title: The complement system and adverse pregnancy outcomes.
abstract: Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child.
authors: Department of Biomedical Sciences, University of Minnesota Medical School, 1035 University Drive, Duluth, MN 55812, USA. Electronic address: jregal@d.umn.edu.
authors: Jean F
authors: JF
authors: Regal
authors: Department of Biomedical Sciences, University of Minnesota Medical School, 1035 University Drive, Duluth, MN 55812, USA. Electronic address: jgilbert@d.umn.edu.
authors: Jeffrey S
authors: JS
authors: Gilbert
authors: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Oregon Health & Science University, Mail Code: L-458, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: burwick@ohsu.edu.
authors: Richard M
authors: RM
authors: Burwick
mesh_terms: D000818:Animals; D003167:Complement Activation; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005333:Fetus; D015870:Gene Expression; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009154:Mutation; D010920:Placenta / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051381:Rats; D050497:Stillbirth
chemical_list: D003165:Complement System Proteins
keywords: Complement system; Fetal growth restriction; Miscarriage; Placenta; Preeclampsia; Pregnancy; Preterm birth