Elevated Creatinine in Pregnancy Doubles Preterm Birth Risk and Predicts Adverse Outcomes in Subsequent Pregnancies

The UK Royal College of Physicians recommends investigating abnormal kidney function in pregnancy when serum creatinine (SCr) is ≥77µmol/L[1,2]. However, this recommendation is based on a single systematic review of older, small-scale studies[1], raising concerns about its applicability to contemporary clinical use.

Using real-world electronic health record data (EHR), we sought to explore whether, in a diverse, real-world population, SCr ≥77 µmol/L resulted in poorer clinical outcomes, both during the index and subsequent pregnancies.

We performed a retrospective analysis of routinely collected EHR data 2016-2023, across two maternity sites within King’s College Hospital NHS Foundation Trust. Ethical approval was granted by the London South-East Research Ethics Committee (KERRI project 20241210B). Biochemistry results were linked with maternity records and pregnancy outcomes, including gestational age at delivery, mode of birth, birth weight, and fetal outcomes, using the CogStack informatics platform, which integrates structured and unstructured data from maternity, pathology, and inpatient systems. Pregnancies were classified as having elevated creatinine if any recorded value exceeded 77 µmol/L. Preterm birth was defined as delivery before 37 weeks’ gestation and low birth weight as < 2,500 g. Temporal trends in creatinine were assessed across gestational age, and comparisons between groups were performed using chi-squared and t-tests depending on data distribution.

In total, 54,814 pregnancy episodes in 45,662 women were identified. Creatinine measurements were available for 20,165 pregnancies in 18,488 women (36.7%), yielding 58,955 measurements overall. Elevated creatinine occurred in 1,748 pregnancies (8.67 % of tested cohort).

Women with a high creatinine had significantly worse outcomes compared to those with normal: preterm birth, 19.4% vs 9.9% (p<0.0001); low birth weight, 20.3% vs 9.8% (p<0.0001). Mean gestational age was reduced by 0.77 weeks (37.77 vs 38.54, p<0.0001) and mean birth weight by 205g (3034g vs 3238g, p<0.0001) in the elevated creatinine group. Elevated creatinine in any trimester was associated with adverse outcomes.

Among 3,599 women with sequential pregnancies and complete outcome data, elevated creatinine showed high recurrence risk. If the first pregnancy (P1) had elevated creatinine, 14.67% had recurrence in the second (P2) compared to only 3.10% if P1 was normal (OR 5.37, 95% CI 3.42-8.43, p<0.0001). Elevated creatinine in P1 predicted adverse outcomes in the P2 even in women who did not have recurrent elevation. P2 preterm birth rates were 11.4% if P1 had elevated creatinine, versus 7.3% if normal (OR 1.64, 95% CI 1.02-2.63, p=0.005). Mean gestational age in P2 was reduced by 0.37 weeks (38.67 vs 38.30, p=0.001) if P1 had elevated creatinine.

In this large, real-world, multi-ethnic pregnancy cohort, SCr >77μmol/L in pregnancy was strongly associated with adverse maternal and fetal outcomes. highlighting the importance of recognising creatinine elevation as an early biomarker of maternal and fetal risk. Routine creatinine monitoring in pregnancy, especially among high-risk groups, may enable earlier identification of women at risk of complications.

References

[1] Wiles K et al. Serum creatinine in pregnancy: a systematic review. Kid Int Rep 2019;4: 408-19.

[2] Royal College of Physicians Acute care toolkit 15: Managing acute medical problems in pregnancy. 2019.