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" The Effect of Prenatal Vitamin D Supplementation on Maternal Blood Pressure and Placental Angiogenesis in Bangladesh "
Subramanian, Anita
Gernand, Alison D.
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1053888
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| Doc. No
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TL53005
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| Main Entry
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Subramanian, Anita
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| Title & Author
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The Effect of Prenatal Vitamin D Supplementation on Maternal Blood Pressure and Placental Angiogenesis in Bangladesh\ Subramanian, AnitaGernand, Alison D.
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| College
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The Pennsylvania State University
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| Date
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2019
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| Degree
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Ph.D.
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| student score
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2019
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| Note
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173 p.
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| Abstract
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Vitamin D deficiency has become a problem of public health concern with high prevalence rates among pregnant women especially in South Asia. Maternal vitamin D deficiency during pregnancy has been associated with adverse maternal and birth outcomes such as increased risk of preeclampsia and fetal growth restriction. Although vitamin D has been associated with hypertensive disorders of pregnancy, the effect of vitamin D on blood pressure trajectory across pregnancy is unclear. The placenta functions in the metabolism of vitamin D during pregnancy and is related to growth and development of the fetus, but limited understanding exists on the role of vitamin D in placental angiogenesis. Further, there is some evidence to show that angiogenic factors released from the placenta into the maternal circulation may impact maternal vasculature. However, few studies have examined both placental angiogenic factors and maternal blood pressure in humans. The overall goal of this dissertation was to examine the effect of prenatal vitamin D supplementation on maternal blood pressure and placental angiogenesis within the context of a large randomized controlled trial in Bangladesh. The studies in this dissertation are nested within the Maternal Vitamin D for Infant Growth (MDIG) trial, a randomized, placebo-controlled, doseranging trial of vitamin D supplementation in Dhaka, Bangladesh (n=1298). Participants were individually randomized to one of four vitamin D doses during the prenatal period: placebo, 4200 IU/week, 16800 IU/wk or 28000 IU/wk. The MDIG trial enrolled healthy pregnant women at 17-24 weeks that had a singleton gestation and did not have preexisting hypertension or other health conditions. The first aim was to examine the dose-dependent effect of prenatal vitamin D supplementation on maternal blood pressure from mid to late pregnancy. Blood pressure was measured at enrollment, 24 weeks, and 30 weeks, and weekly from 36 weeks until delivery. This sub-study examined 1257 women with at least 2 blood pressure measurements prior to the onset of labor. The prevalence of vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <30 nmol/L) at enrollment was 64%. Vitamin D treatment did not have an effect on SBP or DBP at 24 or 30 weeks gestation; blood pressure was higher at 36 weeks gestation for the highest dose of vitamin D compared to placebo (mean difference (95% CI): SBP (mm Hg) = 2.32 (0.91, 3.72); DBP (mm Hg) = 1.86 (0.71, 3.00)), adjusting for baseline blood pressure and gestational age at enrollment. The differences in changes of SBP and DBP between vitamin D groups and placebo across intervals were all small (p values >0.10), but the difference for 28000 IU/wk vs. placebo was the highest from 30 to 36 weeks (SBP 0.2 (-0.1, 0.5) and DBP 0.19 (-0.0, 0.4) mm Hg) and lowest from 36 weeks to delivery (SBP -0.3 (-0.9, 0.3) mm Hg; DBP 0.1 (-0.6, 0.4). The second aim was to examine the dose-dependent effect of prenatal vitamin D supplementation on placental angiogenesis. We examined expression of two key angiogenic factors in the placenta: vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), as well as placental terminal villi quantity and surface area. A subset of placentas with a full thickness core collected at birth (n=80, 20 per treatment group) were stained for VEGF and PlGF using immunofluorescence. Images were quantified to measure percent area and intensity for VEGF and PlGF, and number of terminal villi and surface area were also recorded. The overall mean (SD) percent area of expression was 17.0 (4.0) for VEGF and 15.0 (1.9) for PlGF; and mean (SD) intensity was 6520 (1549) for VEGF and 5716 (734) for PlGF. There were no differences in VEGF, PlGF, number of terminal villi, or surface area between any vitamin D treatment groups compared to placebo. The third aim was to examine the association between angiogenic factors in maternal circulation and blood pressure from mid to late pregnancy. This sub-study included pregnant women with plasma angiogenic factor concentrations measured at baseline (17-24 weeks) and 30 weeks gestation, and at least two blood pressure measurements prior to the onset of labor (n=689). Maternal plasma samples were analyzed for pro-angiogenic factors: VEGF-A, VEGFC, VEGF-D, PlGF and angiopoietin (Ang)-2; anti-angiogenic factors: soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng); and sFlt-1/PlGF ratio. In cross-sectional analysis, concentrations of Ang-2, PlGF and sFlt-1 at mid-pregnancy and 30 weeks gestation were negatively associated with blood pressure. In longitudinal analysis, positive associations were observed between PlGF and blood pressure from baseline to 24 weeks; sEng at 30 weeks and blood pressure from 30 to 36 weeks, and 36 weeks until term. PlGF at 30 weeks was negatively associated with blood pressure from 30-36 weeks; and VEGF-D at 30 weeks had a negative association with blood pressure from 36 weeks until term. No associations were found between VEGF-A, VEGF-C and the sFlt-1/PlGF ratio and blood pressure. In a setting with a high prevalence of vitamin D deficiency, vitamin D supplementation did not have a statistically significant effect on blood pressure changes from mid to late pregnancy but the highest dose of vitamin D resulted in higher blood pressure near term. Vitamin D supplementation did not have an impact on expression of placental angiogenic factors or on placental terminal villi in the delivered placenta. Higher concentrations for most angiogenic factors were related to lower blood pressure from mid to late pregnancy but there was not a clear pattern of connection. These findings from studies nested within a randomized controlled trial, contribute to the understanding of the effect of prenatal vitamin D on maternal physiology and placental development, yet do not support a beneficial role of vitamin D supplementation starting mid-pregnancy for lowering blood pressure or impacting placental development.
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| Descriptor
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Nutrition
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Obstetrics
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South Asian studies
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Womens studies
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Gernand, Alison D.
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The Pennsylvania State University
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