title: The phenotype of spontaneous preterm birth: application of a clinical phenotyping tool.
abstract: OBJECTIVE
  Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible causes. We hypothesized that a comprehensive classification system appropriately could group women with similar STPB causes and could provide an explanation, at least in part, for the disparities in SPTB that are associated with race and gestational age at delivery.
  
  
  METHODS
  This was a planned analysis of a multicenter, prospective study of singleton SPTBs. Women with SPTB at <34 weeks' gestation were included. We defined 9 potential SPTB phenotypes based on clinical data: infection/inflammation, maternal stress, decidual hemorrhage, uterine distention, cervical insufficiency, placental dysfunction, premature rupture of the membranes, maternal comorbidities, and familial factors. Each woman's condition was evaluated for each phenotype. Delivery gestational age was compared between those with and without each phenotype. Phenotype profiles were also compared between women with very early (20.0-27.9 weeks' gestation) SPTB vs those with early SPTB (28.0-34.0 weeks' gestation) and between African American and white women. Statistical analysis was by t test and χ(2) test, as appropriate.
  
  
  RESULTS
  The phenotyping tool was applied to 1025 women with SPTBs who delivered at a mean 30.0 ± 3.2 (SD) weeks' gestation. Of these, 800 women (78%) had ≥2 phenotypes. Only 43 women (4.2%) had no phenotypes. The 281 women with early SPTBs were more likely to have infection/inflammation, decidual hemorrhage, and cervical insufficiency phenotypes (all P ≤ .001). African American women had more maternal stress and cervical insufficiency but less decidual hemorrhage and placental dysfunction compared with white women (all P < .05). Gestational age at delivery decreased as the number of phenotypes that were present increased.
  
  
  CONCLUSIONS
  Precise SPTB phenotyping classifies women with SPTBs and identifies specific differences between very early and early SPTB and between African American and white women.
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah School of Medicine, and Department of Maternal-Fetal Medicine, Intermountain Healthcare, Salt Lake City, UT. Electronic address: tmanuck@med.unc.edu.
authors: Tracy A
authors: TA
authors: Manuck
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah School of Medicine, and Department of Maternal-Fetal Medicine, Intermountain Healthcare, Salt Lake City, UT.
authors: M Sean
authors: MS
authors: Esplin
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, and Center for Women's Reproductive Health, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors: Joseph
authors: J
authors: Biggio
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX.
authors: Radek
authors: R
authors: Bukowski
authors: Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Samuel
authors: S
authors: Parry
authors: Collaborative Center for Statistics in Science, Yale University School of Public Health, New Haven, CT.
authors: Heping
authors: H
authors: Zhang
authors: Collaborative Center for Statistics in Science, Yale University School of Public Health, New Haven, CT.
authors: Hao
authors: H
authors: Huang
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah School of Medicine, and Department of Maternal-Fetal Medicine, Intermountain Healthcare, Salt Lake City, UT.
authors: Michael W
authors: MW
authors: Varner
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, and Center for Women's Reproductive Health, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors: William
authors: W
authors: Andrews
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX.
authors: George
authors: G
authors: Saade
authors: Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors: Yoel
authors: Y
authors: Sadovsky
authors: Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.
authors: Uma M
authors: UM
authors: Reddy
authors: Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.
authors: John
authors: J
authors: Ilekis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D010641:Phenotype; D011247:Pregnancy; D047928:Premature Birth / Q000145:classification* / Q000208:ethnology / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States
keywords: phenotype; preterm; racial disparity; spontaneous preterm birth