Downregulation of nicotinate and nicotinamide metabolism and neurodevelopment in DCDA-D twins
Nicotinate and nicotinamide are precursors of the coenzyme nicotinamide-adenine dinucleotide (NAD+) and nicotinamide-adenine dinucleotide phosphate (NADP+). Our study demonstrated that a lower hair concentration of nicotinamide was identified in DCDA-D-L compared to DCDA-C twin (Figure 2B ). In addition, the downregulation of nicotinate and nicotinamide metabolism was detected in both DCDA-D-L and DCDA-D-S twins compared to DCDA-C twins (Figure 3A ). Consistently, we also observed that the activity of nicotinate and nicotinamide metabolism was positively correlated with gross motor and problem solving in both smaller and larger DCDA-D twins (Figure 4C ). It has been reported myelinization and effective synaptic connections in the third trimester are key factors in the formation of coordinated motor development in children.44 Souza et al. reported that maternal vitamin B3 (nicotinamide) intake in pregnancy contributes to increased BW.45 A previous study showed that dietary nicotinamide prolonged pregnancies and prevented FGR in mice with preeclampsia.46 Moreover, recent literature identified maternal nicotinamide riboside enhanced offspring development and neurogenesis.47 Nicotinamide has been identified to be associated with neuron differentiation by reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth, and neurotransmitter expression.48,49 We speculate that nicotinamide has a protective effect on fetal neurodevelopment during gestation, especially aiding the differentiation and maturation of nerve cells involved in motor and neurocognitive development.