Adverse pregnancy outcomes and long-term risk of chronic kidney disease in women: national cohort and co-sibling study

Abstract

Women with adverse pregnancy outcomes may have higher subsequent risk of chronic kidney disease, but the long-term independent risks and potential causality are unclear. This study aimed to determine long-term risks of chronic kidney disease associated with 5 major adverse pregnancy outcomes in a large population-based cohort, and to assess for familial confounding using co-sibling analyses. A national cohort study was conducted of all 2,201,279 women with a singleton delivery in Sweden from 1973 to 2015, followed up for chronic kidney disease identified from nationwide diagnoses through 2018. Cox regression was used to compute hazard ratios for chronic kidney disease associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes, adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. In 56 million person-years of follow-up, 11,572 (0.5%) women were diagnosed with chronic kidney disease (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with increased chronic kidney disease risk. Within 10 years following delivery, adjusted hazard ratios associated with specific adverse pregnancy outcomes were: 7.12 for other hypertensive disorders (95% confidence interval, 5.88-8.62), 4.38 for preeclampsia (3.72-5.16), 3.50 for preterm delivery (2.95-4.15), 3.15 for gestational diabetes (2.53-3.92), and 1.22 for small for gestational age (1.02-1.44). All hazard ratios remained significantly elevated even 30 to 46 years after delivery (gestational diabetes, 3.32 [95% confidence interval, 2.96-3.72]; other hypertensive disorders, 2.44 [1.91-3.11]; preeclampsia, 2.03 [1.90-2.16]; preterm delivery, 1.56 [1.44-1.68]; and small for gestational age, 1.24 [1.16-1.31]). These findings were only partially (0%-45%) explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk. In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for chronic kidney disease up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term monitoring to reduce risk of chronic kidney disease.