Association of Proteinuria Threshold in Pre-Eclampsia with Maternal and Perinatal Outcomes: A Nested Case Control Cohort of High Risk Women

Abstract

ObjectivesTo evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499mg and ≥500mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension.DesignSecondary analysis of the Vitamins in Pre-Eclampsia Trial.Setting25 UK hospitals in ten geographical areas.Population946 women with pre-existing risk factors for pre-eclampsia.MethodsWomen with pre-eclampsia and proteinuria 300-499mg/24h (PE300, referent group, n=60) or proteinuria ≥500 mg/24h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110).Main Outcome MeasuresMaternal: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5th centile, gestation at delivery.ResultsSevere hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2w) than PE300 (37.3w; P≤0.001), and later in CHT (38.3w; P≤0.05) and GH (39.1w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05).ConclusionWomen with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.

Proteinuria in preeclampsia: is it important?

“…A study by Bramham et al showed an increase in the rates of gestational complications, low fetal birth weight and severe preeclampsia as the proteinuria levels increased and when the proteinuria levels were measured as 300 mg/day and 500 mg/day [22].…”

Clinical features of isolated gestational proteinuria progressing to pre-eclampsia: retrospective observational study

“…A P/Cr level around 0.27 is a reasonable cut-off level to exclude or detect proteinuria of 0.3 g/day,14 although the prognostic value of different quantities of urinary protein is unclear and further studies to identify diagnostic thresholds of proteinuria that are accurate for predicting clinically important outcomes is needed 10. A recent study examining the occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (0.3–0.49 and >0.5 g/day, respectively) in women with PE confirmed that 0.3 g/day is an appropriate threshold 15. It may be clinically beneficial to be aware of physiological changes in the amount of protein loss in the urine of pregnant women.…”

Massive Urinary Protein Excretion Associated with Greater Neonatal Risk in Preeclampsia

“…14 The relationship between heavy proteinuria and adverse clinical events in pregnancies complicated by PE has been investigated in multiple studies. [15][16][17][18][19][20][21][22][23] Some studies have shown that the level of proteinuria is not associated with adverse maternal [15][16][17][18]20 or perinatal outcomes. [15][16][17][18][19][20] However, others have reported that heavy proteinuria increases both maternal and perinatal morbidities including severe hypertension, preterm delivery, cesarean delivery, small for GA (SGA) infants, maternal symptoms, and perinatal mortality rate.…”

“…[15][16][17][18][19][20] However, others have reported that heavy proteinuria increases both maternal and perinatal morbidities including severe hypertension, preterm delivery, cesarean delivery, small for GA (SGA) infants, maternal symptoms, and perinatal mortality rate. [21][22][23][24][25] These conflicting results likely reflect limitations of previous studies including retrospective design, 15 proteinuria quantification by qualitative dipstick method, [16][17][18] performance in single-care settings, 17,22,23 and inclusion of hypertensive disorders other than PE to examine pregnancy outcomes. 19 Given the recent revision of the diagnostic criteria for PE, we believe it is appropriate to reconsider the association between the degree of proteinuria with the clinical course and pregnancy outcome of PE.…”