Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps. Does oral magnesium substitution relieve pregnancy-induced leg cramps? Randomised, cross-over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps. The effect of oral magnesium substitution on pregnancy-induced leg cramps. Calcium supplementation to prevent hypertensive disorders of pregnancy. Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial. Calcium treatment of leg cramps in pregnancy. Effect on clinical symptoms and total serum and ionized serum calcium concentrations. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Calcium supplementation and prevention of pregnancy induced hypertension.
60 pregnant women underwent a double blind trial with calcium or ascorbic acid (1 g twice daily) as treatment for leg cramps. There was no significant difference between the two treatment groups with respect to clinical improvement. In 14 out of 60 patients the symptoms were totally abolished and in another 27 patients the symptoms were significantly decreased by the treatment (irrespective of drug used). In 17 patients the symptoms were unaffected while only two patients experienced an increase in frequency of their leg cramps during therapy. Serum total and ionized calcium concentrations, serum total magnesium and albumin concentrations were determined and were not significantly changed throughout therapy in any of the groups. No biochemical differences were found between the different treatment regimens or between those patients relieved or not relieved of their symptoms. Serum magnesium concentrations were at or just below the lower normal limit (for non pregnant women) in treated women and pregnant controls. Our aim was to assess the effect of 360mg magnesium oral substitution daily among pregnant women suffering from leg cramps in pregnancy, defined as painful cramps different from restless legs symptoms.
                In a double blind randomised controlled trial healthy pregnant women between 18 and 36 weeks of pregnancy suffering from painful leg cramps, at least twice a week, were invited to participate. Forty-five women were enrolled initially, 38 completed the treatment and were treated during 2 weeks with either magnesium (360mg=15mmol magnesium lactate and magnesium citrate, Nycoplus Magnesium), or placebo tablets. Serum magnesium and calcium were investigated together with urine magnesium and magnesium-creatinin ratio on day 1 and day 15. Frequency and intensity of leg cramps were recorded. The study was powered to detect a 50% reduction in leg cramps.
                Registration of pain frequency and intensity during the two study weeks demonstrated no significant differences between the two groups. Mean number and intensity of cramps were 9.5 (S.D. 5.1) and 13.2 (S.D. 6.5) in the magnesium group, compared to 7.7 (S.D. 4.7) and 11.4 (S.D. 8.5) in the placebo group. Baseline magnesium levels were 0.77 and 0.74mmol/L in the magnesium group and the placebo group, respectively No significant differences between the two groups, or within the groups, were found when comparing serum values of serum magnesium and total calcium at inclusion time and at the end of the treatment. There was a statistically significant increase in magnesium excretion in the magnesium treatment group (p<0.01). The number of dropouts was two in the treatment group and five in the control group.
                No significant effect on frequency or intensity of leg cramps in pregnant women of magnesium treatment with 360mg daily could be detected in this trial. Nocturnal leg cramps are common and distressing. The only treatment of proven effectiveness is quinine, but this has a number of side effects. Magnesium salts have been shown to reduce leg cramp distress in pregnancy. This study tests whether magnesium citrate is effective in the treatment of leg cramps in non-pregnant individuals by conducting in a randomised, double-blind, cross-over placebo-controlled trial.
                Volunteers suffering regular leg cramps were recruited. Magnesium citrate equivalent to 300 mg magnesium and matching placebo were given for 6 weeks each. The number of cramps recorded in the cramp diary during the final 4 weeks of magnesium and placebo treatment, severity and duration of cramps and the participants' subjective assessment of effectiveness were analysed.
                In subjects who started with placebo (n=29) the median (95% CI) number of cramps was 9 (6-17) on placebo and 5 (4-8) on magnesium. For the group starting with magnesium (n=17) the median no of cramps was 9 (5-13) on magnesium and 8 (4-14) on placebo. There was no significant carry-over effect (p=0.88), but a highly significant period effect (p=0.008). There was a trend towards less cramps on magnesium (p=0.07). There was no difference in cramp severity and duration between the groups. Significantly more subjects thought that the treatment had helped after magnesium than after placebo 36 (78%) and 25 (54%) respectively, (p=0.03). Diarrhoea was recorded as a side effect of magnesium.
                The results suggest that magnesium may be effective in treatment of nocturnal leg cramps. Further evaluation is recommended. Our purpose was to determine whether women with pregnancy-related leg cramps would benefit from oral magnesium supplementation.
                Seventy-three women with pregnancy-related leg cramps were interviewed about their symptoms in a prospective, double-blind, randomized trial. Initial serum magnesium levels and diurnal magnesium excretion was determined in 50% of the patients. Oral magnesium or placebo was given for 3 weeks, after which new interviews and laboratory analyses were performed.
                Serum magnesium levels in these patients were at or below the lower reference limit, as is also often the case in healthy pregnant patients. Oral magnesium substitution decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001 compared with initial complaints), but did not significantly increase serum magnesium levels, excess magnesium being excreted as measured by an increase in urinary magnesium levels (p < 0.002).
                Oral magnesium supplementation seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg cramps. Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response.
                We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined.
                The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by life-table analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller.
                Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy. A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone. Up to 30 per cent of pregnant women suffer from leg cramps. The cause of these cramps is not known, but changes in calcium concentration have been suggested. Therefore 42 pregnant women with leg cramps were studied. No differences in total serum or ionized serum calcium concentrations were found as compared with a control group of pregnant women without leg cramps. Twenty-one patients were treated with 1 g calcium orally twice daily for 2 weeks and in this group good clinical improvement was achieved (p less than 0.001). The treatment increased the total serum calcium concentration from 2.25 mmol/l to 2.30 mmol/l but did not alter the ionized serum calcium concentration. Twenty-one untreated patients had the same frequency of cramps and showed no change in serum calcium concentrations throughout the investigation. Results are presented of a randomized, double-blinded controlled clinical trial of calcium supplementation (2.0 gm of elemental calcium as calcium carbonate) and a placebo. All participants were 17 years of age or less and clinically healthy. Patients were enrolled by the twenty third week of gestation. The mean duration of calcium supplementation or placebo was approximately 14 weeks. Treatment consisted of 2.8 (+/- 1.5) tablets per day in the placebo group (N = 95) and 3.0 (+/- 1.4) tablets per day in the calcium group (N = 94). Dietary calcium intake was similar in both groups at about 1200 mg/day. The calcium group had a lower incidence of preterm delivery (less than 37 weeks; 7.4% vs 21.1%; p = 0.007); spontaneous labor and preterm delivery (6.4% vs 17.9%; p = 0.01); and low birth weight (9.6% vs 21.1%; p = 0.03). This effect was also present after stratified analysis by level of treatment compliance, urinary tract infection, and chlamydial infection. Life-table analysis demonstrated an overall shift to a higher gestational age in the calcium group compared with the placebo group (log-rank test, p = 0.02). As suggested previously, the observed effect could be mediated by a reduction in uterine smooth muscle contractibility. If confirmed by future research, these results could represent an important preventive intervention for prematurity in high-risk populations. In a randomized controlled trial 201 healthy nulliparous women were randomly allocated by means of a computer generated randomization list. From 20 weeks of gestation until delivery they received either 2 g of oral elemental calcium (n = 103) per day or an identical placebo (n = 98). Eleven women (5.47%) were lost to follow-up after randomization. The study groups were very similar at the time of randomization; with respect to several clinical and demographic variables. Treatment compliance was very similar in both groups as was determined by pill count. The rate of pregnancy induced hypertension was lower in the calcium group than in the placebo group 8.24%; vs 29.03%; (RR = 0.28; 95% CI 0.14-0.59). The incidence of gestational hypertension was 6.18% in the calcium group and 17.20% in the placebo group (RR = 0.28; 95% CI 0.08-0.80), and the incidence of preeclampsia was 2.06% in the calcium group and 11.82% in the placebo group (RR = 0.13; 95% CI 0.01-0.64). In conclusion calcium supplementation given in pregnancy to nulliparous women reduces the incidence of pregnancy induced hypertension.
The evidence that calcium reduces cramp is weak and seems to depend on placebo effect. The evidence for sodium chloride is stronger but the results of the sodium chloride trial may no longer be relevant because of dietary changes which include an increased sodium intake in the general population. It is not possible to recommend multivitamins with mineral supplementation, as it is not clear which ingredient, if any, is helping. If a woman finds cramp troublesome in pregnancy, the best evidence is for magnesium lactate or citrate taken as 5mmol in the morning and 10mmol in the evening.
[Note: The five citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]