Michael Esplin

Amniotic fluid levels of immunoreactive monocyte chemotactic protein-1 increase during term parturition

Objective: Parturition is characterized by an influx of inflammatory cells into gestational tissues, a phenomenon conducive to increased myometrial contractility, cervical ripening and decidual/membrane activation. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant and activator of monocytes/macrophages, is expressed in gestational tissues and, thus, may participate in the final common pathway of labor. This study was undertaken to determine whether the amniotic fluid concentrations of immunoreactive MCP-1 are altered with gestational age or spontaneous labor at term with and without prelabor rupture of the gestational membranes. We also sought to identify intrapartum differences in the concentrations of immunoreactive MCP-1 between the upper and lower amniotic fluid compartments. Methods: A cross-sectional study was conducted to assess the concentrations of immunoreactive MCP-1 in amniotic fluid. Amniotic fluid samples were obtained from 225 women as follows: (1) women undergoing mid-trimester (14-18 weeks of gestation) amniocentesis for genetic indications, whose pregnancy outcome was normal (n = 84); (2) women in labor (n = 52) and not in labor (n = 31) at term, with intact gestational membranes; (3) women with rupture of the gestational membranes in labor (n = 18) and not in labor (n = 26), at term; and (4) women in labor at term for whom paired amniotic fluid samples were obtained through transvaginal and transabdominal amniocenteses (n = 14). Immunoreactive MCP-1 was assessed with a specific and sensitive immunoassay that had been validated for amniotic fluid. Non-parametric statistics were used for analysis. Results: Immunoreactive MCP-1 was detected in all amniotic fluid samples. Spontaneous human parturition was associated with a significant increase in the amniotic fluid concentrations of immunoreactive MCP-1 (not in labor: median 595 pg/ml, range 183-3579 pg/ml vs. in labor: median 862 pg/ml, range 183-9609 pg/ml; p = 0.01). The median amniotic fluid concentrations of immunoreactive MCP-1 were significantly higher in the lower amniotic fluid compartment than in the upper amniotic fluid compartment (lower compartment: median 2913 pg/ml, range 1360-17 080 pg/ml vs. upper compartment: median 1603 pg/ml, range 1070-8062 pg/ml; p = 0.004.). Spontaneous rupture of the gestational membranes at term was not associated with a significant change in the amniotic fluid concentrations of immunoreactive MCP-1. Conclusions: Immunoreactive MCP-1 is a physiological constituent of the amniotic fluid. The amniotic fluid levels of immunoreactive MCP-1 increase during spontaneous labor at term. A topographic difference in the concentration of immunoreactive MCP-1 was observed in the amniotic cavity, with higher concentrations being noted in the lower amniotic fluid compartment, as compared with the upper amniotic fluid compartment. These findings support the hypothesis that MCP-1 may play a role in the final common pathway of spontaneous labor.

Preterm birth: a review of genetic factors and future directions for genetic study.

Preterm birth remains the leading cause of neonatal morbidity and mortality and is likely the result of interactions between specific genes and the maternal or fetal environment. The strong familial clustering of disease with documented increased risks in patients with a personal or family history of preterm birth and the racial disparities in the incidence of preterm birth support a genetic component of this condition. New technologies such as microarray, single nucleotide polymorphism analysis, and proteomics will lead to the eventual identification and characterization of the genetic etiology of preterm birth. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall that preterm birth (PTB) continues to be the leading cause of neonatal morbidity and mortality, explain that the causes are multifactorial and that there are indications of genetic/environmental causes, and state that new genetic technologies may assist in early identification and possible prevention.

Evaluation of the use of anti-TNF-α in an LPS-induced murine model

OBJECTIVE Tumor necrosis factor alpha (TNF-alpha) may play a critical role in inflammatory-mediated preterm labor. Medications blocking the activity of TNF-alpha have been shown to be effective in the treatment of conditions such as rheumatoid arthritis; however, the use of these medications for an event like preterm birth or fetal death is unknown. We hypothesized that treatment with anti-TNF-alpha may decrease the rate of fetal death and preterm birth in a LPS-induced murine model. METHODS Pregnant C57BL/6J mice received intraperitoneal (IP) injections of either vehicle or 2mg anti-TNF-alpha. After 24h, 10 microg of LPS was administered IP. Mice were sacrificed 24h later and outcomes between groups were assessed. A second set of experiments utilizing RT-PCR was performed to determine the influence of anti-TNF-alpha on production of inflammatory cytokines in response to LPS. RESULTS There were 72 resultant pups in the LPS+saline group, and 91 in the group receiving LPS+anti-TNF-alpha. Pretreatment with anti-TNF-alpha reduced the rate of fetal death and preterm birth after LPS administration (p<0.01). Expression of IL-6, IL-1beta, TLR-2, CD14 and COX-1 were found to be significantly reduced in mice treated with anti-TNF-alpha and LPS compared to LPS alone. CONCLUSION The use of anti-TNF-alpha decreased fetal deaths and preterm deliveries in an LPS-induced model of preterm birth. In addition, there were critical gene expression alterations in the group receiving anti-TNF-alpha. Further evaluation of TNF-alpha blockade as a potential treatment for preterm labor is warranted.

Uterine rupture with attempted vaginal birth after cesarean delivery: decision-to-delivery time and neonatal outcome.

OBJECTIVE: To estimate the time from the diagnosis of uterine rupture to delivery that would prevent adverse neonatal sequelae. METHODS: Cases of uterine rupture from January 1, 2000, to December 31, 2009, were identified in nine hospitals in the Intermountain Health Care system and at the University of Utah. Maternal demographics, labor characteristics, and neonatal outcomes were obtained. Primary adverse outcome was abnormal umbilical artery pH level less than 7.0 or 5-minute Apgar score less than 7. Adverse secondary outcome included fetal or neonatal death and neonatal neurologic injury attributed to uterine rupture. RESULTS: Thirty-six cases of uterine rupture occurred during 11,195 trials of labor after cesarean delivery. Signs of uterine rupture were fetal (n=24), maternal (n=8), or a combination of maternal and fetal (n=3). In one case, uterine rupture was not suspected. Mean time to delivery from the onset of symptoms or signs for the primary adverse outcome group (n=13) was 23.3 (±10.8) minutes compared with 16.0 (±7.7) minutes for those without an adverse outcome (P=.02). No neonate delivered in fewer than 18 minutes had an umbilical pH level below 7.0. Three neonates delivered at more than 30 minutes met criteria for an adverse secondary outcome. CONCLUSION: The frequency of uterine rupture was 0.32% in patients attempting a trial of labor after cesarean delivery. Neonates delivered within 18 minutes after a suspected uterine rupture had normal umbilical pH levels or 5-minute Apgar scores greater than 7. Poor long-term outcome occurred in three neonates with a decision-to-delivery time longer than 30 minutes. LEVEL OF EVIDENCE: II

Second trimester termination of pregnancy: a review by site and procedure type

BACKGROUND We hypothesized that complications for second trimester terminations are higher in a low-volume residency training program than in a high-volume private practice. STUDY DESIGN Complications and cost were compared between three groups undergoing second trimester terminations: patients undergoing dilation and evacuation (D&E) at a university hospital (Hospital D&E, n=83) or medical pregnancy termination at a university hospital (Hospital Induction, n=89) and D&E at a private outpatient facility (Clinic D&E, n=253). RESULTS Major complications occurred in 11% of the Hospital D&E, 10% of the Hospital Induction, and 1% of the Clinic D&E patients (p=.0019). Complication rates remained statistically significant when a logistic regression model was applied to the data. The mean total charge for the three respective groups was US

Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs

4625, US

A risk stratification model to predict adverse neonatal outcome in labor

5029 and US

Association of cord blood digitalis-like factor and necrotizing enterocolitis

1105 (p<.001). CONCLUSION Second trimester terminations of pregnancy by D&E in well-selected patients in a dedicated outpatient facility can be safer and less expensive than hospital-based D&E or induction of labor.

Heparin-induced thrombocytopenia is rare in pregnancy

OBJECTIVE We sought to estimate the optimal time to deliver uncomplicated monochorionic-diamnionic (MCDA) twins. STUDY DESIGN Data were retrospectively obtained from twin pregnancies from 2000 through 2009. The gestational week-specific prospective perinatal mortality risk was calculated. A cohort of MCDA twins with nonindicated deliveries was analyzed separately. Neonatal outcomes and costs were compared between MCDA twins with nonindicated deliveries born at specific weeks of gestation, and those born the subsequent week. RESULTS There were 5894 dichorionic-diamnionic twins and 1704 MCDA twins. After 28 weeks, the gestational week-specific prospective risk of perinatal mortality did not differ between groups. There were 948 MCDA twins with nonindicated deliveries. Until 37 weeks, the risk of severe neonatal morbidity, perinatal mortality, and hospital costs were greater for fetuses delivered compared to fetuses born in a subsequent week. CONCLUSION To optimize neonatal outcome and decrease hospital costs, MCDA twins should not be delivered <37 weeks unless medically indicated.

Differential hybridization and other strategies to identify novel ovarian genes.

Objective:The development and evaluation of a labor risk model consisting of a combination of antepartum risk factors and intrapartum fetal heart rate (FHR) characteristics that can reliably identify those infants at risk for adverse neonatal outcome in labor.Study design:A nested case–control study of term singleton deliveries at the nine hospitals between March 2007 and December 2009. Eligibility criteria included: gestational age ⩾37.0 weeks; singleton pregnancy; documented continuous FHR monitoring for ⩾2 h before delivery; assessment of FHR tracing at least every 20 min; and, available maternal and neonatal outcomes. Adverse neonatal outcome was defined as nonanomalous infants admitted to the newborn intensive care unit with either a 5 minute Apgar score <7 or an umbilical artery pH<7.1. Initial risk score was determined using data available at 1 h after admission. Patients with an initial risk score between 7 and 15 were considered high risk. Intrapartum risk scores were then created for these patients using FHR tracing data and labor characteristics.Result:A total of 51 244 patients were identified meeting study criteria. Of the antepartum variables evaluated (n=31), 10 were associated with an adverse outcome. The high-risk group made up 28% of the population and accounted for 59.8% of the adverse outcomes. Intrapartum characteristics were then evaluated in this high-risk group. Intrapartum evaluation identified the highest risk group with a C/S rate of 40% and adverse outcome rate of 11.3%.Conclusion:Incorporation of maternal and antepartum risk factors with FHR analysis can improve the ability to identify the fetus at risk in labor.