynthesis, nicotinate and nicotinamide metabolism, and pantothenate and CoA biosynthesis was r > 0.6 (p < 0.05) (Figure 4D ).
4 | DISCUSSION
4.1 | Main findings
We identified neonatal hair metabolic variations associated with growth discordance in DCDA twins and related these to longer-term neurobehavioural outcomes. Significantly downregulated levels of cysteine, threonine, and leucine were identified in DCDA-D (both larger and smaller) co-twins relative to DCDA-C twins. In addition, a higher level of cis-aconitic acid was observed in the DCDA-D smaller twins relative to their larger co-twin. Three downregulated metabolic pathways (cysteine and methionine, aminoacyl-tRNA, nicotinate and nicotinamide metabolism) were correlated with neurocognitive outcomes at 2-3 years of age (Supplemental figure S1) .