BACKGROUND: Placental lesions consistent with maternal vascular underperfusion (MVU) are thought to be pathogenically linked to @entity1468 , small-for-gestational-age newborns, @entity5617 , and spontaneous @entity3152 and delivery; yet, these lesions cannot be diagnosed antenatally. We previously reported that @entity1 with such conditions and lesions have an abnormal profile of the angiogenic placental growth factor ( @entity7309 ) and antiangiogenic factors (eg, soluble vascular endothelial growth factor receptor [sVEGFR]-1). OBJECTIVE: The objectives of this study were to: (1) examine the  relationship between the maternal plasma @entity7309 /sVEGFR-1 concentration ratio (referred to herein as angiogenic index-1) and the burden of histologic placental features consistent with MVU; and (2) test the hypothesis that angiogenic index-1 can identify @entity1 in the midtrimester who are destined to deliver before 34 weeks of gestation with multiple (ie, >= 3) histologic placental features consistent with MVU. STUDY DESIGN: A 2-stage case-cohort sampling strategy was used to select @entity1 from among 4006 @entity1 with singleton gestations enrolled from 2006 through 2010 in a longitudinal study. Maternal plasma angiogenic index-1 ratios were determined using enzyme-linked immunosorbent assays. Placentas underwent histologic examination according to standardized protocols by experienced pediatric pathologists who were blinded to clinical diagnoses and pregnancy outcomes. The diagnosis of lesions consistent with MVU was made using criteria proposed by the Perinatal Section of the Society for Pediatric Pathology. Weighted analyses were performed to reflect the parent cohort; "n*" is used to reflect weighted frequencies. RESULTS: (1) Angiogenic index-1 ( @entity7309 /sVEGFR-1) concentration ratios were determined in 7560 plasma samples collected from 1499 study @entity1 ; (2) the prevalence of lesions consistent with MVU was 21% (n*  = 833.9/3904) and 27% (n*  = 11.4/42.7) of @entity1 with >= 3 MVU lesions delivered before 34 weeks of gestation; (3) a low angiogenic index-1 (<2.5th quantile for gestational age) in maternal plasma samples obtained within 48 hours of delivery had a sensitivity of 73% (n*  = 8.3/11.4; 95% confidence interval [CI], 47-98%), a specificity of 94% (n*  = 3130.9/3316.2; 95% CI, 94-95%), a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29 in the identification of @entity1 who delivered placentas with >= 3 MVU lesions at <34 weeks; (4) prospectively, at 20-23 weeks of gestation, a maternal plasma concentration of angiogenic index-1 <2.5th quantile identified 70% (n*  = 7.2/10.3; 95% CI, 42-98%) of @entity1 who delivered placentas with >= 3 MVU lesions before 34 weeks (specificity, 97% [n*  = 2831.3/2918; 95% CI, 96-98%]; positive likelihood ratio, 23; negative likelihood ratio, 0.31); and (5) among @entity1 without @entity532 who delivered at term, angiogenic index-1 was lower in @entity1 with than without @entity5028 consistent with MVU (P < .05). CONCLUSION: Maternal plasma angiogenic index-1 ( @entity7309 /sVEGFR-1) is the first biomarker for the burden of @entity5028 consistent with MVU. We propose that an accumulation of these lesions in placentas delivered before 34 weeks is a histologic counterpart of an antiangiogenic profile.

Maternal plasma angiogenic index-1 (placental growth factor/soluble  vascular endothelial growth factor receptor-1) is  a  biomarker for the burden of XXXX consistent with  uteroplacental underperfusion: a longitudinal case-cohort study.

@entity1 :: ('9606', 'Species') :: ['participants', 'women', 'patients'] @entity7309 :: ('5228', 'Gene') :: ['PlGF'] @entity3152 :: ('MESH:D007752', 'Disease') :: ['preterm labor'] @entity5028 :: ('MESH:D010922', 'Disease') :: ['placental lesions'] @entity532 :: ('MESH:D003925', 'Disease') :: ['obstetrical complications'] @entity1468 :: ('MESH:D011225', 'Disease') :: ['preeclampsia'] @entity5617 :: ('MESH:D005313', 'Disease') :: ['fetal death']
@entity5028 :: (MESH:D010922,Disease) :: ['placental lesions']
