title: Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.
abstract: 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.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Weissgerber
authors.forename: Robin E
authors.initials: RE
authors.lastname: Gandley
authors.forename: Paula L
authors.initials: PL
authors.lastname: McGee
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong
authors.forename: Leslie
authors.initials: L
authors.lastname: Myatt
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Leveno
authors.forename: John M
authors.initials: JM
authors.lastname: Thorp
authors.forename: Brian M
authors.initials: BM
authors.lastname: Mercer
authors.forename: Alan M
authors.initials: AM
authors.lastname: Peaceman
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ramin
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Carpenter
authors.forename: Philip
authors.initials: P
authors.lastname: Samuels
authors.forename: Anthony
authors.initials: A
authors.lastname: Sciscione
authors.forename: Margaret
authors.initials: M
authors.lastname: Harper
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Tolosa
authors.forename: George
authors.initials: G
authors.lastname: Saade
authors.forename: Yoram
authors.initials: Y
authors.lastname: Sorokin
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016022:Case-Control Studies; D019587:Dietary Supplements; D005260:Female; D056726:Genetic Association Studies; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D011225:Pre-Eclampsia / Q000235:genetics / Q000517:prevention & control*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D006242:Haptoglobins; D014810:Vitamin E; D001205:Ascorbic Acid