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Response of isolated monocytes and lymphocytes to LPS and progesterone
S148 SMFM Abstracts 475 RESPONSE OF ISOLATED MONOCYTES AND LYMPHOCYTES TO LPS AND PROGESTERONE JENNIFER GOTKIN1, JEREMY CELVER1, PATRICK MCNUTT1, SHAD DEERING1, BOBBY HOWARD1, NATHAN HOELDTKE2, PETER NAPOLITANO1, 1 Madigan Army Medical Center, Maternal Fetal Medicine, Tacoma, Washington, 2Tripler Army Medical Center, Maternal Fetal Medicine, Honolulu, Hawaii OBJECTIVE: The mechanisms of progesterone action in the prevention of preterm labor are largely unknown but may result from its anti-inflammatory properties. We previously demonstrated that progesterone (P4) can inhibit lipopolysacharide (LPS) induced interleukin-6 (IL-6) secretion in whole blood and in both maternal and fetal mononuclear cells. To more specifically identify the progesterone-responsive cell type, we further fractionated mononuclear cells into monocyte and other mononuclear populations and evaluated the induction of IL-6 expression following exposure to LPS and/or progesterone. STUDY DESIGN: Fetal cord blood was obtained from uncomplicated, fullterm pregnancies undergoing cesarean section, and Histopaque-isolated mononuclear cells were fractionated into either monocytes or other mononuclear cell types using Dynabeads (Dynal Biotech). Isolated cell populations were treated with LPS (50 ug/mL), P4 (30 ng/mL) or pretreated with P4 and then exposed to LPS. Following incubation, supernatants were collected and evaluated for secreted IL-6 by ELISA. Data was analyzed using Student t-test and a P-value!0.05 was considered significant. RESULTS: Progesterone significantly blocked LPS induced secretion of IL-6 in fetal mononuclear cells. Following fractionation of mononuclear cells into monocyte and other mononuclear cell populations, IL-6 induction was no longer significantly inhibited by P4. CONCLUSION: In this ex vivo model, P4 exposure does not significantly modulate the pro-inflammatory response of isolated monocytes. The lack of response to P4 following fractionation could result from a required interaction between multiple cell types or alternatively be the consequence of monocyte activation during the isolation technique. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.518
477 COMPARING URINE DIPSTICK TO PROTEIN/CREATININE RATIO IN THE SETTING OF SUSPECTED PREECLAMPSIA JASMINE LAI1, JUSTIN TAN2, THOMAS MOORE1, DOUGLAS WOELKERS1, 1University of California, San Diego, Reproductive Medicine, San Diego, California, 2University of California, San Francisco, San Francisco, California OBJECTIVE: Proteinuria is a key diagnostic criteria for preeclampsia, but the commonly used urine dipstick (Dip) is less than optimal because of its lack of precision and reproducibility. The protein:creatinine ratio (P/CR), however, strongly correlates with 24-hour urine protein collection (24 P), the gold standard for protein quantification. This study aims to evaluate the performance of the PC ratio as compared to dipstick in the setting of suspected preeclampsia. STUDY DESIGN: This retrospective cohort study involved data analysis from 2786 pregnant women presenting to UCSD Medical Center over a two-year period (1/2004-1/2006), in whom a P/CR, Dip, or 24 P was performed. Proteinuria was considered present if Dip showed 2C to 4C; if P/CR was O0.3; or if 24 P contained R300 mg. 2-analysis was conducted to determine the association between P/CR and Dip with the 24 collection, when performed within 48hrs of one another. Dip findings were explored for confounders using multivariate analysis; statistical significance was set at p!0.05. RESULTS: All comparisons by 2 were significant at p!0.001. Data from 140 patients comparing Dip to 24 P showed the Dip to have a false positive rate of 5.6%, with a false neg rate (FNR) of over 39%, r = 0.77, p!0.001. In contrast, in 177 patients having both a P/CR and 24 P, the r value was 0.95 (p!0.001), with a 25% FNR for P/CR. Comparing P/CR to Dip (n=244), urine dip underestimates protein 63% of the time. Dip measurements were found to be significantly confounded by the presence of WBC, leukocyte esterase, blood, and squamous epithelial cells (p!0.05). CONCLUSION: We show that P/CR is a more accurate predictor of proteinuria than dipstick. Clinicians are encouraged to consider replacement of dipstick with PC ratio in the quantification of protein for the diagnosis of preeclampsia.
P/CR vs. Dip P/CR vs. 24 Dip vs. 24
2 (p)
Sens
Spec
PPV
NPV
R
!0.001 !0.001 !0.001
0.373 0.747 0.608
0.992 0.963 0.944
0.979 0.959 0.861
0.597 0.767 0.808
d 0.949 0.760
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.520
476 DIFFERENCES IN SERUM CALCIUM AND MAGNESIUM BETWEEN GRAVIDAS WITH SEVERE PREECLAMPSIA AND NORMOTENSIVE CONTROLS JAY BRINGMAN1, CHARLES GIBBS1, ROBERT AHOKAS1, BHATTACHARYA SYAMAL2, RISA RAMSEY1, ROBERT EGERMAN3, 1University of Tennessee Health Science Center, Obstetrics and Gynecology, Memphis, Tennessee, 2University of Tennessee Health Science Center, Surgery and Medicine, Memphis, Tennessee, 3 University of Tennessee Health Science Center, Obstetrics and Gynecology and Medicine, Memphis, Tennessee OBJECTIVE: Both calcium and magnesium are implicated in the pathogenesis of preeclampsia, yet the data are conflicting concerning the serum levels of these cations in severe preeclampsia and normotensive controls. STUDY DESIGN: Gravidas with severe preeclampsia were matched to their normotensive controls. Serum levels of both total and ionized calcium and magnesium were then compared between the two groups. Serum analyses for total Mg and Ca were done by atomic absorption spectroscopy, and ionized Mg and Ca were accomplished by ion-selective electrode technique. Severe preeclampsia was defined according to ACOG criteria. RESULTS: Ten patients with severe preeclampsia and 10 normotensive controls were included in this study. Gravidas with severe preeclampsia had significantly lower serum levels of both total and ionized calcium (see Table). Total and ionized magnesium levels were similar between the groups. CONCLUSION: Gravidas with severe preeclampsia have lower serum levels of total and ionized calcium when compared to normotensive controls. Diminshed intracellular calcium levels may be significant in the pathogenesis of aberrant vascular tone in gravidas with preeclampsia. Serum calcium and magnesium in gravidas wtih severe preeclampsia and normotensive controls Control Total magnesium (mg/dL) Total calcium (mg/dL) Ionized magnesium (mmol/L) Ionized calcium (mmol/L)
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.519
1.52 8.37 0.47 1.20
G G G G
0.16 0.45 0.05 0.09
Preeclampsia
p-value
1.65 6.80 0.53 0.97
0.5681 0.0445 0.5287 0.0281
G G G G
0.71 2.14 0.27 0.28
478 PREDICTORS OF ABNORMAL POSTPARTUM GLUCOSE REGULATION IN A MULTIETHNIC POPULATION OF WOMEN WITH ANTECEDENT GESTATIONAL DIABETES JANA K. SILVA1, J. KEAWE` AIMOKU KAHOLOKULA1, MARJORIE MAU1, E. FRANCIS COOK2, 1University of Hawaii, John A. Burns School of Medicine, Honolulu, Hawaii, 2Harvard University, School of Public Health, Boston, Massachusetts OBJECTIVE: To examine antepartum predictors of abnormal glucose regulation in a multiethnic population of women with recent gestational diabetes. STUDY DESIGN: Maternal and neonatal predictors of abnormal glucose regulation were evaluated among Native Hawaiian/Pacific Islander, Japanese, Chinese, Filipino, and Caucasian women (n = 1131) with recent gestational diabetes who were tested for diabetes mellitus 6 weeks after singleton term delivery. Abnormal glucose regulation was defined as a fasting plasma glucose value R 100mg/dL or a 2 hour 75 gram oral glucose tolerance test value R 140 mg/dL. Insulin was prescribed during pregnancy for all patients with antepartum fasting glucose values R 95 mg/dL or 2 hour postprandial glucose values O 120 mg/dL. Data were analyzed by Chi Square, ANOVA and multiple logistic regression. RESULTS: Two hundred seventy five women (24.3%) had abnormal test results, 14.5% of which met criteria for diabetes mellitus. Predictors of abnormal glucose regulation were heavier maternal weight at delivery, insulin use in pregnancy, neonatal weight R 4,000 grams, increasing maternal age, and earlier gestational age at diagnosis. Ethnic differences were not significant between groups, but ethnicity as a single variable was a significant predictor of abnormal glucose regulation. Predictors of diabetes mellitus were neonatal weight R 4,000 grams, insulin use in pregnancy, and hemoglobin A1c. CONCLUSION: Clinical predictors of pre-diabetes and diabetes mellitus can be identified in pregnancy, providing useful information to counsel and educate women while they are still under medical care. Interventions implemented during this window of opportunity can improve follow-up and support primary prevention aimed at reducing diabetes mellitus related disparities and complications in women at risk. Our findings specifically support intervention for all women requiring insulin for glycemic control in pregnancy and those with neonates weighing R 4,000 grams. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.521
477 COMPARING URINE DIPSTICK TO PROTEIN/CREATININE RATIO IN THE SETTING OF SUSPECTED PREECLAMPSIA JASMINE LAI1, JUSTIN TAN2, THOMAS MOORE1, DOUGLAS WOELKERS1, 1University of California, San Diego, Reproductive Medicine, San Diego, California, 2University of California, San Francisco, San Francisco, California OBJECTIVE: Proteinuria is a key diagnostic criteria for preeclampsia, but the commonly used urine dipstick (Dip) is less than optimal because of its lack of precision and reproducibility. The protein:creatinine ratio (P/CR), however, strongly correlates with 24-hour urine protein collection (24 P), the gold standard for protein quantification. This study aims to evaluate the performance of the PC ratio as compared to dipstick in the setting of suspected preeclampsia. STUDY DESIGN: This retrospective cohort study involved data analysis from 2786 pregnant women presenting to UCSD Medical Center over a two-year period (1/2004-1/2006), in whom a P/CR, Dip, or 24 P was performed. Proteinuria was considered present if Dip showed 2C to 4C; if P/CR was O0.3; or if 24 P contained R300 mg. 2-analysis was conducted to determine the association between P/CR and Dip with the 24 collection, when performed within 48hrs of one another. Dip findings were explored for confounders using multivariate analysis; statistical significance was set at p!0.05. RESULTS: All comparisons by 2 were significant at p!0.001. Data from 140 patients comparing Dip to 24 P showed the Dip to have a false positive rate of 5.6%, with a false neg rate (FNR) of over 39%, r = 0.77, p!0.001. In contrast, in 177 patients having both a P/CR and 24 P, the r value was 0.95 (p!0.001), with a 25% FNR for P/CR. Comparing P/CR to Dip (n=244), urine dip underestimates protein 63% of the time. Dip measurements were found to be significantly confounded by the presence of WBC, leukocyte esterase, blood, and squamous epithelial cells (p!0.05). CONCLUSION: We show that P/CR is a more accurate predictor of proteinuria than dipstick. Clinicians are encouraged to consider replacement of dipstick with PC ratio in the quantification of protein for the diagnosis of preeclampsia.
P/CR vs. Dip P/CR vs. 24 Dip vs. 24
2 (p)
Sens
Spec
PPV
NPV
R
!0.001 !0.001 !0.001
0.373 0.747 0.608
0.992 0.963 0.944
0.979 0.959 0.861
0.597 0.767 0.808
d 0.949 0.760
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.520
476 DIFFERENCES IN SERUM CALCIUM AND MAGNESIUM BETWEEN GRAVIDAS WITH SEVERE PREECLAMPSIA AND NORMOTENSIVE CONTROLS JAY BRINGMAN1, CHARLES GIBBS1, ROBERT AHOKAS1, BHATTACHARYA SYAMAL2, RISA RAMSEY1, ROBERT EGERMAN3, 1University of Tennessee Health Science Center, Obstetrics and Gynecology, Memphis, Tennessee, 2University of Tennessee Health Science Center, Surgery and Medicine, Memphis, Tennessee, 3 University of Tennessee Health Science Center, Obstetrics and Gynecology and Medicine, Memphis, Tennessee OBJECTIVE: Both calcium and magnesium are implicated in the pathogenesis of preeclampsia, yet the data are conflicting concerning the serum levels of these cations in severe preeclampsia and normotensive controls. STUDY DESIGN: Gravidas with severe preeclampsia were matched to their normotensive controls. Serum levels of both total and ionized calcium and magnesium were then compared between the two groups. Serum analyses for total Mg and Ca were done by atomic absorption spectroscopy, and ionized Mg and Ca were accomplished by ion-selective electrode technique. Severe preeclampsia was defined according to ACOG criteria. RESULTS: Ten patients with severe preeclampsia and 10 normotensive controls were included in this study. Gravidas with severe preeclampsia had significantly lower serum levels of both total and ionized calcium (see Table). Total and ionized magnesium levels were similar between the groups. CONCLUSION: Gravidas with severe preeclampsia have lower serum levels of total and ionized calcium when compared to normotensive controls. Diminshed intracellular calcium levels may be significant in the pathogenesis of aberrant vascular tone in gravidas with preeclampsia. Serum calcium and magnesium in gravidas wtih severe preeclampsia and normotensive controls Control Total magnesium (mg/dL) Total calcium (mg/dL) Ionized magnesium (mmol/L) Ionized calcium (mmol/L)
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.519
1.52 8.37 0.47 1.20
G G G G
0.16 0.45 0.05 0.09
Preeclampsia
p-value
1.65 6.80 0.53 0.97
0.5681 0.0445 0.5287 0.0281
G G G G
0.71 2.14 0.27 0.28
478 PREDICTORS OF ABNORMAL POSTPARTUM GLUCOSE REGULATION IN A MULTIETHNIC POPULATION OF WOMEN WITH ANTECEDENT GESTATIONAL DIABETES JANA K. SILVA1, J. KEAWE` AIMOKU KAHOLOKULA1, MARJORIE MAU1, E. FRANCIS COOK2, 1University of Hawaii, John A. Burns School of Medicine, Honolulu, Hawaii, 2Harvard University, School of Public Health, Boston, Massachusetts OBJECTIVE: To examine antepartum predictors of abnormal glucose regulation in a multiethnic population of women with recent gestational diabetes. STUDY DESIGN: Maternal and neonatal predictors of abnormal glucose regulation were evaluated among Native Hawaiian/Pacific Islander, Japanese, Chinese, Filipino, and Caucasian women (n = 1131) with recent gestational diabetes who were tested for diabetes mellitus 6 weeks after singleton term delivery. Abnormal glucose regulation was defined as a fasting plasma glucose value R 100mg/dL or a 2 hour 75 gram oral glucose tolerance test value R 140 mg/dL. Insulin was prescribed during pregnancy for all patients with antepartum fasting glucose values R 95 mg/dL or 2 hour postprandial glucose values O 120 mg/dL. Data were analyzed by Chi Square, ANOVA and multiple logistic regression. RESULTS: Two hundred seventy five women (24.3%) had abnormal test results, 14.5% of which met criteria for diabetes mellitus. Predictors of abnormal glucose regulation were heavier maternal weight at delivery, insulin use in pregnancy, neonatal weight R 4,000 grams, increasing maternal age, and earlier gestational age at diagnosis. Ethnic differences were not significant between groups, but ethnicity as a single variable was a significant predictor of abnormal glucose regulation. Predictors of diabetes mellitus were neonatal weight R 4,000 grams, insulin use in pregnancy, and hemoglobin A1c. CONCLUSION: Clinical predictors of pre-diabetes and diabetes mellitus can be identified in pregnancy, providing useful information to counsel and educate women while they are still under medical care. Interventions implemented during this window of opportunity can improve follow-up and support primary prevention aimed at reducing diabetes mellitus related disparities and complications in women at risk. Our findings specifically support intervention for all women requiring insulin for glycemic control in pregnancy and those with neonates weighing R 4,000 grams. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.521