Proteinuria May Not Help Predict Fetal or Maternal Outcomes in Preeclampsia

Laurie Barclay, MD

March 28, 2009

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March 27, 2009 — The estimation of levels of proteinuria in women with preeclampsia is not a clinically useful test to predict fetal or maternal outcomes, according to the results of a systematic review reported in the March 24 Online First issue of BMC Medicine.

"Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia," write Shakila Thangaratinam, from Birmingham Women's Hospital, United Kingdom, and colleagues. "Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies."

To identify relevant articles, the investigators performed electronic searches without language restrictions in MEDLINE (1951-2007), EMBASE (1980-2007), the Cochrane Library (2007), and the MEDION database. They also hand searched selected specialty journals and reference citations of retrieved articles. Studies assessing the accuracy of proteinuria estimate to predict maternal and fetal complications of preeclampsia were independently selected by 2 reviewers. With use of maternal and fetal complications as reference standards, 2 x 2 tables were constructed from data extracted on study characteristics, quality, and accuracy.

There were 16 primary articles meeting selection criteria. These studies enrolled a total of 6749 women and evaluated the ability of levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria, or urine protein-to-creatinine ratio to predict complications of preeclampsia. There were 10 studies predicting maternal outcomes; in all 10 of these, proteinuria was a poor predictor of maternal complications in women with preeclampsia.

To evaluate the accuracy of proteinuria to predict fetal and neonatal complications, 17 studies used laboratory testing and 8 studies used bedside analysis. For the threshold level of proteinuria of 5 g in 24 hours, summary likelihood ratios of positive and negative test results were 2.0 (95% confidence interval [CI], 1.5 - 2.7) and 0.53 (95% CI, 0.27 - 1) for stillbirths, 1.5 (95% CI, 0.94 - 2.4 ) and 0.73 (95% CI, 0.39 - 1.4) for neonatal deaths, and 1.5 (95% CI, 1- 2) and 0.78 (95% CI, 0.64 - 0.95) for admission to the neonatal intensive care unit.

"Measure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia," the study authors write.

Limitations of this systematic review include those inherent in the methodology and the quality of the included studies; heterogeneity between individual studies in population, definition of preeclampsia, method of performing the test, test thresholds and frequency, interval between the test and outcome, and reference standards; and possible confounding by other risk factors.

"This systematic review has shown that estimation of levels of proteinuria in women with [preeclampsia] is not a clinically useful test to predict fetal or maternal complications," the study authors conclude. "The results of this review [call] into question the commonly used practice of making clinical decisions in women with pre-eclampsia based on the severity of proteinuria. It has highlighted the need for large, well-designed prospective studies on this important question with the hope to expand future research."

University Hospital North Staffordshire Research and Development Department, Stoke-on-Trent, United Kingdom, supported this study. The study authors have disclosed no relevant financial relationships.

BMC Med. Published online March 24, 2009.

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