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Article ; Online: Fetal overgrowth in pregnancies complicated by diabetes: development of a clinical prediction index.

Tomlinson, Tracy M / Mostello, Dorothea J / Lim, Kee-Hak / Pritchard, Jennifer S / Gross, Gil

2018 Volume 298, Issue 1, Page(s) 67–74

Abstract: Purpose: To develop an index to predict fetal overgrowth in pregnancies complicated by diabetes.: Methods: Data were derived from a cohort of 275 women with singleton gestations in a collaborative diabetes in pregnancy program. Regression analysis ... ...

Abstract	Purpose: To develop an index to predict fetal overgrowth in pregnancies complicated by diabetes. Methods: Data were derived from a cohort of 275 women with singleton gestations in a collaborative diabetes in pregnancy program. Regression analysis incorporated clinical factors available in the first 20-30 weeks of pregnancy that were assigned beta-coefficient-based weights, the sum of which yielded a fetal overgrowth index (composite score). Results: Fifty-one (18.5%) pregnancies were complicated by fetal overgrowth. The derived index included five clinical factors: age ≤ 30, history of macrosomia, excessive gestational weight gain, enlarged fetal abdominal circumference, and fasting hyperglycemia. Area under the curve (AUC) for the index is 0.88 [95% confidence interval (CI) 0.82-0.92]. Cut-points were selected to identify "high-risk" and "low-risk" ranges (≥ 8 and ≤ 3) that have positive and negative predictive values of 84% (95% CI 70-98%) and 95% (95% CI 92-98%), respectively. The majority of women in our cohort (n = 182, 66%) had a "low-risk" index while 9% (n = 25) had a "high-risk" index. Sub-analyses of nulliparous women and women with gestational and pre-gestational diabetes revealed that the overgrowth index was equally or more predictive when applied separately to each of these groups. Conclusion: This fetal overgrowth index that incorporates five clinical factors provides a means of predicting fetal overgrowth and thereby serves as a tool for targeting the allocation of healthcare resources and treatment individualization.
MeSH term(s)	Adult ; Birth Weight ; Blood Glucose/metabolism ; Cohort Studies ; Diabetes, Gestational/blood ; Diabetes, Gestational/metabolism ; Female ; Fetal Macrosomia/etiology ; Fetus ; Gestational Age ; Glucose Metabolism Disorders/blood ; Glucose Metabolism Disorders/complications ; Humans ; Hyperglycemia ; Infant, Newborn ; Pregnancy ; Pregnancy Complications ; Weight Gain
Chemical Substances	Blood Glucose
Language	English
Publishing date	2018-04-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	896455-5
ISSN	1432-0711 ; 0932-0067
ISSN (online)	1432-0711
ISSN	0932-0067
DOI	10.1007/s00404-018-4758-9
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Article ; Online: Infant size and the association between maternal circulating angiogenic factors and preeclampsia.

Honigberg, Michael C / Seely, Ellen W / Thomas, Ann M / Lim, Kee-Hak / Parry, Samuel / McElrath, Thomas F

Journal of perinatology : official journal of the California Perinatal Association

2018 Volume 38, Issue 5, Page(s) 456–461

Abstract: Objective: To assess the effect of infant size as a marker of placental function on the association between preeclampsia and the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF).: Study design: The angiogenic ... ...

Abstract	Objective: To assess the effect of infant size as a marker of placental function on the association between preeclampsia and the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF). Study design: The angiogenic factors sFlt-1 and PlGF were measured prospectively at 26 weeks gestation in 2322 women. Pregnancies were stratified by whether or not they were complicated by preeclampsia, the timing of delivery, and birthweight Z-score. Result: Independent of preeclampsia status, women with small infants (Z < -1.0) have an increased sFlt-1/PlGF ratio, and women with large infants (Z > 1.0) have a decreased ratio. Among pregnancies yielding small infants, the sFlt-1/PlGF ratio is markedly elevated in preeclamptic pregnancies requiring delivery before 37 weeks (110.0 vs. 17.9, p < 0.0001) but not in preeclamptic pregnancies delivered at term. The strength of the association between preeclampsia and the sFlt-1/PlGF ratio is increased for small infants compared to normal-sized or large infants. Conclusion: The sFlt-1/PlGF ratio in the late second trimester is similarly elevated in women with preeclampsia and in women with small infant size and more markedly elevated in a syndrome of placental dysfunction characterized by preeclampsia, preterm delivery, and growth restriction.
MeSH term(s)	Adult ; Biomarkers/blood ; Birth Weight ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Small for Gestational Age ; Linear Models ; Multivariate Analysis ; Placenta Growth Factor/blood ; Pre-Eclampsia/blood ; Pregnancy ; Pregnancy Trimester, Second/blood ; Vascular Endothelial Growth Factor Receptor-1/blood ; Young Adult
Chemical Substances	Biomarkers ; PGF protein, human ; Placenta Growth Factor (144589-93-5) ; FLT1 protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2018-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645021-0
ISSN	1476-5543 ; 0743-8346
ISSN (online)	1476-5543
ISSN	0743-8346
DOI	10.1038/s41372-018-0074-2
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Article ; Online: Clinical risk factors for preeclampsia in the 21st century.

Paré, Emmanuelle / Parry, Samuel / McElrath, Thomas F / Pucci, Dominick / Newton, Amy / Lim, Kee-Hak

Obstetrics and gynecology

2014 Volume 124, Issue 4, Page(s) 763–770

Abstract: Objective: We sought to validate several clinical risk factors previously described for preeclampsia in a large contemporary multicenter prospective cohort.: Methods: We enrolled women from three sites before 15 weeks of gestation. Demographic and ... ...

Abstract	Objective: We sought to validate several clinical risk factors previously described for preeclampsia in a large contemporary multicenter prospective cohort. Methods: We enrolled women from three sites before 15 weeks of gestation. Demographic and clinical risk factors were collected through standardized chart review. The main outcome of preeclampsia was diagnosed using the American College of Obstetricians and Gynecologists definitions from 2002. Multivariable logistic regression was used to control for confounders. Results: Two thousand six hundred thirty-seven women are included in this analysis; 237 (9.0%) developed preeclampsia. In adjusted analysis, chronic hypertension (adjusted odds ratio [OR] 2.72; 95% confidence interval 1.78-4.13), pregestational diabetes (adjusted OR 3.88; 2.08-7.26), multiple gestation (adjusted OR 2.96; 1.74-5.03), African American race (adjusted OR 1.91; 1.35-2.71), prior preeclampsia (adjusted OR 3.63; 2.29-5.73), nulliparity (adjusted OR 1.73; 1.26-2.38), assisted reproductive techniques (adjusted OR: 1.72; 1.10-2.68), and being overweight (adjusted OR for body mass index [BMI, kg/m] greater than 25-30: 1.65; 1.13-2.41) or obese (adjusted OR for BMI greater than 30-35: 2.34, 1.51-3.61; adjusted OR for BMI greater than 35-40: 3.59, 2.13-6.03; adjusted OR for BMI greater than 40: 6.04, 3.56-10.24) were associated with preeclampsia, but advanced maternal age was not. Similar associations were found for severe preeclampsia. A dose-response effect was observed in the relationship between BMI and both preeclampsia and severe preeclampsia. Being overweight or obese was the most important risk factor for both preeclampsia and severe preeclampsia with an attributable risk percent of 64.9% and 64.4%, respectively. Conclusion: In this contemporary cohort, increasingly prevalent and potentially modifiable factors were confirmed as significant risk factors for preeclampsia and severe preeclampsia, the most important being overweight or obese. This information is important to guide public health efforts in preeclampsia prevention. Level of evidence: : II.
MeSH term(s)	Adult ; Cohort Studies ; Comorbidity ; Diabetes Mellitus/epidemiology ; Ethnic Groups ; Female ; Humans ; Hypertension/epidemiology ; Incidence ; Logistic Models ; Maternal Age ; Multivariate Analysis ; Obesity/epidemiology ; Pre-Eclampsia/diagnosis ; Pre-Eclampsia/epidemiology ; Predictive Value of Tests ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Reproducibility of Results ; Risk Factors ; Severity of Illness Index
Language	English
Publishing date	2014-08-12
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	207330-4
ISSN	1873-233X ; 0029-7844
ISSN (online)	1873-233X
ISSN	0029-7844
DOI	10.1097/AOG.0000000000000451
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Article ; Online: Urinary tract infection during pregnancy, angiogenic factor profiles, and risk of preeclampsia.

Easter, Sarah Rae / Cantonwine, David E / Zera, Chloe A / Lim, Kee-Hak / Parry, Samuel I / McElrath, Thomas F

American journal of obstetrics and gynecology

2016 Volume 214, Issue 3, Page(s) 387.e1–7

Abstract: Background: Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology of PE is believed to involve aberrant placentation and an ... ...

Abstract	Background: Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology of PE is believed to involve aberrant placentation and an associated increase in systemic inflammation. In this conceptualization, PE becomes more likely when the level of systemic inflammatory burden inherent in pregnancy itself exceeds the maternal capacity to compensate for this additional stress. If this is the case, then it is possible to hypothesize that conditions, such as infectious disease, that increase systemic inflammatory burden should also increase the risk of PE. As urinary tract infection (UTI) represents a common source of inflammation during pregnancy, we tested whether presence of UTI during pregnancy increased the odds of developing PE. Prior work has documented this association. However many of these studies were limited by small cohort sizes and insufficient control for covariates. Objective: The present study is a secondary analysis of a robust contemporary obstetrical cohort recruited to examine the ability of longitudinally sampled maternal angiogenic concentrations to predict PE. We hypothesize that the occurrence of UTI during a pregnancy is associated with the later occurrence of PE in that pregnancy. As PE is believed to be associated with aberrations in systemic angiogenic levels (placental growth factor and soluble isoform of VEGF receptor), we further hypothesize that there will be significant interactions between maternal angiogenic protein levels and the occurrence of UTI. Study design: Women aged ≥18 years (n = 2607) were recruited and followed up prospectively from the initiation of prenatal care through delivery at 3 regional academic centers. PE was defined by American Congress of Obstetricians and Gynecologists criteria and was independently validated by a panel of physicians. UTI was defined by the presence of clinical symptoms necessitating treatment in addition to supportive laboratory evidence. Multivariate logistic regression models were used and controlled for maternal age, race, parity, body mass index, hypertension, diabetes, in vitro fertilization, and smoking status. Results: There were 129 women with diagnosed UTIs and 235 with PE. Patients with UTI in pregnancy had higher rates of PE (31.1% vs 7.8%, P < .001) compared to those without reported UTI. The mean gestational age (SD) for UTI diagnosis in PE cases and controls was 25.6 (10.4) and 21.9 (10.9) weeks, respectively (P = .08). The unadjusted odds ratio for PE in the setting of UTI was 5.29 (95% confidence interval, 3.54-7.89). After controlling for confounders, UTI was associated with an odds ratio for PE of 3.2 (95% confidence interval, 2.0-5.1). Conclusion: Presence of UTI in pregnancy, particularly in the third trimester, is strongly associated with PE. This association supports the hypothesis that the risk of PE is enhanced by an increased maternal inflammatory burden. Prophylaxis against UTI represents a potentially low-cost global intervention to slow or halt the development of PE.
MeSH term(s)	Adolescent ; Adult ; Female ; Follow-Up Studies ; Gestational Age ; Humans ; Middle Aged ; Placenta Growth Factor ; Pre-Eclampsia/blood ; Pre-Eclampsia/epidemiology ; Pregnancy ; Pregnancy Complications, Infectious/blood ; Pregnancy Complications, Infectious/epidemiology ; Pregnancy Proteins/blood ; Pregnancy Trimesters ; Prospective Studies ; Risk Factors ; United States ; Urinary Tract Infections/blood ; Urinary Tract Infections/epidemiology ; Vascular Endothelial Growth Factor Receptor-1/blood ; Young Adult
Chemical Substances	PGF protein, human ; Pregnancy Proteins ; Placenta Growth Factor (144589-93-5) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2015.09.101
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Article ; Online: Rupture of the posterior cul-de-sac during spontaneous labor.

Young, Brett / Takoudes, Tamara / Lim, Kee-Hak / Rana, Sarosh

Obstetrics and gynecology

2010 Volume 115, Issue 2 Pt 2, Page(s) 414–417

Abstract: Background: Women with genital anomalies are at increased risk of labor dysfunction. Rupture of the posterior cul-de-sac causing an intraabdominal delivery is a rare complication of labor that may be related to a congenitally atretic vagina.: Case: A ...

Abstract	Background: Women with genital anomalies are at increased risk of labor dysfunction. Rupture of the posterior cul-de-sac causing an intraabdominal delivery is a rare complication of labor that may be related to a congenitally atretic vagina. Case: A nulliparous woman at 28 weeks of gestation with a known short vagina presented with preterm labor; her cervix could not be palpated or visualized. At cesarean delivery, the cervix was intraabdominal and the fetal head was delivered in the abdomen. A large rent in the posterior cul-de-sac required repair to restore correct anatomical positioning. The uterus was intact. Conclusion: Rupture of the posterior cul-de-sac is a rare event that can cause significant maternal and fetal morbidity.
MeSH term(s)	Adult ; Cervix Uteri/abnormalities ; Cervix Uteri/diagnostic imaging ; Cesarean Section ; Female ; Humans ; Infant, Newborn ; Obstetric Labor Complications/surgery ; Pregnancy ; Rupture, Spontaneous ; Tomography, X-Ray Computed ; Vagina/abnormalities ; Vagina/diagnostic imaging ; Vagina/injuries
Language	English
Publishing date	2010-01-21
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207330-4
ISSN	1873-233X ; 0029-7844
ISSN (online)	1873-233X
ISSN	0029-7844
DOI	10.1097/AOG.0b013e3181bd8a61
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Article ; Online: Angiogenic markers in pregnancies conceived through in vitro fertilization.

Lee, Malinda S / Cantonwine, David / Little, Sarah E / McElrath, Thomas F / Parry, Samuel I / Lim, Kee-Hak / Wilkins-Haug, Louise E

American journal of obstetrics and gynecology

2015 Volume 213, Issue 2, Page(s) 212.e1–8

Abstract: Objective: Pregnancies that have been conceived through in vitro fertilization (IVF) have been associated with higher rates of preeclampsia and other complications that are associated with placental dysfunction. We evaluated whether IVF pregnancies, ... ...

Abstract	Objective: Pregnancies that have been conceived through in vitro fertilization (IVF) have been associated with higher rates of preeclampsia and other complications that are associated with placental dysfunction. We evaluated whether IVF pregnancies, when compared with those conceived spontaneously, would be associated with alterations in serum angiogenic markers. Study design: This was a retrospective cohort study from 3 US academic institutions (2006-2008). Women with singleton pregnancies who conceived via IVF or spontaneously were included. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 4 time points throughout gestation. Pregnancy outcomes that included diagnosis of preeclampsia or other obstetric complications were ascertained from the medical record. The relationship among IVF status, PlGF, and sFlt-1 were modeled over gestation and stratified by clinical pregnancy outcome. Results: Of the included 2392 singleton pregnancies, 4.5% (108 pregnancies) were conceived though IVF. IVF pregnancies were significantly more likely to be complicated by preeclampsia (15.7% vs 7.7%). IVF pregnancies had significantly higher levels of sFlt-1 at 18, 26, and 35 weeks of gestation (P = .04, P = .004, P < .0001, respectively) and lower levels of PlGF at 18 and 35 weeks of gestation (P = .007 and .0006, respectively). These differences persisted even after being controlled for maternal comorbidities or obstetric outcomes such as preeclampsia. Conclusion: Pregnancies conceived via IVF were found to have an increased antiangiogenic profile (elevated sFlt-1 and decreased PlGF) at multiple time points throughout gestation when compared with spontaneously conceived pregnancies. Alterations in the angiogenic profile persisted even after we controlled for maternal comorbidities of clinically evident disorders of abnormal placentation such as preeclampsia. The increased antiangiogenic profile suggests fundamentally aberrant placentation related to in vitro fertilization, which may warrant closer fetal surveillance in these pregnancies.
MeSH term(s)	Adult ; Biomarkers/metabolism ; Case-Control Studies ; Cohort Studies ; Female ; Fertilization in Vitro ; Humans ; Neovascularization, Physiologic ; Placenta Growth Factor ; Pre-Eclampsia/epidemiology ; Pre-Eclampsia/metabolism ; Pregnancy ; Pregnancy Proteins/metabolism ; Retrospective Studies ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; Young Adult
Chemical Substances	Biomarkers ; PGF protein, human ; Pregnancy Proteins ; Placenta Growth Factor (144589-93-5) ; FLT1 protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2015.03.032
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Article ; Online: The association of body mass index with serum angiogenic markers in normal and abnormal pregnancies.

Zera, Chloe A / Seely, Ellen W / Wilkins-Haug, Louise E / Lim, Kee-Hak / Parry, Samuel I / McElrath, Thomas F

American journal of obstetrics and gynecology

2014 Volume 211, Issue 3, Page(s) 247.e1–7

Abstract: Objective: Because obesity is a risk factor for placental dysfunction, we hypothesized that maternal body mass index (BMI) would be associated with alterations in serum angiogenic markers.: Study design: We included 2399 singleton pregnancies with ... ...

Abstract	Objective: Because obesity is a risk factor for placental dysfunction, we hypothesized that maternal body mass index (BMI) would be associated with alterations in serum angiogenic markers. Study design: We included 2399 singleton pregnancies with and without placental dysfunction in a prospective longitudinal cohort study of angiogenic markers. We modeled the relationship between categorical and continuous BMI, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) over gestation, stratified by pregnancy outcome. Results: In women with normal pregnancies, a higher BMI was associated with lower sFlt-1 values across gestation (P < .0001), lower PlGF in the second and third trimesters (P < .0001), and lower rate of change in PlGF (P < .0001). Similar relationships were seen between maternal BMI, sFlt-1 (P < .0001), and PlGF (P = .0005) in women with clinically evident placental dysfunction. Conclusion: The sFlt-1 value is inversely associated with maternal BMI. The pattern of change in PlGF is also dependent on maternal BMI, indicating that obese women may have abnormalities in angiogenesis near term.
MeSH term(s)	Adult ; Body Mass Index ; Female ; Humans ; Obesity/blood ; Obesity/physiopathology ; Placenta Growth Factor ; Pregnancy/blood ; Pregnancy Complications/blood ; Pregnancy Proteins/blood ; Vascular Endothelial Growth Factor Receptor-1/blood
Chemical Substances	PGF protein, human ; Pregnancy Proteins ; Placenta Growth Factor (144589-93-5) ; FLT1 protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2014.03.020
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Article ; Online: Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia.

Lam, Chun / Lim, Kee-Hak / Karumanchi, S Ananth

Hypertension (Dallas, Tex. : 1979)

2005 Volume 46, Issue 5, Page(s) 1077–1085

Abstract: Preeclampsia is a major cause of maternal, fetal, and neonatal mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, high blood pressure and proteinuria, are due in part to excess ... ...

Abstract	Preeclampsia is a major cause of maternal, fetal, and neonatal mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, high blood pressure and proteinuria, are due in part to excess circulating soluble fms-like tyrosine kinase-1 concentrations. Soluble fms-like tyrosine kinase-1 is an endogenous antiangiogenic protein that is made by the placenta and acts by neutralizing the proangiogenic proteins vascular endothelial growth factor and placental growth factor. High serum soluble fms-like tyrosine kinase-1 and low serum free placental growth factor and free vascular endothelial growth factor have been observed in preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia but also antedate clinical symptoms by several weeks. Therefore, this raises the possibility of measuring circulating angiogenic proteins in the blood and the urine as a diagnostic and screening tool for preeclampsia. The availability of a test to predict preeclampsia would be a powerful tool in preventing preeclampsia-induced mortality, especially in developing nations, where high-risk specialists are limited. This review will summarize our current understanding of the role of circulating angiogenic proteins in the pathogenesis and clinical diagnosis/prediction of preeclampsia.
MeSH term(s)	Angiogenesis Inducing Agents/blood ; Animals ; Female ; Humans ; Placenta Growth Factor ; Pre-Eclampsia/diagnosis ; Pre-Eclampsia/etiology ; Predictive Value of Tests ; Pregnancy ; Pregnancy Proteins/blood ; Vascular Endothelial Growth Factor A/blood
Chemical Substances	Angiogenesis Inducing Agents ; PGF protein, human ; Pregnancy Proteins ; Vascular Endothelial Growth Factor A ; Placenta Growth Factor (144589-93-5)
Language	English
Publishing date	2005-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/01.HYP.0000187899.34379.b0
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Article: Circulating Levels of the Antiangiogenic Marker Soluble FMS-Like Tyrosine Kinase 1 Are Elevated in Women With Pregestational Diabetes and Preeclampsia: Angiogenic markers in preeclampsia and preexisting diabetes

Cohen, Allison / Lim, Kee-Hak / Lee, Young / Rana, Sarosh / Karumanchi, S. Ananth / Brown, Florence

Diabetes care. 2007 Feb., v. 30, no. 2

2007

Language	English
Dates of publication	2007-02
Size	p. 375-377.
Publishing place	American Diabetes Association
Document type	Article
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Plasma concentrations of soluble endoglin versus standard evaluation in patients with suspected preeclampsia.

Rana, Sarosh / Cerdeira, Ana Sofia / Wenger, Julia / Salahuddin, Saira / Lim, Kee-Hak / Ralston, Steven J / Thadhani, Ravi I / Karumanchi, S Ananth

PloS one

2012 Volume 7, Issue 10, Page(s) e48259

Abstract: Background: The purpose of this study was to compare plasma soluble endoglin (sEng) levels with standard clinical evaluation or plasma levels of other angiogenic proteins [soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF)] in ...

Abstract	Background: The purpose of this study was to compare plasma soluble endoglin (sEng) levels with standard clinical evaluation or plasma levels of other angiogenic proteins [soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF)] in predicting short-term adverse maternal and perinatal outcomes in women with suspected preeclampsia presenting prior to 34 weeks. Methods and findings: Data from all women presenting at <34 weeks for evaluation of preeclampsia with singleton pregnancies (July 2009-October 2010) were included in this analysis and sEng levels were measured at presentation. Data was analyzed for 170 triage encounters and presented as median {25-75(th) centile}. Thirty-three percent of patients (56 of 170) experienced an adverse outcome. sEng levels (ng/ml) were significantly elevated in patients who subsequently experienced adverse outcomes compared to those who did not (32.3 {18.1, 55.8} vs 4.8 {3.2, 8.6}, p<0.0001). At a 10% false positive rate, sEng had higher detection rates of adverse outcomes than the combination of highest systolic blood pressure, proteinuria and abnormal laboratory tests (80.4 {70.0, 90.8} vs 63.8 {51.4, 76.2}, respectively). Subjects in the highest quartile of sEng were more likely to deliver early compared to those in the lowest quartile (HR: 14.96 95% CI: 8.73-25.62, p<0.0001). Natural log transformed sEng correlated positively with log sFlt1 levels (r = 0.87) and inversely with log PlGF levels (r = -0.79) (p<0.0001 for both). Plasma sEng had comparable area under the curve for prediction of adverse outcomes as measurement of sFlt1/PlGF ratio (0.88 {0.81, 0.95} for sEng versus 0.89 {0.83, 0.95} for sFlt1/PlGF ratio, p = 0.74). Conclusions: In women with suspected preeclampsia presenting prior to 34 weeks of gestation, sEng performs better than standard clinical evaluation in detecting adverse maternal and fetal outcomes occurring within two weeks of presentation. Soluble endoglin was strongly correlated with sFlt1 and PlGF levels, suggesting common pathogenic pathways leading to preeclampsia.
MeSH term(s)	Adult ; Antigens, CD/blood ; Endoglin ; Female ; Humans ; Kaplan-Meier Estimate ; Placenta Growth Factor ; Pre-Eclampsia/blood ; Pregnancy ; Pregnancy Proteins/blood ; Receptors, Cell Surface/blood ; Vascular Endothelial Growth Factor Receptor-1/blood
Chemical Substances	Antigens, CD ; ENG protein, human ; Endoglin ; PGF protein, human ; Pregnancy Proteins ; Receptors, Cell Surface ; Placenta Growth Factor (144589-93-5) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2012-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0048259
Database	MEDical Literature Analysis and Retrieval System OnLINE

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