1.
Interventions for leg cramps in pregnancy.
Luo, L, Zhou, K, Zhang, J, Xu, L, Yin, W
The Cochrane database of systematic reviews. 2020;(12):CD010655
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Abstract
BACKGROUND Leg cramps are a common problem in pregnancy. Various interventions have been used to treat them, including drug, electrolyte and vitamin therapies, and non-drug therapies. This Cochrane Review is an update of a review first published in 2015. OBJECTIVES To assess the effectiveness and safety of different interventions for treating leg cramps in pregnancy. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (25 September 2019), and reference lists of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs) of any intervention for the treatment of leg cramps in pregnancy compared with placebo, no treatment or other treatments. Quinine was excluded for its known adverse effects. Cluster-RCTS were eligible for inclusion. Quasi-RCTs and cross-over studies were excluded. DATA COLLECTION AND ANALYSIS Three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS We included eight small studies (576 women). Frequency of leg cramps was our primary outcome and secondary outcomes included intensity and duration of leg cramps, adverse outcomes for mother and baby and health-related quality of life. Overall, the studies were at low or unclear risk of bias. Outcomes were reported in different ways, precluding the use of meta-analysis and thus data were limited to single trials. Certainty of evidence was assessed as either low or very-low due to serious limitations in study design and imprecision. Oral magnesium versus placebo/no treatment The results for frequency of leg cramps were inconsistent. In one study, results indicated that women may be more likely to report never having any leg cramps after treatment (risk ratio (RR) 5.66, 95% confidence interval (CI) 1.35 to 23.68, 1 trial, 69 women, low-certainty evidence); whilst fewer women may report having twice-weekly leg cramps (RR 0.29, 95% CI 0.11 to 0.80, 1 trial, 69 women); and more women may report a 50% reduction in number of leg cramps after treatment (RR 1.42, 95% CI 1.09 to 1.86, 1 trial, 86 women, low-certainty evidence). However, other findings indicated that magnesium may make little to no difference in the frequency of leg cramps during differing periods of treatment. For pain intensity, again results were inconsistent. Findings indicated that magnesium may make little or no difference: mean total pain score (MD 1.80, 95% CI -3.10 to 6.70, 1 trial, 38 women, low-certainty evidence). In another study the evidence was very uncertain about the effects of magnesium on pain intensity as measured in terms of a 50% reduction in pain. Findings from another study indicated that magnesium may reduce pain intensity according to a visual analogue scale (MD -17.50, 95% CI -34.68 to -0.32,1 trial, 69 women, low-certainty evidence). For all other outcomes examined there may be little or no difference: duration of leg cramps (low to very-low certainty); composite outcome - symptoms of leg cramps (very-low certainty); and for any side effects, including nausea and diarrhoea (low certainty). Oral calcium versus placebo/no treatment The evidence is unclear about the effect of calcium supplements on frequency of leg cramps because the certainty was found to be very low: no leg cramps after treatment (RR 8.59, 95% CI 1.19 to 62.07, 1 study, 43 women, very low-certainty evidence). In another small study, the findings indicated that the mean frequency of leg cramps may be slightly lower with oral calcium (MD -0.53, 95% CI -0.72 to -0.34; 1 study, 60 women; low certainty). Oral vitamin B versus no treatment One small trial, did not report on frequency of leg cramps individually, but showed that oral vitamin B supplements may reduce the frequency and intensity (composite outcome) of leg cramps (RR 0.29, 95% CI 0.11 to 0.73; 1 study, 42 women). There were no data on side effects. Oral calcium versus oral vitamin C The evidence is very uncertain about the effect of calcium on frequency of leg cramps after treatment compared with vitamin C (RR 1.33, 95% CI 0.53 to 3.38, 1 study, 60 women, very low-certainty evidence). Oral vitamin D versus placebo One trial (84 women) found vitamin D may make little or no difference to frequency of leg cramps compared with placebo at three weeks (MD 2.06, 95% CI 0.58 to 3.54); or six weeks after treatment (MD 1.53, 95% CI 0.12 to 2.94). Oral calcium-vitamin D versus placebo One trial (84 women) found oral calcium-vitamin D may make little or no difference to frequency of leg cramps compared with placebo after treatment at three weeks (MD -0.30, 95% CI -1.55 to 0.95); and six weeks (MD 0.03, 95% CI -1.3 to 1.36). Oral calcium-vitamin D versus vitamin D One trial (84 women) found oral calcium-vitamin D may make little or no difference to frequency of leg cramps compared with vitamin D after treatment at three weeks (MD -1.35, 95% CI -2.84 to 0.14); and six weeks after treatment (MD -1.10, 95% CI -2.69 to 0.49). AUTHORS' CONCLUSIONS It is unclear from the evidence reviewed whether any of the interventions provide an effective treatment for leg cramps. This is primarily due to outcomes being measured and reported in different, incomparable ways so that data could not be pooled. The certainty of evidence was found to be low or very-low due to design limitations and trials being too small to address the question satisfactorily. Adverse outcomes were not reported, other than side effects for magnesium versus placebo/no treatment. It is therefore not possible to assess the safety of these interventions. The inconsistency in the measurement and reporting of outcomes meant that meta-analyses could not be carried out. The development of a core outcome set for measuring the frequency, intensity and duration of leg cramps would address these inconsistencies and mean these outcomes could be investigated effectively in the future.
2.
Clinical characteristics and bisphosphonates treatment of rare pregnancy- and lactation-associated osteoporosis.
Li, LJ, Zhang, J, Gao, P, Lv, F, Song, YW, Chang, XY, Zhao, DC, Wang, O, Jiang, Y, Xing, XP, et al
Clinical rheumatology. 2018;(11):3141-3150
Abstract
Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disorder with poorly known etiology, pathophysiology, and therapy. We aimed to investigate the clinical characteristics of PLO and evaluate the effectiveness and safety of bisphosphonates on it. A total of 12 patients were diagnosed with PLO on the basis of medical history, bone mineral density (BMD), and/or fragility fractures during pregnancy and lactation. We investigated the clinical, biochemical, and radiological characteristics of patients. We assessed the effects of alendronate or zoledronic acid through observing the changes of bone turnover biomarkers and BMD during the treatment. Secondary osteoporosis was excluded by comprehensive differential diagnosis. The mean age of these patients was 31 ± 5 years old. All of these patients presented severe back pain. Multiple vertebral compression fractures (VCFs) were found in 10 patients, and the median (P25th, P75th) number of compressed vertebra was 3 (3, 5). Ten patients had vitamin D insufficiency or deficiency. Serum level of bone resorption marker (β-CTX with mean of 0.68 ± 0.41 ng/ml) was moderately higher than the normal range. BMD at lumbar spine, femoral neck, and total hip were low as 0.894 ± 0.153 g/cm2, 0.728 ± 0.090 g/cm2, and 0.728 ± 0.080 g/cm2, respectively. Either alendronate or zoledronic acid could effectively relieve bone pain, reduce β-CTX level, and increase BMD. PLO is a rare type of osteoporosis, which was characterized by increased bone resorption and decreased BMD, even VCFs. Bisphosphonate therapy was well tolerated and effective in management of PLO, but needed to be further verified in randomized controlled trial.
3.
Interventions for leg cramps in pregnancy.
Zhou, K, West, HM, Zhang, J, Xu, L, Li, W
The Cochrane database of systematic reviews. 2015;(8):CD010655
Abstract
BACKGROUND Leg cramps are a common problem in pregnancy. Various interventions have been used to treat them, including drug, electrolyte and vitamin therapies, and non-drug therapies. OBJECTIVES To assess the effectiveness and safety of different interventions for treating leg cramps in pregnancy. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Register (31 March 2015) and reference lists of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs) of any intervention (drug, electrolyte, vitamin or non-drug therapies) for treatment of leg cramps in pregnancy compared with placebo, no treatment or other treatment. Quinine was excluded for its known adverse effects (teratogenicity). Cluster-RCTS were considered for inclusion. Quasi-RCTs and cross-over studies were excluded. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS We included six studies (390 women). Four trials compared oral magnesium with placebo/no treatment, two compared oral calcium with no treatment, one compared oral vitamin B versus no treatment, and one compared oral calcium with oral vitamin C. Two of the trials were well-conducted and reported, the other four had design limitations. The process of random allocation was sub-optimal in three studies, and blinding was not attempted in two. Outcomes were reported in different ways, precluding the use of meta-analysis and limiting the strength of our conclusions.The 'no treatment' group in one four-arm trial has been used as the comparison group for the composite outcome (intensity and frequency of leg cramps) in magnesium, calcium, and vitamin B versus no treatment. This gives it disproportionate weight in the overall analysis, thus interpretation of these results should be cautious. Oral magnesium versus placebo/no treatmentMagnesium (taken orally for two to four weeks) did not consistently reduce the frequency of leg cramps compared with placebo or no treatment. Outcomes that showed differences were: frequency of leg cramps after treatment: never, and twice a week (risk ratio (RR) 5.66, 95% confidence interval (CI) 1.35 to 23.68, one trial, 69 women, evidence graded low; RR 0.29, 95% CI 0.11 to 0.80, one trial, 69 women), and frequency of leg cramps: 50% reduction in number of leg cramps after treatment (RR 1.42, 95% CI 1.09 to 1.86, one trial, 86 women, evidence graded low). The outcomes that showed no difference were: frequency of leg cramps during two weeks of treatment (mean difference (MD) 1.80, 95% CI -1.32 to 4.92, one trial, 38 women, evidence graded low); frequency of leg cramps after treatment: daily, every other day, and once a week (RR 1.20, 95% CI 0.45 to 3.21, one trial, 69 women; RR 0.44, 95% CI 0.12 to 1.57, one trial, 69 women; RR 1.54, 95% CI 0.62 to 3.87, one trial, 69 women).Evidence about whether magnesium supplements reduced the intensity of pain was inconclusive, with two studies showing that it may slightly reduce pain, while one showed no difference. There were no differences in the experience of side effects (including nausea, flatulence, diarrhoea and intestinal air) between pregnant women receiving magnesium compared with placebo/no treatment. Oral calcium versus no treatmentA greater proportion of women receiving calcium supplements experienced no leg cramps after treatment than those receiving no treatment (frequency of leg cramps after treatment: never RR 8.59, 95% CI 1.19 to 62.07, one study, 43 women, evidence graded very low). There was no difference between groups for a composite outcome (intensity and frequency) for partial improvement (RR 0.64, 95% CI 0.36 to 1.15, one trial, 42 women); however, the same trial showed a greater proportion of women experiencing no leg cramps after treatment with calcium compared with no treatment (RR 5.50, 95% CI 1.38 to 21.86).Other secondary outcomes, including side effects, were not reported. Oral vitamin B versus no treatment Frequency of leg cramps was not reported in the one included trial. According to a composite outcome (frequency and intensity), more women receiving vitamin B fully recovered compared with those receiving no treatment (RR 7.50, 95% CI 1.95 to 28.81). Those women receiving no treatment were more likely to experience a partial improvement in the intensity and frequency of leg cramps than those taking vitamin B (RR 0.29, 95% CI 0.11 to 0.73, one trial, 42 women), or to see no change in their condition. However, these results are based on one small study with design limitations.Other secondary outcomes, including side effects, were not reported. Oral calcium versus oral vitamin CThere was no difference in the frequency of leg cramps after treatment with calcium versus vitamin C (RR 1.33, 95% CI 0.53 to 3.38, one study, 60 women, evidence graded very low). Other outcomes, includingside effects, were not reported. AUTHORS' CONCLUSIONS It is unclear from the evidence reviewed whether any of the interventions (oral magnesium, oral calcium, oral vitamin B or oral vitamin C) provide an effective treatment for leg cramps. This is primarily due to outcomes being measured and reported in different, incomparable ways, and design limitations compromising the quality of the evidence (the level of evidence was graded low or very low). This was mainly due to poor study design and trials being too small to address the question satisfactorily.Adverse outcomes were not reported, other than side effects for magnesium versus placebo/no treatment. It is therefore not possible to assess the safety of these interventions.The inconsistency in the measurement and reporting of outcomes, meant that data could not be pooled, meta-analyses could not be carried out, and comparisons between studies are difficult.The review only identified trials of oral interventions (magnesium, calcium, vitamin B or vitamin C) to treat leg cramps in pregnancy. None of the trials considered non-drug therapies, for example, muscle stretching, massage, relaxation, heat therapy, and dorsiflexion of the foot. This limits the completeness and applicability of the evidence.Standardised measures for assessing the frequency, intensity and duration of leg cramps to be used in large well-conducted randomised controlled trials are needed to answer this question. Trials of non-drug therapies are also needed.