Threshold Effects of Maternal Vitamin C in Late Pregnancy on Infant Social Competence: A Nonlinear Dose‐Response Analysis in a Birth Cohort

This study aims to investigate the nonlinear dose-effect relationship between late-pregnancy serum vitamin C concentration and early personal-social behavioral abilities in offspring among the northern Chinese population. It will also parse the threshold characteristics and clinical significance of this relationship. This prospective mother-infant cohort study enrolled 442 mother-offspring pairs. Late-pregnancy (28-40 weeks) serum concentrations of vitamins A, E, and C were measured using high-performance liquid chromatography (HPLC). Offspring social ability at 6 months of age was assessed using the Gesell Developmental Diagnosis Scale combined with the Infant-Junior High School Student Social Life Ability Scale (S-M). A generalized additive mixed model (GAMM) and a piecewise linear regression model were constructed to analyze the associations. These analyses were adjusted for confounding factors, including parental demographic characteristics, pregnancy complications, and nutritional supplementation patterns. Univariate analysis revealed significant positive correlations between late-pregnancy serum vitamin C, A, and E concentrations and offspring social ability (<i>β</i> = 0.082, 0.387, 0.039; all <i>p</i> < 0.05). Factors associated with improved social ability scores included at least 8 h of daily sleep during pregnancy (<i>β</i> = 0.504), an Apgar score of 9 (<i>β</i> = 7.825), and intermittent folic acid supplementation (<i>β</i> = 1.693) (all <i>p</i> < 0.05). Conversely, pregnancy complications (<i>β</i> = -1.130) and poor sleep quality (<i>β</i> = -1.582) significantly reduced scores (all <i>p</i> < 0.05). GAMM and piecewise linear regression analyses demonstrated a significant nonlinear association between late-pregnancy serum vitamin C concentration and early offspring social ability: the strongest effect occurred at low concentrations (≤ 4.9 μmol/L, <i>β</i> = 0.654/μmol, <i>p</i> = 0.018); a still-significant but gradually attenuated positive association was observed at moderate concentrations (4.9-49 μmol/L, <i>β</i> = 0.086/μmol, <i>p</i> = 0.001); and the effect diminished and became statistically insignificant at high concentrations (≥ 49 μmol/L, <i>β</i> = 0.061, <i>p</i> = 0.118). The present study discloses a nonlinear dose-response relationship between maternal vitamin C levels in late pregnancy and early offspring social ability. The association was most pronounced at concentrations ≤ 4.9 μmol/L, remained significant but attenuated within the 4.9-49 μmol/L range, and became nonsignificant beyond 49 μmol/L. The optimal window for neurodevelopmental benefit was identified as 23-49 μmol/L. These findings call into question the conventional approach to deficiency supplementation and support the implementation of personalized, biomarker-guided nutrition strategies during pregnancy to optimize offspring neurodevelopmental outcomes.