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: 6.2). 06/2009; 20(5):727-32. DOI: 10.1097/EDE.0b013e3181aba664
Source: PubMed


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.

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    • "However, this diminution was not significant. A case–control study [12] nested in a cohort does not support the previous finding. According to the authors, unmeasured confounding or reverse causation may account for the positive association previously reported as discussed above. "
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    ABSTRACT: BACKGROUND: Several randomized clinical trials (RCTs) indicate that flavanol-rich chocolate has beneficial effects on flow-mediated dilation (FMD) and blood pressure (BP). However, no RCTs have evaluated these outcomes in pregnant women. The objective of this 2-group, parallel, double-blind RCT was to examine the effects of flavanol-rich chocolate on FMD and BP in pregnant women with normal BP. METHODS: Forty-four healthy, pregnant women were randomized to the high-flavanol (n = 23) or low-flavanol (n = 21) chocolate consumption for 12 weeks. At randomization (0, 60, 120 and 180 min after a single 40-g dose of chocolate), 6 and 12 weeks after daily 20-g chocolate intake, we evaluated plasma concentrations of flavanols and theobromine, as well as the FMD and BP. RESULTS: Plasma epicatechin was significantly increased (p < 0.001) 180 min after the consumption of 40-g high-flavanol chocolate compared to low-flavanol chocolate. Theobromine concentrations were significantly higher 180 min and 12 weeks after the intake of experimental chocolate or low-flavanol chocolate (p < 0.001). FMD was not different between the 2 groups at all pre-defined time periods. No other significant within-group or between-group changes were observed. CONCLUSION: These results confirm the feasibility of a large-scale RCT comparing daily consumption of flavanol-rich chocolate to an equivalent placebo during pregnancy and demonstrate higher plasma epicatechin and theobromine concentration in the intervention group after acute ingestion.Trial registration: Identifier: NCT01659060.
    Full-text · Article · Apr 2013 · Nutrition Journal
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    • "Our findings are also consistent with their report of a 60% reduction in preeclampsia associated with levels of cord blood theobromine at or above the 2 nd quartile of exposure (9). In contrast, our findings are not consistent with those of Klebanoff et al. (2009) who found no protective effect of theobromine measured in maternal serum after the 26 th week of gestation for preeclampsia (9). They found also reported that preeclampsia risk increased in a dose-response fashion with increasing levels of theobromine measured in maternal serum collected before 20 weeks gestation. "
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    ABSTRACT: Chocolate consumption is associated with favorable levels of blood pressure and other cardiovascular disease risk markers. We analyzed a prospective cohort study to determine whether regular chocolate intake during pregnancy is associated with reduced risks of preeclampsia and gestational hypertension (GH). Subjects were recruited from 13 prenatal care practices in Connecticut (1988-1991). In-person interviews were administered at <16 weeks' gestation to ascertain risk factors for adverse pregnancy outcomes. Hospital delivery and prenatal records were abstracted to classify preeclampsia (n = 58), GH (n = 158), and normotensive pregnancies (n = 2351). Chocolate consumption (servings/week) during the first and third trimesters was ascertained at initial interview and immediately postpartum, respectively. Consumers of less than 1 serving/week comprised the referent group. Adjusted odds ratios (aORs) were estimated by the use of logistic regression. Chocolate intake was more frequent among normotensive (80.7%) than preeclamptic (62.5%) or GH women (75.8%), and associated with reduced odds of preeclampsia (first trimester: aOR, 0.55; 95% confidence interval [95% CI], 0.32-0.95; third trimester: aOR, 0.56; 95% CI, 0.32-0.97). Only first trimester intake was associated with reduced odds of GH (aOR,0.65; 95% CI, 0.45-0.87). These findings provide additional evidence of the benefits of chocolate. Prospective studies are needed to confirm and delineate protective effects of chocolate intake on risk of preeclampsia.
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    ABSTRACT: Summarize recent studies exploring the relationship between paternal and maternal environmental exposures to chemicals before, at the time of and after conception to adverse developmental outcomes including preterm birth, death, structural and functional abnormalities and growth restriction. Recent studies have demonstrated that human pregnancy and development are vulnerable to environmental exposures of the father and mother to chemical, biological and physical agents. Exposures associated with adverse developmental outcomes include air and water pollution, chemicals in foods, occupational exposures, agricultural chemicals, metals, persistent and volatile organics. Developmental endpoints which are linked with these exposures include growth restriction, functional abnormalities, structural abnormalities, preterm delivery and death. Despite this general understanding we still have incomplete knowledge concerning most exposures and the biological interactions responsible for impaired development and preterm delivery. Whereas single genes and individual chemical exposures are responsible for some instances of adverse pregnancy outcome or developmental disease, gene-environment interactions are responsible for the majority. These gene-environment interactions may occur in the father, mother, placenta or fetus, suggesting that critical attention be given to maternal and paternal exposures and gene expression as they relate to the mode of action of the putative developmental toxicant both prior to and during pregnancy.
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