Associations Of Maternal Serum 25-hydroxyvitamin D Concentrations In Second And Third Trimester With Risk Of Gestational Diabetes, Macrosomia And Other Pregnancy Outcomes

Maternal vitamin D deficiency is common in pregnancy due to the combined effects of additional growth needs of the fetus,inadequate intake and limited sunlight exposure,which has become a significant public health problem globally.The most important role of vitamin D is to maintain calcium and phosphate levels for bone formation by promoting the absorption of calcium in intestines and enhancing calcium mobilization from the skeleton,which was critical for fetal skeletal growth and development and maternal calcium homeostasis.25-Hydroxyvitamin D [25(OH)D],the storage form of vitamin D,is an indicator of vitamin D levels.It has been widely accepted that vitamin D also has multiple non-calcitropic functions.It has been shown to stimulate thyroid-stimulating hormone secretion and insulin production,promote cell differentiation,and regulate immune function during pregnancy that enables successful implantation and promotes antibacterial and anti-inflammatory actions.Therefore,any vitamin D effects on pregnancy may have a wide range of consequences.It is reported that the maternal serum vitamin D levels doubled starting at the second trimester and reached a maximum in the third trimester.The pregnant women may have a high cellular exposure to vitamin D starting at the second trimester,also suggesting a role for vitamin D in pregnancy outcomes.Therefore,we performed a large nested case-control study to describe serum.25(OH)D concentrations in second-and third-trimester and evaluate its associations with risks of gestational diabetes,macrosomia and a series of other pregnancy outcomes(maternal health,fetal or neonatal health and delivery mode).Part ⅠAssociations of maternal serum 25-hydroxyvitamin D concentrations in second and third trimester with risk of gestational diabetes and other pregnancy outcomes Objectives: To evaluate the maternal serum 25(OH)D concentrations and its association with gestational diabetes and other pregnancy outcomes.Methods: In our nested case-control study,4718 pregnancy women were included,who were attending second-and third-trimester screening in Nanjing,China.Serum25(OH)D were tested by enzyme-linked immunoassay,and the pregnancy and birth outcomes were obtained via electronic medical record collection and information extraction.The associations of 25(OH)D concentrations with gestational diabetes and other pregnancy outcomes were assessed by logistic regression analysis.And receiver-operator characteristic curve analysis was also conducted.Results: For the total population,the median(IQR)concentrations of 25(OH)D was43.7(35.5-57.9)nmol/L,and 63.1% of women had concentrations < 50.0 nmol/L.The25(OH)D concentrations was significant lower in gestational diabetes patients than controls.Moreover,after adjustment for confounders,women with low 25(OH)D concentrations had significantly increased risks of gestational diabetes and some adverse pregnancy outcomes(anemia,macrosomia,abnormal amniotic fluid,and miscarriage or stillbirth).We also observed a threshold for 25(OH)D of 50.0 nmol/L for gestational diabetes and a nice predictive accuracy of the 25(OH)D concentrations included panel,with an area under the curve(AUC)of 0.625 for gestational diabetes.Conclusions: Low 25(OH)D concentrations(< 50.0 nmol/L)in pregnancy was significantly associated with gestational diabetes risk,and it may serve as biomarkers for the surveillance of high-risk pregnant women.Part ⅡAssociation of maternal serum 25-hydroxyvitamin D concentrations in second and third trimester with risk of macrosomia Objectives: To evaluate the association of maternal serum 25-hydroxyvitamin D[25(OH)D] concentrations with risk of macrosomia.Methods: In this nested case-control study(545 women subsequently delivered macrosomia and 1090 controls),we measured serum 25(OH)D concentrations by enzyme immunoassay.Logistic regression analysis was conducted to assess the association of 25(OH)D concentrations with macrosomia risk.And receiver-operator characteristic curve analysis and graphical nomogram were also used.Results: The 25(OH)D concentrations was significantly lower in women delivered macrosomia than in controls.For women with concentrations < 50.0 nmol/L,they had a 33% increase in macrosomia risk(95% CI = 1.01-1.74),when compared with women with 25(OH)D from 50.0 to 74.9 nmol/L.T he risk of macrosomia was significantly increased with the decreasing concentrations of the serum 25(OH)D in a dose-dependent manner(P for trend = 0.001).Interestingly,the risk effect on delivering macrosomia was more prominent among pregnant woman with a male fetus.Further interactive analysis detected a significantly multiplicative interaction between serum 25(OH)D concentrations and fetus gender on macrosomia risk(P =0.031).We also observed a threshold for 25(OH)D of 50.0 nmol/L for delivering macrosomia and a nice predictive accuracy of the25(OH)D concentrations included panel,with an area under the curve of 0.712 for delivering macrosomia.Conclusions: Maternal serum 25(OH)D< 50.0nmol/L may be an independent risk factor for delivering macrosomia,and it should be monitored for the high-risk pregnant women.