The use of placebo-controlled trials in situations where established therapies are available is considered ethically problematic since the patients randomised to the placebo group are deprived of the beneficial treatment. The pharmaceutical industry and drug regulators seem to argue that placebo-controlled trials with extensive precautions and control measures in place should still be allowed since they provide necessary scientific evidence for the efficacy and safety of new drugs. On the other hand, the scientific value and usefulness for clinical decision-making may be much higher if the new drug is compared directly to existing therapies. As such, it may still be unethical to impose the burden and risk of placebo-controlled trials on patients even if extensive precautions are taken. A few exceptions do exist. The use of placebo-controlled trials in situations where an established, effective and safe therapy exists remains largely controversial.

Background: Breastfeeding is recognized as the optimal form of nutrition for the physical and neurological development of infants and is considered the most significant way to prevent child mortality. This study aimed to assess the effectiveness of metoclopramide for enhancing milk production in lactating women. Methods: We searched the Cochrane Central Register of Controlled Trials and MEDLINE for randomized controlled trials comparing metoclopramide with a placebo, no treatment, or other galactagogue drugs. We included breastfeeding women with term or preterm infants. Results: We retrieved 164 records from our search of the electronic databases and 20 records from other sources. Eight trials involving 342 lactating women that used metoclopramide were included in this review after assessing the eligibility criteria. The meta-analysis of these trials revealed that metoclopramide did not increase the milk volume of the intervention groups compared to that of the control groups. There was a significant increase in the serum concentrations of prolactin when the mothers were administered metoclopramide. No significant adverse events were reported. Conclusion Metoclopramide did not improve milk production in lactating women. Therefore, we do not recommend using metoclopramide to increase milk production in lactating women.

Background: Vitamin D may enhance immune system function and provide a protective effect against infections. Feto-maternal circulation plays an important role in supplying the developing fetus with nutrients and antibodies for its development and health during pregnancy and for its early years of life after birth. This meta-analysis aimed to determine the effectiveness of maternal vitamin D supplementation in preventing respiratory tract infections (RTIs) in children. Methods: We searched the Central and MEDLINE databases and went through all the reference lists in the related articles. We also searched for ongoing trials at http://www.who.int/ictrp/en/ and www.clinicaltrials.gov. Randomized controlled trials comparing vitamin D supplementation with a placebo or no treatment in pregnant women published in the English language up to March 2019 were included. Two reviewers extracted data independently using a predefined protocol and assessed the risk of bias using the Cochrane risk of bias tool, with differences agreed upon by consensus. The predefined primary outcome was the number of offspring who had RTIs. The secondary outcome was the presence of measurable serum immunoglobulin E levels. Results: Three trials involving 3,224 participants (mother–child pairs) met the inclusion criteria and were included in this review. The present analysis reported that maternal supplementation with vitamin D had no effect on RTIs among children (n=1,486 offspring; risk ratio, 0.95; 95% confidence interval, 0.82–1.11; random effects; I2 statistics, 0%). Conclusion Maternal vitamin D supplementation had no effect on RTIs in children. Therefore, consideration of other prevention methods in this regard is recommended.