title: Maternal Antioxidant Levels in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Oxidative stress in preeclampsia and small for gestational age (SGA) birth suggests antioxidant supplementation could prevent these conditions. However, it remains unclear whether maternal antioxidant levels are systematically lower in these pregnancies.
  
  
  OBJECTIVE
  To conduct a systematic review of the association between maternal antioxidant levels during pregnancy and preeclampsia or SGA.
  
  
  METHODS
  We searched PubMed, Embase, and several other databases from 1970-2013 for observational studies that measured maternal blood levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) during pregnancy or within 72 hours of delivery. The entire review process was done in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale and additional questions. We pooled the standardized mean difference (SMD) across studies, stratified by outcome and pregnancy trimester, and investigated heterogeneity using meta-regression.
  
  
  RESULTS
  We reviewed 1,882 unique citations and 64 studies were included. Most studies were small with important risk of bias. Among studies that addressed preeclampsia (n = 58) and SGA (n = 9), 16% and 66%, respectively, measured levels prior to diagnosis. The SMDs for vitamins A, C, and E were significantly negative for overall preeclampsia, but not for mild or severe preeclampsia subtypes. Significant heterogeneity was observed in all meta-analyses and most could not be explained. Evidence for lower carotenoid antioxidants in preeclampsia and SGA was limited and inconclusive. Publication bias appears likely.
  
  
  CONCLUSIONS
  Small, low-quality studies limit conclusions that can be drawn from the available literature. Observational studies inconsistently show that vitamins C and E or other antioxidants are lower in women who develop preeclampsia or SGA. Reverse causality remains a possible explanation for associations observed. New clinical trials are not warranted in light of this evidence; however, additional rigorous observational studies measuring antioxidant levels before clinical detection of preeclampsia and SGA may clarify whether levels are altered at a causally-relevant time of pregnancy.
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Beddaoui
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kramer
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Basso
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Centre 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: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D002338:Carotenoids / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency; D019587:Dietary Supplements; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D011247:Pregnancy; D017594:Publication Bias; D012306:Risk; D014815:Vitamins / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000975:Antioxidants; D014815:Vitamins; D002338:Carotenoids