Geophagia, nutrition and health of women with pregnancy-induced hypertension

Background Calcium is a major nutrient implicated in pregnancy-induced hypertension (PIH). Aside dietary sources, geophagia has been reported to provide calcium needed to prevent PIH. These soils are shown to contain significant amount of heavy metals which have been associated with hypertension. Objective The aim of this study was to determine the relationship between geophagia and PIH, assess the dietary intakes and health of participants. Methods This study was a case-control involving 30 women with PIH and 70 normotensive pregnant women. Results Geophagia was not significantly associated with PIH. Women with PIH practicing geophagia recorded significantly low levels of haemoglobin, calcium and ferritin. Hypertensives recorded impaired fasting blood glucose (5.77±1.71mmol/L, p=0.051), higher levels of urea (3.60±1.29 mmol/L, p=0.000) and creatinine (382.67±11.66 µmol/L, p=0.000). Percentage intakes of macronutrients for normotensives were within the Adequate Macronutrient Distribution Range and PIH group recorded higher intakes of carbohydrate (72.75±16.16 %), lower protein (9.77±5.61 %) and fat (17.15±11.99%). Dietary calcium intakes in both groups were lower than recommended (< 1,000 mg/day). Conclusion In this study, geophagia during pregnancy is not directly associated with PIH but is detrimental to maternal health. The pregnant women in this study had considerably low intakes of energy and nutrients. There is a need for measures to ensure adequate maternal nutrition for a positive health and pregnancy outcomes.


Introduction
Nutrients requirement during pregnancy increases with the stage of pregnancy to meet the nutrient demands for the growth of the foetus and prepare the mother for been associated with the development of pregnancy-induced hypertension 5 .
Calcium is a major nutrient associated with hypertension during pregnancies, and the most documented 6,7 . Studies indicate that mothers with low dietary intakes of calcium have increased risk of pregnancy-induced hypertensive disorders 6 . Several clinical trials suggest that women receiving supplements of calcium have lower blood pressure, hence calcium supplements being used as a form of intervention in women diagnosed with pre-eclampsia 8,9 . This is however true among populations with low calcium intakes 10 . Studies by Eiley and Katz 11 . hypothesized that the ingestion of geophagic clay during pregnancy may provide the calcium needed to improve maternal calcium status as well as reduce the risk of hypertension in pregnancy. The aim of this study was to determine the relationship between geophagia and hypertensive disorders of pregnancy, and assess dietary intakes and health outcome of participants.

Subjects and methods Subjects
The case-control study was conducted at the Obstetrics and Gynaecology unit of the Komfo Anokye Teaching Hospital in the Kumasi Metropolis of Ghana. Pregnant women with singleton pregnancy between the ages of 20 and 40 years with gestational age of 20 weeks or more were eligible participants for the study. Pregnant women with medical conditions such as diabetes, pre-existing hypertension, autoimmune disease and kidney or liver diseases and systemic diseases were excluded. The cases were 30 pregnant women with pregnancy-induced hypertension without proteinuria. The control groups were 70 normotensive pregnant women. The groups were also matched for weight and body mass index to control for confounding variables.

Sample size calculation
The sample size was determined using Cochrane's formula; N= Z 2 p (1-p)/d 2 where N is the sample size, Z is the standard score for the confidence interval of 95% which is 1.96. P, the average prevalence of hypertension com-plicating pregnancy in Ghana is 1.75% 12 , d is marginal error which is 5%. N = z 2 p (1-p) / d 2 N= 1.96 2 * 0.0175 (1-0.0175)/0.05 2 N= 26.42 The estimated minimum sample size for women with hypertension was therefore, 26.

Blood pressure measurement
Blood pressure measurement was done in accordance with recommendations by the American Heart Association using a digital sphygmomanometer (Omron, Japan). A replicate measurement was taken for each participant and the mean value recorded as the blood pressure. The systolic and diastolic blood pressure was measured.

Routine urine examination
As part of antenatal routine examination, pregnant women visiting the facility reported with 5-10ml of the freshly voided early morning urine in clean, easy access and leak proof containers. Test strips (Combi 10 SGL, Yercon Diagnostic Co. Ltd. China) were dipped into urine samples and removed. After 5-10 seconds, the strips were observed for colour change.

Dietary assessment
A two-day 24-hour recall was used to assess the nutrient intakes and analyzed with the West African Food Composition Table 13 . The food frequency questionnaire was used to assess the habitual intakes of participants from food groups such as whole-grains, animal proteins, plant proteins, fruits, vegetables and dairy products.

Anthropometric assessment
Anthropometric measurements including pregnancy weight, body mass index, mid upper arm circumference (MUAC), body fat and visceral fat percentage were assessed. Mid Upper-arm Circumference was measured with a tape measure. The heights of pregnant women were measured by standing vertical, without footwear on a stadiometer. The Bio impedance analyser (Omron, Japan) was used to calculate the weight, body fat percentage and visceral fat. BMI was calculated using the formula weight (kg)/height 2 (m 2 ) Biochemical assessment Upon recruitment, a volume of 7 ml of venous blood samples were collected from participants by a phlebotomist after an overnight fast (8-12 hours). The blood samples were apportioned into 3 suitable test-tubes namely the fluoride tube, the ethylenediaminetetra-acetic acid (EDTA) tube and the gel activator tube for fasting blood glucose, full blood count and kidney function test (urea and creatinine), serum calcium and ferritin respectively. Full blood Count analysed with Sysmex XP-300 Haematology Analyzer (North America), fasting blood glucose with Randox (RXmonzaTM, United Kingdom), urea, creatinine and calcium with Biolabo Diagnostics (Kenza BiochemistryTM, France) and serum ferritin with Mindray (MR-96A, China). All determinations were performed according to manufacturers' instructions.

Data analysis
Data was entered and stored in Microsoft Excel and analyzed using SPSS version 22.0 (IBM Inc. Chicago). Categorical variables were analyzed using Chi-square and Fischer's test whilst continuous variables were analyzed using the unpaired t-test. Data was represented as means ± standard deviation. Pearson's correlation was per-formed to determine the relationship between variables. Risk factors of hypertension were estimated by odds ratio. In all statistical tests, p-value <0. 05 were considered significant.

Ethical consideration
Approval was sought from the Committee on Human Research, Publication and Ethics of the Kwame Nkrumah University of Science and Technology (CHRPE/ AP/002/17), and the Research and Development Office of Komfo Anokye Teaching Hospital (RD/CR16/243). Participation was voluntary and evidenced by a written consent.

Results
The population of respondents was 70 normotensive pregnant women and 30 women with PIH. There were significant differences in their ages, marital status and age of gestation. Seventy percent of normotensives were between 25-35 years, 87.2% were married and 80% were in their 3 rd trimesters of pregnancy, compared to PIH women with 43.3%, 66.7% and 100% respectively. Table  1 shows the socio-demographic and obstetric characteristics of participants. Table 2 compares the mean age, blood pressure and anthropometries of participants. Systolic blood pressures of normotensive pregnant women were within the normal range (115.87±14.75 mmHg) and also lower than in the hypertensive group, with blood pressure within the range for diagnosing hypertension (145.97±22.75 mmHg, p = 0.000). Likewise, diastolic pressure for normotensives was 70.63±11.65 mmHg while that of hypertensive group was 93.73±14.23 (p = 0.000). There was no statistically significant difference in the mean age, weight, BMI, and visceral fat percentage. However, body fat percentage was significantly higher among normotensives (41.27±5.82) than the hypertensive group (31.49±11.19, p= 0.000).   Table 3 shows the effect of geophagia on blood pressure and biochemical parameters of participants. There were significant differences in diastolic pressure, urea, creatinine and WBC between normotensives and hypertensives practicing geophagia (HG). HG group recorded significantly low levels of haemoglobin (8.35±1.91g/dL), hae-matocrit (28.45±5.38%), (14.89±3.73 ng/mL) and total calcium (7.05±1.05mg/dL) than hypertensives without geophagia (HN). Total calcium levels among normotensives without geophagia (NN) were lower than the reference range, but normal among those practicing geophagia within the group.  Table 4 shows the association of some dietary practices with pregnancy-induced hypertension. Geophagia and energy drink intake did not significantly increase the risk of developing hypertension in pregnancy. Coffee intake increased the risk of hypertension by 4 times (OR, 4.10; 95% CI: 2.10 -8.00, p = 0.004). Women who had received a form of nutrient supplement during pregnancy were at a reduced risk of hypertension by 67.3% (OR, 0.33; 95% CI: 0.17 -0.61, p = 0.017). Table 5 compares the mean nutrient intakes of participants with recommended intakes. The general intake of energy, minerals and anti-oxidant micronutrients nutrients for the entire population was poor, however, normotensives recorded healthier intakes than the hypertensive group. Percentage intakes of carbohydrates, protein and fat among normotensives were within the adequate macronutrient distribution range. There were significant differences in the percentage intakes of carbohydrate, protein and fat between normotensive and hypertensive pregnant women (p = 0.003, 0.006, and 0.007 respectively). Hypertensive group had higher percentage intakes of carbohydrate, i.e. 72.75±16.16, and lower percentage intakes of protein and fat (9.77±5.61 and 17.15±11.99 respectively). Table 6 compares mean haematological and biochemical data of normotensive and hypertensive pregnant women. The mean fasting blood glucose level was within the normal range among normotensives (5.08±1.13 mmol/L) but hypertensives recorded impaired fasting blood glucose (5.77±1.71 mm/L) although the differenc-es between the groups were not statistically significant. For serum parameters, urea and creatinine was within the normal range for normotensives, and significantly higher among hypertensives (p = 0.000). For total calcium and ferritin levels, normal readings were recorded for both groups.

Discussion
Hypertension in pregnancy, if not properly managed, can lead to foetal and maternal morbidity, and it is known to be a leading cause of maternal deaths 14 . This study assessed maternal dietary intakes and investigated the association of some practices with PIH, and how these are able to influence their general well-being.
In this case-control study, there was no significant difference in the family history of hypertension, parity, mean age, BMI, and MUAC between women with PIH and normotensives. A study by Owiredu et al 15 reports that marital status or nulliparity does not increase the risk of hypertension (aOR 1.8; 95% CI 0.8-4.0) but women with a family history of hypertension were 10 times at risk of developing hypertension in pregnancy than those without history (95% CI 1.2-12.2). Ephraim et al 16 in Ghana reported higher indices of obesity and high blood pressure among women with PIH with BMI correlating positively with systolic blood pressure (r=0.575, p < 0.01). According to Valensise et al 17 on the total body water and extracellular water among pregnant women showed that women with gestational hypertension had higher intracellular fluids due to fluid retention hence their increased weight may be due to water retention. Also, the reduced body fat percentage can be explained by their very low intakes of energy and therefore reduced store of energy.
Poor nutritional intakes were observed in the overall study population, however, normotensives had higher energy intakes than hypertensives. The low intakes of energy have also been reported in other studies among women with PIH and this has been attributed conceivably as a response to their present condition rather than the cause 6 . Dietary fibre intakes among normotensives were 21.95±10.10g/d and 14.22±9.41 g/d for hypertensives. A prospective cohort study by Qiu et al 18 shows that women who consume diet containing at least 21.2g of total fibre per day were at a 67% reduced risk of developing hypertension in pregnancy than those consuming less than 11.9d/day (RR = 0.33; 95% CI = 0.14-0.79) in addition to a reduction in triglycerides by 11.9mg/dL and improving HDL-cholesterol 19,20,21 .
A prospective cohort study conducted in Denmark on dietary intakes during pregnancy and the risk of hypertension, concluded that calcium, magnesium, folate, vitamin C, D, E or milk, did not affect the risk of hypertension 22 . Another prospective study in USA by Morris et al 23 also found no association between nutrition and hypertensive disorders of pregnancy. A decreased calcium intake signals the parathyroid gland to secrete parathyroid hormone. This hormone, together with vitamin D, leads to an increase in intracellular calcium by causing cell membrane permeability. The influx of calcium ions in the intracellular space leads to an increase in vascular smooth muscle contraction, and thus, an elevation in blood pressure 24 . Recommendations by the World Health Organization 25 for the prevention and treatment of hypertension in pregnancy, is to administer 1.5-2.0g of elemental calcium to pregnant women in areas where dietary intakes of calcium are low. Magnesium also plays a role in blood pressure regulation by stimulating the release of prostacyclin, a potent vasodilator, from endothelial cells which inhibits the activation of platelets for blood clots to increase blood pressure 26,27 .
Dietary anti-oxidant micronutrients have been shown to play a key role in endothelial function and the prevention of oxidative stress, which has been shown to be involved in PIH 28,29,30,31  For both hypertensive and normotensive groups, serum calcium levels were lower than the reference ranges (8.2-9.7 mg/dL), with the PIH women having higher levels than normotensives, although not statistically significant. Serum levels were higher among hypertensives, although did not reach statistical significance. A study by Biswas et al 36 reported that serum ferritin levels were significantly higher among hypertensives (90.41±37.39 ng/mL) than normotensives (25.71±11.38 ng/mL), with ferritin levels correlating positively with systolic (r = 0.5079, p-value = 0.004) and diastolic (r = 0.0660, p-value = 0.729) blood pressure. Serum ferritin is a reliable indicator for iron stores among healthy individuals, where low concentrations may indicate iron deficiency, however, among unhealthy individuals, and an increased level of ferritin signifies cellular damage or haemolysis 37 . High ferritin levels in pregnancy especially in the third trimester have been associated with poor pregnancy outcomes 37 . The low level of ferritin in healthy pregnancy is explained by the high foetal demand for iron in the third trimester for blood cell production 38 .
The abnormally elevated levels of urea and creatinine among hypertensives signifies impaired kidney function, which when not managed, may lead to chronic kidney disease 39,40 . This shows that high blood pressure is harmful to the health and functioning of the kidney. Also, the impaired fasting blood glucose levels among women with PIH may result in gestational diabetes, given blood glucose levels are not monitored and controlled. Owiredu 41 reported that women with PIH are at risk of metabolic syndrome.
Iron deficiency anaemia has been widely reported among pregnant women practicing geophagia 42 . In this study population, there was no significant effect of geophagia among normotensives, however, pregnant women practicing geophagia within the hypertensive group had significantly low levels of haemoglobin, haematocrit and ferritin levels. These parameters are indicators of iron deficiency which may complicate maternal disease condition, affect foetal health, lead to low birth weight infants and result in complication during delivery 43,44 . Low levels of calcium among the hypertensive group practicing geophagia may result in a further increase in blood pressure and lead to poor pregnancy outcomes.

Conclusion
In this study, the practice of geophagia during pregnancy is not associated with pregnancy-induced hypertension, however, this practice is detrimental to maternal health, especially those with pregnancy-induced hypertension. Women with PIH have altered haematology parameters, impaired fasting blood glucose and impaired kidney function, hence, have an increased risk of pregnancy and health complications such as anaemia and chronic kidney disease. Pregnant women under study had considerably low intakes of energy and micronutrients which is crucial in the third trimester as foetal demands for nutrients are increased.

Recommendations
During antenatal visits, pregnant women should be made aware of some dietary practices which are harmful during pregnancy, and increase education regarding the benefit of adequate nutrition. Nutrient supplementation should be administered to pregnant women, especially those living in low socioeconomic areas to supplement dietary intakes. A prospective cohort study of maternal dietary intakes in the entire pregnancy period should be conducted as well as blood biomarkers of nutrients to properly determine the role of nutrients in the development of hypertension in pregnancy.