Abstract:

BACKGROUND:Stillbirth is a devastating adverse pregnancy outcome which may occur without any obvious reason, or may occur in the context of fetal growth restriction, preeclampsia or other obstetric complications. There is increasing evidence that women who experience stillbirths are at higher risk of long-term cardiovascular disease (CVD), but little is known about their risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We conducted the largest study to date to investigate the subsequent risk of maternal CKD and ESRD following stillbirth. OBJECTIVE:To identify whether pregnancy complicated by stillbirth is associated with subsequent risk of maternal CKD and ESRD, independent of underlying medical or obstetric comorbidities. STUDY DESIGN/METHODS:We conducted a population-based cohort study using nationwide data from the Swedish Medical Birth Register, National Patient Register and Swedish Renal Register. We included all women who had live births and stillbirths from 1973 to 2012, with follow-up to 2013. Women with pre-existing renal disease were excluded. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for associations between stillbirth and maternal CKD and ESRD respectively. We controlled for maternal age, year of delivery, country of origin, parity, body mass index, smoking, gestational diabetes, preeclampsia, and small for gestational age (SGA) deliveries. Women who had a history of medical comorbidities, which may predispose to renal disease (pre-pregnancy CVD, hypertension, diabetes, lupus, systemic sclerosis, hemoglobinopathy, or coagulopathy), were excluded from the main analysis and examined separately. RESULTS:There were 1,941,057 unique women who had 3,755,444 singleton pregnancies, followed up over 42,313,758 person-years. The median follow-up time was 20.7 years (interquartile range 9.9-30.0 years). 13,032 women (0.7%) had at least one stillbirth. Women who had experienced at least one stillbirth had a higher risk of developing CKD (adjusted hazard ratio (aHR) 1.26, 95% CI 1.09-1.45) and ESRD (aHR 2.25, 95% CI 1.55-3.25) compared to women who only had live births. These associations persisted after removing all stillbirths which occurred in the context of preeclampsia, SGA or congenital malformations (for CKD, aHR 1.33, 95% CI 1.13-1.57; for ESRD, aHR 2.95, 95% CI 1.86-4.68). There was no significant association observed between stillbirth and either CKD or ESRD in women who had pre-existing medical comorbidities (CKD, aHR 1.13, 95% CI 0.73-1.75; ESRD, aHR 1.49, 95% CI 0.78-2.85). CONCLUSION:Women who have a history of stillbirth may be at increased risk of CKD and ESRD compared to women who have only had live births. This association persists independently of preeclampsia, SGA, maternal smoking, obesity, and medical comorbidities. Further research is required to determine whether affected women would benefit from closer surveillance and follow-up for future renal disease.