Nutritional Status and Nutrients Related to Pre-Eclampsia Risk

Abstract

Elevated blood pressure during pregnancy, pre-eclampsia, is in part a result of inflammatory processes related to pregnancy. Reducing risk for pre-eclampsia is important to improve birth outcomes and reduce morbidity and mortality. Nutritional status and dietary intake of key foods and nutrients can aid in the reduction of pre-eclampsia risk. Excessive gestational weight gain is associated with pre-eclampsia risk, however, fluid retention, may be the driver of this relationship. While diets rich in fruits, vegetables, and dietary fiber can reduce pre-eclampsia risk and adherence to a western diet pattern can increase risk. Other nutrients, which may improve hypertension, such as sodium or salt, have little to no effect on pre-eclampsia risk. Key nutrients impacting pre-eclampsia risk are described in this article.

“Women who experience excessive adipose tissue or body fat are at increased risk for developing pre-eclampsia compared to counterparts with healthy body compositions.”

Pre-eclampsia, defined as a blood pressure ≥140 or ≥90 mmHg after 20 weeks of gestation, is related to a number of modifiable dietary risk factors. Driven by a pro-inflammatory response related to pregnancy, the condition affects between 3 and 5% of pregnant women. Cases of pre-eclampsia have risen in the recent decades, related in part to an increase in obesity as well as an increased maternal age during pregnancy.

Unlike chronic hypertension, the evidence on diet and nutrition for prevention and treatment of pre-eclampsia, or hypertension during pregnancy, is less definitive. Though there are some similarities in the nutrition-related risk factors for hypertension and pre-eclampsia due to similar underlying pathophysiology, recommendations for one condition are not necessarily effective in addressing the other. This article describes and discusses the nutrition-related risk factors and evidence on key nutrients and foods for the prevention and treatment of pre-eclampsia, based on findings from a recent meta-analysis.^1,2

Pre-Pregnancy Obesity

Women who experience excessive adipose tissue or body fat are at increased risk for developing pre-eclampsia compared to counterparts with healthy body compositions. One underlying mechanism that may contribute to this risk is the increased oxidative stress, inflammation, and damaged endothelial cells that contribute to pre-eclampsia. In addition, leptin, which is also dysregulated in individuals with obesity, is linked to increased blood pressure and placental growth factor.

Elevated body mass index (BMI) pre-pregnancy is positively associated with risk of pre-eclampsia, where a 70% great odds for experiencing pre-eclampsia was noted among women with a higher BMI, while controlling for body composition. ³

Gestational Weight Gain (GWG)

Weight gain in excess of the American College of Oncology and Gynecology recommendations is also associated with increased risk for pre-eclampsia. ⁴ Evidence has shown that weight gain in excess of 3.7 kg was related to a significant increase in risk for pre-eclampsia, with a 1 kg increase in GWG relating to a 1.3 time greater odds for pre-eclampsia. ³ However, upon examination of GWG by body component type (body fat, body water, lean body mass), total body water was found to be more strongly related to pre-eclampsia than fat mass at week 36. ³ In fact, excessive GWG early in pregnancy is likely related to edema (fluid retention) and be an early sign of pre-eclampsia risk. Nonetheless, among hypertensive women with a BMI in the healthy or overweight category (BMI = 18.5-30 kg/m²), excessive GWG increased pre-eclampsia risk by 40 to 90%. ⁵ Considering the evidence pre-eclampsia risk is driven by edema related GWG, a focus on improved diet quality and lifestyle interventions to reduce the stress response to pregnancy may be preferred over weight loss promotion.^6-8

Dietary Patterns and Pre-Eclampsia

Dietary patterns are defined as the quantity, variety, or combination of different foods and beverages in a diet, including the frequency in which they are consumed. ⁹ Trends in nutrition research have shifted from a focus on single nutrients’ impact on specific health outcomes to dietary patterns, which more accurately represent the totality of how these nutrients are consumed. Dietary patterns of adult women in the US could be improved. Seventy percent of pregnant women in the US exceed the recommended levels of intake for added sugar, 75% exceed recommended saturated fat intake, and most consume more than one cup less than the recommended amounts of vegetables. ¹⁰

Dietary patterns higher in fruits and vegetables, before and during pregnancy have generally been found to be protective against pre-eclampsia. Dietary patterns rich in fat, added sugar, and salt, and Western eating patterns are observed to increase risk for pre-eclampsia.

Overwhelmingly, higher intake of fruits and vegetables is protective against pre-eclampsia.^11-15 Consuming a minimum of one and one-fourth cups of fresh fruits was found to be associated with nearly a 20% reduction in odds for pre-eclampsia ¹⁴ and consumption of fruits and vegetables at least 3 times per week also significantly reduced pre-eclampsia, odds ratio (OR) .51 and .45 for fruits and vegetables, respectively. ¹⁶

On the contrary, more frequent consumption of processed meat, salty snacks, and sugary beverages increases risk for pre-eclampsia. ¹³ Sugar-sweetened beverage consumption greater than one-half cup per day was found to increase risk for pre-eclampsia (OR 1.27). ¹³ Western diets are typically high in processed meat, red meat, fried potatoes, and high salt foods. Greater adherence to a western style of eating has also been found to increase risk for pre-eclampsia.^17-19 Diets rich in these foods are noted to contribute to increased inflammation, which may be an underlying mechanism that contributes to the associations found in these studies.

Foods and Nutrients Linked to Reduced Pre-Eclampsia Risk

Dietary Fiber

Dietary fiber intake between 25 and 30 g per day has demonstrated a protective effect against pre-eclampsia. ²⁰ Evidence from case control studies has found increased pre-eclampsia risk to be associated with increased serum triglycerides (TAGs) and low-density lipoprotein cholesterol (LDL-c) levels. Compared to the lowest quartile of fiber consumers, the highest quartile experienced a relative risk for pre-eclampsia of .28. ²⁰ These high fiber consuming individuals also experienced significantly lower LDL-c and TAGs where intakes of 25 to 30 g of dietary fiber per day were optimal. Notably, a diet rich in dietary fiber often contains foods such as fruits and vegetables, which are also good sources of dietary fiber. ²¹

Calcium

Calcium aids in regulating blood pressure by increasing intracellular calcium concentration while inadequate intake can contribute to stimulation of renin and thyroid hormones that increase blood pressure. High dosages of calcium supplementation (>1000 mg per day) is well supported by research to reduce pre-eclampsia risk. ²² However evidence for lower levels of supplementation (500 mg per day) is mixed, where duration of supplementation and when to begin supplementation is less well understood. ²³ A supplement containing 1000 mg of calcium is recommended for all pregnant women beginning at 20 weeks gestation through delivery, regardless of pre-eclampsia risk and dietary calcium intake, based on cost-benefit analysis. ²⁴ Additionally, women who are at heightened risk for pre-eclampsia or who have low dietary calcium intake, may benefit from up to 2000 mg per day. ²⁵

Vitamin D

Vitamin D modulates inflammatory processes, which aids in the support for reducing pre-eclampsia risk. Vitamin D deficiencies are linked with endothelial cell dysfunction. Evidence from both observational and experimental research leans in favor of vitamin D supplementation for reduction of pre-eclampsia risk.^26-28 Vitamin D status of pregnant women should be monitored and deficiencies corrected with supplemental doses of vitamin D (400 to 1000 IU per day) to achieve optimal pre-eclampsia risk reduction.^29,30

Milk-Based Probiotics

Probiotic foods contain live strains of bacteria that improve the balance of the gut microbiome and have demonstrated positive associations between cholesterol and blood pressure. ³¹ Among pregnant women, probiotic foods may specifically aid in reducing systemic inflammation. ¹³ This is supported by RCT where pregnant women who consumed probiotic yogurt for 9 weeks had reductions in C-reactive protein, as well as a cohort study that compared probiotic intake between women with and without pre-eclampsia. Consumption of probiotics significantly reduces risk for pre-eclampsia (OR .80). ³²

Nutrients with Low Evidence for Pre-Eclampsia Risk

Researched focused on nutrients related to pre-eclampsia risk demonstrates little impact of vitamin C, vitamin E, omega-3 fatty acids, magnesium, salt, and zinc consumption.

Vitamins C and E

Recent evidence on the impact of vitamins C and E have demonstrated little protection against pre-eclampsia.^33-37 Randomized control trials, ³³ cohort studies, ³⁴ and systematic reviews^35-37 have examined vitamin C and E intake from foods and supplements. Therefore, evidence for recommending vitamin C and E supplementation or increased intake is not warranted for individuals looking to reduce pre-eclampsia risk.

Omega-3 Fatty Acids

A majority of evidence linking omega-3 fatty acid consumption, both from diet and supplements, have yielded inconclusive evidence on protection against pre-eclampsia. A small case control study (n = 62) and another prospective cohort study (n = 1718) had evidence suggestive of a protective effect of omega-3 fatty acid intake on pre-eclampsia;^12,38 however, four recent systematic reviews and met-analyses found no evidence to support these benefits.^39-42 Notably, omega-3 fatty acid consumption is inadequate among many pregnant women; thus, intake of this nutrient may have health benefits unrelated to pre-eclampsia and should be examined by practitioners. ⁴³

Magnesium

Adequate dietary intake of magnesium may be protective against hypertension, however recently the United States Food and Drug Administration released a statement that there is inconclusive and inconsistent evidence in support of magnesium’s protective effects against hypertension. ⁴⁴ Evidence points to the same being true for pre-eclampsia. A 2014 systematic review of experimental and quasi-experimental research studies found no association between magnesium supplementation and pre-eclampsia. ⁴⁰

Salt

Salt restrictions during pregnancy have weak and low impacts on the prevention of pre-eclampsia. A Cochrane review of randomized trials found no protection of lowered salt intake on pre-eclampsia. ⁴⁵ One observational study of salt intake among Danish women found that intake of over 2300 mg of salt per day was associated with the onset of pre-eclampsia (hazard ratio 5.68), however after adjusting for covariates such as BMI, maternal age, smoking status, parity, blood pressure, length of gestation, and sex of the baby, the relationship was non-significant. ⁴⁶

Zinc

Zinc deficiencies are hypothesized to be linked to hypertension via regulation of proteins that impact sodium reabsorption in the kidneys. ⁴⁷ In the limited body of research on this relationship, zinc supplementation among pregnant women showed no association with pre-eclampsia risk or other pregnancy outcomes. ⁴⁸

Conclusion and Implications for Practice

Women who present with increased risk for pre-eclampsia require special assessment of their nutritional status and dietary intake of key nutrients. Physicians and health care providers should consider a thorough nutritional assessment which might include anthropometric measures (height, weight, weight gain), biochemical data (LDL-c, TAG), client history (previous diagnosis of pre-eclampsia, medical conditions), and dietary history (food and dietary supplement intake both pre-pregnancy and during pregnancy). Key signs and symptoms to identify and address include early and excessive GWG, adherence to a western diet, low intake of fruits, vegetables, dietary fiber, calcium, and compromised vitamin D status. Interventions should include referral to a Registered Dietitian Nutritionist (RDN) when possible, as well as efforts to increase intake of fruits, vegetables, and dietary fiber, while simultaneously seeking to reduce intake of highly processed foods. An RDN can provide patients with individualized and tailored dietary recommendations, which support nutritional status, reduce disease risk, and meet cultural food preferences.