Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.