Preeclampsia at delivery is associated with lower serum vitamin D and higher antiangiogenic factors: a case control study

David B Seifer,Robert L Goldenberg,Halit Pinar,Donald J Dudley,Radek Bukowski,Corette Parker,Geralyn Lambert-Messerlian,George R Saade,Glenn E Palomaki,Uma M Reddy,Carol J Rowland Hogue,Robert M Silver,Barbara J Stoll

doi:10.1186/s12958-021-00885-z

Abstract

BackgroundPreeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Vitamin D plays an important role in pregnancy influencing implantation, angiogenesis and placental development. The objective of this study was to determine whether there is an association between serum vitamin D levels, and anti-angiogenic factors at the time of delivery and the occurrence of preeclampsia.MethodsThis nested case control study analyzed frozen serum samples at the time of delivery and related clinical data from women with singleton liveborn pregnancies who had participated in studies of the NICHD Stillbirth Collaborative Research Network. Women with a recorded finding of preeclampsia and who had received magnesium sulfate treatment prior to delivery were considered index cases (N = 56). Women without a finding of preeclampsia were controls (N = 341).ResultsWomen with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher sFlt-1 levels (11,600 pg/ml vs. 7050 pg/ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001). After controlling for gestational age at delivery and maternal BMI, vitamin D levels were 0.88 times lower (P = 0.051), while endoglin levels were 2.5 times higher and sFlt-1 levels were 2.1 times higher than in control pregnancies (P < 0.001).ConclusionsWomen with preeclampsia at time of delivery have higher maternal antiangiogenetic factors and may have lower maternal serum vitamin D levels. These findings may lead to a better understanding of the underlying etiology of preeclampsia as well as possible modifiable treatment options which could include assuring adequate levels of maternal serum vitamin D prior to pregnancy.

Highlights

It is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation, and compromised placentation with poor uteroplacental perfusion
Women with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher Soluble VEGF receptor-1 (sFlt-1) levels (11,600 pg/ml vs. 7050 pg/ ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001)
Since the results are expressed in multiples of the median (MoM) levels, the controls are centered at MoM of 1.00

Summary

Introduction

Preeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Preeclampsia (PEC) is a major cause of maternal and perinatal morbidity and mortality which is observed in 3–10% of pregnancies It is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation, and compromised placentation with poor uteroplacental perfusion. Fetal cord serum from PEC pregnancies was associated with reduced invasion of endothelial cells into the monolayer as compared to fetal cord serum from uncomplicated pregnancies. This reduction was reversed by addition of vitamin D [7]. It is hypothesized that low levels of vitamin D may contribute to the decreased trophoblastic angiogenesis seen in preeclampsia

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