Maternal Serum Theobromine and the Development of Preeclampsia

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.
Epidemiology (Cambridge, Mass.) (Impact Factor: 6.18). 06/2009; 20(5):727-32. DOI: 10.1097/EDE.0b013e3181aba664
Source: PubMed

ABSTRACT 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.
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.
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.
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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Pre-eclampsia (PE) is one of the most common pregnancy complication characterized by placental and maternal vascular dysfunction. It affects about 3 - 8% of women during the second half of pregnancy and represents one of the major causes of neonatal morbidity and mortality. The etiology of PE largely remains unknown. Areas covered: PE is considered a syndrome with multisystem involvement, so the ideal predictive test for it should utilize a combination of many predictors. Measurement in early pregnancy of a variety of biophysical and biochemical markers implicated in the pathophysiology of PE associated with clinical risk factors has been proposed to predict the development of the syndrome, thereby mitigating an adverse outcome. Expert opinion: The identification of reliable indicators is a clinically relevant issue that could result in early therapeutic intervention and leading to the prevention of maternal and fetal injuries before the manifestation of clinical signs. Many factors complicate the prevention of PE cases. Most are attributed to unknown etiology, the low predictive value of current screening tests and the several presentations of the disease. Although preventative treatments have been studied extensively, an effective intervention to avoid the development of PE has not yet been discovered.
    Expert opinion on biological therapy 04/2014; DOI:10.1517/14712598.2014.912271 · 3.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Previous studies suggest that abnormalities in maternal immune activity during pregnancy alter the offspring's brain development and are associated with increased risk for schizophrenia (SCZ) dependent on sex. Method. Using a nested case-control design and prospectively collected prenatal maternal sera from which interleukin (IL)-1 beta, IL-8, IL-6, tumor necrosis factor (TNF)-alpha and IL-10 were assayed, we investigated sex-dependent associations between these cytokines and 88 psychotic cases [SCZ=44; affective psychoses (AP)=44] and 100 healthy controls from a pregnancy cohort followed for >40 years. Analyses included sex-stratified non-parametric tests adjusted for multiple comparisons to screen cytokines associated with SCZ risk, followed by deviant subgroup analyses using generalized estimating equation (GEE) models. Results. There were higher prenatal IL-6 levels among male SCZ than male controls, and lower TNF-alpha levels among female SCZ than female controls. The results were supported by deviant subgroup analyses with significantly more SCZ males with high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)(75)=3.33, 95% confidence interval (CI) 1.13-9.82], and greater prevalence of low TNF-alpha levels (<lowest quartile) among SCZ females compared with their controls (OR25=6.30, 95% CI 1.20-33.04) and SCZ males. Higher levels of IL-6 were only found among SCZ compared with AP cases. Lower TNF-alpha levels (non-significant) also characterized female AP cases versus controls, although the prevalence of the lowest levels was higher in SCZ than AP females (70% v. 40%), with no effect in SCZ or AP males. Conclusions. The results underscore the importance of immunologic processes affecting fetal brain development and differential risk for psychoses depending on psychosis subtype and offspring sex.
    Psychological Medicine 03/2014; 44(15):1-13. DOI:10.1017/S0033291714000683 · 5.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cocoa consumption began in America and in the mid 16th Century it quickly spread to Europe. Beyond being considered a pleasant habit due to its rich sweet lingering taste, chocolate was considered a good nutrient and even a medicine. Traditionally, health benefits of cocoa have been related with the high content of antioxidants of Theobroma cocoa beans. However, the direct psychoactive effect due to methylxanthines in cocoa is notable. Theobromine and caffeine in the proportions found in cocoa are responsible for the liking of the food/beverage. These compounds influence in a positive way our moods and our state of alertness. Theobromine, which is found in higher amounts than caffeine, seems to be behind several effects attributed to cocoa intake. The main mechanisms of action are inhibition of phosphodiesterases and blockade of adenosine receptors. Further mechanisms are being explored to better understand the health benefits associated to theobromine consumption. Unlike what happens in other mammals –pets included-, theobromine is safe for humans and has fewer unwanted effects than caffeine. Therefore, theobromine deserves attention as one of the most attractive molecules in cocoa.
    Frontiers in Pharmacology 02/2015; 6. DOI:10.3389/fphar.2015.00030