Strengths and Limitations
Several limitations of our study should be acknowledged. First, the
study is limited by the relatively small number of participants in the
study. Second, the study is retrospective in design, therefore
susceptible to confounding factors. The retrospective observational
design of the study precludes comments on causality in the association
between aPL antibodies and the severity of preeclampsia and preterm
birth. Third, the study lacks adequate power to detect differences in
rare events, i.e. neonatal mortality and significant neonatal morbidity.
Nevertheless, since women with positive-aPL and early-onset preeclampsia
with severe features delivered significantly earlier compared with those
with negative-aPL, it is possible that a larger sample size would have
found a statistically significant benefit in neonatal outcome. Lastly,
aPL antibodies were determined once due to lack of success at obtaining
repeat testing. It is clinically important to pursue repeat confirmatory
testing, but we acknowledge the difficulties in obtaining it. Of note,
Erkan et al. showed that positive aPL antibodies remained stable in 75%
of cases.40 We promote caution in defining
aPL-positive women as suffering from full-blown APS. Nevertheless, it is
interesting to note that although not complying with the definition of
APS, these women still demonstrate important clinical differences when
compared with aPL-negative women.
Among the strengths of our study is the novel association between the
presence of aPL antibodies and the clinical severity of early-onset
preeclampsia. We specifically targeted a pre-defined phenotype of
preeclampsia that resulted in preterm delivery prior to 34 weeks
gestation to delineate severe disease. All aPL antibodies were tested
using standardized techniques, and pregnancy outcomes were diagnosed
using guidelines and international criteria or definitions.