Defining vitamin D status using multi-metabolite mathematical modelling: A pregnancy perspective

Area of Science:

• Biochemistry
• Mathematical Biology
• Reproductive Endocrinology

Background:

• Vitamin D deficiency is linked to adverse pregnancy outcomes, including pre-eclampsia (PET).
• Current definitions rely solely on 25-hydroxyvitamin D3 (25(OH)D3) serum levels.
• Pregnancy involves significant alterations in vitamin D metabolism.

Purpose of the Study:

• To investigate comprehensive changes in vitamin D metabolism during normal and PET pregnancies.
• To develop and apply a mathematical model of the vitamin D metabolic pathway.
• To identify improved biomarkers for pre-eclampsia risk assessment.

Main Methods:

• Developed a fully parametrised mathematical model of the vitamin D metabolic pathway using ordinary differential equations.
• Utilized serum vitamin D metabolite data from non-pregnant controls, normal pregnant women (1st and 3rd trimesters), and PET patients.
• Applied the model to a separate 2nd-trimester pregnancy cohort with prospective PET development.

Main Results:

• Simple statistical analysis showed no significant difference in 25(OH)D3 or 24,25(OH)2D3 between late-term normal and PET pregnancies.
• Model-informed analysis revealed that ratios of vitamin D metabolites in late pregnancy are better indicators of PET.
• No significant predictive difference was found between groups at 15 weeks gestation using the model.

Conclusions:

• Mathematical modeling provides a novel approach to understanding vitamin D's impact on health, particularly in pregnancy.
• Altered ratios of vitamin D metabolites, rather than single metabolite levels, may serve as key indicators in pre-eclampsia.
• This approach highlights the complexity of vitamin D metabolism during gestation and its dysregulation in pre-eclampsia.