title: Baseline placental growth factor levels for the prediction of benefit from early aspirin prophylaxis for preeclampsia prevention.
abstract: OBJECTIVE
  Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin.
  
  
  METHODS
  Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60mg/d (n=102) or placebo (n=72), with PlGF collected at 13w 0d-16w 6d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders.
  
  
  RESULTS
  ROC analysis indicated 87.71pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p=0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p=0.445).
  
  
  CONCLUSIONS
  Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated.
  
  
  CONCLUSIONS
  High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin.
authors.affiliation: University of Colorado, Department of Obstetrics and Gynecology, United States. Electronic address: gaeamoore@gmail.com.
authors.forename: Gaea S
authors.initials: GS
authors.lastname: Moore
authors.affiliation: Colorado School of Public Health, United States.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Allshouse
authors.affiliation: University of Colorado, Department of Obstetrics and Gynecology, United States.
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Winn
authors.affiliation: University of Colorado, Department of Obstetrics and Gynecology, United States.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Galan
authors.affiliation: University of Colorado, Department of Obstetrics and Gynecology, United States; Denver Health Hospital, United States.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Heyborne
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000517:prevention & control*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011262:Pregnancy Trimester, Second; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014481:United States
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D001241:Aspirin
keywords: Aspirin; MFMU; Placental growth factor (PlGF); Preeclampsia