Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Antioxidants/*therapeutic use ; Ascorbic Acid/*therapeutic use ; Haptoglobins/*genetics ; Pre-Eclampsia/*prevention & control ; Vitamin E/*therapeutic use; Adolescent ; Adult ; Antioxidants/pharmacokinetics ; Ascorbic Acid/pharmacokinetics ; Case-Control Studies ; Dietary Supplements ; Female ; Genetic Association Studies ; Humans ; Odds Ratio ; Phenotype ; Pre-Eclampsia/genetics ; Pregnancy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Young Adult

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.

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HD36801 United States HD NICHD NIH HHS; UG1 HD027869 United States HD NICHD NIH HHS; U10 HD034136 United States HD NICHD NIH HHS; U10 HD040485 United States HD NICHD NIH HHS; HD40485 United States HD NICHD NIH HHS; HD40560 United States HD NICHD NIH HHS; UL1 TR000439 United States TR NCATS NIH HHS; U10 HD040560 United States HD NICHD NIH HHS; U01 HD036801 United States HD NICHD NIH HHS; U10 HD053118 United States HD NICHD NIH HHS; UL1 RR024989 United States RR NCRR NIH HHS; UL1 TR000005 United States TR NCATS NIH HHS; U10 HD040500 United States HD NICHD NIH HHS; P01 HD030367 United States HD NICHD NIH HHS; U10 HD040544 United States HD NICHD NIH HHS; UL1 RR024153 United States RR NCRR NIH HHS; UG1 HD034116 United States HD NICHD NIH HHS; HD27869 United States HD NICHD NIH HHS; HD34136 United States HD NICHD NIH HHS; UG1 HD040560 United States HD NICHD NIH HHS; HD53118 United States HD NICHD NIH HHS; K12 HD065987 United States HD NICHD NIH HHS; UG1 HD053097 United States HD NICHD NIH HHS; HD27860 United States HD NICHD NIH HHS; UG1 HD027915 United States HD NICHD NIH HHS; Canada CAPMC CIHR; HD40512 United States HD NICHD NIH HHS; UG1 HD040544 United States HD NICHD NIH HHS; UG1 HD034208 United States HD NICHD NIH HHS; M01 RR00080 United States RR NCRR NIH HHS; UG1 HD040512 United States HD NICHD NIH HHS; HD40545 United States HD NICHD NIH HHS; U10 HD034116 United States HD NICHD NIH HHS; HD21410 United States HD NICHD NIH HHS; U10 HD027869 United States HD NICHD NIH HHS; U10 HD027917 United States HD NICHD NIH HHS; HD34116 United States HD NICHD NIH HHS; U10 HD027915 United States HD NICHD NIH HHS; UG1 HD040545 United States HD NICHD NIH HHS; UG1 HD040485 United States HD NICHD NIH HHS; U10 HD027860 United States HD NICHD NIH HHS; HD40500 United States HD NICHD NIH HHS; U10 HD034208 United States HD NICHD NIH HHS; U10 HD053097 United States HD NICHD NIH HHS; HD34208 United States HD NICHD NIH HHS; HD27915 United States HD NICHD NIH HHS; UG1 HD040500 United States HD NICHD NIH HHS; R24 HD050924 United States HD NICHD NIH HHS; U10 HD040512 United States HD NICHD NIH HHS; HD27917 United States HD NICHD NIH HHS; U10 HD021410 United States HD NICHD NIH HHS; M01 RR000080 United States RR NCRR NIH HHS; U10 HD036801 United States HD NICHD NIH HHS; HD53097 United States HD NICHD NIH HHS; U10 HD040545 United States HD NICHD NIH HHS; K12HD065987 United States HD NICHD NIH HHS; HD40544 United States HD NICHD NIH HHS

0 (Antioxidants)
0 (Haptoglobins)
1406-18-4 (Vitamin E)
PQ6CK8PD0R (Ascorbic Acid)

Date Created: 20130411 Date Completed: 20131022 Latest Revision: 20211021

20221216

PMC3616124

10.1371/journal.pone.0060479

23573260