MICA: A pragmatic approach to the prevention of gestational diabetes and pre-eclampsia in obese pregnant women in resource poor settings

在低收入和中等收入国家，妊娠期糖尿病(妊娠期血液中糖分过高)和妊娠期高血压(妊娠期发生的高血压，可能导致母亲发病和婴儿死亡)造成大量孕产妇和新生儿死亡和发病率，而且没有系统的预防办法。据估计，全球妊娠期糖尿病患病率为16%，南亚和非洲的患病率较高[1]。妊娠期糖尿病会增加剖腹产、妊娠高血压疾病、出生体重过大、出生损伤、未来肥胖和未来糖尿病的不良后果的发生率：如果不进行治疗，它会导致一个循环，促进后代肥胖和糖尿病[2]。在社会经济水平较低的国家，妊娠期高血压疾病占孕产妇死亡的17.3%，是继出血之后第二常见的孕产妇死亡原因[3]。在资源丰富的国家，对高危妇女进行妊娠期糖尿病检测，同时对受影响的妇女进行治疗，并定期自我监测血糖水平。这种方法在资源匮乏的环境中是不合适的，因为测试和血糖监测的成本很高，而且缺乏血糖监测试剂盒。然而，测量孕妇的体重指数(体重和身高)廉价而有效地确定了妊娠期糖尿病和妊娠期高血压疾病的高危人群。此外，无论血糖水平如何，妊娠期糖尿病的一种治疗方法(二甲双胍)相对便宜、随处可得且安全。最近的体外和临床数据表明，二甲双胍可以降低妊娠期高血压疾病的发生率和严重程度[6-8]。我们认为二甲双胍可能是在资源匮乏的肥胖孕妇中预防妊娠期糖尿病和妊娠期高血压疾病的实用方法。这是一项临床试验的可行性研究，以确定二甲双胍在这两种疾病的高危女性中是否有效预防妊娠期糖尿病和妊娠期高血压疾病。在这项可行性研究中，我们将了解我们是否可以进行全面试验，这种试验的规模有多大，以及费用有多高。我们将要求马拉维和赞比亚参与试验地点的肥胖孕妇服用二甲双胍或匹配的安慰剂片。我们将看看有多少女性愿意参与，有多少人接受治疗，以及治疗产生了什么效果。我们还将能够看到妊娠期糖尿病和妊娠期高血压疾病在这一人群中的普遍程度。虽然这项可行性研究规模太小，无法回答这样一个问题，即在资源匮乏的情况下，常规应用二甲双胍是预防肥胖孕妇妊娠期糖尿病和妊娠期高血压疾病的务实方法吗？它将有助于开展一项更大规模(可能更昂贵)的研究。我们在马拉维、赞比亚和英国的临床医生、研究人员和政策制定者团队拥有必要的专业知识来开展可行性研究和进一步的实质性研究，我们处于有利地位，能够将研究结果转化为临床实践。国际糖尿病联合会糖尿病地图集，第7版，2015.2。尼斯，妊娠期糖尿病。不错的指导方针2015.3。全球疾病负担、孕产妇死亡率和发病率合作者，《柳叶刀》，2016。第388页：第1775-1812.4页。鲍尔赛尔斯，M.等人，《英国医学杂志》，2015年。350：P.H102.5。Chiswick等人，《柳叶刀糖尿病内分泌》，2015。3：第778-86.6页。等人，N Engl J Med，2016。374：第434-43.7页。布朗福特，F.C.，等人，Am J Obstet Gyneol，2016。214：第356页e1-356 e15.8页。罗梅罗，R.等人，Am J Obstet Gyneol，2017。第217页：第282-302页

Gestational diabetes (too much sugar in the blood in pregnancy) and pregnancy hypertensive disorders (high blood pressure that occurs in pregnancy, and which can lead to fits in the mother and death in the baby) cause significant maternal and neonatal mortality and morbidity in low and middle income countries and there is no systematic approach to prevention. The estimated global prevalence of gestational diabetes is 16%, with higher rates in in South Asia and Africa [1]. Gestational diabetes increases the incidence of the adverse outcomes of caesarean section, pregnancy induced hypertensive disease, excessive birthweight, birth injury, future obesity and future diabetes: untreated, it contributes to a cycle which promotes obesity and diabetes in future generations[2]. Pregnancy hypertensive disorders account for 17.3% of maternal deaths in low socio-economic countries, and are the second commonest cause of maternal death after haemorrhage[3].In resource rich countries, testing for gestational diabetes is undertaken in women at high risk, together with treatment of those affected and regular self-monitoring of blood sugar levels. Such an approach is inappropriate in resource poor settings due to the high cost of testing and blood sugar monitoring, and the lack of availability of blood sugar monitoring kits. However, measurement of maternal body mass index (weight and height) cheaply and effectively identifies a high-risk group for both gestational diabetes and pregnancy hypertensive disorders. Additionally, one of the treatments (metformin) for gestational diabetes is relatively cheap, widely available, and safe, regardless of blood sugar levels [4-6]. Recent in vitro and clinical data suggest that metformin might reduce the incidence and severity of pregnancy hypertensive disorders [6-8]. We propose that metformin could be a pragmatic approach to preventing gestational diabetes and pregnancy hypertensive disorders in obese pregnant women in resource poor settings.This is a feasibility study of a clinical trial to determine whether metformin is effective in preventing gestational diabetes and pregnancy hypertensive disorders in women at high risk of both conditions. In this feasibility study, we will find out if it is possible for us to do a full trial, how big such a trial would be, and how expensive it would be. We will ask obese pregnant women in participating sites in Malawi and Zambia to take either metformin or matching placebo tablets. We will see how many women wish to participate, how many take the treatment, and what effect the treatment has. We will also be able to see how common gestational diabetes and pregnancy hypertensive disorders are in this population. Although this feasibility study is too small to answer the question "Is routine administration of metformin a pragmatic approach to preventing gestational diabetes and pregnancy hypertensive disorders in obese pregnant women in resource poor settings" it will facilitate a larger (and likely more expensive study) to be able to do so. Our group of clinicians, researchers and policy makers in Malawi, Zambia and the UK has the necessary expertise to carry out both the feasibility study and a further substantive study, and we are well placed to be able to translate the results of the research into clinical practice.References1. International Diabetes Federation (IDF) IDF Diabetes Atlas, 7th Edition, 2015.2. NICE, Diabetes in pregnancy. NICE guideline 2015.3. Global Burden of Disease Maternal Mortality and Morbidity Collaborators, Lancet, 2016. 388: p. 1775-1812.4. Balsells, M., et al., BMJ, 2015. 350: p. h102.5. Chiswick, C., et al., Lancet Diabetes Endocrinol, 2015. 3: p. 778-86.6. Syngelaki, A., et al., N Engl J Med, 2016. 374: p. 434-43.7. Brownfoot, F.C., et al., Am J Obstet Gynecol, 2016. 214: p. 356 e1-356 e15.8. Romero, R., et al., Am J Obstet Gynecol, 2017. 217: p. 282-302