Antiphospholipid antibodies and the placenta: a systematic review of their in vitro effects and modulation by treatment

BACKGROUND: Antiphospholipid antibodies (aPL) are a family of auto-antibodies that are associated with an increased risk of recurrent miscarriage, intrauterine growth restriction and preterm birth. The placenta is a major target of aPL and it is likely that these antibodies promote pregnancy morbidity by affecting trophoblast function. Numerous studies have investigated the effect of aPL on trophoblast function in vitro. However, different trophoblast models and a variety of culture conditions have been employed, resulting in a myriad of different reported findings. This review systematically summarized those published studies that have investigated the effect of aPL on trophoblast function in vitro. In addition, the reported effects of pharmacological treatment on trophoblast function in the presence of aPL were also systematically reviewed. METHODS: PubMed, Scopus, Embase and Web of Science databases were searched using the keywords 'placenta OR trophoblast 'AND' antiphospholipid antibody OR antiphospholipid syndrome' up to 25 April 2014. Studies were excluded based on the absence of appropriate controls. The effects of aPL on trophoblast proliferation, death, syncytialization, invasion, hormone production, cytokine production, coagulation and complement activation were recorded. The effects of different treatments on the function of trophoblasts in the presence of aPL were also recorded. RESULTS: A total of 1071 records were retrieved from the four databases. After removing duplicates, the titles and abstracts of 529 articles were reviewed. Of those, 48 articles were read and relevant experimental results were extracted from 47 articles. CONCLUSIONS: This systematic review provides an overview of all the studies performed to date on the effects of aPL on trophoblast function in vitro. There is considerable support for aPL decreasing trophoblast viability, syncytialization and invasion in vitro. Some work has also suggested that aPL may affect the production of hormones and signalling molecules by trophoblasts, and may stimulate coagulation and complement activation in vitro. Current reports of the in vitro effects of therapeutic treatments on trophoblast function in the presence of aPL are inconclusive. This systematic review has highlighted many gaps in our knowledge of how aPL work and may direct future research in this area.