First-trimester Placental Growth Factor Research Articles

High early pregnancy body mass index is associated with alterations in first- and second-trimester angiogenic biomarkers

BACKGROUNDObesity is associated with various placenta-mediated adverse pregnancy outcomes, including preeclampsia, preterm birth, and stillbirth. Mechanisms linking obesity with placental dysfunction are not completely understood. OBJECTIVEThis study aimed to examine the relationship between early pregnancy body mass index and placental angiogenic biomarkers soluble fms-like tyrosine kinase-1, placental growth factor, and the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio. STUDY DESIGNWe conducted secondary analyses of an existing substudy within a multisite, prospective observational cohort study of nulliparous pregnant women in the United States. First- and second-trimester maternal blood samples, first-trimester body mass index, and demographic, lifestyle, and pregnancy outcomes data were collected. Soluble fms-like tyrosine kinase-1 and placental growth factor concentrations were measured at 6 to 13 and 16 to 22 weeks of gestation for women (cases) who experienced one of several adverse pregnancy outcomes (delivery at <37 weeks of gestation, preeclampsia or eclampsia, birthweight for gestational age <5th percentile, or stillbirth) and for those who had none of those outcomes (controls). We used multivariable mixed-effects linear regression models to estimate the association of body mass index with angiogenic biomarkers at both time points. We evaluated mean change between first- and second-trimester biomarker concentrations using multivariable linear regression models. Lastly, we used logistic regression models to estimate the risk of a high second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratio, using clinically established cutoffs for risk prediction. RESULTSAngiogenic biomarker and early pregnancy body mass index data were available for 2363 women (1467 with adverse pregnancy outcomes and 896 controls). High early pregnancy body mass index was associated with consistently lower soluble fms-like tyrosine kinase-1 concentrations across the first and second trimesters of pregnancy. We found lower first-trimester placental growth factor concentrations in the group with class II or III obesity (P<.001) and lower second-trimester placental growth factor concentrations among groups who were overweight, with class I obesity, and class II or III obesity (P<.001). For every unit increase in early pregnancy body mass index, there was a −4.4 pg/mL (95% confidence interval, −3.6 to −5.2) smaller mean increase in placental growth factor concentrations between the first and second trimesters of pregnancy. These differences resulted in significantly lower mean first-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratios among groups who were overweight, with class I obesity, and class II or III obesity (P<.05) and in a significantly higher second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratio among the group with class II or III obesity (P<.001), compared with the group with normal body mass index. Each unit of increase in body mass index was associated with a 0.5 (95% confidence interval, 0.3–0.7) greater mean increase in the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio between the first and second trimesters of pregnancy. In stratified analyses, associations between body mass index and angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were similar in nonadverse pregnancy outcome and adverse pregnancy outcome subgroups, whereas associations between body mass index and the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio were attenuated in the subgroups. Participants in the group with class II or III obesity were 3.13 (95% confidence interval, 1.15–8.49) times more likely than participants with normal weight to have a second-trimester ratio of ≥38 in univariate analysis. CONCLUSIONHigh early pregnancy body mass index was associated with lower soluble fms-like tyrosine kinase-1 and placental growth factor concentrations across early pregnancy. Maternal body mass was inversely associated with first-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratios and positively associated with second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratios, driven by a diminished rise in placental growth factor between the first and second trimesters of pregnancy. Women with class II or III obesity have an increased risk of a high second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratio associated with placental dysfunction.

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction.

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study

Background: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. Subjects and Methods: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11–13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). Results: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57–0.65) and preterm PE (AUC = 0.73, 95% CI 0.64–0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62–0.71; AUC for preterm PE 0.81, 95% CI 0.72–0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. Conclusion: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.

Importance of Timing First-Trimester Placental Growth Factor and Use of Serial First-Trimester Placental Growth Factor Measurements in Screening for Preeclampsia

Objective: The aims of this study were to test whether the performance of first-trimester placental growth factor (PlGF) in screening for preterm preeclampsia (PE) is gestational age dependent and to assess the value of serial first-trimester PlGF measurements in discriminating women at risk for PE. Methods: PlGF was measured in women with singleton pregnancies at their first antenatal visit at 8+0 to 10+6 and additionally at 11+0 to 14+0 weeks of gestation. The difference in absolute values of serial PlGF measurements was expressed as Δ-PlGF. Values were compared between pregnancies with normal outcome and those complicated by PE. Results: A total of 814 pregnancies were included, 18 (2.19%) developed PE that required delivery before 37 weeks of gestation. PlGF increases significantly from 8 to 14 weeks of gestation (ρ = 0.63; p < 0.0001) in normal pregnancies, but not so in preterm PE (ρ = 0.034; p = 0.893). PlGF discriminates between PE and uneventful pregnancies only after 10 weeks of gestation. Δ-PlGF was significantly lower in PE 5.3 (-1.1 to 9.3) pg/mL compared to uneventful pregnancies 17.3 (9.8-26.0) pg/mL (p = 0.0011). Conclusion: The discriminatory accuracy of PlGF increases from 10 to 14 weeks of gestation, and serial PlGF measurements might be of particular interest in PE screening.

First-Trimester Placental Growth Factor in Screening for Gestational Diabetes

Objective: The aim of this study was first to assess whether first-trimester serum concentrations of placental growth factor (PlGF) differ between patients with and without gestational diabetes (GDM) and second to test whether there is a correlation between glycosylated hemoglobin (HbA1c), a factor recently shown to be useful in predicting GDM, and PlGF. Methods: PlGF was measured at 8-14 weeks with the Kryptor Immunoassay Analyzer (Brahms, Berlin, Germany). Absolute values were converted to multiples of the median using the software provided by the Fetal Medicine Foundation London. GDM was diagnosed using internationally accepted criteria. HbA1c levels were quantified using the TOSOH G7 automated hemoglobin analyzer. Results: From January to December 2014, 328 women were included in the study, 51 (15.5%) of whom developed GDM. First-trimester PlGF quantification does not discriminate between women at risk to develop GDM and controls, while HbA1c is able to do so. No correlation was found between PlGF and HbA1c. Conclusion: Our findings do not lend support to the hypothesis that early PlGF values are different in women who later develop GDM.

Repeated Measures of Placental Growth Factor, Placental Protein 13, and A Disintegrin and Metalloprotease 12 at First and Second Trimesters for Preeclampsia Screening

To determine the utility of cross-trimester repeated measures of placental protein 13 (PP13), A disintegrin and metalloprotease 12 (ADAM12), and placental growth factor (PlGF) for preeclampsia (PE) screening. A prospective cohort study of 893 nulliparous women who had serum sampling at 11 to 14 and 18 to 22 weeks. Biomarker levels were adjusted on maternal characteristics and gestational age. The accuracy and validity of maternal characteristics with single and repeated markers to predict PE were evaluated. First-trimester PlGF was the best biomarker for PE (mean: 0.85 multiples of the expected median [MoM]) and early onset PE (0.79 MoM). First-trimester screening performances were not significantly improved by second-trimester markers. Area under the receiver operating characteristic curve was 0.73 (95% confidence interval [CI] 0.65 to 0.81) with first-trimester PlGF and 0.71 (95% CI 0.63 to 0.80) with first- and second-trimester PlGF (p = 0.301). Repeated measures of PlGF, ADAM12, and PP13 at second trimester did not improve PE screening compared with first-trimester measures.

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589 First-trimester prediction of preeclampsia using soluble P-selectin,follistatin-related protein 3, complement 3a, soluble TNF receptor type 1, PAPP-A, AFP, inhibin A, placental growth factor, uterine artery Doppler and maternal characteristics Lorraine Dugoff, Howard Cuckle, Nicholas Behrendt, Darleen Cioffi-Ragan, Leslie Myers, John Hobbins University of Pennsylvania, Obstetrics and Gynecology, Philadelphia, PA, Columbia University Medical Center, Obstetrics and Gynecology, New York, NY, University of Colorado, Obstetrics and Gynecology, Aurora, CO OBJECTIVE: To estimate the efficiency of first-trimester serum markers and uterine artery Doppler (UtA) in the prediction of severe preeclampsia (SPE). STUDY DESIGN: This is a prospective cohort study of patients presenting for aneuploidy screening between 11-14 weeks’ gestation. Maternal serum levels of soluble P-selectin, follistatin-related protein 3, complement 3a, soluble TNF receptor type 1, PAPP-A, AFP, inhibin A(inhA) and placental growth factor(PlGF) were measured by immunoassay and mean UtA resistance indices(RI) were calculated. The primary outcome was SPE. A secondary outcome of all PE including mild preeclampsia was also evaluated. Marker levels were expressed in multiples of the normal median (MOM), adjusting for gestation, weight, smoking and ethnicity. Logistic regression analysis was used to model performance. Maternal characteristics identified as significant in a univariate analysis were included in the models. Predicted sensitivity, specificity, and area under the receiver-operating characteristic curves were used to compare the screening efficiency of the models. RESULTS: Of 1028 patients, 26(2.5%) had SPE and 56(5.4%) had PE. Median PlGF levels were lower in patients with SPE (0.83 MoM vs 0.98 MoM, P 0.05) and PE(0.90 MoM vs 0.98 MoM, P 0.05) compared to those without PE. AFP was significantly higher (1.15 MoM vs 1.00 MoM, P 0.05; 1.20 MoM vs 0.99 MoM, P 0.01). Median RI was significantly increased in PE (1.05 MoM vs 1.00 MoM, P 0.05) but not in SPE; similarly for inhA (1.09 MoM vs 0.99 MoM, P 0.05). For a fixed false positive rate of 20%, PlGF and AFP identified 49% of patients with SPE; combining these with prior risk factors did not improve the model efficiency. The detection rate for PE was 44% modeling with PlGF, AFP, inhA and RI. CONCLUSION: First-trimester PlGF and AFP are each modestly predictive of SPE, but combining both improves detection.

Angiogenic and Fibrinolytic Factors in Blood During the First Half of Pregnancy and Adverse Pregnancy Outcomes

To estimate whether the imbalance of angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and fibrinolytic factors (plasminogen activator inhibitor-2 [PAI-2]) might affect placentation in early pregnancy. We studied the associations of maternal soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 concentrations in the first trimester (before 18 weeks of gestation) and soluble fms-like tyrosine kinase-1 and placental growth factor concentrations in the second trimester (18-25 weeks of gestation) with placental function and adverse pregnancy outcomes. This study was embedded in a population-based prospective cohort study. Data were used from 7,519 women. Biomarker concentrations were divided into deciles and evaluated in multivariable linear and logistic regression models. First-trimester high soluble fms-like tyrosine kinase-1 was associated with a 5.2% lower uterine artery index in the second-trimester and a 1.6% higher birth weight (55 g, confidence interval [CI] 15-95). Neither in the first nor in the second trimester were soluble fms-like tyrosine kinase-1 concentrations significantly associated with preeclampsia. First-trimester low placental growth factor was associated with a 6.1% higher uterine artery index and a 3.4% lower birth weight (-115 g, CI -157 to -74). First-trimester low placental growth factor was associated with fetal growth restriction (odds ratio [OR] 2.62, CI 1.68-4.08) and preeclampsia (OR 2.46, CI 1.49-4.08). First-trimester low PAI-2 was associated with a 1.9% higher uterine artery index and a 2.7% lower birth weight (-94 g, CI -136 to -51). First-trimester low PAI-2 was associated with a higher risk of fetal growth restriction (OR 2.22, CI 1.39-3.55). First-half-of-pregnancy concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 are associated with uteroplacental vascular resistance, placental weight, and birth weight. Moreover, first-trimester placental growth factor and PAI-2 are associated with an increased risk of adverse pregnancy outcomes. II.

First‐trimester placental growth factor as a marker for hypertensive disorders and SGA

The objective of this study was to examine first-trimester maternal serum placental growth factor (PlGF) levels in pregnancies which later develop hypertensive and growth complications. In this case-control study, PlGF levels were measured by AutoDELFIA immunoassay platform. There were 47 cases of at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age (SGA), haemolysis elevated liver enzymes and low platelets (HELLP) and gestational hypertension (GH) and 452 matched controls. PlGF levels were significantly lower in cases of all PE, early PE, HELLP, all SGA, early SGA and SGA without PE, but not in GH, late PE, late SGA, PE with SGA or PE without SGA or HELLP. Low levels of first-trimester PlGF provide a good indicator of SGA complications and some hypertensive disorders, in particular severe cases of PE such as early onset and HELLP syndrome.

First-trimester placental growth factor, SFLT-1, and risk for preeclampsia

First-trimester placental growth factor, SFLT-1, and risk for preeclampsia