title: Signs and symptoms associated with early pregnancy loss: findings from a population-based preconception cohort.
abstract: OBJECTIVE
  What is the relationship between signs and symptoms of early pregnancy and pregnancy loss <20 weeks' gestation?
  
  
  CONCLUSIONS
  Vaginal bleeding is associated with increased incidence of early pregnancy loss, with more severe bleeding and bleeding accompanied by lower abdominal cramping associated with greater incidence of loss; conversely, vomiting is associated with decreased incidence of early pregnancy loss, even in the setting of vaginal bleeding, while nausea alone is not.
  
  
  BACKGROUND
  Two previous cohort studies with preconception enrollment suggested that bleeding is associated with loss while nausea is inversely associated with loss though these studies were limited by small study size and reporting after loss ascertainment. No prior preconception cohort study has examined multiple signs and symptoms in relation to pregnancy loss.
  
  
  METHODS
  Population-based preconception cohort of 501 couples discontinuing contraception to try for pregnancy in 16 counties in Michigan and Texas, USA. Participants were followed daily until positive home pregnancy test or 12 months of trying without an hCG pregnancy; women who became pregnant were followed daily from 2 to 7 weeks post-conception.
  
  
  METHODS
  Three hundred and forty-seven women had a positive home pregnancy test denoting hCG pregnancy. Three hundred and forty-one women remained after excluding ineligible pregnancies. Women recorded daily from 2 to 7 weeks post-conception their signs and symptoms, including vaginal bleeding (none, spotting, light, moderate and heavy), lower abdominal cramping, nausea and vomiting. Pregnancy losses were ascertained by a subsequent negative home pregnancy test, clinical confirmation or onset of menses, depending on gestational age at loss; time-to-loss was measured in days post-conception. Cumulative incidence functions and 95% confidence intervals (CIs) were constructed for each sign or symptom, and hazard ratios (HRs) and 95% CIs for presence compared with absence of signs or symptoms were estimated using Cox proportional hazard models.
  
  
  RESULTS
  Women experienced lower abdominal cramping (85%), nausea (48%), vomiting (46%) and light/moderate/heavy vaginal bleeding (24%) during early pregnancy. Ninety-five (28%) women experienced a loss. Cumulative incidence of pregnancy loss varied by symptomatology: 19% for vomiting, 27% for lower abdominal cramping, 35% for nausea only, 52% for vaginal bleeding, 81% for vaginal bleeding with lower abdominal cramping. Incidence of pregnancy loss was increased among women with vaginal bleeding (HR: 3.62, 95% CI: 2.29-5.74) and among women with vaginal bleeding and lower abdominal cramping (HR: 5.03, 95% CI: 2.07-12.20). Incidence of pregnancy loss was decreased for women with vomiting (HR: 0.51, 95% CI: 0.30-0.86). In the setting of vaginal bleeding with lower abdominal cramping, vomiting reduced the incidence of pregnancy loss (HR: 0.24, 95% CI: 0.11-0.56).
  
  
  CONCLUSIONS
  There were few losses beyond 14 weeks gestation; thus, the precision of our findings related to losses occurring after the first trimester is limited.
  
  
  CONCLUSIONS
  By using sensitive home pregnancy tests, we are able to document and characterize the cumulative incidence of the earliest pregnancy losses, which constitute the majority of losses. The use of daily, prospective capture of signs and symptoms relative to ascertainment of pregnancy loss minimizes potential biases associated with reporting after rather than before a loss, which could potentially distort the relationship between signs and symptoms and pregnancy loss. The findings of our study suggest that it may be useful to develop prognostic models for pregnancy loss based on signs and symptoms.
  
  
  BACKGROUND
  This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract numbers N01-HD-3-3355; N01-HD-3-3356; N01-HD-3-3358). The authors have no conflict of interest to declare.
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, NY, USA saprakj@mail.nih.gov.
authors.forename: K J
authors.initials: KJ
authors.lastname: Sapra
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Buck Louis
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sundaram
authors.affiliation: Department of Obstetrics and Gynaecology, School of Population and Public Health, University of British Columbia, The Children's and Women's Hospital of British Columbia, Vancouver, Canada.
authors.forename: K S
authors.initials: KS
authors.lastname: Joseph
authors.affiliation: Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Bates
authors.affiliation: Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, NY, USA School of Public Health, Boston University, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Galea
authors.affiliation: Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, NY, USA Department of Obstetrics and Gynecology, College of Physicians and Surgeons, New York, NY, USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Ananth
mesh_terms: D015746:Abdominal Pain / Q000209:etiology* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005327:Fetal Resorption / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008824:Michigan / Q000453:epidemiology; D009325:Nausea / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D015995:Prevalence; D011446:Prospective Studies; D012306:Risk; D012720:Severity of Illness Index; D013781:Texas / Q000453:epidemiology; D014592:Uterine Hemorrhage / Q000209:etiology* / Q000503:physiopathology; D014839:Vomiting / Q000209:etiology / Q000503:physiopathology; D055815:Young Adult
keywords: bleeding; cramping; miscarriage; nausea; pregnancy loss; prospective cohort studies; signs; symptoms; threatened abortion; vomiting