title: Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects.
abstract: BACKGROUND
  There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy) are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the "confounding" effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs.
  
  
  METHODS
  We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records.
  
  
  RESULTS
  To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation) is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy). These comparisons can be then examined to infer the extent to which prenatal effects are genetically and environmentally mediated.
  
  
  CONCLUSIONS
  A study based on children born by IVF treatment and who differ in genetic relatedness to the woman undergoing the pregnancy is feasible. The present report outlines a novel experimental method that permits disaggregation of maternally provided inherited genetic and post-implantation prenatal effects.
authors.affiliation: Department of Psychological Medicine, School of Medicine, Heath Park, Cardiff University, UK. thapar@cf.ac.uk
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
authors.forename: Gordon
authors.initials: G
authors.lastname: Harold
authors.forename: Frances
authors.initials: F
authors.lastname: Rice
authors.forename: XiaoJia
authors.initials: X
authors.lastname: Ge
authors.forename: Jacky
authors.initials: J
authors.lastname: Boivin
authors.forename: Dale
authors.initials: D
authors.lastname: Hay
authors.forename: Marianne
authors.initials: M
authors.lastname: van den Bree
authors.forename: Allyson
authors.initials: A
authors.lastname: Lewis
mesh_terms: D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002908:Chronic Disease / Q000453:epidemiology / Q000517:prevention & control; D005240:Feasibility Studies; D005260:Female; D005307:Fertilization in Vitro / Q000706:statistics & numerical data; D047109:Fetal Development / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology* / Q000235:genetics*; D011256:Pregnancy Outcome; D011254:Pregnancy in Diabetics / Q000453:epidemiology / Q000235:genetics; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000503:physiopathology; D012098:Reproduction / Q000235:genetics*; D027724:Reproductive Techniques, Assisted / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics