Effect of labour induction on rates of stillbirth and cesarean section in post-term pregnancies.

BACKGROUND: Meta-analyses of randomized controlled trials suggest that elective induction of labour at 41 weeks' gestation, compared with expectant management with selective labour induction, is associated with fewer perinatal deaths and no increase in the cesarean section rate. The authors studied the changes over time in the rates of labour induction in post-term pregnancies in Canada and examined the effects on the rates of stillbirth and cesarean section. METHODS: Changes in the proportion of total births at 41 weeks' and at 42 or more weeks' gestation, and in the rate of stillbirths at 41 or more weeks' (versus 40 weeks') gestation in Canada between 1980 and 1995 were determined using data from Statistics Canada. Changes in the rates of labour induction and cesarean section were determined using data from hospital and provincial sources. RESULTS: There was a marked increase in the proportion of births at 41 weeks' gestation (from 11.9% in 1980 to 16.3% in 1995) and a marked decrease in the proportion at 42 or more weeks (from 7.1% in 1980 to 2.9% in 1995). The rate of stillbirths among deliveries at 41 or more weeks' gestation decreased significantly, from 2.8 per 1000 total births in 1980 to 0.9 per 1000 total births in 1995 (p < 0.001). The stillbirth rate also decreased significantly among births at 40 weeks' gestation, from 1.8 per 1000 total births in 1980 to 1.1 per 1000 total births in 1995 (p < 0.001). The magnitude of the decrease in the stillbirth rate at 41 or more weeks' gestation was greater than that at 40 weeks' gestation (p < 0.001). All hospital and provincial sources of data indicated that the rate of labour induction increased significantly between 1980 and 1995 among women delivering at 41 or more weeks' gestation. The associated changes in rates of cesarean section were variable. INTERPRETATION: Between 1980 and 1995 clinical practice for the management of post-term pregnancy changed in Canada. The increased rate of labour induction at 41 or more weeks' gestation may have contributed to the decreased stillbirth rate but it had no convincing influence either way on the cesarean section rate.

Fetal fibronectin as a predictor of preterm birth: an overview.

The objective of this study was to determine if cervicovaginal fibronectin is predictive of preterm birth. Articles involving human subjects published in English between January 1976 and December 1997 were retrieved from MEDLINE using the keywords: fibronectin, fetal fibronectin, oncofetal fibronectin, preterm, PROM, preterm birth, and preterm labor. We included studies that were prospective, enrolled women at less than 37 weeks' gestation and blinded caregivers to the fetal fibronectin test results. Of the 24 studies meeting the inclusion criteria, 15 included symptomatic women; 8 included asymptomatic women; and 1 study included both. Data were abstracted independently by two authors and a meta-analysis of results of test characteristics, using summary values, was undertaken where possible. For symptomatic women, the sensitivity for delivery within 7 to 10 days of sampling was excellent (summary value [95% confidence interval ¿CI¿]: 98% [95%, 100%]). For delivery within 14 days, the sensitivity was somewhat lower (summary value [95% CI]: 82% [74%, 90%]) and lower still for delivery within 21 days (summary value [95% CI]: 73% [67%, 80%]). For delivery less than 34 weeks the sensitivity was good, but poor for delivery less than 37 weeks (summary value [95% CI]: 87% [81%, 94%], 54% [51%, 58%] respectively). For asymptomatic women, the sensitivity of fetal fibronectin for delivery less than 34 and less than 37 weeks was poor (summary value [95% CI]: 43% [36%, 50%] and 64%[57%, 71%] respectively). The specificity of fetal fibronectin for symptomatic and asymptomatic women was over 80% for all outcomes. For symptomatic women, a negative test for fetal fibronectin should be useful at ruling out the likelihood of delivery within 7 to 10 days of sampling. For asymptomatic women, testing for fetal fibronectin is unlikely to be useful as many women at risk will be misclassified as normal.

Inhibition of neutrophil oxidative burst and granule secretion by wortmannin: potential role of MAP kinase and renaturable kinases.

Exposure of neutrophils to a variety of agonists including soluble chemoattractant peptides and cytokines results in degranulation and activation of the oxidative burst (effector functions) that are required for bacterial killing. At present, the signaling pathways regulating these important functions are incompletely characterized. Mitogen-activated protein (MAP) kinases (MAPK) as well as members of a family of "renaturable kinases" are rapidly activated in neutrophils in response to diverse physiological agonists, suggesting that they may regulate cell activation. Antagonists of phosphatidyl inositol-3-(OH) kinase (PI3-kinase) such as wortmannin (Wtmn) inhibit these effector responses as well as certain of the above-mentioned kinases, leading to the suggestion that these enzymes lie downstream of PI3-kinase in the pathway regulating the oxidative burst and granule secretion. However, an apparent discrepancy exists in that, while virtually obliterating activity of PI3-kinase and the oxidase at low concentrations (ID50 < 20 nM), Wtmn has only variable inhibitory effects on MAPK even at substantially higher concentrations (75-100 nM). This raises the possibility that the inhibitory effects of Wtmn are mediated via other enzyme systems. The purpose of the current study was therefore to compare the effects of Wtmn on PI3-kinase activity and on the chemoattractant-activated kinases, and to determine the potential relationship of these pathways to microbicidal responses. In human neutrophils, both the oxidative burst and granule secretion induced by fMLP were inhibited by Wtmn but at markedly different concentrations: the oxidative burst was inhibited with an ID50 of < 5 nM while granule secretion was only partially inhibited at concentrations exceeding 75 nM. Activation of both MEK-1 and MAPK in response to fMLP was only partially inhibited by high doses of Wtmn (ID50 of > 100 nM and approximately 75 nM, respectively). In contrast, Wtmn potently inhibited fMLP-induced activation of the 63 and 69 kDa renaturable kinases (ID50 approximately 5-10 nM). We speculate that the renaturable kinases may be involved in the regulation of the oxidative burst, whereas the MAPK pathway may play a role in other neutrophil functions such as granule secretion.

Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin.

Exposure of neutrophils to a variety of agonists including chemoattractant peptides and cytokines induces degranulation and activation of the oxidative burst which are required for bacterial killing. The signaling pathways regulating these important functions are incompletely characterized. Mitogen-activated protein (MAP) kinases, which include the extracellular signal-regulated kinases (ERKs), are activated rapidly in neutrophils, suggesting that they may regulate cell activation. We found that neutrophils express two isoforms of MAP/ERK kinase (MEK), mixed-function kinases that are responsible for phosphorylation and activation of ERK. Like MEK-1, MEK-2 was found to reside in the cytosol both before and after stimulation. Studies were undertaken to define the relative abundance and functional contribution of MEK-1 and MEK-2 in neutrophils and to characterize the signaling pathways leading to their activation. Although the abundance of the two isoforms was similar, the activity of MEK-2 was at least 3-fold greater than that of MEK-1. A rise in cytosolic [Ca2+] was insufficient for MEK stimulation, and blunting the [Ca2+] change with intracellular chelators failed to prevent receptor-mediated activation of either isoform, implying that cytosolic Ca2+ transients are not necessary. In contrast, both MEK-1 and MEK-2 were activated by exposure of cells to protein kinase C (PKC) agonists. Conversely, PKC antagonists inhibited the chemotactic stimulation of both isoforms, suggesting that PKC was required for their activation. Despite these similarities, clear differences were also found in the pathways leading to activation of the MEK isoforms. In particular, MEK-2 was considerably more sensitive than MEK-1 to the phosphatidylinositol 3-kinase inhibitor wortmannin. Phosphorylation and activation of ERK-1 and ERK-2 were also reduced by this inhibitor. In summary, MEK-2 is stimulated in formyl-methionyl-leucyl-phenylalanine-treated neutrophils, where it appears to be functionally the predominant isoform. The time course and inhibitor sensitivity of MEK-2 activation parallel those of several components of the microbicidal response, suggesting a signaling role of the MEK-ERK pathway.