(P07-037-25) The Dose-Response Effect of Calcium Supplementation on Biomarkers Associated With the Pathogenesis of Preeclampsia in Tanzania

Objectives: To evaluate the dose-response effect of daily prenatal calcium supplementation on biomarkers involved in the pathogenesis of preeclampsia.

Methods: We conducted a nested case-cohort study embedded within an individually randomized, non-inferiority trial of daily prenatal calcium supplementation (1500 mg ‘high-dose’ vs. 500 mg ‘low-dose’) in 11,000 nulliparous pregnant women enrolled at < 20 weeks of gestation in Dar es Salaam, Tanzania. An observational cohort of pregnant women not receiving any calcium supplements was also enrolled. Blood samples were collected at enrollment and 32-week gestation for a sub-cohort of participants. The analysis included all preeclampsia cases (n=141) and a random sample of controls (n=1747). We quantified plasma angiogenic (soluble fms-like tyrosine kinase receptors [sFlt1], placental growth factor [PlGF], soluble endoglin [sEng]), inflammatory (C-reactive protein [CRP], soluble tumor necrosis factor receptor 2 [sTNFR2], IFN-gamma, interleukin 6), endocrine (parathyroid hormone [PTH]), and metabolic (leptin, and renin) biomarkers using Luminex 8-plex multiplex assays, enzyme-linked immunosorbent assays (ELISA), or chemiluminescence. Linear regression estimated mean differences in biomarkers concentrations by calcium dose (1500 mg/day vs. 500 mg/day or no calcium) in the third trimester.

Results: Compared to high-dose 1500 mg/day calcium supplementation, women not receiving calcium supplements had higher concentrations of angiogenic (adjusted mean difference [adj. MD] 95% confidence intervals [CI]: sFlt-1, 0.29 ng/ml [0.14, 0.44]), inflammatory (adj. MD: TNFR2, 0.21 ng/ml [0.06, 0.36]), and endocrine biomarkers (adj. MD: 0.28 ng/ml [0.13, 0.42]) in the third trimester. There were no differences in biomarker levels between low-dose 500 mg/day and high-dose 1500 mg/day groups.

Conclusions: In the context of low calcium diets, concentrations of biomarkers associated with preeclampsia did not differ among women supplemented with 500 mg/day compared to 1500 mg/day of prenatal calcium, supporting the non-inferiority of low dose calcium. Pregnant women in the observational cohort who did not receive calcium supplements had higher angiogenic and inflammatory and endocrine biomarkers.

Funding Sources: Bill & Melinda Gates Foundation