Prediction of pre-eclampsia in early pregnancy by estimating the spot urinary albumin: creatinine ratio using high-performance liquid chromatography.

OBJECTIVE: To establish whether a spot urinary albumin: creatinine ratio (ACR) measured before 20 weeks of gestation can predict subsequent pre-eclampsia when urinary albumin is measured by high-performance liquid chromatography (HPLC). DESIGN: Prospective exploratory study. SETTING: Antenatal clinic in a tertiary teaching hospital, Victoria, Australia. POPULATION: A cohort of 265 women with a singleton pregnancy, normal renal function, and no evident proteinuria, attending antenatal clinics between 12 and 20 weeks of gestation. METHODS: The ACR was determined from a mid-stream urine (MSU) sample taken between 17 and 20 weeks of gestation. Intact urinary albumin was determined by HPLC; creatinine was measured by modified Jaffe's method. OUTCOME MEASURES: Pre-eclampsia (primary); gestational hypertension, small for gestational age (SGA), gestational diabetes mellitus, gestational age at delivery, and prematurity (secondary). RESULTS: The median ACR was 28 mg/mmol (IQR 16-46 mg/mmol). Women who subsequently developed pre-eclampsia had a significantly higher ACR (median 50 mg/mmol; IQR 33-90 mg/mmol) compared with women suffering from gestational hypertension (median 27 mg/mmol; IQR 8-35 mg/mmol), and compared with unaffected women (median 28 mg/mmol; IQR 16-46 mg/mmol). Mothers of SGA infants also had a significantly higher median ACR. By ROC analysis, the optimum ACR to predict pre-eclampsia was 35.5 mg/mmol: the relative risk of developing pre-eclampsia in women with a urinary ACR ≥ 35.5 mg/mmol was 7.8 times more than in those with a urinary ACR < 35.5 mg/mmol. CONCLUSIONS: When urinary albumin is measured by HPLC, spot urinary ACR values are higher in early uncomplicated pregnancy compared with previously reported conventional methods. When measured early in the second trimester, an ACR ≥ 35.5 mg/mmol predicted pre-eclampsia well before the onset of clinical manifestations.