Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance.

Qualitative and quantitative measurement of urine protein excretion is one of the most common tests performed during pregnancy. For more than 100 years, proteinuria was necessary for the diagnosis of preeclampsia, but recent guidelines recommend that proteinuria is sufficient but not necessary for the diagnosis. Still, in clinical practice, most patients with gestational hypertension will be diagnosed as having preeclampsia based on the presence of proteinuria.

Accuracy of angiogenic biomarkers at ⩽20weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study.

Objective: To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia.

Design: Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers).

Increased protein-coding mutations in the mitochondrial genome of African American women with preeclampsia.

Preeclampsia occurs more frequently in women of African ancestry. The cause of this hypertensive complication is unclear, but placental oxidative stress may play a role. Because mitochondria are the major sites of oxidative phosphorylation, we hypothesized that placentas of preeclamptic pregnancies harbor mitochondrial DNA (mtDNA) mutations.

Pregnancy and chronic kidney disease.

This article reviews the association of chronic renal disease and pregnancy. Included are discussions of guidelines for counseling pregnant women with underlying chronic renal disease who are considering conceiving as well as management of those already pregnant. Specifically highlighted are recent studies that question the validity of using estimated glomerular filtration rate and other formulae and questions of whether we should strive to replace the classic counseling approaches based primarily on serum creatinine levels with guidelines based on chronic kidney disease classification.

Effect of smoking on circulating angiogenic factors in high risk pregnancies.

Objective: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia.

Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies.

Background: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.

Methods: This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies.

Does C-reactive protein predict recurrent preeclampsia?

Objective: Evaluate association of the inflammatory marker C-reactive protein with recurrent preeclampsia.

Methods: Serum samples collected longitudinally in women with previous preeclampsia from the Maternal-Fetal Medicine Units Network trial of aspirin to prevent preeclampsia were assayed for CRP.

Results: Of 255 women studied, 50 developed recurrence.

Hypertension in pregnancy.

Hypertension complicates 5% to 7% of all pregnancies. A subset of preeclampsia, characterized by new-onset hypertension, proteinuria, and multisystem involvement, is responsible for substantial maternal and fetal morbidity and is a marker for future cardiac and metabolic disease. This American Society of Hypertension (ASH) position paper summarizes the clinical spectrum of hypertension in pregnancy, focusing on preeclampsia.

Influence of maternal asthma and asthma severity on newborn morphometry.

Objective: To determine if maternal asthma or asthma severity affects newborn morphometry.

Study Design: A secondary analysis was performed on data collected in a multicenter prospective observational cohort study of asthma in pregnancy. Patients enrolled included women with asthma stratified by severity of disease and controls.

Interpreting abnormal proteinuria in pregnancy: the need for a more pathophysiological approach.

This review and opinion article focuses on the definitions and meanings of abnormal protein excretion in pregnancy, asking the following questions: Are our tests to determine abnormal proteinuria adequately performed? Are current guidelines for diagnosis of excessive proteinuria, especially when used to identify preeclampsia, supported by adequate data? Can the magnitude of proteinuria be used as a reliable clinical biomarker of the gravity of preeclampsia? Should timed urine collections, primarily 24-hour excretions, be supplanted by the urine protein/creatinine ratio in clinical practice? The answers to most of these questions are: We are not sure, or some guidelines are poorly supported by data and may prove erroneous. We suggest a more physiologic approach to assessment of proteinuria and believe that if clinicians and investigators looked at proteinuria in terms of how the kidney handles protein in health and disease it would lead to a more rational and evidence-based approach to proteinuria in pregnancy. Finally, we recommend that current cutoff for abnormal proteinuria be used to diagnose preeclampsia, but the level of proteinuria should not guide management.

Angiogenic dysfunction in molar pregnancy.

Objective: Molar pregnancy is associated with very early-onset preeclampsia. Since excessive circulating antiangiogenic factors may play a pathogenic role in preeclampsia, we hypothesized that molar placentas produce more antiangiogenic proteins than normal placentas.

Study Design: This retrospective case-control study used a semiquantitative immunohistochemical technique to compare histologic sections of molar placentas to normal controls.

ASH position paper: hypertension in pregnancy.

The American Society of Hypertension is publishing a series of Position Papers in their official journals throughout the 2008-2009 years. The following Position Paper originally appeared: JASH. 2008;2(6):484-494.

Maternal plasma concentrations of the soluble tumor necrosis factor receptor 2 are increased prior to the diagnosis of preeclampsia.

Objective: Soluble receptor levels of tumor necrosis factor (sTNF-R)-1 and -2 are increased during preeclampsia. We postulated the increase preceded overt disease.

Study Design: Archived plasma from the Eunice Kennedy Shriver National Institute of Child Health and Human Development aspirin to prevent preeclampsia in high risk women trial were used to measure serial sTNF-R1 and sTNF-R2 (enrollment, 24-28 week's gestation) in 986 women (577 also sampled at 34-38 weeks).

Hypertension in pregnancy.

Hypertension complicates 5% to 7% of all pregnancies. A subset of preeclampsia, characterized by new-onset hypertension, proteinuria, and multisystem involvement, is responsible for substantial maternal and fetal morbidity and is a marker for future cardiac and metabolic disease. This American Society of Hypertension (ASH) position paper summarizes the clinical spectrum of hypertension in pregnancy, focusing on preeclampsia.

Advances in the understanding of eclampsia.

Preeclampsia, a serious hypertensive complication of pregnancy characterized by new-onset hypertension and proteinuria after midpregnancy, is a multisystem disorder that often involves the central nervous system. Neurologic signs and symptoms include hyperreflexia, headaches, visual disturbance, seizures, and cerebral hemorrhage. Eclampsia-new-onset seizures in the setting of preeclampsia-usually occurs before or within 48 hours of delivery, but can present as late as 1 month postpartum (late postpartum eclampsia).