The Relationship Between Plasma Inflammatory Cytokines and Labor Pain.

BACKGROUND: Proinflammatory cytokines are increased in maternal blood at term pregnancy and are associated with cervical ripening and the initiation of labor. We hypothesize that maternal plasma cytokines also affect the sensitivity to labor pain. METHODS: By using a previously validated model describing labor pain, we used a deidentified database derived from healthy nulliparous parturients who delivered singleton pregnancies at term. Numerical rating scores for pain were recorded after the onset of regular contractions using an 11-point scale. Maternal blood was drawn for the measurement of interleukin (IL)-1ß, IL-4, IL-6, IL-8, and IL-10; interferon-γ; and tumor necrosis factor-α on admission or at the onset of painful contractions, whichever occurred later. Individual demographic, physiognomic, and cytokine variables that significantly affected labor pain at P < 0.05 were reported and included stepwise into a multivariable model. RESULTS: One hundred sixty parturients provided 411 numerical analog scores for pain that were evaluated with our model. The relationship between numerical analog scores and cervical dilation was significantly affected by the type of membrane rupture, membrane status, induction, oxytocin administration, maternal race, and plasma IL-1ß concentration as individual variables. Only the association between the highest IL-1ß quartile and slower acceleration of pain during labor remained significant in the multivariate model (P = 0.0003). Women with IL-1ß concentration in the highest quartile arrived at the labor room with a more dilated cervix than those with lower plasma concentrations of IL-1ß (5.1 ± 3.0 vs 4.1 ± 2.6 cm; P < 0.02) and had faster labor progress. CONCLUSIONS: Inflammatory cytokines including IL-1ß play a role in cervical ripening. High maternal plasma concentrations of IL-1ß may serve as a marker of advanced cervical ripening and readiness for labor that proceeds with less pain.

Maternal inflammatory markers and term labor performance.

OBJECTIVE: We sought to examine the relationship between maternal markers of inflammation and labor performance. STUDY DESIGN: A nested cohort study was performed utilizing an established cohort of term nulliparous patients. Maternal blood was collected at the onset of regular, painful contractions in patients undergoing labor induction or at admission in patients with spontaneous labor. Levels of cytokines including interleukin (IL)-1, IL-6, and tumor necrosis factor-α were determined using standard multiplex methodology. Maternal demographic data were collected prospectively. Detailed retrospective chart review was performed to extract data on cervical dilation, effacement, and station during labor. Subjects were excluded if they failed to achieve complete dilation. Mixed effects modeling was used to examine the association between serum cytokine quartiles and labor progress in the latent and active phases. RESULTS: In all, 334 women were included in our analysis. The lowest quartile of IL-6 was associated with slower latent labor (P = .001). In contrast, the highest quartiles of IL-1 and tumor necrosis factor-α were associated with slower active labor (P = .03 and .0002, respectively). CONCLUSION: Proinflammatory activation is important in labor initiation. However, once active labor is established, excess inflammation can be detrimental to efficient labor progress. These data may explain, in part, the known associations among clinical chorioamnionitis, cesarean delivery, and postpartum hemorrhage.

Maternal inflammation in spontaneous term labor.

OBJECTIVE: The purpose of this study was to examine the association between peripheral markers of maternal inflammation and the onset of term labor. STUDY DESIGN: A nested case-control study was performed with serum that had been collected at routine visits from a cohort of 607 term nulliparous women. Cases (n = 20) labored spontaneously within 48 hours of enrollment, and control subjects (n = 80) labored spontaneously ≥14 days after enrollment. Maternal serum cytokines were determined with the use of standard multiplex protocols. Median levels of interleukin-1, -4, -6, -8, and -10, interferon-γ, and tumor necrosis factor-α were compared with the use of the Mann-Whitney U test. Correlations between cytokine levels and maternal factors were performed (Spearman's rho). RESULTS: Median interleukin-1 and -6 and tumor necrosis factor-α levels were significantly higher in cases vs control subjects (0.76 vs 0.31 pg/mL [P < .01]; 2.05 vs 0.95 pg/mL [P = .03]; 0.81 vs 0.51 pg/mL [P = .02], respectively). Latency until delivery was inversely correlated with interleukin-1 and tumor necrosis factor-α (-0.28 [P < .01]; -0.246 [P = .01]), but not with interleukin-6. CONCLUSION: Maternal proinflammatory markers increase before spontaneous term labor.

Preterm birth after mature fetal lung indices: is there any neonatal morbidity?

OBJECTIVE: To determine the frequency of immediate morbidities in neonates with evidence of mature fetal lung indices who delivered before 37 weeks gestation. METHODS: A retrospective analysis was performed on pregnancies resulting in birth at < 37 weeks after mature fetal lung was documented by phosphatidylglycerol, lecithin/sphingomyelin ratio, or TDx-FLM studies. Pregnancies with multifetal gestations, maternal diabetes, or fetal anomalies were excluded. RESULTS: 179 patients were included. Eighty-one (45.3%) neonates did not sustain any morbidity, and 98 (54.7%) neonates sustained one or more morbidities. Compared to neonate without any morbidity, neonates experiencing morbidities were delivered at significantly younger gestation (35.7 ± 1.1 vs. 34.9 ± 1.5 weeks, respectively, p < 0.001) had lower birth- weight (2632.2 ± 475.5 vs. 2395.3 ± 496 g, respectively, p < 0.001), and required longer hospital stay (3.7 ± 2.8 vs. 6.9 ± 7.5 days, p < 0.001). A multivariate regression model was performed to control for the effect of birth-weight, steroid administration, and preterm premature rupture of membrane. An earlier gestational age at delivery was associated with a higher risk of neonatal morbidity. The risk of neonatal morbidity decreased by 40% (OR = 0.60, 95% CI = 0.41-0.88; p = 0.009) for each 1 week increase in gestational age. CONCLUSION: Even in the presence of documented fetal lung maturity, major morbidities--including respiratory distress - may still occur.