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Volume 168 Nu mber I, Pan 2 316 CALCIUM SUPPLEMENTATION IN MILD 317 PREECLAMPSIA REMOTE FROM TERM: A PROSPECTIVE RANDOMIZED DOUBLE-BLIND CLINICAL TRIAL l Sanchez-Ramos CD Adair. x GO DelValle, F Gaudier. I Oelke. Department of Obstetrics and Gynecology, University of Florida, Jacksonville, FL. OBJECTIVE: The purpose of this study was to determine the effect of calcium supplementation on the clinical course and the incidence of severe disease in patients with pre-term mild preeclampsia. STUDY DESIGN: Sixty-eight patients with mild preeclampsia at 24-36 weeks' gestation were randomly allocated to in-hospital treatmenl with a daily dose of 2000 mg of calcium (n=34) or matching placebo (n=34). Both groups were similar wtth regard to mean maternal age. gravidity. and gestational age at admission. The initial systolic and diastolic blood pressure and amount of proteinuria were also comparable. The clinical management and criteria for severe preeclampsia were consistent throughout the study. RESUL TS: The incidence of delivery because of severe preeclampsia was 53% in the calcium group and 54% in the placebo group (p=.95). There was a trend towards a lower incidence of severe preeclampsia in patients who received at least 7 days of treatment. No differences were noted in the blood pressure. p latelet count. serum uric acid and liver enzymes before or during labor in both groups. CON C L U S ION S : Our results indicate that calcium supplementation does not avert severe preeclampsia once clinical signs are present. Perhaps. iniliation of Iherapy days or weeks before clinical signs appear may be prevenlive. DIURNAL VARIATION OF URINARY CALCIUM EXCRETION IN WOMEN WITH PREECLAMPSIA. .I..... ID!il!". K. Hales x G. Thurnau. Dept. of OB/GYN. Uoiv. of Oklahoma. Okla. City. OK. OBJECTIVE: The purpose of this study is to measure diurnal variations of urinary calcium excretion by means of fractionated urine collections in preeclamptic gravidae (Group I; n = 6) and to compare the results with those of normotensive gravidae (Group II; n = 7) and nonpregnant normotensive controls (Group III; n = 10). STUDY DESIGN: Blood pressures (Supine and LLR). urine protein. hand and facial edema. complete blood counts. and serum Chem 18 proftles were evaluated. Urine calcium levels on voided specimens, obtained every 3 hours over a 24 hour period, were measured using a colorimetric autoanalyzer. No study subject received calcium supplementation or magnesium therapy prior to or after enrollment. RESULTS: Significant differences in the mean 3-hour interval calcium levels were found among the preeclamptic. normotensive gravidae. and nonpregnant normotensive controls (3.0 to 10.2 mg/dl, 17.1 to 30.9 mg/dI, and 7.1 to 17.9 mg/d!. respectively; p < 0.01). Also. the mean 24-hour urine calcium levels varied significantly among the three groups (5.7. 22.8. and 10.8 mg/dl. respectively; p < 0.01). Diurnal variation in urinary calcium excretion was observed in all groups with nadirs occuring between 4 and 10 a.m. and peaks between 7 and 10 p.m. CONCLUSION: Individual and 24-hour mean urinary calcium levels of the preeclamptic women were significantly lower than those of normotensive gravidae and nonpregnant c.ontrols. Also, diurnal variation was attenuated in the preeclampllc group. 318 SPO Abstracts 385 URINARY DIPSTICK PROTEIN IS A POOR PREDICTOR OF ABSENT OR SEVERE PROTEINURIA. N L Meyer,' B.M. Men:er,x S. A. Friedman,' BM. Sibai. DepL ofOB/GYN, Univ. ofTenn., Memphis. BACKGROUND: A urine protein dipstick of frequently on 2 occasions 4 hours apart, is traditionally used to establish proteinuria in studies dealing with hypertensive disorders of pregnancy. In addition, a dipstick value is considered diagnostic of severe preeclampsia, since it is said to correspond with a quantitative value of g/24 h. OBJECTIVE: To compare urine protein dipstick values to standard 24·hour protein excretion in women with hypertensive diseases of pregnancy. STUDY DESIGN: Serial urine protein dipstick performed at least every 8 hours and 24·hour urinary protein excretion were studied in 271 pregnancies complicated by hypertensive disease. Results of 2 consecutive dipsticks obtained during a 24-hour urinary collection Were compared to the total protein excretion in the 24-hour sample. RESULTS: Ninety-six patients had negative to trace protein on dipstick on 2 occasions at least 8 hours apart. Sixty-four (67%) of these patients had significant proteinuria mg/24 h). Seventy-seven patients had 3+ to 4+ protein on dipstick in 2 samples. Of these, 26 (34%) had nephrotic range proteinuria g/24 h), and 44 (57%) had proteinuria g/24 h. ur\ne dipstick values of 1+ to 2+, of whom 86 (88%) had slgruficant protemurla. Urw Protein (mg/24 h) Dipstick neg trace 1 + 2+ 3+ 4+ <300 (n=49) 16 16 6 6 4 1 ................. ...... ..... .. .. .. .. .... ...... <5000 (n=236) 47 49 45 44 26 25 (n=35) 0 0 I 8 II 15 CONCLUSION: Urinary protein dipstick values have a positive predictive value of 90% (158/175) for predicting mg/24 h. 1n contrast, a dipstick of negative to trace should not be used to rule out significant proteinuria because its negative predictive value is only 33% (32/96). Moreover. urine dipstick values of 3+ to 4+ should not be used to diagnose severe preeclampsia because their positive predictive value is only 34% (26(17). 319 PLASMA INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP)-3IN PREECLAMPSIA (PE). AN Taylor 1 .x• M Varma 2 , x, S Lanyi 2 . x . 1Dept. of OblGyn, U.C. San Francisco (UCSF) and 2Adeza Biomedical, Sunnyvale, CA. Evaluation of the therapeutic efficacy of agents to prevent PE has hampered by the low prevalence of this disorder (5- 7%) In pregnancy. Selection of women at high risk of developing PE will require specific and precise screening tests. findings at UCSF indicate that plasma mitogenIC activity IS elevated from early pregnancy in women to develop PE (Taylor et al., AJOG 163 :1839, 1990) . mitoqen(s) behaves as an acid- and heat-labile complex with a native molecular mass of 150,000. A major plasma IGF carrier protein with similar molecular characteristics IGFBP-3 is enzymatically degraded during normal pregnancy (Giudice ei al.. JCEM 71 :806, 1990). We hypotheSized that in pregnant destined to develop PE there might be failure of activation of the pregnancy-specific protease, resulting in elevated IGFBP-3 concentrations, higher circulating levels of IGFs and hence, increased plasma mitogenic activity. STUDY DESIGN: IGFBP-3 concentrations were determined by [ 125 1]IGF-1J Western ligand blots of nonreducing gels in 22 norm.al and 22 plasma samples collected as part of an ongoing prospective, nested case-control study of PE. RESULTS: Our data corroborated the trend of decreasing plasma IGFBP-3 levels with advancing gestation. However, IGFBP-3 concentrations were not different in women destined to have normal VS. PE pregnancies I-test, n=44). CONCLUSIONS: The findings indicate that IGFBP-3 d.o not account for the elevated mitogenic activity observed In plasma from women with PE and are not a useful screening test for PE risk.

318 Urinary Dipstick Protein Is a Poor Predictor of Absent or Severe Proteinuria

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Volume 168 Nu mber I , Pan 2

316 CALCIUM SUPPLEMENTATION IN MILD

317

PREECLAMPSIA REMOTE FROM TERM: A PROSPECTIVE RANDOMIZED DOUBLE-BLIND CLINICAL TRIAL l Sanchez-Ramos CD Adair. x GO DelValle, F Gaudier. I Oelke. Department of Obstetrics and Gynecology, University of Florida, Jacksonville, FL. OBJECTIVE: The purpose of this study was to determine the effect of calcium supplementation on the clinical course and the incidence of severe disease in patients with pre-term mild preeclampsia. STUDY DESIGN: Sixty-eight patients with mild preeclampsia at 24-36 weeks' gestation were randomly allocated to in-hospital treatmenl with a daily dose of 2000 mg of calcium (n=34) or matching placebo (n=34). Both groups were similar wtth regard to mean maternal age. gravidity. and gestational age at admission. The initial systolic and diastolic blood pressure and amount of proteinuria were also comparable. The clinical management and criteria for severe preeclampsia were consistent throughout the study. RESUL TS: The incidence of delivery because of severe preeclampsia was 53% in the calcium group and 54% in the placebo group (p=.95). There was a trend towards a lower incidence of severe preeclampsia in patients who received at least 7 days of treatment. No differences were noted in the blood pressure. platelet count. serum uric acid and liver enzymes before or during labor in both groups. CON C L U S ION S : Our results indicate that calcium supplementation does not avert severe preeclampsia once clinical signs are present. Perhaps. iniliation of Iherapy days or weeks before clinical signs appear may be prevenlive.

DIURNAL VARIATION OF URINARY CALCIUM EXCRETION IN WOMEN WITH PREECLAMPSIA. .I.....ID!il!". K. Halesx• G. Thurnau. Dept. of OB/GYN. Uoiv. of Oklahoma. Okla. City. OK. OBJECTIVE: The purpose of this study is to measure diurnal variations of urinary calcium excretion by means of fractionated urine collections in preeclamptic gravidae (Group I; n = 6) and to compare the results with those of normotensive gravidae (Group II; n = 7) and nonpregnant normotensive controls (Group III; n = 10). STUDY DESIGN: Blood pressures (Supine and LLR). urine protein. hand and facial edema. complete blood counts. and serum Chem 18 proftles were evaluated. Urine calcium levels on voided specimens, obtained every 3 hours over a 24 hour period, were measured using a colorimetric autoanalyzer. No study subject received calcium supplementation or magnesium therapy prior to or after enrollment. RESULTS: Significant differences in the mean 3-hour interval calcium levels were found among the preeclamptic. normotensive gravidae. and nonpregnant normotensive controls (3.0 to 10.2 mg/dl, 17.1 to 30.9 mg/dI, and 7.1 to 17.9 mg/d!. respectively; p < 0.01). Also. the mean 24-hour urine calcium levels varied significantly among the three groups (5.7. 22.8. and 10.8 mg/dl. respectively; p < 0.01). Diurnal variation in urinary calcium excretion was observed in all groups with nadirs occuring between 4 and 10 a.m. and peaks between 7 and 10 p.m. CONCLUSION: Individual and 24-hour mean urinary calcium levels of the preeclamptic women were significantly lower than those of normotensive gravidae and nonpregnant c.ontrols. Also, diurnal variation was attenuated in the preeclampllc group.

318

SPO Abstracts 385

URINARY DIPSTICK PROTEIN IS A POOR PREDICTOR OF ABSENT OR SEVERE PROTEINURIA. N L Meyer,' B.M. Men:er,x S.A. Friedman,' BM. Sibai. DepL ofOB/GYN, Univ. ofTenn., Memphis. BACKGROUND: A urine protein dipstick of ~1+, frequently on 2 occasions 4 hours apart, is traditionally used to establish proteinuria in studies dealing with hypertensive disorders of pregnancy. In addition, a dipstick value ~3+ is considered diagnostic of severe preeclampsia, since it is said to correspond with a quantitative value of ~5 g/24 h. OBJECTIVE: To compare urine protein dipstick values to standard 24·hour protein excretion in women with hypertensive diseases of pregnancy. STUDY DESIGN: Serial urine protein dipstick performed at least every 8 hours and 24·hour urinary protein excretion were studied in 271 pregnancies complicated by hypertensive disease. Results of 2 consecutive dipsticks obtained during a 24-hour urinary collection Were compared to the total protein excretion in the 24-hour sample. RESULTS: Ninety-six patients had negative to trace protein on dipstick on 2 occasions at least 8 hours apart. Sixty-four (67%) of these patients had significant proteinuria (~300 mg/24 h). Seventy-seven patients had 3+ to 4+ protein on dipstick in 2 samples. Of these, 26 (34%) had nephrotic range proteinuria (~5 g/24 h), and 44 (57%) had proteinuria ~3 g/24 h. ,,!in~ty-eight ha~ ur\ne dipstick values of 1 + to 2+, of whom 86 (88%) had slgruficant protemurla.

Urw Protein (mg/24 h) Dipstick neg trace 1 + 2+ 3+ 4+

<300 (n=49) 16 16 6 6 4 1 !;~~.(~::.~~) ................. ~.~ ...... ~? ..... ~g ...... ~~ ...... ~.~ ...... ~.~ <5000 (n=236) 47 49 45 44 26 25 ~5()()() (n=35) 0 0 I 8 II 15

CONCLUSION: Urinary protein dipstick values ~I+ have a positive predictive value of 90% (158/175) for predicting ~300 mg/24 h. 1n contrast, a dipstick of negative to trace should not be used to rule out significant proteinuria because its negative predictive value is only 33% (32/96). Moreover. urine dipstick values of 3+ to 4+ should not be used to diagnose severe preeclampsia because their positive predictive value is only 34% (26(17).

319 PLASMA INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP)-3IN PREECLAMPSIA (PE). AN Taylor1.x• M Varma2,x, S Lanyi2.x. 1Dept. of OblGyn, U.C. San Francisco (UCSF) and 2Adeza Biomedical, Sunnyvale, CA. Evaluation of the therapeutic efficacy of agents to prevent PE has b~en hampered by the low prevalence of this disorder (5-7%) In pregnancy. Selection of women at high risk of developing PE will require specific and precise screening tests. O~JEC,!IVE:. ~ec~nt findings at UCSF indicate that plasma mitogenIC activity IS elevated from early pregnancy in women destin~d to develop PE (Taylor et al., AJOG 163:1839, 1990). T~e mitoqen(s) behaves as an acid- and heat-labile complex with a native molecular mass of 150,000. A major plasma IGF carrier protein with similar molecular characteristics IGFBP-3 is enzymatically degraded during normal pregnancy (Giudice ei al.. JCEM 71 :806, 1990). We hypotheSized that in pregnant wo~e~ destined to develop PE there might be failure of activation of the pregnancy-specific protease, resulting in elevated IGFBP-3 concentrations, higher circulating levels of IGFs and hence, increased plasma mitogenic activity. STUDY DESIGN: IGFBP-3 concentrations were determined by [1251]IGF-1J Western ligand blots of nonreducing gels in 22 norm.al and 22 ~E plasma samples collected as part of an ongoing prospective, nested case-control study of PE. RESULTS: Our data corroborated the trend of decreasing plasma IGFBP-3 levels with advancing gestation. However, IGFBP-3 concentrations were not different in women destined to have normal VS. PE pregnancies (p~0.75, I-test, n=44) . CONCLUSIONS: The findings indicate that IGFBP-3 co~c.entrations d.o not account for the elevated mitogenic activity observed In plasma from women with PE and are not a useful screening test for PE risk.