Abstract / Summary
Background: Hypertensive disorders of pregnancy (HDP) may impair placental function and disrupt foetal nephrogenesis, increasing kidney vulnerability in offspring. However, the magnitude and phenotype-specific pattern of offspring kidney risk remain uncertain. We aimed to systematically assess the association between maternal HDP and offspring kidney outcomes. Methods: PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure were searched from inception to October 2025. Cohort and case–control studies evaluating maternal HDP and offspring kidney outcomes were included. Outcomes were grouped into three final categories, including chronic kidney disease (CKD), acute kidney injury (AKI), and congenital anomalies of the kidney and urinary tract (CAKUT). Two reviewers independently screened studies, extracted data, and assessed risk of bias. Pooled effect estimates were derived from random-effects meta-analysis using the generic inverse variance method, prioritising the adjusted estimates. The protocol was registered with PROSPERO (CRD420251175714). Results: Thirty studies (20 cohort and 10 case–control studies), including 10,954,573 participants, were included. Maternal preeclampsia was associated with an increased risk of offspring CKD (pooled adjusted relative effect 1.26, 95% CI 1.16, 1.37; I2 = 0%). Although crude analysis suggested a significant association between maternal HDP and offspring CAKUT (odds ratio [OR] 1.18, 95% CI 1.07, 1.31; I2 = 18%), the pooled adjusted estimate was not significant (adjusted OR 1.07, 95% CI 0.87, 1.31; I2 = 0%). A pooled adjusted estimate for offspring AKI was not derived, as this was reported in only 2 studies with considerable population heterogeneity. The overall crude risk ratio (RR) showed no statistically significant association but substantial heterogeneity (pooled crude RR 0.82, 95% CI 0.61, 1.10; I2 = 78%). Crude AKI RRs varied by criteria: Kidney Disease: Improving Global Outcomes 0.71 (95% CI 0.55, 0.91; I2 = 51%) versus Acute Kidney Injury Network 1.09 (95% CI 0.60, 1.96; I2 = 83%). Conclusions: Maternal HDP, particularly preeclampsia, was associated with elevated risks of offspring CKD; however, the pooled adjusted estimate for CAKUT was not statistically significant. Evidence for offspring AKI remains inconclusive, providing no reliable evidence for either an increased or decreased risk. Prospective studies using harmonised definitions and robust confounding control are needed to assess these associations and determine their clinical relevance.