Gary M. Joffe

Trial of calcium to prevent preeclampsia

Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 wome...

The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women

OBJECTIVE The studys aim was to determine whether healthy nulliparous women with abnormal glucose tolerance during pregnancy are at increased risk for development of pregnancy-associated hypertension or preeclampsia. STUDY DESIGN A series of 4589 healthy nulliparous women from 5 university centers were evaluated prospectively to determine whether calcium supplementation would prevent preeclampsia. Pregnancy-associated hypertension was a diastolic blood pressure > or = 90 mm Hg on 2 occasions 4 hours to 1 week apart. Pregnancy-associated proteinuria was proteinuria > or = 1+ by dipstick testing on 2 occasions 4 hours to 1 week apart, proteinuria > or = 300 mg/24 h, a protein to creatinine ratio of > or = 0.35, or a single dipstick measurement of > or = 2+. Preeclampsia was defined as pregnancy-associated hypertension and pregnancy-associated proteinuria documented within 7 days of each other. Normal glucose tolerance was a plasma glucose level < 140 mg/dL 1 hour after a 50-g oral glucose challenge. Abnormal glucose tolerance was a plasma glucose level > or = 140 mg/dL 1 hour after a 50-g oral glucose challenge followed by a 3-hour 100-g oral glucose tolerance test yielding < 2 abnormal values. Gestational diabetes mellitus was a plasma glucose level > or = 200 mg/dL 1 hour after a 50-g oral glucose challenge in the absence of an oral glucose tolerance test or > or = 2 abnormal plasma glucose values in a 3-hour 100-g oral glucose tolerance test (> or = 105 mg/dL fasting, > or = 190 mg/dL at 1 hour, > or = 165 mg/dL at 2 hours, or > or = 145 mg/dL at 3 hours). For purposes of this study women with preeclampsia were excluded from the category of pregnancy-associated hypertension. RESULTS Calcium supplementation did not prevent pregnancy-associated hypertension or preeclampsia. Of 3689 women with complete glucose testing data, 227 (6%) had abnormal glucose tolerance and 81 (2%) had gestational diabetes mellitus. Compared with women with normal glucose tolerance, women with abnormal glucose tolerance were significantly older, had greater body mass index, and were more likely to be white non-Hispanic, to smoke, and to have private medical insurance. Among women with gestational diabetes mellitus, after adjustment for clinical center the relative risks of preeclampsia and of all hypertensive disorders were increased (relative risk 1.67, 95% confidence interval 0.92-3.05, and relative risk 1.54, 95% confidence interval 1.28-2.11, respectively). Risk ratios were not substantially reduced after further adjustment for race and body mass index (odds ratios 1.41 and 1.48, respectively). Even within the normal range, multivariate analysis demonstrated that the level of plasma glucose 1 hour after a 50-g oral glucose challenge was an important predictor of preeclampsia. CONCLUSION Even within the normal range, the level of plasma glucose 1 hour after a 50-g oral glucose challenge was positively correlated with the likelihood of preeclampsia. Women with gestational diabetes mellitus were at increased risk for hypertensive disorders during pregnancy after adjustment for clinical center, race, and body mass index, although the increase was not statistically significant. These findings suggest that insulin resistance may play a role in the pathogenesis of the hypertensive disorders of pregnancy.

Trial of calcium for preeclampsia prevention (CPEP): Rationale, design, and methods

The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods.

Will cervicovaginal interleukin-6 combined with fetal fibronectin testing improve the prediction of preterm delivery?

OBJECTIVE We sought to investigate if determination of cervicovaginal interleukin-6 (IL-6) levels would enhance the positive predictive value of fetal fibronectin (fFN) for preterm birth. METHODS A prospective cohort study was undertaken of 135 women between 24 and 34 weeks gestation with symptoms of suspected preterm labor. Cervicovaginal secretions were collected for both IL-6 and fFN and measured by immunoassay and ELISA, respectively. Outcome variables included preterm delivery in less than 48 h, within 7 days, and prior to 37 weeks. Statistical analysis was performed with Fishers exact test, regression for logarithmic transform levels, and multivariate logistic regression. ROC curves were created for IL-6 levels. RESULTS IL-6 and fFN levels were both elevated in cervicovaginal secretions of women with symptoms of preterm labor. IL-6 values >100 pg/ml resulted in a odds ratio for delivery at <37 weeks of 1.57 (95%CI=0.89-2.75, P=.11), whereas fFN values >50 ng/ml resulted in a preterm delivery risk of 4.58 (95%CI=1.54-13.35, P=.003). Combining IL-6 and fFN results did not improve upon the predictive value of fFN alone for preterm birth [odds ratio 4.00 (95%CI=1.31-12.17, P=.015)]. CONCLUSION Cervicovaginal IL-6 levels did not provide any additional, independent effect on the prediction of preterm birth beyond that of fFN testing alone.

Diagnosis of cervical change in pregnancy by means of transvaginal ultrasonography

There are no absolute objective diagnostic criteria for cervical incompetence. Abdominal and endovaginal ultrasonographic assessment of endocervical length, both of which have been associated with technical problems, have been used to establish the diagnosis. Cervical cerclage may be useful in preventing silent cervical dilatation; however, no prospective trials with and without cerclage have been performed when endocervical shortening has been demonstrated by ultrasonography.

Acute posttraumatic fetal anemia treated with fetal intravascular transfusion

Fetal trauma resulting in acute anemia after maternal blunt abdominal trauma is a rare but potentially lethal condition. We recently managed such a case with the use of fetal intravascular transfusion.

Comparison of absorbable uterine staples and traditional hysterotomy during cesarean delivery

Objective To evaluate the use of the Auto Suture Poly CS-57 disposable surgical stapler to determine if the device offers any advantages over suture closure of the uterus. Methods A matched case-control study design was used. Operative time, estimated blood loss, change in hematocrit, incidence of postoperative endometritis, length of stay, and total patient costs were compared. Patients were recruited from a university hospital setting and a private practice. Results There were 288 patients in the study, 144 in the staple group and 144 matched patients in the standard hysterotomy control group. Patients did not differ in age, parity, gestational age, number of primary or repeat operations, anesthesia, infant weights, or outcomes. Comparing the patients in the staple group and the control group, there was no significant difference in operative time (63.7 ± 22.9 versus 62.0 ± 22.3 minutes, staple group versus controls, respectively), estimated blood loss (822 ± 338 versus 879 ± 318 mL), change in hematocrit (−5.9 versus −6.5 volume percent), incidence of postoperative endometritis (15 versus 20%), length of stay (4.1 ± 1.3 versus 4.0 ± 2.2 days), or total cost (

Impact of the fetal fibronectin assay on admissions for preterm labor

4490 ± 1544 versus

The biophysical profile and the nonstress test: Poor predictors of chorioamnionitis and fetal infection in prolonged preterm premature rupture of membranes

3997 ± 1117). Comparing patients operated upon by residents in the university to those operated upon by the private attending physicians, there were no significant differences noted in the above-mentioned variables between stapled and sutured patients. Conclusion Compared with the usual suture technique for cesarean delivery, the uterine stapling device used in this study was not associated with a significant decrease in the incidence of postoperative anemia, infection, length of hospital stay, or cost. This device appears to offer no advantage over traditional hysterotomy and repair.