Interpretation
Preeclampsia is one of the leading causes of maternal morbidity and mortality, and contributes significantly to neonatal morbidity and mortality, mainly due to indicated preterm delivery.26Preeclampsia constitutes one of the pregnancy complications accompanying APS, and 11-17% of women with preeclampsia will test positive for aPL antibodies.17,27-30 In addition to an increased risk for vascular thrombosis in women with APS, the association between aPL antibodies and placenta mediated pregnancy complications, including early-onset preeclampsia, is part of the definition of APS.17-23,31Nevertheless, the severity of preeclampsia with regard to aPL antibodies status has not been elucidated. The novelty of the present study is in the association of these antibodies with the severity of early onset preeclampsia, including obstetric and neonatal outcomes.
The association between aPL antibodies and preeclampsia is well established, both from cohort and case-control studies,32 as well as two large meta-analyses. The meta-analysis by do Prado et al. included 12 studies, and found a pooled odds ratio (OR) for association of aCL with preeclampsia of 2.86 (95% CI 1.37-5.98). Pooled OR for aCL with preeclampsia with severe features was 11.15 (95% CI 2.66–46.75). In studies involving patients with mild preeclampsia, this association was weaker, indicating a dose–response relationship and supporting the possibility of a causal association.33 A second meta-analysis by Abou-Nassar et al. included 28 studies, and found an association between LAC and preeclampsia in case-control studies (OR 2.34; 95%CI 1.18-4.64), but not in cohort studies. aCL IgG was associated with preeclampsia in case-control studies (OR 1.52, 95% CI 1.05–2.2), and anti-β2GP1 was associated with preeclampsia in cohort studies (OR 19.14, 95% CI 6.34–57.77).34These associations suggest a correlation between preeclampsia and antiphospholipid antibodies. In addition, a prospective evaluation of 1155 women revealed that women with antiphospholipid antibodies had an increased risk for pregnancy-induced hypertension (OR 5.5; 95% CI 2.3-13.5) and severe pregnancy-induced hypertension (OR 8.1 for any aPL antibody, 95% CI 2.2-29.4; and OR 143 for multi-positive).20 These epidemiologic findings are consistent with animal studies.32 Murine studies on the effects of aPL antibodies have found complement mediated fetal injury in APS,35-38 while placentas from human pregnancies affected by APS also show increased complement deposition.35,39 Hence, complement activation is a possible pathway through which aPL antibodies may lead to adverse pregnancy outcomes.
According to the American College of Obstetrics and Gynecology, although preterm preeclampsia with severe features and early-onset placental insufficiency are indicated as clinical criteria for the diagnosis of APS by expert consensus,31 insufficient evidence exists to support screening for the presence of aPL antibodies and treatment of women with these conditions to improve subsequent pregnancy outcomes.17 The findings in our study suggest that the presence of aPL antibodies in women with preeclampsia with severe features that deliver prior to 34 weeks presents at an earlier gestational age and affects the severity of the disease. These findings might strengthen the recommendation to screen for aPL antibodies in cases of past or present early-onset preeclampsia with severe features. Furthermore, the presence of aPL antibodies should be cause for diligent scrutiny of these pregnancies to detect complications and evidence for end-organ damage in a timely fashion, thus allowing for adequate intervention for mother and fetus.