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.