Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: Results of the PROMISSE study

Mimi Kim, Jill P. Buyon, Marta M. Guerra, Sarosh Rana, Dongsheng Zhang, Carl A. Laskin, Michelle Petri, Michael D. Lockshin, Lisa R. Sammaritano, D. Ware Branch, T. Flint Porter, Joan T. Merrill, Mary D. Stephenson, Qi Gao, S. Ananth Karumanchi, Jane E. Salmon

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Background Over 20% of pregnancies in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy outcome (APO) related to abnormal placentation. The ability to identify, early in pregnancy, patients who are destined for poor outcomes would significantly impact care of this high-risk population. In nonautoimmune patients, circulating angiogenic factors are dysregulated in disorders of placentation, such as preeclampsia (PE) and fetal growth restriction. Objective We sought to determine whether early dysregulation of circulating angiogenic factors can predict APO in high-risk SLE and/or APL pregnancies. Study Design We used data and samples from the Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE (PROMISSE), a multicenter prospective study that enrolled 492 pregnant women with SLE and/or APL from September 2003 through August 2013. Patients were followed through pregnancy from 1872 pg/mL; odds ratio, 31.1; 95% CI, 8.0-121.9; PPV, 58%; NPV, 95%). Severe APO rate in this high-risk subgroup was 94% (95% CI, 70-99.8%), if lupus anticoagulant or history of high blood pressure was additionally present. In contrast, among patients with both sFlt1 70.3 pg/mL, rate of severe APO was only 4.6% (95% CI, 2.1-8.6%). Conclusion Circulating angiogenic factors measured during early gestation have a high NPV in ruling out the development of severe adverse outcomes among patients with SLE and/or APL syndrome. Timely risk stratification of patients is important for effective clinical care and optimal allocation of health care resources.

Original languageEnglish (US)
Pages (from-to)108.e1-108.e14
JournalAmerican Journal of Obstetrics and Gynecology
Volume214
Issue number1
DOIs
StatePublished - Jan 1 2016

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Antiphospholipid Antibodies
Angiogenesis Inducing Agents
Pregnancy Outcome
Biomarkers
Systemic Lupus Erythematosus
Pregnancy
Placentation
Antiphospholipid Syndrome
Lupus Coagulation Inhibitor
Health Resources
Pregnancy Rate
Fetal Development
Pre-Eclampsia
Multicenter Studies
Pregnant Women
Odds Ratio
Prospective Studies
Hypertension
Delivery of Health Care
Population

Keywords

  • angiogenic factors
  • antiphospholipid antibodies
  • placental insufficiency
  • preeclampsia
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies : Results of the PROMISSE study. / Kim, Mimi; Buyon, Jill P.; Guerra, Marta M.; Rana, Sarosh; Zhang, Dongsheng; Laskin, Carl A.; Petri, Michelle; Lockshin, Michael D.; Sammaritano, Lisa R.; Branch, D. Ware; Porter, T. Flint; Merrill, Joan T.; Stephenson, Mary D.; Gao, Qi; Karumanchi, S. Ananth; Salmon, Jane E.

In: American Journal of Obstetrics and Gynecology, Vol. 214, No. 1, 01.01.2016, p. 108.e1-108.e14.

Research output: Contribution to journalArticle

Kim, M, Buyon, JP, Guerra, MM, Rana, S, Zhang, D, Laskin, CA, Petri, M, Lockshin, MD, Sammaritano, LR, Branch, DW, Porter, TF, Merrill, JT, Stephenson, MD, Gao, Q, Karumanchi, SA & Salmon, JE 2016, 'Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: Results of the PROMISSE study', American Journal of Obstetrics and Gynecology, vol. 214, no. 1, pp. 108.e1-108.e14. https://doi.org/10.1016/j.ajog.2015.09.066
Kim, Mimi ; Buyon, Jill P. ; Guerra, Marta M. ; Rana, Sarosh ; Zhang, Dongsheng ; Laskin, Carl A. ; Petri, Michelle ; Lockshin, Michael D. ; Sammaritano, Lisa R. ; Branch, D. Ware ; Porter, T. Flint ; Merrill, Joan T. ; Stephenson, Mary D. ; Gao, Qi ; Karumanchi, S. Ananth ; Salmon, Jane E. / Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies : Results of the PROMISSE study. In: American Journal of Obstetrics and Gynecology. 2016 ; Vol. 214, No. 1. pp. 108.e1-108.e14.
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abstract = "Background Over 20{\%} of pregnancies in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy outcome (APO) related to abnormal placentation. The ability to identify, early in pregnancy, patients who are destined for poor outcomes would significantly impact care of this high-risk population. In nonautoimmune patients, circulating angiogenic factors are dysregulated in disorders of placentation, such as preeclampsia (PE) and fetal growth restriction. Objective We sought to determine whether early dysregulation of circulating angiogenic factors can predict APO in high-risk SLE and/or APL pregnancies. Study Design We used data and samples from the Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE (PROMISSE), a multicenter prospective study that enrolled 492 pregnant women with SLE and/or APL from September 2003 through August 2013. Patients were followed through pregnancy from 1872 pg/mL; odds ratio, 31.1; 95{\%} CI, 8.0-121.9; PPV, 58{\%}; NPV, 95{\%}). Severe APO rate in this high-risk subgroup was 94{\%} (95{\%} CI, 70-99.8{\%}), if lupus anticoagulant or history of high blood pressure was additionally present. In contrast, among patients with both sFlt1 70.3 pg/mL, rate of severe APO was only 4.6{\%} (95{\%} CI, 2.1-8.6{\%}). Conclusion Circulating angiogenic factors measured during early gestation have a high NPV in ruling out the development of severe adverse outcomes among patients with SLE and/or APL syndrome. Timely risk stratification of patients is important for effective clinical care and optimal allocation of health care resources.",
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T2 - Results of the PROMISSE study

AU - Kim, Mimi

AU - Buyon, Jill P.

AU - Guerra, Marta M.

AU - Rana, Sarosh

AU - Zhang, Dongsheng

AU - Laskin, Carl A.

AU - Petri, Michelle

AU - Lockshin, Michael D.

AU - Sammaritano, Lisa R.

AU - Branch, D. Ware

AU - Porter, T. Flint

AU - Merrill, Joan T.

AU - Stephenson, Mary D.

AU - Gao, Qi

AU - Karumanchi, S. Ananth

AU - Salmon, Jane E.

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N2 - Background Over 20% of pregnancies in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy outcome (APO) related to abnormal placentation. The ability to identify, early in pregnancy, patients who are destined for poor outcomes would significantly impact care of this high-risk population. In nonautoimmune patients, circulating angiogenic factors are dysregulated in disorders of placentation, such as preeclampsia (PE) and fetal growth restriction. Objective We sought to determine whether early dysregulation of circulating angiogenic factors can predict APO in high-risk SLE and/or APL pregnancies. Study Design We used data and samples from the Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE (PROMISSE), a multicenter prospective study that enrolled 492 pregnant women with SLE and/or APL from September 2003 through August 2013. Patients were followed through pregnancy from 1872 pg/mL; odds ratio, 31.1; 95% CI, 8.0-121.9; PPV, 58%; NPV, 95%). Severe APO rate in this high-risk subgroup was 94% (95% CI, 70-99.8%), if lupus anticoagulant or history of high blood pressure was additionally present. In contrast, among patients with both sFlt1 70.3 pg/mL, rate of severe APO was only 4.6% (95% CI, 2.1-8.6%). Conclusion Circulating angiogenic factors measured during early gestation have a high NPV in ruling out the development of severe adverse outcomes among patients with SLE and/or APL syndrome. Timely risk stratification of patients is important for effective clinical care and optimal allocation of health care resources.

AB - Background Over 20% of pregnancies in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy outcome (APO) related to abnormal placentation. The ability to identify, early in pregnancy, patients who are destined for poor outcomes would significantly impact care of this high-risk population. In nonautoimmune patients, circulating angiogenic factors are dysregulated in disorders of placentation, such as preeclampsia (PE) and fetal growth restriction. Objective We sought to determine whether early dysregulation of circulating angiogenic factors can predict APO in high-risk SLE and/or APL pregnancies. Study Design We used data and samples from the Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE (PROMISSE), a multicenter prospective study that enrolled 492 pregnant women with SLE and/or APL from September 2003 through August 2013. Patients were followed through pregnancy from 1872 pg/mL; odds ratio, 31.1; 95% CI, 8.0-121.9; PPV, 58%; NPV, 95%). Severe APO rate in this high-risk subgroup was 94% (95% CI, 70-99.8%), if lupus anticoagulant or history of high blood pressure was additionally present. In contrast, among patients with both sFlt1 70.3 pg/mL, rate of severe APO was only 4.6% (95% CI, 2.1-8.6%). Conclusion Circulating angiogenic factors measured during early gestation have a high NPV in ruling out the development of severe adverse outcomes among patients with SLE and/or APL syndrome. Timely risk stratification of patients is important for effective clinical care and optimal allocation of health care resources.

KW - angiogenic factors

KW - antiphospholipid antibodies

KW - placental insufficiency

KW - preeclampsia

KW - systemic lupus erythematosus

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