Chronic Kidney Disease and Adverse Pregnancy Outcomes: A Systematic Review and Meta-analysis.

Abstract Objective Limited evidence exists on the role that cause of CKD plays in determining pregnancy outcomes. The aim of this systematic review and meta-analysis was to examine the association between CKD and adverse pregnancy outcomes, by cause and severity of CKD where reported. Protocol registration (PROSPERO, CRD:42020211925). Data sources PubMed, Embase, and Web of Science were searched until May 24, 2021, supplemented with reference list checking. Study eligibility criteria Studies that compared pregnancy outcomes in women with or without CKD were included. Two reviewers independently screened titles, abstracts, and full-text articles according to a priori defined inclusion criteria. Study appraisal and synthesis methods: Data extraction and quality appraisal were performed independently by three reviewers. The GRADE approach was used to assess the overall certainty of the evidence. Random-effects meta-analyses were used to calculate pooled estimates using the generic inverse variance method. Primary outcomes included pre-eclampsia, Caesarean section (CS), preterm birth (PTB) [ Results Of 4,076 citations, 31 studies were included. Pre-pregnancy CKD was associated significantly with a higher risk of pre-eclampsia [pooled crude odds ratio (OR)= 8.13 (95% confidence interval (CI), 4.41–15), and adjusted OR (aOR)=2.58 (1.33–5.01)], CS [aOR=1.65 (1.21–2.25)], PTB [aOR=1.73 (1.31–2.27)] and SGA [aOR= 1.93 (1.06–3.52)]. The association with stillbirth was not statistically significant [aOR=1.67 (0.96–2.92)]. Subgroup analyses indicated that different causes of CKD might confer different risks and that severity of CKD is associated with risk for adverse pregnancy outcomes, as pregnancies with later stages CKD, compared to earlier stages, had higher odds of pre-eclampsia, PTB and SGA. The GRADE certainty of the evidence was ‘very low’ across all outcomes. Conclusions This meta-analysis quantified associations between pre-pregnancy CKD, overall and according to cause and severity, and adverse pregnancy outcomes. These findings might support clinicians aiming to counsel women with CKD, by allowing them to tailor their advice according to cause and severity of CKD. We identified gaps in the literature and further studies examining the effect of specific kidney diseases, and other clinical characteristics (e.g. proteinuria, hypertension), on adverse pregnancy outcomes are warranted.