Lian Jia, Men Zhaoyue, Xu Xiuyang, Li Yandi, Li Jinbo, Wang Weigang, Yao Tian, Li Yuping, Qu Yiqun, Feng Yongliang, Wang Suping
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, China.
Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China.
Front Nutr. 2025 Apr 23;12:1526053. doi: 10.3389/fnut.2025.1526053. eCollection 2025.
Folic acid has been associated with fetal development, especially in fetal immunity. Therefore, limited evidence regarding the effects of different folic acid supplementation of hepatitis B surface antigen (HBsAg) positive mothers in innate immunity in offspring. Herein, this study aimed to explore the association between folic acid supplementation and the innate immunity of neonates and the immunological efficacy of hepatitis B vaccine (HepB), which may provide insights that could inform pre-pregnancy health management in HBsAg-positive mothers.
It is an ambispective cohort study with 293 pairs of HBsAg-positive mothers-offspring in Taiyuan, Shanxi Province, China. Mothers were classified into three groups according to the time of starting folic acid supplementation, non-supplementation group, pre-pregnancy group and post-pregnancy supplementation group. Immunological indexes such as immune cells proportion and innate immune mediators in cord blood and anti-HBs in infants were measured. Differences in immunological indexes were analyzed by One-Way ANOVA test. Univariate and multivariate analyses were performed for factors associated with abnormal immunological indexes and potential confounders were adjusted.
The preconception folic acid group showed a significantly higher expression levels of STING ( = 0.005) and pNF-κB ( = 0.010) in cord blood along with higher anti-HBs titres ( = 0.006), when compared to both non-supplementation group and post-pregnancy supplementation group. Higher anti-HBs levels indicate a stronger immune response to HepB and may enhance protection against HBV infection during early life. Infants in the high pNF-κB expression group exhibited a significantly elevated seropositive rate of HepB compared to those in the low pNF-κB expression group ( = 0.037). There were no mediation effects and no moderation effects in this study, potentially due to the direct influence of folic acid supplementation on immune responses or the limited sample size.
In conclusion, our findings demonstrate that preconception folic acid supplementation may enhance HepB vaccine responsiveness in infants of HBsAg-positive mothers. Meanwhile, high pNF-κB expression in cord blood can increase seropositive rates in infants. This discovery has significant public health implications, as it may provide a simple and accessible intervention to improve vaccination outcomes and reduce HBV transmission in endemic regions.
叶酸与胎儿发育有关，尤其是在胎儿免疫方面。因此，关于乙肝表面抗原（HBsAg）阳性母亲补充不同剂量叶酸对后代先天免疫影响的证据有限。在此，本研究旨在探讨叶酸补充与新生儿先天免疫以及乙肝疫苗（HepB）免疫效果之间的关联，这可能为HBsAg阳性母亲的孕前健康管理提供参考依据。
这是一项在中国山西省太原市进行的双向队列研究，涉及293对HBsAg阳性的母婴。母亲们根据开始补充叶酸的时间分为三组，即未补充组、孕前补充组和孕后补充组。检测脐血中的免疫细胞比例、先天免疫介质等免疫指标以及婴儿体内的抗-HBs。通过单因素方差分析检验免疫指标的差异。对与免疫指标异常相关的因素进行单因素和多因素分析，并对潜在混杂因素进行调整。
与未补充组和孕后补充组相比，孕前叶酸补充组脐血中STING（P = 0.005）和pNF-κB（P = 0.010）的表达水平显著更高，同时抗-HBs滴度也更高（P = 0.006）。较高的抗-HBs水平表明对乙肝疫苗的免疫反应更强，可能增强对生命早期乙肝病毒感染的保护。与低pNF-κB表达组相比，高pNF-κB表达组婴儿的乙肝血清学阳性率显著升高（P = 0.037）。本研究中未发现中介效应和调节效应，这可能是由于叶酸补充对免疫反应的直接影响或样本量有限所致。
总之，我们的研究结果表明，孕前补充叶酸可能增强HBsAg阳性母亲婴儿对乙肝疫苗的反应性。同时，脐血中高pNF-κB表达可提高婴儿的血清学阳性率。这一发现具有重要的公共卫生意义，因为它可能提供一种简单易行的干预措施，以改善疫苗接种效果并减少流行地区的乙肝病毒传播。
