Why preeclampsia is 5X more likely if vitamin D insufficient – Jan 2015

[256-POS]: Vitamin D restores functional abilities of fetal endothelial progenitor cells from pregnancies complicated by preeclampsia.

Pregnancy Hypertens. 2015 Jan;5(1):129. doi: 10.1016/j.preghy.2014.10.262. Epub 2015 Feb 23.
Brodowski L1, Burlakov J1, Hubel CA2, Versen-Höynck Fv1.

OBJECTIVES:
Vitamin D insufficiency is associated with a 5-fold increased risk for development of preeclampsia. We hypothesize that vitamin D plays an important role in the health of endothelial progenitor cells that participate in maternal and placental vasculogenesis and vascular endothelial repair. We asked if vitamin D antagonizes the negative effects of preeclampsia, or a preeclampsia-like environment, on fetal endothelial progenitor cell function.

METHODS:
Umbilical cord blood was obtained from preeclamptic and uncomplicated pregnancies. The mononuclear cells were isolated and seeded onto culture plates for outgrowth of endothelial colony forming progenitor cells (ECFCs). Placental explants from uncomplicated term pregnancies were incubated for 48 h under 2%, 8% or 21% O2. Explant conditioned media (CM) was collected and pooled according to oxygen level. Migration, proliferation, and tubule formation of ECFCs was determined in the presence/absence of CM or maternal serum, and 1,25(OH)2 vitamin D3. We inhibited the VEGF signaling pathway with Su5416 and blocked the VDR with VDR antagonist pyridoxal-5-phosphate or antiVDR siRNA.

RESULTS:
The number of cord blood-derived ECFC colonies was decreased in PE compared with controls (P=0.04). Preeclampsia ECFCs showed reduced proliferation (P<0.001), tubule formation (P=0.02), and migration (P=0.049) vs.

CONTROLS:
Vitamin D3 significantly improved preeclampsia ECFC functions. VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3. Vitamin D3 reversed the adverse effects of preeclampsia serum or hypoxic CM on ECFCs tubule formation and migration. Silencing of VDR or VEGF pathway blockade significantly reduced ECFC functional abilities. Vitamin D significantly rescued ECFC migration after blocking the VDR, but not the VEGF, pathway.

CONCLUSIONS:
Physiological concentrations of vitamin D3 promote the migration and capillary-like tubule formation of ECFCs in culture, minimizing negative effects of preeclampsia or preeclampsia-related factors. Such positive effects of vitamin D on progenitor cell function might improve placental and endothelial function and pregnancy outcome.

PMID: 25787608

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See also VitaminDWiki

• Risk of preeclampsia might be cut in half if take an amount of Vitamin D – meta-analysis Sept 2017
• Preeclampsia rate cut in half by high level of vitamin D – meta-analysis March 2014
• 7X increase in early severe preeclampsia associated with low vitamin D – Aug 2012
• Dark-skined mothers: preeclampsia 12X more likely if gestational hypertension – May 2014
• 5,000 IU Vitamin D was not enough to reduce preeclampsia but did help future infant – RCT April 2014
• Effects of low vitamin D on pregnancy and neonate – review Jan 2015
• Pregnancy category listing has 918 items along with related searches
• Overview Pregnancy and vitamin D has the following summary

IU	Cumulative Benefit	Blood level	Cofactors	Calcium	$*/month
200	Better bones for mom with 600 mg of Calcium	6 ng/ml increase	Not needed	No effect	$0.10
400	Less Rickets (but not zero with 400 IU) 3X less adolescent Schizophrenia Fewer child seizures	20-30 ng/ml	Not needed	No effect	$0.20
2000	2X More likely to get pregnant naturally/IVF 2X Fewer dental problems with pregnancy 8X less diabetes 4X fewer C-sections (>37 ng) 4X less preeclampsia (40 ng vs 10 ng) 5X less child asthma 2X fewer language problems age 5	42 ng/ml	Desirable	< 750 mg	$1
4000	2X fewer pregnancy complications 2X fewer pre-term births	49 ng/ml	Should have cofactors	< 750 mg	$3
6000	Probable: larger benefits for above items Just enough D for breastfed infant More maternal and infant weight		Should have cofactors	< 750 mg	$4