Effect of levothyroxine on pregnancy outcomes in women with thyroid autoimmunity: a systematic review with meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate whether levothyroxine is associated with improved live birth and other benefits in women with thyroid autoimmunity. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women positive for thyroid peroxidase antibody. INTERVENTION(S): MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched without any language restrictions. Pooled effect sizes were calculated using random-effects models. MAIN OUTCOME MEASURE(S): The primary outcome was the incidence of live birth, miscarriage, preterm birth, clinical pregnancy, ectopic pregnancy, neonatal admission, and birth weight. The summary measures were reported as relative risk (RR) with 95% confidence interval. RESULT(S): Levothyroxine supplementation was not associated with an increased rate of live birth or a decreased risk of miscarriage. Results were similar in subgroup analyses of live birth by age, baseline thyrotropin, baseline thyroid peroxidase antibody, body mass index, and use of assisted conception. For live birth, the effect estimate lay within the futility boundary for RR of 20% and 15%, but at a 10% RR, the effect estimate lay between the futility boundary and the inferior boundary. CONCLUSION(S): High- to moderate-quality evidence demonstrated that the use of levothyroxine was not associated with improvements in clinical pregnancy outcomes among women positive for thyroid peroxidase antibody. REGISTRATION NUMBER: PROSPERO CRD42019132976.

Association between vitamin D supplementation and mortality: systematic review and meta-analysis.

OBJECTIVE: To investigate whether vitamin D supplementation is associated with lower mortality in adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group. MAIN OUTCOME MEASURES: All cause mortality. RESULTS: 52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality. CONCLUSIONS: Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality. STUDY REGISTRATION: PROSPERO registration number CRD42018117823.