Reflux nephropathy and the risk of preeclampsia and of other adverse pregnancy-related outcomes: a systematic review and meta-analysis of case series and reports in the new millennium

BACKGROUND: Reflux nephropathy is a common urinary tract malformation, and a substantial cause of morbidity in women of childbearing age. While recent studies provide further new information on pregnancy-related outcomes, their results are heterogeneous and a systematic meta-analysis may help the interpretation. The aim of this review was to analyze pregnancy-related outcomes in the recent literature on reflux nephropathy (2000-2016), to perfect the estimation of risks, and to identify specific research needs. METHODS: We searched Medline, EMBASE and the Cochrane review databases for the period 2000-2016 (PROSPERO registration no. 42016042713). SELECTION CRITERIA: all case series and case reports dealing with reflux nephropathy and reporting on at least one pregnancy outcome. Data were extracted from eligible case series (≥ 6 cases). For the outcomes preeclampsia (PE), pregnancy-induced hypertension (PIH), preterm birth, and newborns small for gestational age, we employed as a control group the low-risk pregnancies from a multicenter database including 1418 live-born singletons. Case reports were analyzed narratively. RESULTS: The search retrieved 2507 papers, of which 7 case series and 4 case reports were retained. The series report on 434 women with 879 pregnancies; no study reported controls. Compared to the low-risk controls, the meta-analysis showed an increased risk of PIH (odds ratio, OR 5.55; confidence interval, CI 3.56-8.66), PE (OR 6.04; CI 2.41-15.13), and all hypertensive disorders combined (OR 10.43; CI 6.90-15.75). No difference was observed in preterm delivery and caesarean sections. A higher incidence of stillbirth was reported in one paper. Conversely, the 4 case reports (on 10 pregnancies) alert us to a potentially severe complication, hydro(uretero)nephrosis with or without infection. CONCLUSION: Reflux nephropathy is associated with an increased risk of PIH and PE, but not of preterm delivery, suggesting the occurrence of late 'maternal' PE. The finding of a higher incidence of stillbirths in one series requires further analysis. Strict follow-up of these women is needed, in particular in late pregnancy stages, to avoid and manage in particular hypertensive pregnancy complications