Serum Creatinine Levels Before, During, and After Pregnancy

Abstract

This study uses Canadian administrative health databases to estimate gestational age–specific serum creatinine levels before, during, and after pregnancy among women without antecedent kidney disease.

Estimating renal function before and during pregnancy has clinical importance: kidney dysfunction can affect maternal and perinatal health. Glomerular hyperfiltration is a typical physiological adaptation to pregnancy, reflected by a decrease in levels of serum creatinine (SCr) with advancing gestational age. Creatinine-based equations used to estimate glomerular filtration may misclassify renal function during pregnancy,¹ as they depend on a steady state of creatinine balance. Moreover, a 24-hour collection of urine to measure creatinine clearance is impractical.² Accordingly, physicians typically rely on SCr level.

Previous studies attempted to define a normal SCr level in pregnancy, but they had few participants and may have been confounded by sampling bias.^3,4 The current study was undertaken to generate gestational age–specific estimates of renal function—before, during, and after pregnancy—among women without antecedent kidney disease.

Methods

Using linked administrative health databases, a retrospective population-based serial cross-sectional study was completed in Ontario, Canada, where universal health care is available to all residents. The included databases contain all in-hospital births in Ontario, with 98% successful linkage of maternal and newborn records and prior validation of sociodemographic data, primary diagnoses, laboratory data, and physician billing claims.

Eligible participants were women aged 16 to 50 years with a singleton live birth at more than 20 weeks’ gestation between April 2006 and March 2015 and 1 or more outpatient measurements of SCr concentration starting from 10 weeks preconception and up to 18 weeks postpartum. Measurement of SCr concentrations is not a routine part of pregnancy care, so measurements could be for either a specific condition or for general health screening. Women were excluded if they had an SCr concentration greater than 125 μmol/L (to convert creatinine values to milligrams per deciliter, divide by 88.4),⁵ preexisting renal disease, an estimated glomerular filtration rate less than 60 mL/min, or recorded prepregnancy albuminuria—any within 4 years before the current estimated date of conception. Women whose index pregnancy was complicated by gestational hypertension or preeclampsia were also excluded, as these conditions may worsen renal function.

Mean SCr values, with 95% CIs, were plotted weekly. The 50th, 75th, and 95th percentiles for SCr concentration were also plotted to define cut points above which clinicians may be concerned about impaired kidney function. Analyses were performed using SAS version 9.4 (SAS Institute Inc). The research ethics board at Sunnybrook Hospital approved the study and waived need for informed consent.

Results

Among 1 241 286 pregnancies in Ontario during the study period, 243 534 (20%) were included in the final cohort. There were 361 945 measurements of SCr concentration among the cohort, with a median of 1 measurement per pregnancy. The mean SCr concentration was 60 (95% CI, 60-60) μmol/L before pregnancy, rapidly declining by 4 weeks’ gestation to a nadir of 47 (95% CI, 47-47) μmol/L between 16 and 32 weeks (Figure). After 32 weeks’ gestation, there was a steady rise in SCr concentrations, peaking at 64 (95% CI, 63-64) μmol/L within a few weeks postpartum, and then a gradual return to mean prepregnancy concentrations by 18 weeks’ postpartum (Figure).

Figure. Mean Serum Creatinine Concentrations With 50th, 75th, and 95th Percentile Values Among 243 534 Women With Singleton Pregnancies and Apparently Healthy Renal Function.

A, Dashed curves indicate upper and lower 95% CI bounds. B, Values adjacent to each curve indicate the percentile-specific corresponding serum creatinine values at each time point. To convert creatinine values to mg/dL, divide by 88.4.

Weekly 50th, 75th, and 95th percentiles of SCr concentrations are shown in the Figure. There was a difference of approximately 15 μmol/L between the 95th and 50th percentiles during pregnancy and of approximately 20 μmol/L postpartum.

Discussion

In this study of pregnant women, SCr concentrations rapidly declined in the first trimester, reached a plateau in the second, and slowly increased in the third trimester toward the prepregnancy concentration. This study also provided specific cut points for SCr concentrations at different gestational ages. A 95th-percentile SCr concentration may suggest impaired kidney function and prompt further investigation or specialty referral.

This study has some limitations. First, measurement of SCr concentration was ordered on clinical grounds, and the indication for testing was not known. Hence, it is conceivable that some women included in this study may not be representative of healthy pregnant women, despite the strict exclusion criteria. Second, this study did not assess a change in SCr concentrations within a given pregnant woman. Third, some variability in measured SCr concentrations could be partly attributable to racial differences not accounted for.

While SCr concentration can likely distinguish abnormal from healthy renal function before, during, and after pregnancy, validation of this measure in relation to adverse maternal, obstetric, and perinatal outcomes is warranted.

Section Editor: Jody W. Zylke, MD, Deputy Editor.