title: The Welsh study of mothers and babies: protocol for a population-based cohort study to investigate the clinical significance of defined ultrasound findings of uncertain significance.
abstract: BACKGROUND
  Improvement in ultrasound imaging has led to the identification of subtle non-structural markers during the 18 - 20 week fetal anomaly scan, such as echogenic bowel, mild cerebral ventriculomegaly, renal pelvicalyceal dilatation, and nuchal thickening. These markers are estimated to occur in between 0.6% and 4.3% of pregnancies. Their clinical significance, for pregnancy outcomes or childhood morbidity, is largely unknown. The aim of this study is to estimate the prevalence of seven markers in the general obstetric population and establish a cohort of children for longer terms follow-up to assess the clinical significance of these markers.
  
  
  METHODS
  All women receiving antenatal care within six of seven Welsh Health Boards who had an 18 to 20 week ultrasound scan in Welsh NHS Trusts between July 2008 and March 2011 were eligible for inclusion. Data were collected on seven markers (echogenic bowel, cerebral ventriculomegaly, renal pelvicalyceal dilatation, nuchal thickening, cardiac echogenic foci, choroid plexus cysts, and short femur) at the time of 18 - 20 week fetal anomaly scan. Ultrasound records were linked to routinely collected data on pregnancy outcomes (work completed during 2012 and 2013). Images were stored and reviewed by an expert panel.The prevalence of each marker (reported and validated) will be estimated. A projected sample size of 23,000 will allow the prevalence of each marker to be estimated with the following precision: a marker with 0.50% prevalence to within 0.10%; a marker with 1.00% prevalence to within 0.13%; and a marker with 4.50% prevalence to within 0.27%. The relative risk of major congenital abnormalities, stillbirths, pre-term birth and small for gestational age, given the presence of a validated marker, will be reported.
  
  
  CONCLUSIONS
  This is a large, prospective study designed to estimate the prevalence of markers in a population-based cohort of pregnant women and to investigate associations with adverse pregnancy outcomes. The study will also establish a cohort of children that can be followed-up to explore associations between specific markers and longer-term health and social outcomes.
authors.affiliation: Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK. HurtL@cardiff.ac.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hurt
authors.forename: Melissa
authors.initials: M
authors.lastname: Wright
authors.forename: Fiona
authors.initials: F
authors.lastname: Brook
authors.forename: Susan
authors.initials: S
authors.lastname: Thomas
authors.forename: Frank
authors.initials: F
authors.lastname: Dunstan
authors.forename: David
authors.initials: D
authors.lastname: Fone
authors.forename: Gareth
authors.initials: G
authors.lastname: John
authors.forename: Sue
authors.initials: S
authors.lastname: Morris
authors.forename: David
authors.initials: D
authors.lastname: Tucker
authors.forename: Marilyn Ann
authors.initials: MA
authors.lastname: Wills
authors.forename: Lyn
authors.initials: L
authors.lastname: Chitty
authors.forename: Colin
authors.initials: C
authors.lastname: Davies
authors.forename: Shantini
authors.initials: S
authors.lastname: Paranjothy
mesh_terms: D015415:Biomarkers; D002831:Choroid Plexus; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging / Q000453:epidemiology; D003560:Cysts / Q000000981:diagnostic imaging / Q000453:epidemiology*; D004108:Dilatation, Pathologic / Q000000981:diagnostic imaging / Q000453:epidemiology; D058535:Echogenic Bowel / Q000000981:diagnostic imaging / Q000453:epidemiology*; D005260:Female; D005269:Femur / Q000002:abnormalities* / Q000000981:diagnostic imaging; D005865:Gestational Age; D006801:Humans; D006849:Hydrocephalus / Q000000981:diagnostic imaging / Q000453:epidemiology*; D007236:Infant, Small for Gestational Age; D007670:Kidney Calices / Q000000981:diagnostic imaging* / Q000473:pathology; D008498:Medical Record Linkage; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D047928:Premature Birth / Q000453:epidemiology; D015995:Prevalence; D012107:Research Design; D050497:Stillbirth / Q000453:epidemiology; D016216:Ultrasonography, Prenatal; D014852:Wales / Q000453:epidemiology
chemical_list: D015415:Biomarkers