title: Maternal serum theobromine and the development of preeclampsia.
abstract: BACKGROUND
  Preeclampsia, a disorder with prominent cardiovascular manifestations, is a cause of maternal, fetal, and infant morbidity and mortality. Chocolate contains compounds that may promote cardiovascular health. A recent study found chocolate consumption during pregnancy, and, particularly, increasing cord serum concentration of theobromine (the primary methylxanthine alkaloid in chocolate), to be associated with reduced occurrence of preeclampsia.
  
  
  METHODS
  We studied 2769 women who comprised the control group from a case-control study of caffeine metabolites and spontaneous abortion nested within the Collaborative Perinatal Project. These women were pregnant between 1959 and 1966, with liveborn infants of at least 28 weeks' gestation. Serum was drawn at <20 weeks and >26 weeks' gestation, and assayed for theobromine by high-performance liquid chromatography. Odds ratios (ORs) for preeclampsia were estimated using logistic regression, and adjusted for age, education, prepregnant weight, race, parity, smoking, and gestation at blood draw.
  
  
  RESULTS
  Preeclampsia occurred in 68 (2.9%) of 2105 eligible women. Adjusted ORs for preeclampsia were near unity across most third-trimester theobromine concentrations. Adjusted ORs for preeclampsia according to theobromine concentration in serum at <20 weeks' gestation increased with increases in concentration, although estimates were imprecise.
  
  
  CONCLUSIONS
  This study does not support the previous finding that chocolate consumption is associated with a reduced occurrence of preeclampsia. Unmeasured confounding or reverse causation may account for the positive association between early-pregnancy theobromine and preeclampsia.
authors.affiliation: Epidemiology Branch, Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. mk90h@nih.gov
authors.forename: Mark A
authors.initials: MA
authors.lastname: Klebanoff
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Cuilin
authors.initials: C
authors.lastname: Zhang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levine
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy; D013805:Theobromine / Q000097:blood*; D014481:United States / Q000453:epidemiology; D014665:Vasodilator Agents / Q000009:adverse effects / Q000097:blood*; D055815:Young Adult
chemical_list: D014665:Vasodilator Agents; D013805:Theobromine