The literature surrounding calcium supplementation in pre-eclampsia is conflicting and the mechanism by which calcium prevents pre-eclampsia remains unclear. Pre-eclampsia has a high prevalence in developing countries, which is where the greatest effect of calcium supplementation has been seen. A possible explanation may be that body calcium status and the need for supplementation in pregnancy vary by geographical location and diet within an area. Poverty in developing countries contributes to poor calcium intake, and therefore an association between developing countries, insufficient dietary calcium and a high prevalence of pre-eclampsia has been made.
Serum calcium is a poor indicator of chronic calcium status and cannot reflect calcium level over time. Hair is a stable and reliable indicator of long-term calcium status. Although there is no recognised normal range of hair calcium, the values obtained in this study have been used as a means to compare long-term calcium status between groups.
By matching women with pre-eclampsia to normotensive women with regard to age, gravidity, race and gestational age at delivery, no difference in demographic measurements was found between the groups. This was important as total body calcium levels may differ in women of varying ages and gestational age, and calcium intake may differ between ethnic groups as a result of dietary customs. The mean gestational age at booking for all participants in the study was 21 ± 6.64 weeks with few women having early pregnancy scans. Late booking and limited access to ultrasound scanning are common problems in our antenatal service. Differences in gestational age at delivery reached statistical significance in the total and HIV-negative groups, where woman suffering from pre-eclampsia delivered approximately 1 week earlier than matched controls. This result was anticipated, as women who are diagnosed with pre-eclampsia at Mowbray Maternity Hospital or Groote Schuur Hospital have their delivery expedited after 34 weeks of gestation.
The similarities in socio-economic status between the two groups make it possible to assume that women with pre-eclampsia and matched controls had equal opportunity to access similar diets and thus calcium intake.
The dietary questionnaire, previously used in a similar study, provided a broad dietary history of each participant. Although the questionnaire does not focus on exact quantities of food, it indicates definite deficiencies if they exist. During statistical analysis, it was found that the median value of the quantity of certain foodstuffs that were consumed was often zero, and data were converted from a continuous to a dichotomous variable (consumers or non-consumers) to facilitate analysis.
The dietary parameters measured in our study reviewed three groups of food: those naturally rich in calcium, foodstuffs that have been fortified with calcium and foods that impair calcium absorption in the gut. Generally, there was little difference in diet composition between women in the groups. In the HIV-positive group, some dietary differences reached statistical significance; however, this group contained few participants and these results were viewed with some reserve.
Insufficient caloric and nutrient intake associated with malnutrition in HIV infection may alter dietary calcium and long-term calcium status. In our study, calcium and magnesium levels in serum and hair did not differ between women with pre-eclampsia or matched controls when compared by HIV status. The similar values in calcium and magnesium levels in hair between the HIV-negative and HIV-positive groups might be because any real difference was obscured by the small numbers in the HIV-positive group or because immune suppression is not necessarily accompanied by weight loss.
In this study, serum calcium concentrations of non-supplemented women at delivery were significantly lower in those with pre-eclampsia than in matched controls in the total and HIV-negative groups. Although this difference was statistically significant, its clinical relevance is difficult to assess, given that all participants, with one exception, had serum calcium levels within the normal range.
Hair calcium levels showed no difference between women with pre-eclampsia and matched controls in any of the three groups, supporting the null hypothesis that there is no difference in the long-term calcium status between women with pre-eclamptic and normotensive pregnancies. Our analysis confirms that neither socio-economic status nor dietary intake had any influence on the outcome of the hair results.
Serum magnesium was higher in women with pre-eclampsia than in matched controls in all three groups. This finding was unexpected and was not attributable to impaired renal function. All women with pre-eclampsia in this study had normal or marginally raised creatinine levels (80–100 μmol/l) at recruitment. Women with pre-eclampsia who received magnesium sulphate therapy had significantly higher mean serum magnesium levels (0.88 ± 0.22 mmol/l) than women with pre-eclampsia who did not receive magnesium sulphate (0.74 ± 0.08 mmol/l). There was no statistically significant difference in serum magnesium level between those women with pre-eclampsia who did not receive magnesium sulphate therapy (0.74 ± 0.08 mmol/l) and the total matched control group (0.72 ± 0.07 mmol/l). Blood samples of participants who had received magnesium sulphate were drawn after a period of not less (and often longer) than 12 hours following completion of magnesium sulphate therapy to ensure complete excretion of exogenous magnesium. There was no significant difference in hair magnesium levels between women with pre-eclampsia and matched controls in the three groups. Residual exogenous magnesium probably contributed to the higher serum levels in women with pre-eclampsia. In future studies, the waiting period before sampling blood will need to be extended.
To date, this is the first study to investigate the long-term calcium status of women with pre-eclampsia through hair analysis. Using hair as an indicator of chronic calcium status in pre-eclamptic women is an accurate and reproducible method which future studies may use.
Women with early-onset pre-eclampsia were not recruited to this study as it would not be possible to match them to suitable controls, as women who deliver prior to 34 weeks of gestation cannot be considered to have had an uncomplicated pregnancy. Gestational age could be better determined with improved resources and access to antenatal care. Approximately 10% of recruited women were not included in the final analysis as they were unable to be matched, although statistical calculations showed that the findings of this study would not have been altered significantly had they been included. We acknowledge that the HIV group is too small to perform definitive analysis, and that the results presented in this study may not be applicable to ethnic groups other than black African women.
As this is the only study to investigate the relationship between hair calcium and pre-eclampsia, there is no literature against which we can compare our findings. It is reassuring to note that the hair calcium values in our study (range, 331–4654 ppm) were similar to those of studies performed in America (range, 188–4900 ppm), China (mean, 946 ppm) and Sweden (median, 1290 ppm; range, 231–5360 ppm). A study to compare the long-term calcium status of pregnant women in Cape Town and in developed countries will be necessary to investigate and confirm these results.