The following is a summary of the stated research mentioned above. The content summarized here, including the figures and tables, all belong to the researchers (unless otherwise indicated). The summary attempts to stay as close to the original paper as much as possible with some adjustments in regards to jargon, length, or to focus on bean to bar aspects.

Introduction

Preeclampsia is a leading cause of morbidity and mortality worldwide in both infants and mothers. It involves similar risk factors involved in cardiovascular disease. As well, it appears women with a history of preeclampsia also face increased risk of developing chronic hypertension, insulin resistance, and lipid abnormalities later in life (see references 1-3).

Clinical trials to prevent preeclampsia have focused on administering pregnant women low-dose aspirin, calcium supplements, and vitamins C and E, but none have proven effective (see references 4-7).

More recent studies have indicated that regular consumption of dark chocolate has beneficial effects on cardiovascular disease risk but lowering blood pressure, insulin resistance, serum triglycerides, vascular reactivity, endothelial dysfunction, oxidative stress, indicators of inflammation, and antiplatelet activity (8). Therefore, it makes sense to test for the possible protective effect of chocolate consumption on the risk of preeclampsia.

Two published studies looked at this effect, and used theobromine as a biomarker, but reported conflicting findings (9, 10). Klebanoff et al. (9) found no protective effect of increased theobromine in maternal serum, but did not assess dietary chocolate consumption. Triche et al. (10) reported greater levels of theobromine in cord blood have a protective effect against preeclampsia.

In this study, the following questions were addressed:

Is regular chocolate consumption during pregnancy associated with a reduced risk of preeclampsia and gestational hypertension?
Do the risks of preeclampsia and gestational hypertension vary by amount of chocolate consumed?
Is the timing or pattern of chocolate consumption during the first and third trimesters of pregnancy associated with the risks of preeclampsia and gestational hypertension.

This study adds to current publications by examining trimester-specific chocolate intake, and considering gestational hypertension (GH) as an additional outcome.

Materials & Methods:

An ancillary study was conducted within the Yale Health in Pregnancy Study cohort to identify risk factors for preeclampsia. This required detailed reviews of all prenatal and medical records belonging to subjects who were noted to have evidence of high blood pressure in the parent study (11).

Study design and population

Nearly 2500 women took part in this study. Interviews were conducted in-person, before 16-weeks gestation, and usually conducted in the woman’s home. The interviewers obtained information on maternal demographics, medical and reproductive history, height, pregnancy weight, atenatal smoking, alcohol, caffeine, and chocolate consumption, occupational factors, and exercise habits. A postpartum interview was also completed within the first few days of delivery. Study abstractors were trained to carefully document chart notations of increased blood pressure as well.

classification of hypertension in pregnancy

A supplementary review was conducted for all prenatal and hospital delivery records for the 15% of women who had some indications of elevated blood pressure during pregnancy. The abstractors recorded blood pressure readings, urine protein values, laboratory test results, and other signs and symptoms of preeclampsia. These women were assigned to one of the following categories according to the American College of Obstetricians and Gynecologists:

no hypertension (n=98 women)
chronic hypertension (n=73 women)
Gestational Hypertension (GH) (n= 158 women)
Preeclampsia (n=58 women)
Superimposed preeclampsia (n=14 women)
Uncategorized hypertension or unknown hypertension (n=14 women)

Women with HELLP syndrome (n=13) were coded as superimposed preeclampsia or preeclampsia according to the presence or absence of chronic hypertension.

assessment and classification of chocolate intake

Average weekly consumption of chocolate drinks and foods were assessed by two questions included in the initial interview and the postpartum interview. During the initial interview women were asked:

Since you have become pregnant, have you been drinking one or more cups of hot chocolate, cocoa, or chocolate milk per week?
Since you have become pregnant, have you been eating one or more servings of chocolate candy, chocolate cake, chocolate cookies, or chocolate ice cream per week?

Women who responded “yes” were asked to recall their average weekly intake of the above mentioned using the following close-ended responses:

1-3 cups (or servings) a week
4-6 cups (or servings) a week
1 cup (or serving) daily
2 cups (or servings) daily
3-4 cups (or servings) daily
5-10 cups (or servings) daily
More than 10 cups (or servings) daily

These questions were repeated for the postpartum interview. The chocolate consumption during the third trimester were correlated with cord blood theobromine levels.

Results

General statistics with Preeclampsia & GH

No difference was found whether participants consumed chocolate in the form of food or drinks. Therefore, chocolate consumption from these combined sources were analyzed. Table 1 shows the frequency distributions of demographic, reproductive, and lifestyle characteristics of the final analysis population (n = 2508). They are categorized by trimester of chocolate consumption during pregnancy, and the proportion with preeclampsia (2.4%) and GH (6.4%).

Of the total participants, 48% reported regular weekly intake of chocolate drinks or foods during both first and third trimesters. Only 10% reported intake during the first trimester only, and 22% reported intake during the third trimester only. No regular chocolate consumption was reported by 20% of the participants. Chocolate consumption appears to be highest with those who were:

younger than 35
white
had a BMI under 25
drank caffeinated beverages
did not develop gestational diabetes during pregnancy

The major risk factors for preeclampsia and GH tended to be nulliparity (has not had previous offspring), and obesity. Male fetal sex was also significantly associated with increased risk of preeclampsia, but not with gestational hypertension. Maternal age under 30 years was significantly associated with increased risk of gestational hypertension, but not with preeclampsia. Maternal race, education, smoking during pregnancy, caffeine intake, and gestational diabetes were not significantly associated with preeclampsia and gestational hypertension. However, rates of preeclampsia were greater among nonwhite patients and gestational diabetes.

chocolate consumption with Preeclampsia & GH

Figure 1 illustrates that preeclamptic women were also less likely to regularly consume chocolate (37.5%) than normotensive women (19.3%) or those with gestational hypertension (24.2%). Almost half (48%) of the normotensive women reported regular consumption of chocolate in both trimesters 1 and 3 than those with preeclampsia (35.7%) and gestational hypertension (40.8%). Regular chocolate consumption was substantially more prevalent in the third trimester (19.6-27.4%) than in the first trimester (7.1%-10.5%).

Table 2 summarizes the influence of regular chocolate intake by number of weekly servings and by trimester on risk of preeclampsia and gestational hypertension. Regular consumption of 1-3 servings per week in the first trimester was associated with reduced risk of preeclampsia, while intake of 4 or more per week seemed to have a similar protection. Women who reported any regular consumption during the first trimester had a significantly reduced risk of 0.55 (0.32-0.95), the same as those with any regular consumption during trimester 3. Overall, it appears according to these results that any regular consumption of chocolate is associated with significantly reduced risk of preeclampsia relative to women who reported no regular consumption in both trimesters 1 and 3.

Regular chocolate intake was also associated with a reduced risk of gestational hypertension, but only among those who consumed it in the first trimester. Consumption during the third trimester was not associated with reduced risk of GH in this study. A regular consumption of 1-3 servings in the first trimester appeared to be protective against GH, consuming 4 or more did not appear to add anymore protection. According to the results in this study, it appears that consumption of chocolate in first trimester alone was protective, but not in third trimester alone.

Discussion

Women who reported regular chocolate consumption of at least 1-3 servings a week had a 50% greater reduced risk of preeclampsia. This did not appear to be dose dependent. Whether the regular consumption was during the first or third trimester, protective impact against preeclampsia appeared to be the same. Women with the greatest risk of preeclampsia (4.5%) were those who did not regularly consume chocolate in the first and third trimesters. Interestingly, women who consumed chocolate regularly during the first trimester alone had a reduced risk of gestational hypertension.

Preeclampsia is a “2-stage disease process”, so it appears that trimesters 1 and 3 could be critical windows for exposure to intervention. Defective placentation of preeclampsia begins in the first trimester (16 & 17), and it is suggested that the resulting placental oxidative stress and inflammation triggers the release of proinflammatory syncytiotrophoblast-derived factors. This can then lead to maternal systemic vascular endothelial disruption, and eventually result in preeclampsia in the third trimester (16).

This study is consistent with Triche et al. (10) in that regular consumption in the third trimester was protective against preeclampsia, but they did not find such protective effects of first trimester consumption. Results here contrasted with Klebanoff (9) (a study conducted 40 years prior to this one)who found no protective effect of theobromine measured in maternal serum. They also found that preeclampsia risk increased in a dose-response fashion with increasing levels of theobromine. The reasons for this discrepancy may be: very different study populations, differences in the length of storage of the serum, different definitions of preeclampsia, and differences in the sources of theobromine.

Triche et al. (10) did find evidence for an inverse dose-response relationship of theobromine levels in cord serum with preeclampsia risk. However, the questionnaire used in this study was not adequate enough to look at a dose-response effect of chocolate. As well, different products contain different amounts of cocoa and makes it difficult to assess for dose-response relationships.

Other Studies of chocolate and cardiovascular health

A recent review looked at findings of 11 human studies of direct beneficial effects of cocoa exposure on endothelial function including: improvements in vasodilation, coronary circulation, nitric oxide levels, blood pressure, and platelet function (8). Endothelial dysfunction is linked as a central feature of preeclampsia. A 16-year follow-up study on post-menopausal women reported reduced rates of cardiovascular disease mortality (19).

A recent study reviewed 10 randomized controlled trials that assessed the antihypertensive effects of flavanol-rich cocoa, and reported a significant decrease in systolic (-4.5 mmHg) and diastolic (-2.5 mmHg) blood pressure (20). In one trial, the authors examined very low doses of dark chocolate consumption during an 18 week study (6.3 g/d) and still found a significant reduction of blood pressure (21), with similar findings in other reports (22, 23).

The study by Desch et al. (20) found no difference in the blood pressure changes of either low-dose or high-dose chocolate intake study. A study by Buijsse et al. (22) saw significant reduction in blood pressure with low-dose consumption (6g/d), and a larger reduced risk for myocardial infarction and stroke. A study by di Giuseppe et al., saw a consumption level of 6.7g/d of dark chocolate associated with a decreased serum C-reactive proteins, which are a marker for inflammation (24). Other studies have suggested sustained benefits in vascular function after consumption of cocoa products, including a study that found plasma levels of flavanols peak at 2-3 hours after ingestion, but are still detected in the blood plasma 8 hours after ingestion (25-28).

Limitations

Self-reported data by the participant may have led to misclassification, and it’s very difficult to quantify both serving sizes and cocoa content accurately. There was no differentiation between types of chocolate (dark, milk, etc.). The study would have benefited from having biomarker data such as theobromine to validate the associations between self-reported chocolate consumption and risk of preeclampsia and gestational hypertension. As well, only caffeinated beverages were assessed, so the results in this study may be confounding with other dietary constituents. However, there are no dietary factors associated with preeclampsia to date, so it is unlikely other foods may have changed the findings in any significant way (29).

Another consideration is of reverse causality. Women who developed high blood pressure may be less likely to consume chocolate after being diagnosed with high blood pressure. However, women who had high blood pressure before 20 weeks gestation were excluded from the study. As well, women with gestational diabetes reported reduced chocolate consumption, especially in later gestation periods. There was no evidence that gestational diabetes was a confounder of the association of chocolate consumption and risk of preeclampsia or GH. When the analysis models were restricted to nondiabetic women, no changes in risk were noted.

Does Chocolate Intake During Pregnancy Reduce The Risks Of Preeclampsia And Gestational Hypertension?