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

MICA：资源匮乏地区肥胖孕妇预防妊娠期糖尿病和先兆子痫的实用方法

• 批准号: MR/R019142/1
• 负责人: Jane Norman
• 金额: $ 22.78万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR019142%2F1
• 关键词: MICA; pragmatic; approach; prevention; gestational

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

妊娠糖尿病（妊娠期血糖过高）和妊娠期高血压疾病（妊娠期发生的高血压，可导致母亲发病和婴儿死亡）在低收入和中等收入国家造成严重的孕产妇和新生儿死亡率和发病率，而且没有系统的预防办法。妊娠糖尿病的全球患病率估计为16%，南亚和非洲的患病率更高[1]。妊娠糖尿病增加了剖腹产、妊娠高血压疾病、出生体重过高、出生损伤、未来肥胖和未来糖尿病等不良结局的发生率：未经治疗，它会促成一个循环，促进后代的肥胖和糖尿病[2]。妊娠期高血压疾病占社会经济水平低的国家孕产妇死亡的17.3%，是仅次于出血的第二大孕产妇死亡原因[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。由于检测和血糖监测的成本高，而且缺乏血糖监测工具包，这种方法在资源贫乏的环境中是不合适的。然而，测量孕妇体重指数（体重和身高）便宜，有效地确定了一个高风险组的妊娠糖尿病和妊娠高血压疾病。此外，妊娠期糖尿病的治疗方法之一（二甲双胍）相对便宜，广泛可用，并且安全，无论血糖水平如何[4-6]。最近的体外和临床数据表明，二甲双胍可能降低妊娠期高血压疾病的发生率和严重程度[6-8]。我们建议二甲双胍可能是一种预防资源匮乏地区肥胖孕妇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，以确定二甲双胍是否能有效预防妊娠期糖尿病和妊娠期高血压疾病的高危妇女。在这项可行性研究中，我们会看看是否有可能进行全面试验，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研究中心的肥胖孕妇服用二甲双胍或匹配的安慰剂片剂。我们将看到有多少女性希望参与，有多少人接受治疗，以及治疗的效果如何。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有多常见。尽管这项可行性研究规模太小，无法回答“二甲双胍常规给药是否是预防资源匮乏环境中肥胖孕妇妊娠期糖尿病和妊娠期高血压疾病的实用方法”这一问题，但它将有助于开展更大规模（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开展可行性研究和进一步实质性研究所需的专业知识，我们有能力将研究结果转化为临床实践。国际糖尿病联合会（IDF）糖尿病地图集，第7版，2015.2。妊娠期糖尿病NICE指南2015.3。全球疾病负担孕产妇死亡率和死亡率合作者，柳叶刀，2016年。388：第1775-1812.4页。巴塞尔，M.，例如，BMJ，2015. 350：第h102.5页。奇斯威克，例如，柳叶刀糖尿病内分泌，2015。[3]第778-86.6页。Syngelaki，A.，例如，N Engl J Med，2016. 374：第434-43.7页。布朗富特足球俱乐部例如，Am J Obstet Gynecol，2016. 214：第356 e1-356 e15.8页。罗梅罗河，巴西-地例如，Am J Obstet Gynecol，2017. 217：第282-302页