Leili Shi

Use of uterine electromyography to diagnose term and preterm labor

Current methodologies to assess the process of labor, such as tocodynamometry or intrauterine pressure catheters, fetal fibronectin, cervical length measurement and digital cervical examination, have several major drawbacks. They only measure the onset of labor indirectly and do not detect cellular changes characteristic of true labor. Consequently, their predictive values for term or preterm delivery are poor. Uterine contractions are a result of the electrical activity within the myometrium. Measurement of uterine electromyography (EMG) has been shown to detect contractions as accurately as the currently used methods. In addition, changes in cell excitability and coupling required for effective contractions that lead to delivery are reflected in changes of several EMG parameters. Use of uterine EMG can help to identify patients in true labor better than any other method presently employed in the clinic.

Inhibition of uterine contractility with various tocolytics with and without progesterone: in vitro studies.

OBJECTIVE Various tocolytics are used to suppress uterine contractility in patients in preterm labor. Progesterone (P4) is used in patients at high risk for preterm delivery. In this study, we evaluated the effects of various tocolytics with and without P4 to examine effects on uterine contractility. STUDY DESIGN Uterine tissues (n = 280) from women undergoing cesarean at term were exposed in vitro to various agents (vehicle, magnesium sulfate [MgSO(4)], nifedipine, indomethacin, or pinacidil-all with and without P4). Contractility was measured before and after addition of the various agents. RESULTS P4 alone at 10(-5) mol/L concentration has little effect to inhibit contractility (P ≥ .05). MgSO(4) (2-8 × 10(-3) mol/L) inhibits uterine contractility (P < .05) but there is no change when combined with P4 (P > .05). Nifedipine (10(-8) mol/L) and indomethacin (10(-5) mol/L) inhibit contractions alone (P < .05) and to a greater extent when combined with P4 (P < .05). P4 significantly (P < .05) reduced the effects of pinacidil (10(-6.5) mol/L). CONCLUSION Combinations of P4 with nifedipine or indomethacin, but not MgSO(4), might be used to effectively suppress preterm labor.

Progestin treatment for the prevention of preterm birth

Progestin supplementation appears to be a promising approach to both preventing initiation of preterm labor and treating it once it is already established, given the role of progesterone in maintaining pregnancy, as well as support from basic and clinical research. Progesterone and 17α‐hydroxyprogesterone acetate slow the process of cervical ripening, and this is the rationale for prophylactic long‐term progestin supplementation mostly studied so far. However, progesterone (but not 17α‐hydroxyprogesterone acetate) also inhibits myometrial activity even after the cervix has already ripened. Moreover, these effects depend greatly on the vehicle used and the route of administration. Understanding different mechanisms of action, as well as the importance of progestin formulation, vehicle and route of administration, is the key to finding the optimal progestin treatment for prevention of preterm birth.

A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor

OBJECTIVE The purpose of this study was to determine whether optical methods can estimate cervix function during pregnancy and whether progestins modify this process. STUDY DESIGN Photos of the external cervix of timed-pregnant rats were taken every other day from day 13 until postpartum day 5 after daily treatments with vehicle (controls) or progestin treatments (progesterone, subcutaneously or vaginally; 17-alpha-hydroxyprogesterone caproate [17P] and RU-486 subcutaneously, once on day 16). The surface area of the cervix was estimated from photos. RESULTS The surface area of cervix increases throughout pregnancy and reverses after delivery in controls. In the progesterone subcutaneously or 17P subcutaneously groups, increases in surface area are lower (17P group until day 19 only; P < .05). Vaginal progesterone does not prevent surface area increases. Only the progesterone subcutaneously blocked delivery. RU-486 increases the surface area of the cervix (P < .05) during preterm delivery. CONCLUSION An optical method is useful for quantitative assessment of the cervix and evaluation of agents that modify cervical function.

Nicotine, an α7 nAChR agonist, reduces lipopolysaccharide-induced inflammatory responses and protects fetuses in pregnant rats

OBJECTIVE The objective of the study was to examine the effects of nicotine, an α7 nicotinic acetylcholine receptor agonist, on lipopolysaccharide (LPS)-induced inflammatory responses in rats during pregnancy. STUDY DESIGN Pregnant Sprague Dawley rats were randomly divided into groups (n = 6 rats/group): group 1 rats each received a single intraperitoneal injection of LPS (25 μg/kg) on gestation day 16; group 2 rats were first pretreated with nicotine (1 mg/kg per day, subcutaneously) on gestation days 14 and 15 and then were treated with single injections of LPS on gestational day 16; group 3 rats were treated with the vehicle (saline) used for groups 2 and 3 (controls). Maternal blood was collected at 6 hours and 24 hours after LPS and vehicle treatments and assayed for tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-10 (IL-10). In addition, the number of live pups and pup weights were obtained at the time of delivery. RESULTS LPS treatment significantly (P < .001) elevates maternal blood levels of TNF-α and IL-6 but not IL-10 (P > .05). Nicotine treatment significantly reduces LPS-induced TNF-α and IL-6 concentrations (P < .001) but does not change (P > .05) IL-10 levels. The number of live pups in the LPS group are significantly lower (P < .001) than the vehicle treated controls, and nicotine treatment significantly (P < .011) reverses this change. Similarly, fetal weights are lower following LPS (P < .016) and higher (P < .024) in the group treated with nicotine plus LPS. CONCLUSION Nicotine reduces the LPS-induced inflammatory responses and rescues the fetus in rats during pregnancy. Thus, nicotine exerts dramatic antiinflammatory effects. These observations have important implications for control of inflammatory responses during pregnancy.

Direct electrical stimulation softens the cervix in pregnant and nonpregnant rats

OBJECTIVE The objective of the study was to determine the effects of electrical stimulation (ES) on cervical ripening in pregnant and nonpregnant rats. STUDY DESIGN Timed pregnant and nonpregnant Sprague-Dawley rats (n = 6-7/group) were used. Cervical ES for pregnant rats was performed in vivo on day 15 of gestation by inserting an electrical probe into the vagina in contact with the cervix. Parameters of ES varied from 0.1 to 0.2 mA, 10 pulses per second, 20 milliseconds pulse duration, and repeating pulses for 15, 30, 60, and 120 minutes for pregnant ES groups and similar times for sham control groups with electrode but without ES. Nonpregnant ES groups were stimulated with only 0.2 mA for 30 minutes. Cervical collagen was measured in controls and following ES at various times using light-induced fluorescence (LIF) of collagen. Photographs were taken following ES, and some rats were killed, the cervices were isolated, and cervical extensibility was estimated. RESULTS LIF values of pregnant rats are significantly lower (P < .001) and extensibility greater (P < .05) in the ES treatment groups compared with the control groups on days 16 and 17 of pregnancy. Similarly LIF is lower (P < .05) and extensibility values greater (P < .05) in nonpregnant rats treated with ES. No adverse effects, including altered delivery time, pup weights, or damage to cervix, were produced by low current levels of ES needed to soften the cervix. CONCLUSION The following conclusions were reached: (1) application of ES rapidly produces softening and ripening of the cervix in pregnant and nonpregnant rats; (2) ES treatment does not produce early delivery; (3) the exact mechanism for ES ripening is not yet known; and (4) ES might be used clinically to ripen the cervix when needed.