The SCOPE study - an international search for answers
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Authors list
Dr Dharmintra Pasupathy, Mr Paul Seed, Professor Lucilla Poston, Dr Matias Vieira, Professor Louise Kenny (collaborator and principal investigator for SCOPE)
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Research centre
This study took place at our London centre which operated between 1995 and 2021.
The SCOPE study is an international study looking at how to predict and prevent the major diseases of late pregnancy: pre-eclampsia, preterm birth and fetal growth restriction. Tommy’s London and Manchester research centres were both involved in the project. A total of 5,690 first-time mothers took part in New Zealand, Australia, the UK and Ireland, and more than 50 papers have been published.
The study has already led to useful ways to predict pre-eclampsia and also identify healthy pregnancies. It has also given us valuable information about many problems during pregnancy, including miscarriage and the influence of smoking on the developing baby.
The SCOPE study has established a unique, international pregnancy biobank that will serve as a platform to:
- identify novel molecular markers that predict in early pregnancy women who will subsequently develop late pregnancy complications.
- test and validate combinations of key clinical, known and novel molecular markers to predict each disease .
- develop predictive tests that offer first time mothers an accurate, personalised risk rating for each disease.
The SCOPE study exists because we know there are a number of potential clinical and molecular markers (certain proteins, fats and small molecules in blood) for these complications.
None of these candidate markers are useful as individual predictive tests, but combinations of markers are likely to result in clinically useful screening tests.
Further, recent advances in proteomic and metabolomic technologies and bioinformatics (advanced mathematics) allow us to discover and map differences in molecules circulating in the blood of women who later develop these conditions. This has created the opportunity to develop effective methods of predicting these diseases, with the potential to dramatically improve maternal and infant health worldwide.
Research papers
- Effects of pre-eclampsia and fetal growth restriction on C-type natriuretic peptide. BJOG 2015 [Epub ahead of publication 5 Apr 2015]. DOI: 10.1111/1471-0528.13397.
- Early Pregnancy Prediction of Preeclampsia in Nulliparous Women, Combining Clinical Risk and Biomarkers: The Screening for Pregnancy Endpoints (SCOPE) International Cohort Study. Hypertension. 2014 Sep;64(3):644-52. doi: 10.1161/HYPERTENSIONAHA.114.03578.
- Psycol. Med. 1-12, 2014. Second-trimester maternal distress increases the risk of small for gestational age. A. S. Khashan, C. Everard, L. M. E. McCowan, G. Dekker, R. Moss-Morris, P. N. Baker, L. Poston, J. J. Walker, L. C. Kenny; the SCOPE Consortium.
- KL Gatford, GK Heinemann, SD Thompson, JV Zhang, S Buckberry, JA Owens, GA Dekker and CT Roberts. Circulating IGF1 and IGF2 and SNP genotypes in pregnant and non-pregnant 1 women and men. Endocrine Connections Vol. 3 no. 3 138-149, 2014.
- de Seymour J, Conlon C, Sulke K, Bôas SV, McCowan L, Kenny L, Baker P. Early pregnancy metabolite profiling discovers a potential biomarker for the subsequent development of Gestational Diabetes Mellitus. Acta Diabetologica Acta Diabetologica [Epub ahead of publication 27 July 2014] DOI: 10.1007/s00592-014-0626-7, 2014.
- Authors' reply: Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study. Myers JE, Kenny LC, McCowan LM, Chan EH, Dekker GA, Poston L, Simpson NA, North RA; SCOPE consortium. BJOG. 2014 Mar ;121(4):507. doi: 10.1111/1471-0528.12565. 2014
- Patterns of change in uterine artery Doppler studies between 20 and 24 weeks of gestation and pregnancy outcome Obstet Gynecol 2009; 113:332-8
- An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia. J Lipid Res 2009; 50: 71-80.
- Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study BMJ 2009
- Proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between predisposition to preeclampsia and cardiovascular disease_Proteomics 2009.
- Doppler flow velocity waveforms and fetal size at 20 wks in smokers_BJOG_2009
- Duration of sexual relationship and its effect on preeclampsia and SGA perinatal outcome_JReprodImmunol_2009
- Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers_Hypertension_2010
- Risk factors for infants small for gestational age_BJOG_2010
- Paternal Contribution to Small for Gestational Age Babies: A Multicentre Prospective Study_Obesity_2011
- Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells_Placenta_2011
- Transabdominal scanning of cervix at the 20 week scan_Aust NZ J Obstet Gynaecol_2010
- A novel statistical model to identify differentially expressed proteins in 2D PAGE gels_PLOS Comput. Biol_2009;
- Urinary Proteomics for Prediction of Pre-eclampsia_Hypertension_2011
- Aberrant Processing of Plasma Vitronectin and High-Molecular-Weight Kininogen Precedes the Onset of Preeclampsia_Reproductive Sciences_2009
- Clinical Risk Prediction for Preeclampsia in nulliparous women BMJ 2011
- Gender- and Gestational Age-Specific Body Fat Percentage at Birth. Paediatrics 2011
- Risk of first and second stage cesarean by maternal BMI among nullipara in labor at term. Obstet Gynecol 2011
- Preeclampsia is Associated with Elevated CXCL12 Levels in Placental Syncytiotrophoblasts and Maternal Blood 2011
- Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy. J Proteome Research 2011
- SGA & Vascular EndothelialGrowthFactor +936 C/T Single-Nucleotide Polymorphism_2011
- SGA & functional variant in the thrombospondin-1 gene_2011
- Antepartum haemorrhage of unknown origin and maternal smoking_2012
- Hyperemesis gravidarum and cognitive, behavioural &emotional well-being_2011
- Impact of maternal body mass index on the phenotype of pre-eclampsia_2012
- Functional variant in ANGPT1 & risk of hypertensive disorders and SGA_2011
- Single-Nucleotide Polymorphisms in the KDR Gene_2012
- Placental expression of VEGF family mRNA in adverse pregnancy outcomes_2012
- Prediction of pre-eclampsia and delivery of SGA babies in high risk women_2010
- Plasma clusterin and association with SGA and preeclampsia
- Maternal BMI, angiogenic gene polymorphisms and risk of preterm birth
- Bayesian Model for Classifying all Differentially Expressed Proteins in 2D PAGE Gels
- Patterns of vaginal bleeding during the first 20 weeks of pregnancy and risk of preeclampsia
- Risk factors for preterm birth
- Perinatal outcomes in large infants using customized birthweight centiles
- Association of AGT2R polymorphisms with preeclampsia and uterine artery bilateral notching
- Gestational weight gain and adverse pregnancy outcomes
- Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia
- Integrated Proteomics pipeline yields novel biomarkers for predicting preeclampsia
- Human maternal plasma angiotensin II and angiotensin 1-7 levels in early gestation pregnancy and fetal sex.
- Clinical prediction in early pregnancy of infants small for gestational age
- Maternal lipids in early pregnancy are not associated with risk of intrapartum caesarean in overweight and obese nulliparous women.
- A label-free SRM workflow identifies a subset of pregnancy specific glycoproteins as potential predictive markers of early-onset pre-eclampsia
- The association of maternal ACE A11860G with small for gestational age babies is modulated by the environment and by fetal sex: a multicentre prospective case–control study
- Association Between Maternal Alcohol Consumption in Early Pregnancy and Pregnancy Outcomes
- Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth.
- Contribution of modifiable factors associated with uncomplicated pregnancy in nulliparous women: development and validation in a prospective cohort study.
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An achievement of SCOPE is the development of algorithms (flow charts) that can be used to work out the risk of pre-eclampsia early in pregnancy. These use clinical factors, ultrasound measurements and 'biomarkers' found in the blood, and are based on information from all the women involved in SCOPE. However, the way that pre-eclampsia happens in obese women may be different to women of normal weight. In the women taking part in SCOPE, the number of obese women who developed pre-eclampsia (9.2%) was almost three times as high as women of a healthy weight (3.4%).
Researchers found that a protein made by the placenta – placental growth factor or PlGF – was associated with pre-eclampsia in obese women, but not in non-obese women. Meanwhile, blood pressure measurements at 15 weeks of pregnancy were more strongly associated with pre-eclampsia in women of normal weight than in obese women.
This suggests that different tests may be needed for obese and non-obese women when trying to predict the risk of pre-eclampsia.
This study takes place in a Tommy's centre and is funded by Tommy's and the Brazilian Ministry of Education
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Premature birth research projects
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Influence of corticosteroids on the fetal heart
Steroids given to mother at risk of premature birth reduce risk of lung problems in their babies, but may affect how a baby’s heart develops.