title: The association between maternal antioxidant levels in midpregnancy and preeclampsia.
abstract: OBJECTIVE
  We sought to determine whether midpregnancy antioxidant levels are associated with preeclampsia, overall and by timing of onset.
  
  
  METHODS
  We carried out a case-control study, nested within a cohort of 5337 pregnant women in Montreal, Quebec, Canada. Blood samples obtained at 24-26 weeks were assayed for nonenzymatic antioxidant levels among cases of preeclampsia (n = 111) and unaffected controls (n = 441). We excluded women diagnosed with gestational hypertension only. We used logistic regression with the z-score of each antioxidant level as the main predictor variable for preeclampsia risk. We further stratified early-onset (<34 weeks) and late-onset preeclampsia and carried out multinomial logistic regression. Finally, we assessed associations between antioxidant biomarkers and timing of onset (in weeks) by Cox regression, with appropriate selection weights. We summed levels of correlated biomarkers (r(2) > 0.3) and log-transformed positively skewed distributions. We adjusted for body mass index, nulliparity, preexisting diabetes, hypertension, smoking, and proxies for ethnicity and socioeconomic status.
  
  
  RESULTS
  The odds ratios for α-tocopherol, α-tocopherol:cholesterol, lycopene, lutein, and carotenoids (sum of α-carotene, β-carotene, anhydrolutein, α-cryptoxanthin, and β-cryptoxanthin) suggested an inverse association between antioxidant levels and overall preeclampsia risk; however, only lutein was significantly associated with overall preeclampsia in adjusted models (odds ratio, 0.60; 95% confidence interval, 0.46-0.77) per SD. In multinomial logistic models, the relative risk ratio (RRR) estimates for the early-onset subgroup were farther from the null than those for the late-onset subgroup. The ratio of α-tocopherol to cholesterol and retinol were significantly associated with early- but not late-onset preeclampsia: RRRs (95% confidence intervals) for early-onset preeclampsia 0.67 (0.46-0.99) and 1.61 (1.12-2.33), respectively. Lutein was significantly associated with both early- and late-onset subtypes in adjusted models; RRRs 0.53 (0.35-0.80) and 0.62 (0.47-0.82), respectively. Survival analyses confirmed these trends.
  
  
  CONCLUSIONS
  Most antioxidants were more strongly associated with early-onset preeclampsia, suggesting that oxidative stress may play a greater role in the pathophysiology of early-onset preeclampsia. Alternatively, reverse causality may explain this pattern. Lutein was associated with both early- and late-onset preeclampsia and may be a promising nutrient to consider in preeclampsia prevention trials, if this finding is corroborated.
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada. Electronic address: jmcohen@hsph.harvard.edu.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kramer
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Department of Obstetrics and Gynecology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Basso
authors.affiliation: Department of Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Kahn
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000032:analysis*; D002338:Carotenoids / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D011225:Pre-Eclampsia / Q000097:blood* / Q000453:epidemiology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011792:Quebec / Q000453:epidemiology; D018570:Risk Assessment; D055815:Young Adult; D024502:alpha-Tocopherol / Q000097:blood
chemical_list: D000975:Antioxidants; D002338:Carotenoids; D024502:alpha-Tocopherol
keywords: antioxidants; carotenoids; preeclampsia; retinol; vitamin E