Assessment of Potential Therapies for Pre-eclampsia and Fetal Growth Restriction using Murine Models

先兆子痫和胎儿生长受限（婴儿出生时小于应有的尺寸）是影响多达十分之一妊娠的并发症，并会导致受影响的母亲和婴儿患上严重疾病。在英国，每年有多达5名妇女和600名婴儿死于先兆子痫；四分之一的死产是由胎儿生长受限引起的，这是六分之一婴儿猝死的原因。在这些并发症中幸存下来的婴儿患脑瘫的风险更大，在儿童和成人的后期生活中，他们患心脏病、糖尿病、骨病和精神健康问题的风险更高。患有先兆子痫和胎儿生长受限的孕妇所生的婴儿给NHS带来了沉重的负担，所有重症监护婴儿床的20%被先兆子痫妊娠的婴儿所占据，每年约有4.2亿英镑用于生长受限婴儿的重症监护。此外，照顾患有先兆子痫和胎儿生长受限相关疾病的儿童给家庭、国民保健制度和社会服务带来沉重负担。不幸的是，对先兆子痫或胎儿生长受限都没有治疗方法，患有严重问题的妇女必须经历早产，这也带来了慢性疾病和死亡的巨大风险。虽然目前还没有专门用于治疗这些疾病的药物，但有许多可能用于治疗其他疾病的治疗方法，并且已经证明对未怀孕的人是安全的。这些治疗方法不能在孕妇身上进行试验，除非首先确定它们在治疗动物子痫前期症状和胎儿生长受限方面是否有效和安全。我们想测试一些现有的药物，看看它们是否对治疗这些疾病的症状有用，在一些特殊培育的小鼠品系中，这些小鼠在怀孕时表现出先兆子痫和胎儿生长受限的迹象。一旦我们发现哪些治疗方法对小鼠最有治疗潜力，我们将把它们用于从人类胎盘和分娩后的妇女（在知情的书面同意下）提取的血管上，以测试它们是否可能对人类怀孕有效。这些实验将为如何设计临床试验，为患有先兆子痫或胎儿生长受限的孕妇开发这些治疗方法提供信息。

Pre-eclampsia and fetal growth restriction (babies born smaller than they should be) are complications that affect up to 1 in 10 pregnancies and are responsible for grave illness in affected mothers and babies. Each year in the UK, up to 5 women and 600 babies die because of pre-eclampsia; 1 in 4 stillbirths are caused by fetal growth restriction and this is responsible for 1 in 6 sudden infant deaths.Babies who survive these complications are at greater risk of cerebral palsy and, later on in life as children and adults, they are at higher risk of suffering heart disease, diabetes, bone disease and mental health problems.Babies born of pregnancies complicated by pre-eclampsia and fetal growth restriction place a heavy burden on the NHS, with 20% of all intensive care baby cots being occupied by babies from pre-eclampsia pregnancies and around #420m being spent each year on intensive care of growth restricted babies. In addition, looking after children with illnesses related to pre-eclampsia and fetal growth restriction places a heavy burden on families, the NHS and social services.Unfortunately, there are no cures for either pre-eclampsia or fetal growth restriction and women suffering from severe problems have to undergo premature delivery of their baby, which also carries great risks of chronic illness and death. Although there have been no drugs specially designed to treat these illnesses, there are a number of possible treatments that are used to treat other illnesses and that have already been shown to be safe in people who are not pregnant. These treatments cannot be tested on pregnant women without first establishing whether they are effective and safe in treating symptoms of pre-eclampsia and fetal growth restriction in animals. We would like to test a number of existing drugs to see if they are useful at treating the symptoms of these diseases in a number of specially-bred mouse strains that display signs of pre-eclampsia and fetal growth restriction when pregnant. Once we have found which treatments have the greatest potential for treatment in mice, we will use them on blood vessels taken from human placentas and women (with informed written consent) after they have given birth to test whether they might be effective in human pregnancy. Such experiments will provide information on how to design clinical trials for the development of these treatments in pregnant women suffering from pre-eclampsia or fetal growth restriction.