Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania

Darling, Anne Marie; McDonald, Chloë R.; Conroy, Andrea L.; Hayford, Kyla; Liles, W. Conrad; Wang, Molin; Aboud, Said; Urassa, Willy; Kain, Kevin C.; Fawzi, Wafaie W.

doi:10.1016/j.ajog.2014.05.032

Cited by 34 publications

(34 citation statements)

References 46 publications

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“…Other cross-sectional studies have similarly observed inverse associations between CRP, measured at various time points during pregnancy, and birthweight. 26,27 Two small studies (N ≤ 200) with repeated measures of CRP did not analyze associations by trimester, but also observed inverse associations with birthweight. 6,13 Our studies are somewhat consistent with these findings, although we observed null associations with CRP measured at ~10 weeks gestation, and the most precise effect estimates with levels measured at Few studies have examined cytokines in relation to birthweight or fetal growth, 8,10 and to our knowledge none has done so with repeated biomarkers or ultrasound measurements.…”

Section: Discussionmentioning

confidence: 99%

Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy

Ferguson

Kamai

Cantonwine

et al. 2018

American J Rep Immunol

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Section: Discussionmentioning

confidence: 99%

Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy

Ferguson

Kamai

Cantonwine

et al. 2018

American J Rep Immunol

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“…There is a growing body of evidence indicating that an imbalance in maternal plasma concentrations of angiogenic and anti-angiogenic factors is characteristic of a substantial fraction of women who have or will develop preeclampsia [44, 97–107, 110, 111, 130–168], fetal death [114, 115, 169–173], SGA [64, 102–104, 117, 173–178], massive perivillous fibrin deposition [115, 178], twin-to-twin transfusion syndrome [118, 179, 180], and mirror syndrome [181]. We have also found significant differences in angiogenic marker distributions among uncomplicated pregnancies and those who are or will be affected by spontaneous PTL with intact membranes [112].…”

Section: Commentmentioning

confidence: 99%

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

Korzeniewski

Romero

Chaiworapongsa

et al. 2016

American Journal of Obstetrics and Gynecology

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Background Placental lesions consistent with maternal vascular underperfusion (MVU) are thought to be pathogenically linked to preeclampsia, small-for-gestational-age newborns, fetal death, and spontaneous preterm labor and delivery; yet, these lesions cannot be diagnosed antenatally. We previously reported that patients with such conditions and lesions have an abnormal profile of the angiogenic placental growth factor (PlGF) and anti-angiogenic factors [e.g., soluble vascular endothelial growth factor receptor-1 (sVEGFR-1)]. Objectives The objectives of this study were to: 1) examine the relationship between the maternal plasma PlGF/sVEGFR-1concentration 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 patients in the midtrimester who are destined to deliver before 34 weeks of gestation with multiple (i.e., 3 or more) histologic placental features consistent with MVU. Study Design A two-stage case-cohort sampling strategy was used to select participants from among 4,006 women with a singleton gestation 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 (PlGF/sVEGFR-1) concentration ratios were determined in 7,560 plasma samples collected from 1,499 study participants; 2) the prevalence of lesions consistent with MVU was 21% (n* = 833.9/3,904) and 27% (n* = 11.4/42.7) of women with 3 or more 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 (LR+) of 12.2, and a negative likelihood ratio (LR-) of 0.29 in the identification of patients who delivered placentas with 3 or more MVU lesions at <34 weeks; 4) prospectively, at 20–23 weeks of gestation, a maternal plasma concentration of angiogenic index-1 below the 2.5th quantile identified 70% (n* = 7.2/10.3; 95% CI, 42%–98%) of patients who delivered placentas with 3 or more MVU lesions before 34 weeks [specificity, 97% (n* = 2831.3/2918; 95% CI, 96%–98%); LR+, 23; LR−, 0.31]; and 5) among women without obstetrical complications who delivered at term, angiogenic index-1 was lower in women with compared to those without placental lesions consistent with MVU (p < 0.05). Conclusio...

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“…10 At this moment, there is no conclusive evidence that measuring maternal angiogenic biomarkers are (also) useful in the clinical management of fetal growth restriction. Despite many studies linking maternal angiogenic concentrations to the neonatal outcomes (mainly SGA), 3,[11][12][13][14][15][16] there is no systematic review of the predictive performance of PlGF, sFlt-1 and sFlt-1/PlGF ratio at different trimesters of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review

et al. 2019

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Background Fetal growth restriction, i.e. the restriction of genetically predetermined growth potential due to placental dysfunction, is a major cause of neonatal morbidity and mortality. The consequences of inadequate fetal growth can be life-long, but the risks can be reduced substantially if the condition is identified prenatally. Currently, screening strategies are based on ultrasound detection of a small-for-gestational age fetus and do not take into account the underlying vascular pathology in the placenta. Measurement of maternal circulating angiogenic biomarkers placental growth factor, sFlt-1 (soluble FMS-like tyrosine kinase-1) are increasingly used in studies on fetal growth restriction as they reflect the pathophysiological process in the placenta. However, interpretation of the role of angiogenic biomarkers in prediction of fetal growth restriction is hampered by the varying design, population, timing, assay technique and cut-off values used in these studies. Methods We conducted a systematic-review in PubMed (MEDLINE), EMBASE (Ovid) and Cochrane to explore the predictive performance of maternal concentrations of placental growth factor, sFlt-1 and their ratio for fetal growth restriction and small-for-gestational age, at different gestational ages, and describe the longitudinal changes in biomarker concentrations and optimal discriminatory cut-off values. Results We included 26 studies with 2514 cases with small-for-gestational age, 27 cases of fetal growth restriction, 582 cases mixed small-for-gestational age/fetal growth restriction and 29,374 reference. The largest mean differences for the two biomarkers and their ratio were found after 26 weeks of gestational age and not in the first trimester. The ROC-AUC varied between 0.60 and 0.89 with sensitivity and specificity matching the different cut-off values or a preset false-positive rate of 10%. Conclusions Most of the studies did not make a distinction between small-for-gestational age and fetal growth restriction, and therefore the small-for-gestational age group consists of fetuses with growth restriction and fetuses that are constitutionally normal. The biomarkers can be a valuable screening tool for small-for-gestational age pregnancies, but unfortunately, there is not yet a clear cut-off value to use for screening. More research is needed to see if these biomarkers are sufficiently able to differentiate growth restriction on their own and how these biomarkers in combination with other relevant clinical and ultrasound parameters can be used in clinical routine diagnostics.

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Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania

Cited by 34 publications

References 46 publications

Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy

Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy

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

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review

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