A computerized intervention to decrease the use of calcium channel blockers in hypertension. The clinical efficacy of oral tocolytic therapy. Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group. The use of a calcium antagonist (nifedipine) to suppress preterm labour. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Supplementary calcium in prevention of pre-eclampsia. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Trial of calcium to prevent preeclampsia. Terbutaline pump maintenance therapy for prevention of preterm delivery: a double-blind trial.
To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic.
                A randomized trial.
                The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System, Seattle Division.
                Clinic providers were randomized to a control group (n = 35) or intervention group (n = 36). We targeted the providers of patients being treated for hypertension with calcium channel blockers, a class of drug not recommended for initial therapy.
                An automated computer query identified eligible patients and their providers. A guideline reminder was placed in the charts of patients of intervention providers; the charts of patients of control providers received no reminder.
                During the 5-month study period, 346 patients were seen by the 36 primary care providers (staff physicians, nurse practitioners, residents, and fellows) in the intervention group, and 373 patients were seen by the 35 providers in the control group. Intervention providers changed 39 patients (11.3%) to other medications during the study period, compared with 1 patient (<1.0%) of control providers (p < .0001). For patients whose therapy was unchanged, providers noted angina in 23.1%, indications other than those for hypertension in 9.5%, intolerable adverse effects with first-line therapy in 13.9%, and inadequate control with first-line therapy in 13.9%. Of those patients without provider-indicated contraindications, 23.6% were switched from calcium channel blockers to first-line agents during the intervention period.
                The use of a computerized, clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general, and decreased the use of calcium channel blockers for the treatment of hypertension in particular. Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome.
                Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access.
                Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days.
                Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy. A multicentre, randomized controlled double-blind trial in 5 maternity hospitals in Australia assessed the effect of a daily supplement of calcium (1.8g oral calcium or an oral placebo) taken daily until delivery, from less than 24 weeks' gestation, on the frequency of pregnancy-induced hypertension, preeclampsia and preterm birth (< 37 weeks' gestation) in 456 nulliparas with a singleton pregnancy. Treatment with calcium reduced the risk of preeclampsia (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02) and the risk of preterm birth (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02). No significant differences were seen between the 2 groups in the frequency of pregnancy-induced hypertension, although the study only had statistical power to detect large differences in this outcome. An updated systematic review of the 9 randomized trials of calcium supplementation in pregnancy shows a significant reduction in the risk of hypertension and preeclampsia although no effect on preterm birth. Calcium supplementation during pregnancy reduced the risk of preeclampsia and preterm birth in this nulliparous population. The available evidence for systematic review of all the randomized trials of calcium supplementation shows benefit in reducing the risk of hypertension and preeclampsia. The efficacy of an orally administered calcium antagonist, nifedipine, in suppressing premature uterine activity, was compared with intravenous ritodrine and no treatment. Nifedipine was found to be significantly more effective than ritodrine or withholding therapy, and was almost devoid of side-effects. 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. To study the effect of calcium supplementation on reduction of pre-eclampsia in Iranian women at high risk of pre-eclampsia.
                Thirty pregnant women at high risk of developing pre-eclampsia were randomized to 2 g of daily calcium and placebo. Subjects and investigators were blinded to treatment allocation. The inclusion criteria were positive rollover test, having at least one risk factor for pre-eclampsia, between 28 and 32 weeks of pregnancy, and blood pressure less than 140/90 (mm Hg). Exclusion criteria were having any chronic condition. Pre-eclampsia was defined as systolic/diastolic blood pressure over 140/90 plus proteinuria. All the subjects were followed up to delivery.
                A sevenfold reduction in the occurrence of pre-eclamsia were seen among the calcium group compared with the placebo group (7 out of 15 developed pre-eclampsia in control group vs. 1 out of 15 in calcium group, P=0.014). No major effect on pregnancy induced hypertension was seen (66% in placebo and 76% in calcium group developed hypertension) but the onset of hypertension was delayed 3 weeks in the calcium group. A longer duration of pregnancy was seen in calcium than placebo (mean+/-S.D.=37+/-2 for calcium and 34+/-2 for placebo, P<0.05). Infants born to the calcium group, on average, were 552 g heavier than infants born to the placebo group, P<0.05.
                Calcium supplementation is beneficial for preventing pre-eclampsia among Iranian women at high risk of developing pre-eclampsia. The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery.
                Randomized placebo-controlled, double-blinded trial in nulliparous normotensive women from populations with dietary calcium < 600 mg/d. Women who were recruited before gestational week 20 received supplements (1.5 g calcium/d or placebo) throughout pregnancy. Primary outcomes were preeclampsia and preterm delivery; secondary outcomes focused on severe morbidity and maternal and neonatal mortality rates.
                The groups comprised 8325 women who were assigned randomly. Both groups had similar gestational ages, demographic characteristics, and blood pressure levels at entry. Compliance were both 85% and follow-up losses (calcium, 3.4%; placebo, 3.7%). Calcium supplementation was associated with a non-statistically significant small reduction in preeclampsia (4.1% vs 4.5%) that was evident by 35 weeks of gestation (1.2% vs 2.8%; P = .04). Eclampsia (risk ratio, 0.68: 95% CI, 0.48-0.97) and severe gestational hypertension (risk ratio, 0.71; 95% CI, 0.61-0.82) were significantly lower in the calcium group. Overall, there was a reduction in the severe preeclamptic complications index (risk ratio, 0.76; 95% CI, 0.66-0.89; life-table analysis, log rank test; P = .04). The severe maternal morbidity and mortality index was also reduced in the supplementation group (risk ratio, 0.80; 95% CI, 0.70-0.91). Preterm delivery (the neonatal primary outcome) and early preterm delivery tended to be reduced among women who were < or = 20 years of age (risk ratio, 0.82; 95% CI, 0.67-1.01; risk ratio, 0.64; 95% CI, 0.42-0.98, respectively). The neonatal mortality rate was lower (risk ratio, 0.70; 95% CI, 0.56-0.88) in the calcium group.
                A 1.5-g calcium/day supplement did not prevent preeclampsia but did reduce its severity, maternal morbidity, and neonatal mortality, albeit these were secondary outcomes. Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data.
                We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations.
                Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 women in the calcium group (6.9 percent) and 168 of the 2294 women in the placebo group (7.3 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.16). There were no significant differences between the two groups in the prevalence of pregnancy-associated hypertension without preeclampsia (15.3 percent vs. 17.3 percent) or of all hypertensive disorders (22.2 percent vs. 24.6 percent). The mean systolic and diastolic blood pressures during pregnancy were similar in both groups. Calcium did not reduce the numbers of preterm deliveries, small-for-gestational-age births, or fetal and neonatal deaths; nor did it increase urolithiasis during pregnancy.
                Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women. This study's aim was to determine whether maintenance therapy with terbutaline administered by pump prolongs gestation in women after treatment with intravenous magnesium sulfate tocolysis for suspected preterm labor.
                Consenting women with a singleton gestation and intact membranes who had uterine contractions and >1 cm cervical dilation, 80% effacement, or progressive cervical change and whose contractions were successfully arrested with intravenous magnesium were randomly assigned to receive either terbutaline or normal saline solution placebo by subcutaneous infusion pump. Pump therapy was administered with a standardized protocol. Pump therapy was discontinued and parenteral magnesium was resumed if recurrent preterm labor developed while women were on the therapeutic regimen at <34 weeks' gestation and no contraindication for tocolysis existed. If recurrent labor was arrested, pump therapy was restarted according to the original treatment group. A sample size of 48 women was required to detect a 2-week intergroup difference in mean time to delivery. Analyses were based on intent to treat.
                Fifty-two women received terbutaline (n = 24) or placebo (n = 28). At random assignment the groups were similar with respect to age, race, parity, previous preterm delivery, gestational age, and cervical examination. Overall there was a 1-day difference in mean time to delivery between the groups (terbutaline 29 +/- 22 days and placebo 28 +/- 23 days, P = .78). There were no differences in the rates of preterm delivery at <34 and <37 weeks' gestation. Neonatal outcomes were similar.
                Maintenance terbutaline therapy administered by pump does not prolong gestation in women successfully treated for suspected preterm labor.
The role of maintenance therapy with calcium channel blockers for preventing preterm birth is not clear. Well designed randomised trials of sufficient size with relevant outcomes are required.
[Note: The four citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]