Increased urinary excretion of nephrin, podocalyxin, and ßig-h3 in women with preeclampsia.

Emerging evidence has shown that podocyte injury and reduced specific podocyte protein expressions contribute to proteinuria in preeclampsia. We collected urine specimens from women with preeclampsia to study whether podocyte-specific protein shedding is associated with renal barrier dysfunction. Urine specimens from women with normal pregnancies and from pregnant women complicated by chronic hypertension were used for comparison. We determined soluble podocyte slit protein nephrin levels in the urine specimens. Podocalyxin, ßig-h3, and VEGF concentrations were also measured. We found that nephrin and podocalyxin were barely detectable in the urine specimens from normal pregnant women and from women with chronic hypertension. In preeclampsia, urinary nephrin and podocalyxin concentrations were significantly increased and highly correlated to each other, r(2) = 0.595. Nephrin and podocalyxin were also correlated with urine protein concentrations. ßig-h3 was detected in the urine specimens from women with preeclampsia, and it is highly correlated with nephrin and podocalyxin concentrations in preeclampsia. ßig-h3 was undetectable in normal pregnancy and pregnancy complicated by chronic hypertension. Elevated VEGF levels were also found in women with preeclampsia compared with those of normal pregnancy and pregnancy complicated by chronic hypertension. These results provide strong evidence that podocyte protein shedding occurs in preeclampsia, and their levels are associated with proteinuria. The finding of urinary ßig-h3 excretion in preeclampsia suggests that increased transforming growth factor activity might also be involved in the kidney lesion in this pregnancy disorder.

Protein-creatinine ratio and albumin-creatinine ratio for the diagnosis of significant proteinuria in pregnant women with hypertension: Systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: The gold standard for assessment and diagnosis of significant proteinuria in pregnancy has been by 24-hour urine collection and analysis. Determining fast, accurate methods to identify clinically significant proteinuria would aid diagnosis of pre-eclampsia. The objective of this study was to determine the accuracy of spot protein-creatinine ratio (PCR) and albumin-creatinine ratio (ACR) measurements compared with 24-hour urine collection for the identification of clinically significant proteinuria in women with hypertensive disorders of pregnancy. METHODS: Search strategies were developed for electronic databases from inception to 1st October 2020. Data were assessed for methodological quality using the QUADAS-II checklist for risk of bias and quality of the evidence using GRADE. Meta-analysis was performed where there were at least four studies presenting data for the same comparison (test and threshold). This is an update of the review for NICE guideline NG133 (published June 2019) and includes additional data. RESULTS: Twenty-nine studies were included. PCR measurements (28 studies) showed high sensitivity (91%) and specificity (89%) at a threshold of 30 mg/mmol (n = 3577). Higher thresholds (>60 mg/mmol) increased specificity, but reduced sensitivity. At a threshold of PCR 30 mg/mmol, diagnostic accuracy improved for sensitivity and specificity (93% for both) in studies where the first morning void was excluded (n = 1868). Data available (4 studies) for ACR supports ruling out of significant proteinuria at less than 2 mg/mmol, though evidence was limited by paucity of data and wide confidence intervals around the result. CONCLUSIONS: PCR and ACR have high accuracy compared to the gold standard 24-hour urine collection.

The 24-hour urine collection: gold standard or historical practice?

OBJECTIVE: The objective of the study was to determine completeness of 24-hour urine collection in pregnancy. STUDY DESIGN: This was a retrospective laboratory/chart review of 24-hour urine collections at British Columbia Women's Hospital. Completeness was assessed by 24-hour urinary creatinine excretion (UcreatV): expected according to maternal weight for single collections and between-measurement difference for serial collections. RESULTS: For 198 randomly selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of 97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body weight resulted in more inaccurate collections (24-68%). The current weight was frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric) with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31] days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40 women (24.8%) had values 25% or greater, exceeding analytic and biologic variation. CONCLUSION: Twenty-four hour urine collection is frequently inaccurate and not a precise measure of proteinuria or creatinine clearance.

Serum and urine inhibin A but not free activin A are endocrine biomarkers of severe pre-eclampsia.

OBJECTIVE: Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies. STUDY DESIGN: Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated. RESULTS: Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia. CONCLUSION: Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.

Urinary abnormalities and renal function in pregnant women with chronic hypertension. / Avaliação de alterações urinárias e função renal em gestantes com hipertensão arterial crônica.

INTRODUCTION: Renal involvement in pregnant women with chronic hypertension is not widely known. OBJECTIVES: 1- To describe the epidemiological profile of pregnant women with chronic hypertension; 2- To evaluate urinary abnormalities (by urinalysis), renal function (serum creatinine and cystatin C, and estimated glomerular filtration rate (eGFR); 3- To evaluate the pregnancy outcome in chronic hypertension. METHODS: 103 pregnant women with chronic hypertension (blood pressure over 140/90 mmHg, detected previously to pregnancy or until the 20th week) were submitted to clinical and laboratorial evaluation. RESULTS: Pregnant women were 21-45 (mean: 34) years-old. Protein/creatinine ratio in random urine was elevated in 5.2% (0.0-6.4g/g), serum creatinine in 19.6% and cystatin C in 14.7% of them. It was observed that characteristics of pregnant patients and their newborns (vs. frequencies of the cases with CKD-EPI cystatin C < 60 ml/min/1.73 m2) were: 20.5% (33.3%) of preterm birth < 37 weeks, 17.5% (22.2%) of birth weight < 2500g and 17.5% (22.2%) of small for gestational age; superimposed preeclampsia-eclampsia occurred in 24.7% (22.2%) of the cases. CONCLUSIONS: Renal abnormalities were detected by proteinuria, determinations of serum creatinine and cystatin C in 5.2, 19.6 and 14.7% of the cases. The results suggest that the formulas CKD-EPI and MDRD can have applicability in assessing renal function in pregnant women. It was also shown a high frequency of preterm birth or with < 2500g at birth or small for gestational age, as well as of superimposed preeclampsia-eclampsia (24.7%) in pregnant women with chronic hypertension.

[Podocyturia in pregnant women with chronic hypertension may predict kidney injury?]. / Podocitúria em gestantes hipertensas crônicas pode predizer dano renal?

PURPOSE: To evaluate the presence of podocyturia in chronic hypertensive pregnant women in the third trimester of pregnancy and its possible association with renal disease. METHODS: This was an observational study of a convenience sample of 38 chronic hypertensive pregnant women. The podocytes were labeled by the indirect immunofluorescence technique with anti-podocin and diamidino-phenylindole (DAPI). The count was made on 30 random fields analyzed and corrected according to urinary creatinine (podocytes/mg creatinine). The patients were assigned to two groups: NG (normal glomerular function), up to 100 podocytes, and GP (probable glomerulopathy), more than 100 podocytes. Urinary creatinine was measured by the alkaline picrate method. The variables analyzed were body mass index, gestational age, and systolic and diastolic blood pressure at the time of sample collection. Data were analyzed using the SPSS - version 16.0 (IBM - USA). Statistical analysis was performed by the χ2 test, and significant differences were considered when p<0.05. RESULTS: The median podocyte count was 20.3 (0.0-98.1) for group GN, and 176.9 (109.1-490.6) for GP. The mean body mass index was 30.2 kg/m2 (SD=5.6), mean gestational age was 35.1 weeks (SD=2.5), median systolic blood pressure was 130.0 mmHg (100.0-160.0) and median diastolic blood pressure was 80.0 mmHg (60.0-110.0). There was no significant correlation between podocyturia and body mass index (p=0.305), gestational age (p=0.392), systolic blood pressure (p=0.540) or diastolic blood pressure (p=0.540). CONCLUSIONS: In this study, there was no podocyturia pattern consistent with the presence of active renal disease, although some of the women studied (15.8%) exhibited a significant loss. We believe that it is premature to recommend the inclusion of the determination of podocyturia in routine prenatal clinical practice in chronically hypertensive pregnant women.

Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A2 were measured, along with renal prostaglandin E2 and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E2, 6-keto-prostaglandin F1 alpha, and 2,3-dinor-6-keto-prostaglandin F1 alpha were significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B2 and 2,3-dinor-thromboxane B2 showed no significant differences in the two groups. A significant negative correlation (r = -0.636, p less than 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F1 alpha and mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II.

Plasma human atrial natriuretic peptide, endothelin-1, aldosterone and plasma-renin activity in pregnancy-induced hypertension.

OBJECTIVE: To determine the relationship between endothelin-1 (ET-1), human atrial natriuretic peptide (hANP), plasma-renin activity (PRA) and 24-h urinary excretion of aldosterone (U-Ald) in pregnancy-induced hypertension (PIH). DESIGN AND METHODS: Plasma hANP (pg/ml), ET-1 (pg/ml), PRA (ng/ml per h) and U-Ald (microg/24 h) were measured and 24 h ambulatory mean arterial pressure (MAP) was monitored in 178 normotensive subjects (NT) and 79 gravidas with PIH at the 8th, 18th, 23rd, 28th, 32nd and 36th weeks. RESULTS: The PIH group had higher MAP than the NT group from the 23rd week (91.64 +/- 8.76 versus 83.48 +/- 4.36 mmHg, P< 0.01) until the end of the pregnancy. ET-1 levels (pg/ml) in both groups were identical at the beginning of pregnancy and different in the 23rd week [(NT versus PIH) (35.11 +/- 17.42 and 40.2 +/- 19.51, respectively, P < 0.05)] and the 36th week (37.36 +/- 18.07 and 42.7 +/- 16.43, P< 0.05). hANP levels (pg/ml) in the NT group decreased insignificantly from the 8th till the 32nd week, then increased to 101.94 +/- 17.4 in the 36th (P< 0.001 versus any other week). In the PIH group, hANP increased from 104.8 +/- 26.8 pg/ml at the 8th week to 161.3 +/- 28.6 pg/ml at the 36th week (P< 0.0001). hANP correlated with MAP in the NT group (r = 0.252, P< 0.0005) but not the PIH group. U-Ald in the NT group increased from 23.52 +/- 6.83 microg/24 h at the 8th week to 54.07 +/- 19.62 microg/24 h at the 36th week (P < 0.0001) and in the PIH group it increased from 27.90 +/- 11.6 to 53.66 +/- 20.4 microg/24 h (P< 0.0001). In the PIH group, PRA was lower compared with the NT group from the 8th (2.99 +/- 1.26 versus 4.10 +/- 1.82 ng/ml per h, P< 0.05) until the 36th week (3.34 +/- 2.16 versus 4.46 +/- 2.13 ng/ml per h). In the forced multiple regression analysis model with hANP as a dependent variable, a value of P< 0.003 was found with PRA, U-Ald and MAP, which indicates an interaction between the two vasoactive and homeostatic systems: the renin-angiotensin-aldosterone system and hANP. CONCLUSIONS: In PIH, elevated hANP might be important as a counterbalance to the presence of the active vasopressors and sodium retention. By inhibiting renin release, enhancing the transcapillary fluid migration and with its action as vasodilator, it acts as a corrective factor of the imbalance between the contracted circulating fluid volume and the vasoconstricted vascular bed.

Aggravation of the nutcracker syndrome during pregnancy.

BACKGROUND: The nutcracker syndrome is a rare condition thought to be caused by compression of the left renal vein between the descending aorta and the superior mesenteric artery. CASE: Gross hematuria appeared in the third trimester of an otherwise normal pregnancy. It continued despite treatment, and a cesarean was performed at 37 weeks' gestation. The hematuria stopped postpartum. With postpartum angiography and three-dimensional computed tomography, the diagnosis of nutcracker syndrome was finally made. CONCLUSION: Pregnancy can aggravate the nutcracker syndrome. This syndrome should be recognized as one of the diseases that causes gross hematuria.

Reversible tubular lesion in pregnancy-induced hypertension detected by urinary beta 2-microglobulin.

Serum and urine beta 2-microglobulin concentrations were measured in 17 primigravidas with mild pregnancy-induced hypertension and nine normotensive control patients matched for gestational age. Serum beta 2-microglobulin and creatinine clearance values were not different between the two groups but urinary excretion of beta 2-microglobulin was three times higher in the hypertensive patients. This difference disappeared within seven days of delivery. These results indicate that a reversible renal tubular lesion occurs in pregnancy-induced hypertension even in the absence of detectable proteinuria.

Correlation between morning urine estriol concentration and 24-hour estriol excretion.

In an attempt to circumvent the need for 24-hour urine collections for estriol analyses in assessment of fetal status, the possibility of using morning urine samples was investigated. Results indicate 1) good correlation between 24-hour estriol excretion and morning estriol concentration, and between corresponding E/C ratios, 2) similar morning and 24-hour estriol concentrations, 3) high dependence of estriol and creatinine excretion on 24-hour urine volume but not on morning volume, 4) larger variations in 24-hour than in morning urine volume, and 5) better consistency of values in morning than in 24-hour samples in pathologic pregnancy. The use of serial morning urine concentrations at least as an outpatient monitoring procedure is suggested.

Random protein-creatinine ratio for the quantitation of proteinuria in pregnancy.

OBJECTIVE: To compare random urine protein-creatinine ratios with 24-hour urine protein excretion rates in patients hospitalized with hypertensive disorders in pregnancy. METHODS: All hospitalized, hypertensive patients requiring 24-hour urine protein excretion collections were eligible for the study. During the 24-hour urine collection a separate 2-mL aliquot was taken for a protein and creatinine determination. RESULTS: Seventy-one samples were collected from patients with the following diagnoses: gestational hypertension (n = 56), preexisting hypertension and superimposed gestational hypertension (n = 11), and syndrome of hemolysis, elevated liver enzymes and low platelets (n = 4). The correlation coefficient between the random protein-creatinine ratio and the 24-hour urine protein excretion was 0.94. Calculated excretion rates with at least 300 mg protein in 24 hours had a sensitivity of 0.93, specificity of 0.90, and positive and negative predictive values of 0.87 and 0.95, respectively. For those samples with calculated excretion rates at least 5 g protein in 24 hours, the sensitivity was 1.00, specificity was 0.99, and positive and negative predictive values were 0.75 and 0.99, respectively. CONCLUSION: In nonambulatory hypertensive pregnant patients, there is a strong correlation between random voided protein-creatinine ratios and 24-hour urine protein excretions.

The use of urinary albumin-creatinine ratios and calcium-creatinine ratios as screening tests for pregnancy-induced hypertension.

OBJECTIVE: To assess the potential of both urinary albumin creatinine ratios and urinary calcium-creatinine ratios as screening tests for pregnancy-induced hypertension. METHODS: A prospective, non-interventional study was performed in a teaching hospital antenatal clinic. Five hundred normotensive, nulliparous pregnant women provided a urine sample at 19 weeks' gestation. The main outcome measurements were the development of pregnancy-induced hypertension and preeclampsia. RESULTS: No significant differences in urinary albumin/creatinine and calcium/creatinine were demonstrated between patients who developed pregnancy-induced hypertension and those who remained normotensive. Urinary creatinine concentrations were significantly higher at 19 weeks' gestation in patients who subsequently developed pregnancy-induced hypertension. CONCLUSIONS: This study suggests that neither urinary ratio is a potential screening test for pregnancy-induced hypertension. The increased urinary creatinine concentration in patients who subsequently developed pregnancy-induced hypertension has not previously been reported and merits further investigation.

Serum lipoproteins, insulin, and urinary prostanoid metabolites in normal and hypertensive pregnant women.

OBJECTIVE: To determine if hyperinsulinemia, hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein (HDL) cholesterol are present in women with pregnancy-induced hypertension or preeclampsia. METHODS: Serum concentrations of insulin, uric acid, total and lipoprotein cholesterol, triglyceride, and apolipoproteins A-I and B were measured in 31 women with pregnancy-induced hypertension (eight with proteinuria) and in 21 healthy, pregnant, weight-matched controls at 30-39 weeks' gestation. The urinary excretion of the stable metabolites of prostacyclin (PGI2) (6-keto-prostaglandin [PG] F1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and thromboxane A2 (TxA2) (thromboxane B2 and 2,3-dinor-thromboxane B2) was assessed in 17 women with pregnancy-induced hypertension and in eight controls. RESULTS: Women with pregnancy-induced hypertension exhibited 18% lower mean serum HDL2 cholesterol levels (0.9 versus 1.1 mmol/L, P < .05) and 65% higher mean triglyceride levels (3.3 versus 2.0 mmol/L, P < .05) compared to controls, whereas other serum lipid and apolipoprotein values did not differ significantly in the two groups. Mean serum insulin levels (13.3 versus 6.5 mU/L, P < .01) and uric acid levels (339.7 versus 231.2 mumol/L, P < .01) in patients with pregnancy-induced hypertension were significantly higher than those in the controls. Urinary output of PGI2 metabolites was reduced by 35-45% in patients with pregnancy-induced hypertension, whereas no differences were seen in the excretion of TxA2 metabolites. Serum HDL2 cholesterol concentrations correlated positively with 2,3-dinor-6-keto-PGF1 alpha excretion, and serum triglyceride concentrations correlated positively with 2,3-dinor-thromboxane B2 excretion. In addition, insulin levels correlated positively with triglyceride levels but negatively with HDL2 cholesterol concentrations. CONCLUSION: The metabolic characteristics (hypertriglyceridemia, hyperinsulinemia, hyperuricemia, low HDL2 cholesterol) in pregnancy-induced hypertension resemble the main features of the "insulin resistance syndrome." This may result in endothelial cell dysfunction as evidenced by PGI2 suppression.

Random urine protein-creatinine ratio to predict proteinuria in new-onset mild hypertension in late pregnancy.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of random urine protein-creatinine ratio for prediction of significant proteinuria (> or = 300 mg/24 h) in patients with new-onset mild hypertension in late pregnancy. METHODS: Medical records of 185 consecutive pregnant patients with new onset of mild hypertension in late pregnancy were reviewed. Random urine samples were taken before 24-hour urine collection. The predictive values of the random urine protein-creatinine ratio for diagnosis of significant proteinuria were estimated by using at least a 300-mg protein level within the collected 24-hour urine as the gold standard. RESULTS: Thirty-nine patients (21%) had significant proteinuria. There was a significant association between 24-hour protein excretion and the random urine protein-creatinine ratio (rs = 0.56, P <.01). With a cutoff protein-creatinine ratio greater than 0.19 as a predictor of significant proteinuria, sensitivity and specificity were 85% and 73%, respectively. Positive and negative predictive values of the test were 46% and 95%, respectively. CONCLUSION: The random urine protein-creatinine ratio was a poor predictor for significant proteinuria in patients with new-onset mild hypertension in late pregnancy.

Production of urinary 11-keto-thromboxane B2 in normal and hypertensive pregnancies.

Urinary levels of 11-keto-thromboxane B2 (11-keto-TXB2), were elevated at all gestational ages (12-41 weeks) compared with non-pregnant levels. 11-keto-TXB2 levels exceeded those of TXB2 throughout pregnancy, which suggested that 11-keto-TXB2 may be the major urinary metabolite of TXA2 in normotensive pregnancy, as in the non-pregnant state. This was reversed in women with mild pregnancy-induced hypertension (P.I.H.), such that urinary levels of TXB2 were higher (p less than 0.01) than those of 11-keto-TXB2. Since the 11-thromboxane dehydrogenase enzyme is found in the placenta, the low levels of 11-keto-TXB2 may be the result of placental damage decreasing the activity of the enzyme. The relationship between these findings and the aetiology of P.I.H. is not clear, but changes in urinary 11-keto-TXB2 may be of use in identifying those women at risk of developing P.I.H.

9 alpha,11 beta-prostaglandin F2 in pregnancies at high risk for hypertensive disorders of pregnancy, and the effect of acetylsalicylic acid.

Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of prostaglandin D2, in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9 alpha,11 beta-prostaglandin F2. Ninety high risk women were randomised to acetylsalicylic acid and placebo groups at 12-14 weeks of gestation, with 43 women in both groups followed up successfully. 9 alpha,11 beta-prostaglandin F2 was determined at baseline, at 24-26, and at 32-34 weeks of gestation. Fifteen normotensive non-pregnant women, 17 normotensive pregnant women at 12-14, and 15 at 30-34 weeks of gestation served as controls. Urinary 9 alpha,11 beta-prostaglandin F2 was significantly higher in pregnant women at 12-14 weeks of gestation as compared to non-pregnant women. High risk pregnancies had higher 9 alpha,11 beta-prostaglandin F2 as compared to normotensive pregnancies at 12-14, and at 30-34 weeks of gestation. Urinary 9 alpha,11 beta-prostaglandin F2 increased throughout pregnancy unrelated to the outcome of the pregnancy or to the treatment.

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

Pharmacokinetic and pharmacodynamic evaluation of atenolol during and after pregnancy.

STUDY OBJECTIVE: To evaluate changes due to pregnancy on atenolol's pharmacokinetics, response of maternal heart rate to atenolol, and the drug's effect on fetal heart rate. DESIGN: Prospective study. SETTING: Large university teaching hospital. PATIENTS: Fourteen pregnant women who were receiving oral atenolol for cardiac disease were enrolled and 10 completed the study. INTERVENTIONS: Patients were studied for 12 hours during the third trimester (TT) and again 6 weeks postpartum (PP). MEASUREMENTS AND MAIN RESULTS: Fetal heart rates, and maternal heart rates at rest and during exercise were recorded. Maternal plasma and urine atenolol concentrations were measured. Average resting heart rates (TT 68+/-10, PP 62+/-9 beats/min) and maximum heart rate during exercise (TT 100+/-6, PP 87+/-7 beats/min) were significantly higher in the third trimester than postpartum (p<0.05). The 12-hour atenolol area under the curve (TT 0.208+/-0.061, PP 0.215+/-0.089 ng/ml/day) and maximum plasma concentrations during the time of exercise tests (TT 1.07+/-0.39, PP 1.14+/-0.53 mmol/L) were not significantly different. Individual and population pharmacokinetics did not differ significantly between study periods. The fetal heart rate did not correlate with maternal atenolol concentration. CONCLUSION: Constant dosages of atenolol result in higher heart rates during pregnancy compared with the postpartum period. This lack of heart rate control is not due to significant changes in atenolol's pharmacokinetics or plasma concentrations.