The role of angiogenic biomarkers and uterine artery Doppler in pregnant women with systemic lupus erythematosus or antiphospholipid syndrome
Introduction
Systemic lupus erythematosus (SLE) disproportionately affects women during their childbearing ages. Pregnancy in patients with SLE, particularly in those with antiphospholipid syndrome (APS), but also with antiphospholipid antibodies (aPL) alone, is associated with an increased risk of adverse outcomes (AO) due to placental insufficiency and these patients have a much higher risk of preeclampsia (PE) (14–23%) [1], [2], [3], [4], preterm delivery (20–31%) [1], [3], [5], intrauterine growth restriction (IUGR) (5–23%) and intrauterine fetal death [6], [7].
PE is a specific pregnancy syndrome that usually manifests with high systemic blood pressure (SBP) and proteinuria, and resolves following delivery. Severe PE is characterized by very high SBP, as well as other multiorganic manifestations, including cerebral and visual symptoms, thrombocytopenia, hemolysis, renal insufficiency, and liver involvement [8]. In SLE patients, differentiating between disease activity, particularly lupus nephritis (LN), and PE can be challenging because they share symptoms such as hypertension or proteinuria.
Several angiogenic factors have been identified as biomarkers of placental dysfunction. Changes in the ratio between the pro-angiogenic placental growth factor (PlGF) and the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) has demonstrated to be useful for the prediction and diagnosis of PE, especially the early-onset forms [9], [10]. Moreover, detection of increased mean pulsatility index in the uterine arteries (mPI-UtA) has also a high sensitivity and specificity for predicting PE and IUGR [11]. Some combined algorithms using both predictive tools have been proposed for detecting patients at high risk of developing placental dysfunction-related diseases [12]. Moreover, previous results have pointed out that the sFlt-1/PlGF ratio as well as the mPI-UtA can be useful to differentiate between PE and SLE or APS nephropathies [12], [13].
The aim of our study was to assess the value of the mPI-UtA and sFlt-1/PlGF ratio as early markers of placental dysfunction in pregnant patients with either SLE or APS, and to describe how these angiogenesis markers behave in SLE patients with disease activity.
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Study population
Pregnant patients with either SLE diagnosis, with or without aPL, or with APS referred to our high-risk pregnancy clinic from the first trimester of pregnancy were consecutively included from January 2011 to December 2015. SLE and APS diagnosis were established according to the American College of Rheumatology [14] and Sydney criteria [15], respectively. We excluded patients with poorly controlled arterial hypertension, those who were lost for follow-up during pregnancy or delivery, and when
Results
Fifty-seven patients were consecutively included, 46 (81%) with SLE and 11 (19%) with APS diagnosis. Fig. 1 shows the flow chart of the study population from enrollment to final outcome. Among SLE patients, 10 (22%) had spontaneous miscarriage and there were 36 ongoing pregnancies of whom 29 had normal pregnancy outcome (81%), 5 suffered a SLE flare (14%), and 2 (6%) had an AO (1 with early-onset IUGR and abruption placentae at 32 weeks of gestation resulting in severe hypoxic-ischemic
Discussion
Pregnancy in patients with either SLE and/or APS patients is a high risk clinical condition, and these patients are currently recommended not become pregnant until at least 6 months have passed without SLE activity or 12 months since the last episode of LN [26], [27]. In any case, once these patients become pregnant they are more prone to suffering flares or gestational complications such as PE, and it can be extremely difficult to differentiate SLE activity from some AO like PE, using only
Funding
This work was supported by the Instituto de Salud Carlos III (Spanish Ministry of Economy, Industry and Competitiveness) and cofunded by the European Regional Development Fund [project PI10/02102].
Conflicts of interest
Ignacio Herraiz and Alberto Galindo have received lecture fees and consultancy payments from Roche Diagnostics. The other authors do not report any conflicts of interest. The authors alone are responsible for the content and writing of this article.
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