C3G During Pregnancy Linked to Adverse Renal, Obstetric Outcomes

Pregnancies occurring during or after initial C3 glomerulopathy (C3G) presentation may be at an increased risk of adverse renal and obstetric events, according to findings from a recent study.1

Results from the retrospective analysis of patient data from the University of Iowa’s C3G Natural History Study highlight an increased risk of preeclampsia, prematurity, and renal function decline in pregnant patients with C3G compared with healthy controls.1

“Little is known about the outcomes for women who experience pregnancy in the setting of C3G,” Lauren Fergus, of the Molecular Otolaryngology and Renal Research Laboratories at the University of Iowa, and colleagues wrote.1 “While there are older series of data describing the outcomes of pregnancy in all types of MPGN, it is impossible to extract C3G-specific outcomes from these studies to apply to current practice. This paucity of data makes pregnancy counseling incomplete and presents difficulties for patients and physicians alike."

The incidence of C3G in the United States is estimated to be between 0.5 and 3 cases per 1 million, with a point prevalence ranging from 14 to 40 cases per 1 million. Given its ultra-rare nature, variable clinical presentation, as well as its epidemiology and pathogenesis, C3G in the context of pregnancy presents a unique and poorly understood situation.1,2

To address this gap in research, investigators surveyed data on female patients enrolled in the University of Iowa’s C3G Natural History Study and examined the course of their pregnancies, short-term events, and long-term renal outcomes. For inclusion in the pregnancy cohort, patients were required to have had a native kidney biopsy diagnosis of C3G, female sex, be ≥ 15 years of age at time of data extraction, had ≥ 1 pregnancy, and have available both obstetric and renal data.1

Investigators further categorized pregnancies based on whether they occurred before initial C3G presentation or during/after initial C3G presentation.1

Of 43 women with ≥ 1 pregnancy identified in the database, 32 women representing 79 pregnancies had sufficient data to be included in the analysis. Of the 79 pregnancies, 47 (59%) occurred prior to the histologic diagnosis of C3G (P + C3G) and 32 (41%) occurred after histologic diagnosis (C3G + P).1

In the C3G + P group, non-live birth outcomes impacted 10 pregnancies and included 5 spontaneous miscarriages, 1 stillbirth, 1 ectopic pregnancy, and 3 elective abortions. A total of 12 deliveries (44%) were premature, while 16 (59%) were associated with antepartum preeclampsia. Investigators noted these risks were greater in C3G pregnancies than healthy pregnancies and pregnancies of mothers with other glomerular diseases.1

Investigators identified preexisting hypertension, an identified driver of complement dysregulation, and an eGFR prior to pregnancy of < 60 ml/min/1.73m2 as risk factors for complications. Of note, these risk factors also predict progression to ESKD within 5 (16%) and 10 (19%) years following pregnancy.1

Compared to pre-pregnancy values, post-pregnancy serum creatinine levels trended upwards and eGFRs downwards, both by small but significant amounts. Investigators noted change in serum creatinine had a sigmoidal fit (R2 = 0.92), with only increases predicted post-pregnancy. The change is eGFR was similar with a linear fit (R2 = 0.67) and predicted a decrease of 12% in post-pregnancy eGFR (95% CI, -38 to +14%).1

Investigators also called attention to worse individual pre-/post-pregnancy eGFRs in mothers who progressed to ESKD within 5–10 years of pregnancy.1

“These data provide a preliminary maternal-risk profile for C3G patients who are considering pregnancy and allow for certain risk scenarios to be considered and managed prospectively,” investigators concluded.1 “Ultimately, the elevated chances of adverse events support the need for multidisciplinary pre- and peri-pregnancy care involving obstetrics, nephrology, and pediatrics as a mechanism for improving outcome of both mother and baby.”

References

1. Fergus LO, Waldmann M, Hall MD, et al. Pregnancy outcomes in C3 glomerulopathy: a retrospective review. BMC Nephrol. doi:10.1186/s12882-025-04118-y

2. Smith RJH, Appel GB, Blom AM, et al. C3 glomerulopathy—understanding a rare complement-driven renal disease. Nat Rev Nephrol. doi:10.1038/s41581-018-0107-2