Progestogens and preterm birth—not the hoped for panacea?

2066 www.thelancet.com Vol 387 May 21, 2016 Preterm birth is the most common cause of neonatal morbidity and mortality globally, aff ecting about 15 million children every year. Of children born preterm, an estimated 2·4 million (15·6%) are born extremely preterm (before 28 weeks gestation) or very preterm (before 32 weeks gestation). Furthermore, some 1 million children every year die as a consequence of preterm birth or its complications. In 2014, the Preterm Birth Priority Setting Partnership in the UK identifi ed prediction and prevention of preterm birth as the top research priority in this area. Progesterone has been considered a promising therapeutic agent to prevent preterm birth. Having been assessed in several small, randomised trials in the 1960s and 1970s, a meta-analysis by Keirse identifi ed a reduction in the occurrence of preterm birth after antenatal use of progesterone. This fi nding inspired others to undertake new randomised trials, and in 2003, both Meis and colleagues and Da Fonseca and colleagues reported a reduction of preterm birth in women with previous preterm birth after treatment with 17α-hydroxyprogesterone caproate and vaginal progesterone, respectively. Subsequent meta-analysis (incorporating both intramuscular and vaginal preparations) confi rmed that progestogens could prolong pregnancy, and were associated with a reduction in shortterm neonatal mortality and morbidity. However, it remains uncertain whether this approach is associated with improvements in long-term outcomes for children. Whereas longer duration of pregnancy is often related to Progestogens and preterm birth—not the hoped for panacea? long as most of us remember. Its effi cacy has never been properly established or quantifi ed in chronic diseases, and is probably not as great as many would believe. Its safety is also questioned, not just in overdose. Is recommending it as the universal fi rst-line analgesic in osteoarthritis still tenable? Many patients could be suff ering needlessly because of perceived NSAIDs risks and paracetamol benefi ts (which might not be real). Perhaps researchers need to reassess both these perceptions (or misconceptions) and the use of other analgesic options that have been discarded over time, such as dipyrone. Certainly, opioids are not a good solution for benign pain. Chondroitin sulphate or glucosamine might not be very eff ective either but could be safer than paracetamol or opioids. Other herbal preparations might also warrant scrutiny. A crucial need remains to fi nd new painkillers for osteoarthritis. Have any new analgesics been released since ibuprofen and diclofenac came out in the early 1970s, apart from the clinically minor COX-2 selective NSAIDs? All existing painkillers are merely minor variations on those early NSAIDs or opioids. Can’t we do better?