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.