Proteinuria in pre-eclampsia: how much matters?

Objective To determine, in women with proteinuric pre-eclampsia, whether a discriminant value of proteinuria at the time of diagnosis predicts the presence or absence of subsequent adverse maternal and fetal outcomes. Design Retrospective cohort study. Setting One teaching hospital and two primary referral hospitals in Sydney, Australia. Sample Three hundred and twenty-one pregnant women with proteinuric pre-eclampsia, managed according to a uniform management protocol. Methods All women with the diagnosis of proteinuric pre-eclampsia in the years 1998 - 2001 were studied. After exclusion of women with pre-eclampsia superimposed on pre-existing hypertension, a twin pair, unavailable spot urine results, 353 women were analysed using logistic regression to determine separately the predictors of any adverse maternal or fetal outcomes at the time of delivery. Receiver operating characteristic (ROC) curves, sensitivity and specificity were then calculated from the data. Main outcome measures Adverse maternal outcomes: severe maternal hypertension (BP greater than or equal to 170/110 mmHg), renal insufficiency, liver disease, cerebral irritation, haematological disturbances. Adverse fetal outcomes: small for gestational age, perinatal mortality. Results There were 108 (34%) adverse maternal outcomes and 60 (19%) adverse fetal outcomes including two stillbirths. In multivariate analysis, an adverse maternal outcome was significantly associated with higher spot urine protein/creatinine ratio at diagnosis (P < 0.0001) with an odds ratio (OR) of 1.003 per mg/mmol (95% confidence interval [CI] 1.002 - 1.004) and with older maternal age (P = 0.014) with OR 1.06 per year (95% CI 1.01 - 1.11). An increased risk of adverse fetal outcome was associated with higher spot urine protein/creatinine (P = 0.013; OR 1.44 per log [mg/mmol], 95% CI 1.08 - 1.92), gestation at diagnosis < 34 weeks ( P < 0.0001; OR 3.60, 95% CI 1.90 - 6.82) and early pregnancy systolic blood pressure less than or equal to 115 mmHg (P = 0.0002; OR 3.41, 95% CI 1.77 - 6.57). The area under the receiver operating characteristic (ROC) curve was 0.67 for adverse maternal outcomes and 0.72 for adverse fetal outcomes. Conclusions With increasing proteinuria, there is increased risk of adverse maternal and fetal outcomes. Although we did not identify a specific spot protein/creatinine ratio that could be used as a definitive screening value for adverse outcomes, it is possible to utilise data from this study to predict the likelihood of adverse maternal and fetal outcomes. A high spot urine protein/creatinine ratio in pre-eclamptic women of greater than 900 mg/mmol (similar to9 g/day), or greater than 500 mg/mmol (similar to5 g/day) in women over 35 years, is associated with a greatly increased likelihood of adverse maternal outcomes.