Michael L. Socol

Risk of cesarean delivery with elective induction of labor at term in nulliparous women

OBJECTIVE To quantify the risk of cesarean delivery associated with elective induction of labor in nulliparous women at term. METHODS We performed a cohort study on a major urban obstetric service that serves predominantly private obstetric practices. All term, nulliparous women with vertex, singleton gestations who labored during an 8-month period (n = 1561) were divided into three groups: spontaneous labor, elective induction, and medical induction. The risk of cesarean delivery in the induction groups was determined using stepwise logistic regression to control for potential confounding factors. RESULTS Women experiencing spontaneous labor had a 7.8% cesarean delivery rate, whereas women undergoing elective labor induction had a 17.5% cesarean delivery rate (adjusted odds ratio [OR] 1.89; 95% confidence interval [CI] 1.12, 3.18) and women undergoing medically indicated labor induction had a 17.7% cesarean delivery rate (OR 1.69; 95% CI 1.13, 2.54). Other variables that remained significant risk factors for cesarean delivery in the model included: epidural placement at less than 4 cm dilatation (OR 4.66; 95% CI 2.25, 9.66), epidural placement after 4 cm dilatation (OR 2.18; 95% CI 1.06, 4.48), chorioamnionitis (OR 4.61; 95% CI 2.89, 7.35), birth weight greater than 4000 g (OR 2.59; 95% CI 1.69, 3.97), maternal body mass index greater than 26 kg/m2 (OR 2.36; 95% CI 1.61, 3.47), Asian race (OR 2.35; 95% CI 1.04, 5.34), and magnesium sulfate use (OR 2.18; 95% CI 1.04, 4.55). CONCLUSION Elective induction of labor is associated with a significantly increased risk of cesarean delivery in nulliparous women. Avoiding labor induction in settings of unproved benefit may aid efforts to reduce the primary cesarean delivery rate.

Tumor necrosis factor-α is elevated in plasma and amniotic fluid of patients with severe preeclampsia

OBJECTIVE Our purpose was to investigate whether markers for activation of the immune system are present in patients with preeclampsia by assessing maternal plasma and amniotic fluid for tumor necrosis factor-alpha and interleukin-1 beta. STUDY DESIGN Twenty-one patients with severe preeclampsia composed the study group (group A). An antepartum comparison group was composed of healthy nulliparous patients not in labor and matched for gestational age (group B). Another control group consisted of term nulliparous patients in labor with uneventful pregnancies (group C). Maternal plasma samples were collected from all patients at recruitment and from patients in groups A and C immediately after delivery and again 20 to 24 hours post partum. Amniotic fluid was also collected from patients in groups A and C during labor. All samples were collectively assayed for tumor necrosis factor-alpha and interleukin-1 beta by specific enzyme-linked immunoassays. RESULTS Before labor tumor necrosis factor-alpha was detected more frequently in the plasma of preeclamptic patients than in the plasma of patients in group B (12/16 vs 5/16, p < 0.05) and in higher concentrations (median 35 pg/ml vs median 0 pg/ml, p < 0.05). Although tumor necrosis factor-alpha was frequently detected in the plasma of patients in group C in early labor (16/20), concentrations were higher in the four preeclamptic patients first sampled in early labor (210 pg/ml vs 65 pg/ml, p < 0.05). Similarly, amniotic fluid levels of tumor necrosis factor-alpha were increased in preeclamptic patients compared with control patients. At delivery tumor necrosis factor-alpha was more likely to be identified in the plasma of preeclamptic patients and was found in higher concentrations, but by 20 to 24 hours post partum measurements in the preeclamptic and control patients were similar. There were no differences in the frequency with which interleukin-1 beta was detected or the concentration of interleukin-1 beta in any of the samples. CONCLUSIONS Tumor necrosis factor-alpha is increased in the plasma and amniotic fluid of patients with severe preeclampsia. These data are suggestive of a role for abnormal immune activation in the pathophysiologic mechanisms of preeclampsia.

A Controlled Trial of a Program for the Active Management of Labor

BACKGROUND Over the past two decades, the rate of cesarean section in the United States has risen from 5 percent to 25 percent of deliveries, primarily because of the increased frequency of dystocia (arrest of labor). One strategy that has been proposed for increasing the rate of vaginal delivery is a program of active management of labor that encourages early amniotomy, early diagnosis of slow progress in labor, and the use of higher than usual doses of oxytocin; the efficacy and safety of this approach are uncertain, however. METHODS We conducted a randomized trial in which nulliparous women in spontaneous labor at term were randomly assigned to either active management of labor or traditional management. With active management, amniotomy was performed within one hour of the diagnosis of labor, and when the rate of cervical dilation was less than 1 cm per hour, oxytocin was infused at an initial rate of 6 mU per minute. The dose was increased by 6 mU per minute every 15 minutes (to a maximum of 36 mU per minute) until there were seven contractions every 15 minutes. RESULTS For the women assigned to active management (n = 351), the cesarean-section rate was 10.5 percent, as compared with 14.1 percent for those assigned to traditional management (n = 354, P = 0.18). The 26 percent reduction in the cesarean-section rate was due primarily to a decrease in dystocia. After we controlled for potential confounding variables, the reduction in the rate of delivery by cesarean section was statistically significant (odds ratio for women given active as compared with traditional management, 0.57; 95 percent confidence interval, 0.36 to 0.95). With active management, the average length of labor was shortened by 1.66 hours, principally because of earlier amniotomy and earlier use of oxytocin. There was no increase in maternal or neonatal morbidity, and there were significantly fewer infectious complications in the mothers. CONCLUSIONS The program we studied for the active management of labor reduces the incidence of dystocia and increases the rate of vaginal delivery without increasing maternal or neonatal morbidity.

Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with severe preeclampsia

Objective To investigate whether serum and amniotic fluid (AF) levels of soluble tumor necrosis factor receptors and interleukin-6, markers of immune activation and endothelial dysfunction, are altered in patients with severe preeclampsia. Methods Plasma was collected before induction of labor, at delivery, and postpartum from 19 patients with severe preeclampsia. Amniotic fluid was also obtained in early labor from these patients. Similar samples were obtained from an antepartum control group matched for gestational age and a term control group without preeclampsia. All plasma and AF samples were assayed for p55 and p75 soluble tumor necrosis factor receptors and for interleukin-6 by specific enzyme-linked immunoassays. Levels in preeclamptic patients and the control groups were compared. Results Levels of both receptors were significantly elevated in AF and all maternal plasma samples except those collected 24 hours postpartum for patients with preeclampsia relative to levels in controls. Interleukin-6 was detected more frequently and in higher concentrations in the plasma collected before labor for preeclamptic patients compared with controls, but no difference was noted in interleukin-6 detection rates or plasma concentrations at delivery. Conversely, AF concentrations of interleukin-6 were significantly reduced in patients with preeclampsia. Conclusion The increased levels of soluble tumor necrosis factor receptors found in patients with severe preeclampsia may represent a protective response to increased tumor necrosis factor activity and be a marker for immune activation. Increased interleukin-6 concentrations in maternal plasma before labor suggest the involvement of this cytokine as well in the altered immune response and its contribution to endothelial cell dysfunction.

Severe acidosis and subsequent neurologic status

To examine the relationship between severe acidosis at birth and evidence of subsequent neurologic dysfunction, a 4-year review was performed encompassing 15,528 neonates. One hundred forty-two (0.91%) of these neonates had an umbilical cord arterial pH less than or equal to 7.05 with a base deficit greater than or equal to mEq/L. Neurologic assessments found 101 of 110 term neonates (91.8%) and 17 of 32 preterm neonates (53.1%) with severe acidosis to be free of neurologic deficits at the time of hospital discharge. Follow-up developmental evaluation data were available for 7 of 9 term neonates and 8 of 15 preterm neonates with abnormal examinations. Although 5 term and 6 preterm infants demonstrated mild developmental delays or mild tone abnormalities in the first year of life, none exhibited a major motor or cognitive abnormality at 12 to 24 months of age. Consequently, acidosis in umbilical cord blood, even when severe, is a poor predictor of subsequent neurologic dysfunction.

Interlaboratory variation in antiphospholipid antibody testing

OBJECTIVE Because of the widespread use of antiphospholipid antibody testing in the evaluation of patients with recurrent pregnancy loss, we evaluated the consistency of results among laboratories testing for anticardiolipin antibody and the lupus anticoagulant. STUDY DESIGN A questionnaire regarding methods used and samples of blood from 20 patients were sent to five university-based and five commercial facilities for antiphospholipid antibody testing. RESULTS The responses of the participating laboratories to the questionnaires revealed significant differences in methods, standardization, and units of reporting. For anticardiolipin antibody, the number of specimens found to be positive for any isotype (immunoglobulin G, M, or A) varied considerably among laboratories, with a range of 5 to 13. All laboratories were in agreement (i.e., at least one isotype was present or all were absent) for only 5 of 20 specimens (25%). In contrast, lupus anticoagulant results were more reproducible, although one facility reported results markedly discordant from the other four laboratories. CONCLUSION These observations suggest that significant interlaboratory variation exists in antiphospholipid antibody, and particularly anticardiolipin antibody, testing and might lead to unnecessary therapeutic interventions.

Reducing cesarean births at a primarily private university hospital

OBJECTIVE The rise in cesarean birth at Northwestern Memorial Hospital in 1986 to 27.3% prompted implementation of three initiatives to reverse the escalating cesarean section rate. STUDY DESIGN First, vaginal birth after cesarean section was more strongly encouraged. Second, after the 1988 calendar year the cesarean section rate of every obstetrician was circulated annually to each attending physician. Third, on completion of a prospective, randomized trial of the active management of labor in early 1991, this protocol was recommended as the preferred method of labor management for term nulliparous patients. RESULTS The total, primary, and repeat cesarean section rates declined from 27.3%, 18.2%, and 9.1% in 1986 to 16.9%, 10.6%, and 6.4%, respectively, in 1991. At the same time the perinatal mortality dropped from 19.5 to 10.3. Significant reductions in abdominal deliveries occurred for both private patients (30.3% to 19.1%, p < 0.0001) and clinic patients (20.8% to 11.5%, p < 0.0001). A decline in operative deliveries for dystocia and an increase in vaginal birth after prior cesarean section were the principal factors contributing to the lower cesarean section rates. However, in 1991 individual private physicians still had wide variations in primary cesarean section rates (4.6% to 21.1%) and use of vaginal birth after prior cesarean section (5.3% to 90%). CONCLUSION The cesarean section rate has been significantly reduced for both private and clinic patients. Differences in population demographics and individual physician practice patterns contributed to a higher incidence of cesarean birth on the private service.

Factors contributing to the increased cesarean birth rate in older parturient women.

OBJECTIVE Our purpose was to determine factors contributing to the increased use of cesarean section in patients > or = 35 years old. STUDY DESIGN Data were collected prospectively on nulliparous patients in spontaneous labor with term, singleton pregnancies and vertex presentations. Criteria for the diagnosis of labor were standardized: regular, painful uterine contractions at least once every 5 minutes in the presence of either complete cervical effacement or spontaneous rupture of membranes. The labors of women > or = 35 years old (n = 74) were compared with those of women 20 to 29 years old (n = 275). RESULTS The cesarean section rate was significantly greater for patients > or = 35 years old (21.6% vs 10.2%, odds ratio 2.4, 95% confidence interval 1.2 to 5.1). Mean birth weights were similar in the two groups, but when birth weight was > or = 3600 gm patients > or = 35 years old were more likely to be delivered by cesarean section (36.7% vs 12.2%, odds ratio 4.0, 95% confidence interval 1.4 to 11.9). There were no differences between the two age groups in physician factors that could explain the disparate rates of cesarean delivery. Indeed, of patients delivered vaginally the older parturients received oxytocin for longer duration (6.4 +/- 2.6 vs 5.0 +/- 3.1 hours, p < 0.05) and at higher maximum doses (12.4 +/- 6.1 vs 9.8 +/- 6.2 mU, p < 0.05). After controlling for potentially confounding variables with multiple logistic regression analysis, maternal age (R = 0.125, p < 0.005), birth weight (R = 0.196, p < 0.001), the need for oxytocin (R = 0.210, p < 0.001), and epidural anesthesia (R = 0.195, p < 0.001) were found to be independently associated with the increased rate of cesarean section. CONCLUSION We could not identify any controllable physician factors affecting the rate of cesarean section in patients > or = 35 years old. The increased oxytocin requirements and the incidence of dystocia with birth weight > or = 3600 gm suggest that maternal and fetal characteristics contribute to the increased frequency of cesarean section in older parturients.

Platelet activation in preeclampsia

Platelet activation was assessed in hospitalized third-trimester patients with preeclampsia (n = 11) or chronic hypertension with superimposed preeclampsia (n = 11) and in healthy outpatient pregnant controls (n = 10) by measuring plasma beta-thromboglobulin, platelet factor 4, the platelet aggregate ratio, and the amount of collagen required to produce half-maximal aggregation velocity (Kd). Only plasma beta-thromboglobulin levels differed significantly between patients with preeclampsia (50.1 +/- 37.9; p less than 0.05) or chronic hypertension with superimposed preeclampsia (47.6 +/- 16.3; p less than 0.01) and the control subjects (22.5 +/- 11.3). beta-Thromboglobulin values in patients with preeclampsia, but not chronic hypertension with superimposed preeclampsia, correlated directly with 24-hour urinary protein loss (r = 0.93, p less than 0.001) and serum creatinine levels (r = 0.62, p less than 0.05) and inversely with creatinine clearance (r = 0.60, p = 0.05). We conclude that (1) beta-thromboglobulin is elevated in patients with preeclampsia or chronic hypertension with superimposed preeclampsia, (2) the normal platelet aggregate ratio and the Kd indicate that the increase in beta-thromboglobulin is not due to an intrinsic change in platelet responsiveness, and (3) the elevation of beta-thromboglobulin in patients with either preeclampsia or chronic hypertension with superimposed preeclampsia appears to be secondary to platelet consumption in the microvasculature, although in patients with preeclampsia altered renal function may be contributory.

Diminished growth in fetuses born preterm after spontaneous labor or rupture of membranes

We examined biparietal diameter, abdominal circumference, and birth weight in 148 preterm infants to assess fetal growth. A statistically significant proportion of preterm fetuses had biparietal diameter and abdominal circumference values below the fiftieth and tenth percentile levels as compared with that expected in normal fetuses. Similarly, birth weight of infants in the study fell significantly below the fiftieth and tenth percentiles relative to Brenners curve. We conclude that diminished fetal growth is associated with early delivery secondary to preterm labor or preterm premature rupture of membranes or both. Additionally, since biparietal diameters in preterm fetuses are smaller than those of normal fetuses the prediction of gestational age by cephalometry should be advanced by 7 to 10 days.