European Journal of Obstetrics & Gynecology and Reproductive Biology
Anti-phosphatidylserine, anti-cardiolipin, anti-β2 glycoprotein I and anti-prothrombin antibodies in recurrent miscarriage at 8–12 gestational weeks
Introduction
Anti-phospholipid antibodies (aPA) are a heterogeneous group of autoantibodies which target membrane phospholipids, such as phosphatidylserine (PS) and cardiolipin (CL), and phospholipid-binding proteins including β2-glycoprotein-I (β2GPI) and prothrombin (PT), among others [1], [2]. The presence of aPA is associated with characteristic manifestations, collectively grouped as the anti-phospholipid syndrome (APS) [1], a systemic auto-immune disease associated with recurrent arterial and venous thromboembolism and/or obstetric complications [1], [3]. The diagnosis of APS is based on laboratory and clinical findings [4]. The former include positivity for ≥1 aPA: lupus anticoagulant (LAC), anti-CL antibodies (ACA) or anti-β2GPI, while the latter include vascular thrombosis and/or pregnancy complications, including recurrent spontaneous miscarriage (RSM) [2], [3].
RSM is a reproductive problem with poorly understood etiology [5], which affects up to 1–2% of otherwise healthy women [5]. It is multifactorial in nature, and several factors are proposed to contribute to its pathogenesis. These include acquired/lifestyle factors (smoking, diet, obesity, oral contraceptive use) [6], [7], [8]; anatomic factors; endocrine factors; inherited predisposition (positive family history, skewed X-chromosome inactivation, HLA G); coagulation abnormalities such as protein S, protein C, or anti-thrombin III deficiencies [9]; and immunologic factors (altered cytokine production and APS) [10], [11], [12].
Previous studies have described an association between aPA and RSM [13], [14], [15], [16], with respect to anti-PS [16], [17], ACA [15], [16], anti-β2GPI [15], [16], [18], and anti-PT [17]. Other studies failed to demonstrate an association between anti-PS [18], [19], [20], [21], ACA [19], [20], and anti-β2GPI [16], [19], [20] and increased risk of RSM, while others suggested that anti-phosphatidylethanolamine, but not other aPA, is predictive of increased RSM risk [20]. Given the low number of subjects in most of these studies, their findings must be interpreted with caution. In our study, we examined the association of anti-PS, ACA, anti-β2GPI and anti-PT with RSM in 277 RSM cases and 288 age-matched multiparous control women.
Section snippets
Materials and methods
This was a retrospective case–control study. Between February 2010 and October 2010, 309 consecutive women, aged 19–45 years, with confirmed RSM diagnosis, were referred to outpatient OB/GYN clinics in Manama and Rifaa (Bahrain), for assessment and relevant investigations of idiopathic RSM. We adopted the classical definition of RSM, of ≥3 miscarriages with the same partner. As the pathophysiology of first-trimester pregnancy losses differs from that of second-trimester losses, we focused on
Results
The demographic characteristics of cases and controls are shown in Table 1. Age at entry of study (P = 0.88), serum glucose (P = 0.37), and gravida (P = 0.11), along with prevalence of smoking (P = 0.79) and diabetes (P = 0.27) were comparable between cases and control women. Significant differences were noted with respect to mean BMI (P = 0.001), menarche (P = 0.001), and gravida (P < 0.001) between RSM cases and control women. Accordingly, the latter were selected as the covariates controlled for in
Comments
While the association of aPA with APS is well established, a direct link between specific aPA types and pregnancy complications remains unclear [24], [25]. The association between aPA with RSM have been previously described by some [13], [14], [15], [16] by not all studies [18], [26], while others implicated only specific aPA subtypes with RSM pathogenesis [20]. We previously suggested a role for anti-annexin V [11] and anti-protein Z [12] autoantibodies in the pathogenesis of RSM. This study
Disclosures
None of the authors has a conflict of interest to declare.
Author disclaimers
None to declare.
Acknowledgements
The authors acknowledge the assistance of Dr. Khulood Al-Darazi, Dr. Intissar Al-Zaman, and Dr. Fekria E. Mustafa in patient screening and referral. The study was funded by grants from AGU CMMS R&EC funds.
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