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The association of antiphospholipid antibodies with intrauterine fetal death: A case–control study

https://doi.org/10.1016/j.thromres.2011.11.029Get rights and content

Abstract

Introduction

Over the past few decades it has been recognized that antiphospholipid antibodies are associated with pregnancy loss. Other placenta-mediated pregnancy complications have also been associated with the presence of antiphospholipid antibodies. Most studies have measured antiphospholipid antibodies near the time of the event investigated.

Objectives

To investigate the association of antiphospholipid antibodies and a history of intrauterine fetal death (IUFD) in a case–control design.

Materials and methods

A case–control study of 105 women with a history of IUFD after 22 gestational weeks and 262 controls with live births. The prevalence of lupus anticoagulant, anticardiolipin- and anti-β2-glycoprotein 1 antibodies were measured 3–18 years after the event of IUFD.

Results

Total 9.5% of women with a history of IUFD and 5.0% of controls had at least one positive test for antiphospholipid antibodies (OR 2.0; 95% confidence interval (CI) 0.9-4.8). Women with a history of IUFD were significantly more often positive for lupus anticoagulant compared to controls (OR 4.3; 95% CI 1.0-18.4). The association of lupus anticoagulant with a history of IUFD was confined to women positive for other antiphospholipid antibodies in addition to lupus anticoagulant. Being positive for anti-β2-glycoprotein 1 or anticardiolipin antibodies alone was not significantly associated with a history of IUFD.

Conclusions

Women with a history of IUFD after 22 gestational weeks were more often lupus anticoagulant positive. The association was confined to women with multiple positivity for antiphospholipid antibodies, although firm conclusions on the importance of multiple positivity cannot be made from this study.

Introduction

Antiphospholipid antibodies (APAs) are heterogeneous auto-antibodies that may be associated with increased risk of thrombotic and vascular complications [1]. Over the past few decades it has been recognized that APAs may be associated with pregnancy loss and other placenta mediated pregnancy complications (PMPC), such as intrauterine growth restriction, preeclampsia, placental abruption, as well as pregnancy loss in all trimesters [2], [3], [4]. PMPC affect more than one in six pregnancies, are major causes of maternal and fetal morbidity and mortality, and have been attributed to uteroplacental vascular insufficiency [5], [6]. The pathophysiology of PMPC related to APAs probably does not only involve thrombosis of placental vessels, but also impaired conceptus implantation by damage to decidual or chorionic vessels or reduction of trophoblast invasiveness, which can lead to early pregnancy loss, or later in pregnancy, placental insufficiency and PMPC [7].

Previous studies have demonstrated an association of both inherited and acquired thrombophilia with PMPC, and it has been reported that up to 65% of women with PMPC have some form of acquired or inherited thrombophilia [8], [9]. Both case–control and prospective cohort studies have found increased risk of PMPC in APA positive women, and a systematic review reported a positive association between fetal death and the presence of both anticardiolipin (aCL) antibodies of immunoglobulin G (IgG) isotype and lupus anticoagulant (LA) [8], [9], [10], [11], [12].

Studies investigating the association between APAs and intrauterine fetal death (IUFD) have often been of small sample size [13], and they have differed in selection criteria for cases and controls [14], [15]. In addition, laboratory detection of APAs is complicated by the heterogeneity of both the antibodies and the assays used for detection. All these issues can explain the inconsistent findings of the association of APAs with IUFD.

Investigators reporting on the association between APAs and IUFD have usually analyzed the prevalence of APAs in blood samples collected within months after suffering IUFD. To our knowledge the prevalence of APAs several years after the incident, among women with a history of IUFD, has not been reported. Our hypothesis was that women with a history of IUFD were more often APA positive, compared to women with live births only. The aim of our study was to investigate this association between APAs and IUFD.

Section snippets

Ethics statement

The Norwegian South-Eastern Regional Committee for Medical Research Ethics approved the study. Authorization for the use of information from medical records for research purposes was obtained from the Norwegian Ministry of Health and Social Affairs. The Norwegian Data Inspectorate approved the use of data comprising sensitive personal health information, and the merging of clinical and register-data by using the unique 11-digit personal identification number given to all Norwegian citizens

Results

Information from medical records of the eligible participants gave us the opportunity to compare participating women with the non-participating. There were no significant differences in the demographic and clinical data between the participating and non-participating women (data not shown). The maternal characteristics of cases and controls are displayed in Table 1. At the time of the index pregnancy women with IUFD were younger, smoked more often at first visit, had more often placental

Discussion

In the present study, we found that women with a history of IUFD, as compared with women with live births only, were significantly more often positive for LA 3–18 years after the index pregnancy. This was attributed to women positive for LA in combination with other APAs, although this study does not allow firm conclusions on the importance of multi-positivity.

Our finding of increased prevalence of LA among women with a history of IUFD is in agreement with other studies. However, most

Conflict of Interest

No conflicts of interest.

Acknowledgments

Financial support was received from the South-Eastern Norway Regional Health Authority Trust, Hamar, Norway, the Oslo University Hospital Ulleval Scientific Trust, Oslo, Norway, and the Research Council of Norway. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References (35)

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