C3, C4 Levels Linked To Risk For Pregnancy Loss In Patients With Antiphospholipid Antibodies

13 Jan, 2021 ,

Women with antiphospholipid antibodies, with or without antiphospholipid syndrome, having low C3 and/or C4 levels prior to pregnancy are at an increased risk of having adverse pregnancy outcomes. This was found after researchers conducted a study that measured C3 and C4 levels using nephelometry in 487 women. The complement levels could, thus, serve as a means to identify women who would require constant monitoring. Low pre-pregnancy complement levels are, however, not associated with maternal complications such as preeclampsia, eclampsia, DVT, etc.

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Low complement levels prior to pregnancy are associated with an increased risk for adverse outcomes, including stillbirth and fetal loss, among patients with antiphospholipid antibodies, according to a speaker at ACR Convergence 2020.

“Adverse pregnancy outcomes have been correlated with serum C3 and C4 levels and evaluated by nephelometry,” Cecilia Nalli, MD, of ASST Spedali Civili of Brescia, in Italy, told attendees at the virtual meeting

“Decreased C3 and/or C4 levels before pregnancy are associated with increased risk of adverse outcomes in women with antiphospholipid antibodies, with or without antiphospholipid syndrome,” Cecilia Nalli, MD, told attendees. 

To analyze whether low C3 or C4 could be a risk factor for adverse pregnancy outcomes among patients with antiphospholipid syndrome and antiphospholipid antibodies, Nalli and colleagues conducted a multicenter study of 487 pregnancies from 10 Italian rheumatology centers and one Russian center. The researchers collected retrospective data on pregnancies in 293 patients with primary antiphospholipid syndrome, as well as 194 individuals with persistent antiphospholipid antibody positivity.

Adverse pregnancy outcomes were defined as stillbirth, fetal loss or early miscarriage. The researchers assessed serum C3 and C4 levels using nephelometry. Hypocomplementemia was defined based on local laboratory reference values. In all, pre-pregnancy complement levels and gestational outcomes were available in 49% of included patients with antiphospholipid antibodies, and in 46% of those with antiphospholipid syndrome. The statistical analysis was completed using GraphPad.

According to the researchers, patients with low pre-pregnancy C3 or C4 demonstrated a significantly higher prevalence of pregnancy losses (P = .01). This association was also observed in a subgroup analysis of patients with triple antiphospholipid antibody positivity (= .04). However, adverse pregnancy outcomes were not found to be related to pre-pregnancy complement levels in those with single or double antiphospholipid antibody positivity. All pregnancy losses in the triple positivity subgroup were treated with low-dose aspirin and low molecular weight heparin from the pregnancy test positivity.

There was no link between low pre-pregnancy complement levels and maternal complications, such as preeclampsia, eclampsia, deep vein thrombosis or thrombocytopenia.

“Decreased C3 and/or C4 levels before pregnancy are associated with increased risk of adverse outcomes in women with antiphospholipid antibodies, with or without antiphospholipid syndrome,” Nalli said. “Even in the high-risk group of triple antiphospholipid antibody positivity, the presence of low C3 and/or C4 seems to predict a worse prognosis.”

“Eleven different institutions were involved in this study that have validated on large scale the utility of preconceptional measurement of C3 and C4 levels to predict pregnancy loss in patients with antiphospholipid antibodies, even at high risk profile,” she added. “The tests are easy and cheap to be routinely performed and they could therefore represent a valid aid to identify women that need a particular monitoring and management.”