Objective To systematically characterize the serum concentrations of vitamin K isoforms at various stages of pregnancy, investigate their gestational variation and associations with adverse pregnancy events. Methods This retrospective study included 178 women with singleton pregnancies, comprising 38 in early pregnancy, 55 in mid-pregnancy, and 85 in late pregnancy. Demographic characteristics and clinical outcome data were retrieved from electronic medical records, and fasting serum concentrations of vitamin K1 (VK1) and vitamin K2(VK2) isoforms (menaquinone-4 [MK-4] and menaquinone-7 [MK-7]) were measured using high-performance liquid chromatography. Linear regression and restricted cubic spline models were used to explore both linear and nonlinear relationships between vitamin K concentrations, gestational age, and adverse pregnancy events. Results Serum concentrations of VK1, MK-4, MK-7, VK2, and total vitamin K (TVK) positively correlated with gestational age (P < 0.01), while MK-4 concentrations were inversely associated with maternal age (P < 0.05). Compared to participants without gestational diabetes mellitus (GDM), those with GDM had significantly higher VK1, MK-7, and TVK concentrations. In contrast, MK-4 concentrations were lower in cases of gestational hypertension and low birth weight. Regression analysis revealed a significant U-shaped association between MK-7, VK2, and TVK and the risk of GDM (non-linear P < 0.01). Additionally, higher VK1 concentrations were associated with a reduced risk of composite adverse outcomes (P < 0.05), whereas elevated MK-7 concentrations were positively correlated with increased risk (P < 0.01). Conclusion Vitamin K status during pregnancy shows gestational age–related variation. Lower VK1 and MK-4 concentrations were associated with increased risks of adverse pregnancy events, while MK-7 demonstrated a non-linear association with GDM, suggesting that different vitamin K isoforms may play distinct roles during gestation. These findings provide new preliminary insight into the potential metabolic and obstetric relevance of vitamin K during pregnancy; however, they require confirmation in larger, well-designed prospective studies before translation into clinical practice.

Associations between maternal circulating vitamin K isoforms and adverse pregnancy events

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2026年4月18日

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Yunlong Li,
Rui Wang,
Yuping Zhang,
Rui Li,
Yuan Li,
Xiaoqin Zhong,
Yuan Zhang,
Yanping Liu

摘要

Objective

To systematically characterize the serum concentrations of vitamin K isoforms at various stages of pregnancy, investigate their gestational variation and associations with adverse pregnancy events.

Methods

This retrospective study included 178 women with singleton pregnancies, comprising 38 in early pregnancy, 55 in mid-pregnancy, and 85 in late pregnancy. Demographic characteristics and clinical outcome data were retrieved from electronic medical records, and fasting serum concentrations of vitamin K₁ (VK₁) and vitamin K₂(VK₂) isoforms (menaquinone-4 [MK-4] and menaquinone-7 [MK-7]) were measured using high-performance liquid chromatography. Linear regression and restricted cubic spline models were used to explore both linear and nonlinear relationships between vitamin K concentrations, gestational age, and adverse pregnancy events.

Results

Serum concentrations of VK₁, MK-4, MK-7, VK₂, and total vitamin K (TVK) positively correlated with gestational age (P < 0.01), while MK-4 concentrations were inversely associated with maternal age (P < 0.05). Compared to participants without gestational diabetes mellitus (GDM), those with GDM had significantly higher VK₁, MK-7, and TVK concentrations. In contrast, MK-4 concentrations were lower in cases of gestational hypertension and low birth weight. Regression analysis revealed a significant U-shaped association between MK-7, VK₂, and TVK and the risk of GDM (non-linear P < 0.01). Additionally, higher VK₁ concentrations were associated with a reduced risk of composite adverse outcomes (P < 0.05), whereas elevated MK-7 concentrations were positively correlated with increased risk (P < 0.01).

Conclusion

Vitamin K status during pregnancy shows gestational age–related variation. Lower VK₁ and MK-4 concentrations were associated with increased risks of adverse pregnancy events, while MK-7 demonstrated a non-linear association with GDM, suggesting that different vitamin K isoforms may play distinct roles during gestation. These findings provide new preliminary insight into the potential metabolic and obstetric relevance of vitamin K during pregnancy; however, they require confirmation in larger, well-designed prospective studies before translation into clinical practice.