First‐Trimester Serum n‐3/n‐6 Fatty Acids Predict Large‐for‐Gestational‐Age Risk: A Nested Case‐Control Study

Polyunsaturated fatty acids (PUFAs) are critical for fetal development during pregnancy. This study evaluates the association between maternal serum n‐3 and n‐6 PUFAs in early pregnancy and the risk of large‐for‐gestational‐age (LGA) infants. A nested case‐control study was conducted with 45 LGA‐appropriate for gestational age (AGA) matched pairs from a cohort of 2839 pregnant women. Maternal serum samples collected during early pregnancy were analyzed for lipid profiles using gas chromatography–mass spectrometry (GC–MS). Associations between fatty acid levels and LGA risk were assessed using Spearman correlation, chi‐square tests, and logistic regression. The results indicated that higher arachidonic acid (ARA, p = 0.024) and docosahexaenoic acid (DHA, p = 0.039) levels were positively correlated with LGA risk. Linoleic acid (LA, p = 0.009), alpha‐linolenic acid (ALA, p = 0.040), and the n‐6/n‐3 PUFA ratio ( p = 0.034) were negatively correlated with LGA. Adjusted odds ratios indicated that higher quartiles of ARA (OR = 2.293, p = 0.078) and DHA (OR = 2.593, p = 0.038) increased LGA risk, while higher n‐6 PUFA levels reduced the risk (OR = 0.340, p = 0.019). In conclusion, early pregnancy serum n‐3 and n‐6 PUFA levels are associated with LGA risk. Elevated ARA and DHA levels may increase LGA risk, while higher n‐6 PUFA levels may be protective. These findings suggest that PUFA levels could serve as early indicators for targeted nutritional interventions.