Pre-Pregnancy eGFR and the Risk of Adverse Maternal and Fetal Outcomes: A Population-Based Study

Abstract

Significance statement: Pregnancies in women with CKD carry greater risk than pregnancies in the general population. The small number of women in prior studies has limited estimates of this risk, especially among those with advanced CKD. We report the results of a population-based cohort study in Ontario, Canada, that assessed more than 500,000 pregnancies, including 600 with a baseline eGFR < 60 ml/min per 1.73 m 2 . The investigation demonstrates increases in risk of different adverse maternal and fetal outcomes with lower eGFR and further risk elevation with baseline proteinuria.

Background: CKD is a risk factor for pregnancy complications, but estimates for adverse outcomes come largely from single-center studies with few women with moderate or advanced stage CKD.

Methods: To investigate the association between maternal baseline eGFR and risk of adverse pregnancy outcomes, we conducted a retrospective, population-based cohort study of women (not on dialysis or having had a kidney transplant) in Ontario, Canada, who delivered between 2007 and 2019. The study included 565,907 pregnancies among 462,053 women. Administrative health databases captured hospital births, outpatient laboratory testing, and pregnancy complications. We analyzed pregnancies with serum creatinine measured within 2 years of conception up to 30 days after conception and assessed the impact of urine protein where available.

Results: The risk of major maternal morbidity, preterm delivery, and low birthweight increased monotonically across declining eGFR categories, with risk increase most notable as eGFR dropped below 60 ml/min per 1.73 m 2 . A total of 56 (40%) of the 133 pregnancies with an eGFR <45 ml/min per 1.73 m 2 resulted in delivery under 37 weeks, compared with 10% of pregnancies when eGFR exceeded 90 ml/min per 1.73 m 2 . Greater proteinuria significantly increased risk within each eGFR category. Maternal and neonatal deaths were rare regardless of baseline eGFR (<0.3% of all pregnancies). Only 7% of women with an eGFR <45 ml/min per 1.73 m 2 received dialysis during or immediately after pregnancy.

Conclusions: We observed higher rates of adverse pregnancy outcomes in women with low eGFR with concurrent proteinuria. These results can help inform health care policy, preconception counseling, and pregnancy follow-up in women with CKD.

Graphical abstract

Figure 1

Study population. Flow diagram demonstrating the creation of the final study cohort.

Figure 2

Association between eGFR and at (A) least one SMM indicator, (B) preterm birth (gestational age <37 weeks), and (C) low birthweight (weight <2500 g). SMM indicators were measured between 20 weeks of gestation and 42 days after the index delivery. Restricted cubic splines for eGFR were calculated with five percentile knots in a logistic regression model with the binary outcome for SMM, preterm birth, or low birthweight. The figures provide a visual representation of the relationship between the outcomes and eGFR truncated at 100 ml/min per 1.73 m²

Figure 3

Risk of (A) at least one SMM indicator, (B) preterm birth (gestational age<37 weeks), and (C) low birthweight (weight<2500 grams) by eGFR (ml/min per 1.73 m²) and proteinuria categories. Severe Maternal Morbidity indicators were measured between 20 weeks of gestation and 42 days after the index delivery. Preconception proteinuria in the 1–2 years before conception date was measured using a hierarchical combination of ACR or PCR on the basis of availability. Proteinuria values were categorized as severe (ACR value>30 mg/mmol or PCR value >50mg/mmol or urine dipstick 2+ or more), moderate (ACR value 3–30 mg/mmol or PCR value 15–50 mg/mmol or urine dipstick 1+), normal/mild (ACR value<3 mg/mmol or PCR value<5 mg/mmol or urine dipstick normal), and missing, respectively.