Does Metformin Improve Pregnancy Outcomes (Incidence of LGA (≥90% Birth Weight Centile) Babies, Onset of Maternal GDM, Hypertension, PET, Macrosomia, Shoulder Dystocia, Admission to SCBU) in Obese Non-diabetic Women?
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 450
- 试验地点
- 3
- 主要终点
- Birth Weight centile (z-score)
研究概览
简要总结
Obesity is on the rise in all developed countries. Of particular concern is that more young people including children are being recognised as being overweight or obese. We know from a recent large national enquiry into all maternal and child deaths in the UK, known as CEMACH, that obesity is a major risk both for the mother and her child. When all deaths in women during pregnancy are analysed, obesity comes out as the most common risk factor. Babies of obese mothers are more than 3 times as likely to need admission to the Neonatal Intensive Care Unit.
Traditionally, obesity is treated by lifestyle measures encouraging healthy eating and increasing physical activity. Unfortunately these measures are often insufficient to produce significant improvements in weight. If obese women gain little or even no weight during pregnancy, the outcome of the pregnancy is known to be improved. This was shown in a very large study of more than 120, 000 obese women.
The drug metformin has been used for years in the treatment of diabetes and more recently for polycystic ovary syndrome (PCOS). Studies in pregnant PCOS women and women with diabetes in pregnancy have shown it to be safe and effective. Fortunately it is relatively cheap and taken as a tablet with meals.
Metformin has the great advantage of not causing weight gain and often leads to a small amount of weight loss. It works by improving the body's sensitivity to insulin which is important as resistance to insulin is common in obesity.
We have a lot of experience using metformin to treat women with diabetes in pregnancy where it is greatly beneficial. We now wish to examine its potential for obese women who do not have diabetes. We are hoping to show that it will benefit these women by causing less weight gain, less high blood pressure, and less diabetes. We anticipate babies will also have better birth weights, will be easier to deliver naturally, will not need to go to special care baby units and will be healthier.
详细描述
Obesity in Pregnancy has been identified by the Confidential Enquiry into Maternal and Child Health [CEMACH] report (2007) as a major health risk to mother and baby:
- 35% of women who died were obese
- 30% of the mothers who had a stillbirth or a neonatal death were obese
Obesity increases the risk of miscarriages, GDM, pregnancy-induced hypertension/PET, Caesarean sections, deep venous thrombosis, puerperal sepsis and LGA babies. There is a 5-fold increase in costs of antenatal care. Results from various studies have concluded that limited or no weight gain during pregnancy in obese women results in more favourable pregnancy outcomes. By improving insulin sensitivity and enhancing GLP-1 release, metformin is associated with weight reduction by approximately 5.8% with no serious adverse events.
The aim of this study is to test the hypothesis that management of obese non-diabetic pregnant women with standardised life-style intervention (diet and physical activity) plus metformin will lead to improved maternal and perinatal outcomes compared with life-style intervention alone.
The study will also seek to determine whether metformin will improve body fat distribution as measured by bioimpedance during pregnancy with particular emphasis on metabolic active visceral fat.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 19 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Obese pregnant women with BMI>35
- •Informed written consent
排除标准
- •Diabetes at booking
- •Presence of contra-indication to metformin(renal, liver, heart failure)
- •moving out of study area for pregnancy management
- •Participants who suffer with hyperemesis
- •Participants who are 18 years and below
- •Participants with significantly raised creatinine
- •Participants with high alcohol intake
研究组 & 干预措施
Metformin
Tablet Metformin 500 mg, starting dose of 1 tablet twice a day with meals, gradually titrated upwards by 1 tablet every week to a maximum dose of 2 tablets three times a day.
Tablets started at recruitment and continued till the delivery of the baby
干预措施: Metformin (Drug)
Placebo
Tablet Placebo 500 mg, starting dose of 1 tablet twice a day with meals, gradually titrated upwards by 1 tablet every week to a maximum dose of 2 tablets three times a day.
Tablets started at recruitment and continued till the delivery of the baby
干预措施: Placebo (Drug)
结局指标
主要结局
Birth Weight centile (z-score)
时间窗: At Birth
次要结局
- Postpartum haemorrhage(Delivery)
- Caesarian Section(delivery)
- Prematurity(Delivery)
- Maternal Weight gain(Weight at recruitment and at end of pregnancy)
- Development of Gestational Diabetes(28 weeks of pregnancy)
- Development of hypertension/Preeclampsia(Throughout pregnancy)
- Neonatal Hypoglycemia(within 2 hours after birth and immediate post birth)
- Hyperbilirubinemia(at birth and after)
- Polycythaemia(At birth)
- Respiratory Distress(At birth and within 24 hours)
- Macrosomia/Large for Gestational Age(At birth)
- Birth Trauma(At birth)
- Apgar score <6(5 minutes after birth)
- Admission to level 2 or greater neonatal unit(at birth and immediately after)
- Stillbirth/Intrauterine deaths(Throughout pregnancy)
- 2nd trimester miscarriages(in 2nd trimester of pregnancy)