Association Between Blunted Glomerular Hyperfiltration in Pregnancy and Severe Maternal Morbidity—A Research Letter

BACKGROUND: Glomerular hyperfiltration is one physiological adaptation to pregnancy, marked by a decline in serum creatinine (SCr) concentration by 16 weeks’ gestation. It is not known whether blunted glomerular hyperfiltration leads to adverse maternal outcomes, including severe maternal morbidity (SMM). OBJECTIVE: To evaluate the association between blunted glomerular hyperfiltration and subsequent SMM or death. DESIGN: Population-based cohort study SETTING: Ontario, Canada, from 2008 to 2019. PARTICIPANTS: Included were births among women who had ≥ 1 SCr measured as an outpatient within 10 weeks before conception (“preconception”), and again, at 11(0/7) to 20(6/7) weeks’ gestation (“in-pregnancy”). Excluded were women who died before birth, who had end-stage renal disease or kidney transplantation before conception, or whose pre-pregnancy SCr was 125 μmol/L. EXPOSURE: Net glomerular hyperfiltration defined as the preconception minus the in-pregnancy SCr. MEASURES: The primary study outcome was SMM or death arising from 23 weeks’ gestation up to 42 days after the index birth. METHODS: Adjusted relative risks (aRRs) were calculated using Modified Poisson regression per 1-SD net blunting of glomerular hyperfiltration adjusting for important covariates. RESULTS: A total of 10,323 births met all inclusion criteria. The mean (SD) SCr was 61.7 (11.0) μmol/L preconception, 48.0 (9.2) μmol/L in-pregnancy, and the mean net difference 13.6 (8.2) μmol/L. Among these births, the adjusted RR of SMM or death from 23 weeks’ gestation up to 42 days post-partum was 1.16 (95% confidence interval 1.14-1.30) per 1-SD (8.2 μmol/L) net blunting of glomerular hyperfiltration. LIMITATIONS: As SCr assessment is not a routine part of pregnancy care, its measurement could have been for a specific health condition thereby imparting selection bias. CONCLUSIONS: Blunted glomerular hyperfiltration in pregnancy may identify some women at higher risk of SMM. Further prospective research is needed about the implications of glomerular hyperfiltration in early pregnancy.