Adverse Pregnancy Outcomes and Long-term Maternal Kidney Disease A Systematic Review and Meta-analysis

Importance Adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, are associated with increased risk of maternal cardiovascular disease. Little is known about whether adverse pregnancy outcomes are associated with increased risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Objective To review and synthesize the published literature on adverse pregnancy outcomes (hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery) and subsequent maternal CKD and ESKD. Data Sources PubMed, Embase, and Web of Science were searched from inception to July 31, 2019, for cohort and case-control studies of adverse pregnancy outcomes and maternal CKD and ESKD. Study Selection Selected studies included the following: a population of pregnant women, exposure to an adverse pregnancy outcome of interest, and at least 1 primary outcome (CKD or ESKD) or secondary outcome (hospitalization or death due to kidney disease). Adverse pregnancy outcomes included exposure to hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, or chronic hypertension), preterm delivery (<37 weeks), and gestational diabetes. Three reviewers were involved in study selection. Of 5656 studies retrieved, 23 were eligible for inclusion. Data Extraction and Synthesis The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout. Three reviewers extracted data and appraised study quality. Random-effects meta-analyses were used to calculate overall pooled estimates using the generic inverse variance method. Main Outcomes and Measures Primary outcomes included CKD and ESKD diagnosis, defined using established clinical criteria (estimated glomerular filtration rate or albuminuria values) or hospital records. The protocol for this systematic review was registered on PROSPERO (CRD42018110891). Results Of 23 studies included (5& x202f;769& x202f;891 participants), 5 studies reported effect estimates for more than 1 adverse pregnancy outcome. Preeclampsia was associated with significantly increased risk of CKD (pooled adjusted risk ratio [aRR], 2.11; 95% CI, 1.72-2.59), ESKD (aRR, 4.90; 95% CI, 3.56-6.74), and kidney-related hospitalization (aRR, 2.65; 95% CI, 1.03-6.77). Gestational hypertension was associated with increased risk of CKD (aRR, 1.49; 95% CI, 1.11-2.01) and ESKD (aRR, 3.64; 95% CI, 2.34-5.66). Preterm preeclampsia was associated with increased risk of ESKD (aRR, 5.66; 95% CI, 3.06-10.48); this association with ESKD persisted for women who had preterm deliveries without preeclampsia (aRR, 2.09; 95% CI, 1.64-2.66). Gestational diabetes was associated with increased risk of CKD among black women (aRR, 1.78; 95% CI, 1.18-2.70), but not white women (aRR, 0.81; 95% CI, 0.58-1.13). Conclusions and Relevance In this meta-analysis, exposure to adverse pregnancy outcomes, including hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, was associated with higher risk of long-term kidney disease. The risk of ESKD was highest among women who experienced preeclampsia. A systematic approach may be warranted to identify women at increased risk of kidney disease, particularly after hypertensive disorders of pregnancy, and to optimize their long-term follow-up. This systematic review and meta-analysis examines the published literature on adverse pregnancy outcomes (hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery) and subsequent maternal chronic kidney disease and end-stage kidney disease. Question Are adverse pregnancy outcomes associated with risk of long-term kidney disease in women? Findings In this systematic review and meta-analysis of 23 studies (5& x202f;769& x202f;891 participants), the risk of end-stage kidney disease was 4.9 times higher in women who had preeclampsia, and 3.6 times higher in women who had gestational hypertension vs women with normotensive pregnancies. The risk of end-stage kidney disease was 2.1 times higher in women who had preterm deliveries compared with women who delivered at term. Meaning Women who experience hypertensive disorders of pregnancy and other adverse pregnancy outcomes may warrant closer surveillance for long-term kidney disease.