Background
In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB).
Objectives
To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA).
Search strategy
We searched international scientific databases, trial registration websites, and references of identified articles.
Selection criteria
Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.
Data collection and analysis
Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.
Main results
Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97–1.4, vaginal progesterone RR 0.97; 95% CI 0.77–1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47–0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42–0.75).
Author’s conclusions
In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.
Objective Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.Design Randomised controlled double-blind multicentre trial (1:1:1).Setting The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).Population Women with dichorionic diamniotic twin pregnancies.Methods The women self-inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention-to-treat basis.Main outcome measure Preterm birth rate.Results The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone-treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200-versus 400-mg progesterone groups. No serious adverse effects were encountered.Conclusions Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg progesterone dose offered no advantages over the 200-mg regimen.
Rupatadine 10 mg once daily was clearly superior to placebo in alleviating the symptoms of SAR over a 2-week period. In comparison with ebastine, rupatadine shows a trend towards a better profile as regard several secondary efficacy variables.
Temporary epicardial pacing wires are routinely placed in patients undergoing cardiac surgery. Eighteen suitable patients undergoing elective surgery were prospectively studied. Their sensing and stimulating characteristics were studied at various locations. Subepicardial pacing leads were applied to the lateral wall of the LV, apex of the LV, anterior wall of the RV, diaphragmatic wall of the RV, and diaphragmatic wall of the LV. Impedance, R wave amplitude, slew rate, and stimulation thresholds were measured on postoperative days 1 and 5. Impedance remained unchanged in time with no significant differences between locations. R waves and slew rates were significantly lower in the anterior RV wall. Stimulation thresholds displayed no differences on day 1, but they increased significantly in all locations on day 5. These thresholds were significantly lower in the lateral and diaphragmatic LV walls on day 5, and the rate of voltage increase was also lower in these two locations. Five patients presented phrenic nerve stimulation when stimulating the lateral LV wall. The authors advocate the diaphragmatic wall of the LV as the best location for placing temporary leads. The anterior wall of the RV is not recommended for pacing purposes.
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