3rd Place: Kidney Disease in Pregnancy: Initial Blood Pressure as a Risk Factor for Preeclampsia

2018 Research Scholar Winner: 3rd Place Mentor: Sharon Maynard, M

BMI, Gestational Weight Gain and Angiogenic Biomarker Profiles for Preeclampsia Risk

Objective: In May 2009, after considering short and long-term maternal/child outcomes, the Institute of Medicine (IOM) revised recommendations for gestational weight gain (GWG); however preeclampsia was dismissed due to insufficient evidence. Our objective was to evaluate preeclampsia risk by angiogenic-biomarker profile by both BMI and GWGadherence. Given numerous studies showing adipose tissue\u27s ability to stimulate angiogenesis, we hypothesized that overweight/obese (OW-OB) women and over-gainers (OG) would have altered angiogenic profiles as compared to underweight/normal-weight (UN) women and under-/appropriate-gainers (U-AG), respectively. Methods: Between 5/04-1/06, serial serum specimens collected from 94 women at high preeclampsia risk between 22-36 weeks. Soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) measured by ELISA. BMI and GWG adherence categories determined by 1990 IOM recommendations. Within-women correlation and right-skewness handled by estimating linear mixed models for ln-transformed biomarkers and then exponentiating on ln scale (i.e.geometric means). T-test compared means in 3 windows. Results: Analytic sample included 82 subjects (342 specimens) without multiples or pregnancy-related hypertension diagnosis. Mean sFlt1 lower in all windows in OW-OB compared to U-N - significant only at 22-26wks [506.2 (95% CI 438.1-584.9) vs 745.5 (95% CI 595.9-932.6) p=0.04] and in OG compared to U-AG with significant comparisons (p=0.05) [22-26wks: 492.1 (95% CI 420.1-576.3) vs 691.3 (95% CI 574.0-832.6); 27-30 wks: 570.1 (95% CI 488.1-665.9) vs 788.8 (95% CI 656.8-947.4)]. Mean PIGF lower in all windows in OW-OB compared to U-N [22-26wks: 430.5 (95% CI 359.0-516.3) vs 588.6 (95% CI 444.3-779.7) p=0.06; 27-30wks: 475.8 (95% CI 398.7-567.8) vs 811.8 (95% CI 614.3-1072.9) p=0.005; 31-36wks: 428.5 (95% CI 358.0-513.0) vs 724.6 (95% CI 548.5-957.1) p=0.01] and in OG compared to U-AG with no significant comparisons. Mean ratio [(sFlt1+sEng):PIGF] trended higher in OW-OB compared to U-N women at 27-30 and 31-36 wks and in OG compared to UAG at 31-36wks; however no windows with significant comparisons. Conclusion: Findings suggest trends that OW-OB BMI and excessive GWG associated with angiogenic biomarker profiles consistent with higher preeclampsia risk. Exploratory study limited by small numbers. BMI and GWG as potentially modifiable factors merit furtherinvestigation for preeclampsia risk alteration. Presented at the Society of Gynecologic Investigation 2011 Annual Meeting, March 2011, Miami Beach, Florida

Mid-gestation Angiogenic Biomarker Levels are Increased in Women at High Risk for Preeclampsia

Background: Pre-pregnancy hypertension and diabetes mellitus, multiple gestations, prior preeclampsia, are significant risk factors for preeclampsia. Whether altered maternal levels of angiogenic factors contribute to increased preeclampsia risk in these conditions is unknown. Our objective was to compare maternal serum angiogenic biomarker levels in women with major risk factors for preeclampsia and healthy controls. Methods: Women presenting for prenatal care were enrolled if they had one of the following preeclampsia risk factors: pre-pregnancy hypertension and/or diabetes mellitus, nulliparity with pre-pregnancy BMI\u3e30, multiple gestations, or prior preeclampsia. Healthy control pregnancies without these risk factors were enrolled for comparison. Maternal serum samples were collected at 3 pre-specified gestational windows between 23 and 36 weeks gestation. sFlt1, sEng, and PlGF were measured by ELISA. The (sFlt1+sEng):PlGF ratio was calculated and compared for each risk group at each gestational window. Results: Gestational patterns of angiogenic biomarkers differed in high-risk groups vs. healthy control subjects. The angiogenic ratio (sFlt1+sEng):PlGF was higher for all high risk groups except obesity/nulliparity as compared with healthy control subjects after 28 weeks gestation. Biomarker ratio levels were highest in subjects with MG and prior PE, and differences from the health control group became more pronounced as gestation progressed. Women with hypertension/diabetes had more subtle differences as compared with healthy control subjects. Conclusion: Women with preeclampsia risk factors had higher angiogenic ratios compared with healthy control women. This study illuminates the interplay between risk factors and placental angiogenic biomarkers in the pathogenesis of preeclampsia

Maternal Feeding Practices Become More Controlling After and Not Before Excessive Rates of Weight Gain

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93708/1/oby.2009.54.pd

Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis

Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis