Association between plasma leptin and cesarean section after induction of labor: a case control study

Background Obesity in pregnancy is common, with more than 50% of pregnant women being overweight or obese. Obesity has been identified as an independent predictor of dysfunctional labor and is associated with increased risk of failed induction of labor resulting in cesarean section. Leptin, an adipokine, is secreted from adipose tissue under the control of the obesity gene. Concentrations of leptin increase with increasing percent body fat due to elevated leptin production from the adipose tissue of obese individuals. Interestingly, the placenta is also a major source of leptin production during pregnancy. Leptin has regulatory effects on neuronal tissue, vascular smooth muscle, and nonvascular smooth muscle systems. It has also been demonstrated that leptin has an inhibitory effect on myometrial contractility with both intensity and frequency of contractions decreased. These findings suggest that leptin may play an important role in dysfunctional labor and be associated with the outcome of induction of labor at term. Our aim is to determine whether maternal plasma leptin concentration is indicative of the outcome of induction of labor at term. We hypothesize that elevated maternal plasma leptin levels are associated with a failed term induction of labor resulting in a cesarean delivery. Methods In this case-control study, leptin was measured in 3rd trimester plasma samples. To analyze labor outcomes, 174 women were selected based on having undergone an induction of labor (IOL), (115 women with successful IOL and 59 women with a failed IOL). Plasma samples and clinical information were obtained from the UI Maternal Fetal Tissue Bank (IRB# 200910784). Maternal plasma leptin and total protein concentrations were measured using commercially available assays. Bivariate analyses and logistic regression models were constructed using regression identified clinically significant confounding variables. All variables were tested at significance level of 0.05. Results Women with failed IOL had higher maternal plasma leptin values (0.5 vs 0.3 pg, P = 0.01). These women were more likely to have obesity (mean BMI 32 vs 27 kg/m2, P = 0.0002) as well as require multiple induction methods (93% vs 73%, p = 0.008). Logistic regression showed Bishop score (OR 1.5, p < 0.001), BMI (OR 0.92, P < 0.001), preeclampsia (OR 0.12, P = 0.010), use of multiple methods of induction (OR 0.22, P = 0.008) and leptin (OR 0.42, P = 0.017) were significantly associated with IOL outcome. Specifically, after controlling for BMI, Bishop Score, and preeclampsia, leptin was still predictive of a failed IOL with an odds ratio of 0.47 (P = 0.046). Finally, using leptin as a predictor for fetal outcomes, leptin was also associated with of fetal intolerance of labor, with an odds ratio of 2.3 (P = 0.027). This association remained but failed to meet statistical significance when controlling for successful (IOL) (OR 1.5, P = 0.50). Conclusions Maternal plasma leptin may be a useful tool for determining which women are likely to have a failed induction of labor and for counseling women about undertaking an induction of labor versus proceeding with cesarean delivery.

Obstructed uterine venous return: a preventable cause of dysfunctional labor?

Dysfunctional labor is a common cause of cesarean delivery and may be caused by myometrial hypoxia. Obstruction of uterine venous return due to compression of the inferior vena cava by the gravid uterus or the abdominal wall may be an auxiliary cause of myometrial hypoxia which aggravates other causes.

Progesterone and estrogen regulate NALCN expression in human myometrial smooth muscle cells

During pregnancy, the uterus transitions from a quiescent state to an excitable, highly contractile state to deliver the fetus. Two important contributors essential for this transition are hormones and ion channels, both of which modulate myometrial smooth muscle cell (MSMC) excitability. Recently, the sodium (Na+) leak channel, nonselective (NALCN), was shown to contribute to a Na+ leak current in human MSMCs, and mice lacking NALCN in the uterus had dysfunctional labor. Microarray data suggested that the proquiescent hormone progesterone (P4) and the procontractile hormone estrogen (E2) regulated this channel. Here, we sought to determine whether P4 and E2 directly regulate NALCN. In human MSMCs, we found that NALCN mRNA expression decreased by 2.3-fold in the presence of E2 and increased by 5.6-fold in the presence of P4. Similarly, E2 treatment decreased, and P4 treatment restored NALCN protein expression. Additionally, E2 significantly inhibited, and P4 significantly enhanced an NALCN-dependent leak current in MSMCs. Finally, we identified estrogen response and progesterone response elements (EREs and PREs) in the NALCN promoter. With the use of luciferase assays, we showed that the PREs, but not the ERE, contributed to regulation of NALCN expression. Our findings reveal a new mechanism by which NALCN is regulated in the myometrium and suggest a novel role for NALCN in pregnancy.

The assessment of labor: a brief history

In the 1930s, investigators in the US, Germany and Switzerland made the first attempts to quantify the course of labor in a clinically meaningful way. They emphasized the rupture of membranes as a pivotal event governing labor progress. Attention was also placed on the total number of contractions as a guide to normality. Beginning in the 1950s, Friedman determined that changes in cervical dilatation and fetal station over time were the most useful parameters for the assessment of labor progress. He showed all normal labors had similar patterns of dilatation and descent, differing only in the durations and slopes of their component parts. These observations led to the formulation of criteria that elevated the assessment of labor from a rather arbitrary exercise to one guided by scientific objectivity. Researchers worldwide confirmed the basic nature of labor curves and validated their functionality. This system allows us to quantify the effects of parity, analgesia, maternal obesity, prior cesarean, maternal age, and fetal presentation and position on labor. It permits analysis of outcomes associated with labor aberrations, quantifies the effectiveness of treatments and assesses the need for cesarean delivery. Also, dysfunctional labor patterns serve as indicators of short- and long-term risks to offspring. We still lack the necessary translational research to link the physiologic manifestations of uterine contractility with changes in dilatation and descent. Recent efforts to interpret electrohysterographic patterns hold promise in this regard, as does preliminary exploration into the molecular basis of dysfunctional labor. For now, the clinician is best served by a system of labor assessment proposed more than 60 years ago and embellished upon in considerable detail since.