High ratios of C20: 4n-6/C20:5n-3 and thromboxane B₂/6-keto-prostaglandin F_1α in placenta are potential Risk contributors for neural Tube Defects: A case-Control study in Shanxi Province, China

Background: Neural tube defects (NTDs) are severe congenital malformations. Folate supplementation can reduce the risk, but cannot prevent all NTDs, suggesting other reasons for folate-resistant NTDs. The present study assesses placental fatty acid composition, eicosanoids, and cytokines as risk factors for NTDs in a Chinese population with highly incident NTDs. Methods: Seventy-seven aborted fetuses with NTDs during the third trimester were cases and 142 healthy newborns were controls. Placental fatty acid composition, eicosanoids, and cytokines were determined by standard methods. Results: The placental C20:4n-6/C20:5n-3 and thromboxane B₂ (TXB₂)/6-keto-prostaglandin F_1α (6-keto-PGF_1α) ratios were significantly higher for cases than controls (p < 0.001 and 0.05, respectively). For the top versus the lowest tertiles of placental C20:4n-6/C20:5n-3 and TXB₂/6-keto-PGF_1α, odds ratios for NTD occurrence were 3.79 (95% confidence interval, 1.60-8.96) (p for trend < 0.01) and 5.52 (95% confidence interval, 2.07-14.74) (p for trend < 0.001), respectively, adjusted for fetal sex as well as maternal age, occupation, parity, smoking, passive smoking, periconceptional folate supplementation, conception season, and tea drinking. The C20:4n-6/C20:5n-3 and TXB₂/6-keto-PGF_1α ratios were positively correlated (r = 0.14; p < 0.05). The proportions of C18:2n-6, C18:3n-6, C20:3n-6, C18:3n-3, C20:3n-3, C20:5n-3, and C22:5n-3 were significantly lower in cases than controls, and all negatively associated with NTD occurrence (tertile-specific odds ratios); after adjustment for the potential confounders, these associations remained significant (p for trend < 0.05) except for C20:3n-3. Conclusion: High placental ratios of C20:4n-6/C20:5n-3 and TXB₂/6-keto-PGF_1α are risk factors for neural tube defects.