Effects Of Maternal Vitamin D Nutrition Status During Pregnancy On Infantile Eczema And Related Mechanisms

Objective:Vitamin D deficiency is currently prevalent in the world,and vitamin D deficiency in pregnant women has become a global public health problem.Vitamin D Receptor（VDR）has been found to be expressed in all tissues of the body,suggesting that VD has a very wide range of biological effects in the body.Eczema has become one of the most common skin conditions in infancy with the increasing incidence of eczema in infants.The etiology of infantile eczema is complex.Genetic and immune mechanisms and environmental factors influence the development of the disease synergistically.The potential link between VD and the development of allergic diseases has attracted increasing attention in recent years.Some studies have shown that VD deficiency during pregnancy may be related to the development of infantile eczema,but the relevant research is limited,the results are still controversial,and the mechanism is not explored.Therefore,we will investigate the nutritional status and influencing factors of VD in pregnant women,explore the influence of VD deficiency in pregnant women on the development of infantile eczema,and the role of Regulatory T cells（Treg）in this process.Methods:This study is a mother-child cohort study,and 219 mother-child pairs were recruited by convenience sampling method at a tertiary hospital in Shenyang,China between August 2019 and July 2020.A questionnaire was administered face-to-face to obtain basic information about the pregnant women with their informed consent.Fasting venous blood was collected from pregnant women in late pregnancy for measurement and analysis of maternal 25（OH）D₃ levels.Cord blood and placenta samples are collected at the time of delivery for testing the expression of relevant genes,cytokines and proteins and neonatal information is collected from the delivery records.The infants were followed up by pediatrician at 6 and 12 months postnatally,including postnatal feeding,length and weight and diagnosis of eczema onset.Following China’s"Screening Method for Vitamin D Deficiency in the Population（WS/T 677-2020）",pregnant women were split into three groups based on the presence of vitamin D deficiency（VDD）,vitamin D insufficiency（VDI）,and vitamin D sufficiency（VDS）.Results:（1）The mean serum 25（OH）D₃ concentration of 219 pregnant women in this study was（16.14±8.12）ng/ml.The reporting rates of VDD and VDI were 35.6%and28.3%,respectively.Only 36.1%of pregnant women had adequate VD levels,and the serum 25（OH）D₃ levels of pregnant women showed a seasonal distribution.（2）Factors influencing VD deficiency were pre-pregnancy BMI≥24（OR=2.868,95%CI=1.129-7.287）,excessive weight gain during pregnancy（OR=3.121,95%CI=1.029-9.466）,and frequent breakfast during pregnancy（OR=0.187,95%CI=0.043-0.821）.factors influencing VD deficiency were pre-pregnancy BMI≥24（OR=3.815,95%CI=1.494-9.743）,having a lift at home（OR=0.360,95%CI=0.158-0.819）,VD supplementation during pregnancy（OR=0.211,95%CI=0.081-0.550）,walking to work（OR=0.239,95%CI=0.087-0.658）.（3）Maternal VD deficiency and VD insufficiency resulted in an increased risk of eczema in infants（VD deficiency:OR=2.619,95%CI=1.093-6.275;VD insufficiency:OR=2.557,95%CI=1.098-5.954）.（4）Infants with higher levels of FOXP3 gene expression in cord blood had a significantly lower risk of eczema（OR=0.002,95%CI=4e-6-0.905）and maternal serum 25（OH）D3 levels were positively correlated with FOXP3 gene expression in cord blood（rs=0.438,P=0.012）,no association was found between cytokines in cord blood and maternal VD and infant eczema.（5）In the placental tissue test results,FOXP3 protein expression was significantly reduced in the eczema group compared to the non-eczema group（P<0.05）.The placenta of VD-deficient pregnant women showed reduced FOXP3 protein expression and significantly higher levels of PI3K,AKT,p-AKT,mTOR and p-mTOR protein expression compared to VD-sufficient pregnant women（P<0.05）.Conclusion:（1）Vitamin D deficiency and insufficiency are common among pregnant women in Shenyang during late pregnancy,and overweight and obesity during pregnancy are risk factors for VD insufficiency and insufficiency in women during pregnancy.（2）VD deficiency and insufficiency in pregnant women increases the risk of eczema in infants,which may be related to the down-regulation of FOXP3 gene expression in cord blood and the reduction of FOXP3 protein expression in the placenta.The effect of VD deficiency on FOXP3 protein expression is related to the PI3K/AKT/mTOR signaling pathway in the placenta.