Background: Atypical hemolytic uremic syndrome (aHUS) in pregnancy is a rare and life-threatening thrombotic microangiopathy (TMA). It has clinical overlap with other conditions such as preeclampsia and HELLP syndrome, and hence it remains underdiagnosed and poorly understood. With this systematic review and meta-analysis, we aimed to evaluate the incidence, clinical characteristics, treatment approaches, and outcomes of pregnancy-associated aHUS.

Methods: Following PRISMA guidelines, a systematic search on PubMed, Cochrane, and Clinicaltrial.gov was performed from the date of inception to March 30, 2025, using search terms and keywords related to ‘pregnancy OR pregnant OR gestation’ and ‘hemolytic uremic syndrome OR atypical HUS OR HUS’. Of 233 search results, 23 studies reporting patterns of aHUS in pregnancy were included for this review. Basic statistics were used to describe baseline characteristics. Pooled analysis in R (v4.3.3) was done using the Der Simonian-Laird Estimator, calculating inter-study variance and extracting data with 95% confidence intervals (CI).

Results: A total of 712 pregnant patients from 23 studies (one clinical trial, 10 retrospective studies, six observation studies, and six case series) were included in the analysis. The maternal median age ranged from 16 to 45.2 years. The majority of aHUS cases (65.7%, n= 261/397) presented in the post-partum period compared to 34.7% (n= 124/357) in the ante-partum period. A higher incidence was noted during first pregnancies (54.6%, n=164/300) compared to second pregnancies (34.5%, n=104/300). The incidence of previous history of HUS was 10.6% (n = 16/150), and the incidence of family history of HUS was 14.4% (n = 23/159). Preeclampsia was the most common presentation (11/23 studies), followed by anemia (6/23 studies). Among the pregnant patients with atypical HUS, creatinine at presentation ranged from 0.68 to 17.42 mg/dL, platelets at presentation ranged from 2700 to 224000 cells/μL, hemoglobin ranged from 3.7 to 14.5 g/dL, and LDH at presentation ranged from 157 to 12484 U/L. Eculizumab was used in 36% of cases (n = 122/339). Dialysis was required in 54% of patients (n = 170/315), and maternal death was reported in 22% (n = 71/322). Pre-eclampsia occurred in 59.2% of cases (n = 157/265), while cesarean delivery was needed in 44.2% (n = 92/208). The incidence of stillbirth and recurrence of atypical HUS were 16.3% (n = 31/190) and 22.8% (n = 32/140), respectively. The pooled incidence of maternal mortality across studies was 25% (95% CI: 0.19–0.33; p = 0.14).

Conclusion: Atypical HUS in pregnancy is associated with significant maternal morbidity and mortality. It most commonly presents in the postpartum period and during first pregnancies. The high rates of dialysis, preeclampsia, and maternal death highlight the critical nature of this condition. Timely diagnosis and broader access to targeted therapies such as eculizumab may be essential to improving clinical outcomes.

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2025
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