Cytokine profiling: variation in immune modulation with preterm birth vs. uncomplicated term birth identifies pivotal signals in pathogenesis of preterm birth.

OBJECTIVES: To assess deviations in longitudinally measured cytokines with preterm birth (PTB). METHODS: Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T) intervals: first trimester (T1: 8-14 weeks' gestation), second trimester (T2: 18-22 weeks' gestation), and third trimester (T3: 28-32 weeks' gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: "Uncomplicated" (delivered ≥37 weeks) or "Preterm Birth" (<37 weeks). Generalized Linear Modeling determined rate of change T1-T3 by outcome. RESULTS: Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1ß), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1ß, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy. CONCLUSIONS: Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.

Variation in C-reactive protein at 1 month post-partum by etiology of preterm birth: selective identification of those at risk for both poor pregnancy outcome and future health complications.

Objective To assess post-partum inflammation for patients delivering prior to 34 6/7 weeks by birth etiology. Methods This was an observational study of early preterm birth (PTB) occurring between 20 0/7 and 34 6/7 weeks of gestation. Serum C-reactive protein (CRP) levels were measured 1 month post-partum. CRP measurements were compared by birth etiology. Results A total of 399 women were analyzed. Distribution of birth etiology was 35% (n = 138) preterm labor (PTL), 28% (n = 115) preterm premature rupture of membranes (pPROM), and 37% (n = 141) indicated preterm birth (IPTB). Serum CRP varied by birth etiology (P = 0.036). Women with pPROM had elevated median CRP levels compared to women with PTL (P = 0.037). IPTB demonstrated elevated CRP levels when compared to PTL (P = 0.019). Pre-eclamptic/eclamptic subjects exhibited increased median CRP levels compared to PTL (P = 0.04). Conclusion Post-partum inflammation varies by birth etiology. Such variation may serve as identification of subjects whose future pregnancies and, ultimately, overall health status may benefit from inter-pregnancy interventions aimed at reducing inflammatory-associated risk factors.

Gestational Diabetes: Underpinning Principles, Surveillance, and Management.

Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycemia with onset during pregnancy. The article aims to provide clinicians with a working framework to minimize maternal and neonatal morbidity. Landmark historical and recent data are reviewed and presented to provide clinicians with a quick, easy reference for recognition and management of GDM. Data presented tie in insights with underlying pathophysiologic processes leading to GDM. Screening and diagnostic thresholds are discussed along with management upon diagnosis. Good clinical practice regarding screening, diagnosis, and management of GDM effectively reduces risk and improves outcomes of women and fetuses in affected pregnancies.

Effectiveness of Vaginal Delivery Simulation in Novice Trainees.

OBJECTIVE: Simulation training has been demonstrated to increase medical student confidence with vaginal deliveries; however, effect on skill performance is still lacking. To determine if integration of simulation training into the OB/GYN clerkship improves performance of vaginal deliveries, we assessed the effectiveness of simulation in third-year medical students. METHODS: During the OB/GYN clerkship, third-year students were assigned to receive vaginal delivery simulation (n=54) or cervical exam simulation (n=56), with each group serving as a simulation naïve control for the other skill. As a final assessment of their skill, students performed a simulated vaginal delivery scored by a blinded observer using a procedural checklist (score 0-30). A satisfactory score was considered 26 or greater. The individual scores and percentage of satisfactory scores were compared between both groups using a Mann-Whitney U test and chi-square test, respectively. RESULTS: Vaginal delivery students had a significantly higher mean score (27 +/- 3.2) and percentage of students achieving a passing score (85%) than the cervical exam students (22 +/- 3.5 and 15%). There were no differences in vaginal delivery performance based on gender, nor was there any difference in the number of real-life deliveries performed between vaginal delivery and cervical exam students. CONCLUSIONS: Even though medical students had an equivalent clinical rotation experience, a short period of simulation training had a marked effect on their end-of-rotation performance. During initial resident or midwife training more than 5 hours of simulation will likely be required to properly prepare 100% of trainees.

Effectiveness of Labor Cervical Examination Simulation in Medical Student Education.

OBJECTIVE: To estimate whether simulation training improves medical students' cervical examination accuracy. BACKGROUND: The training paradigm for the labor cervical examination exposes patients to additional examinations, lacks a gold standard, and does not objectively assess trainee competence. To address these issues and optimize training, we assessed the effectiveness of cervical examination simulation in third-year medical students. METHODS: During the obstetrics and gynecology clerkship, a cohort study was performed in which third-year students were assigned to receive cervical examination simulation (n=50) or vaginal delivery simulation (n=48), with each group serving as a simulation-naive control for the other skill. As a final assessment, students performed 10 cervical examinations using task trainers. Exact accuracy and accuracy within 1 cm were compared between groups. Cumulative summation analyses were performed on the cervical examination group to assess competence and the average number of repetitions needed to achieve it. RESULTS: Cervical examination students were significantly more accurate (Mann-Whitney, P<.001) in assessing dilation (73% exact, 98% within 1 cm) and effacement (83% and 100%) than vaginal delivery students (dilation 52% and 82%, effacement 51% and 96%). In the cumulative summation analyses, 65-100% of students attained competence during the clerkship depending on the level of accuracy and cervical parameter assessed. On average, competence was achieved with 27-44 repetitions. CONCLUSION: Simulation training dramatically improved student accuracy in labor cervical examinations. Because not all students achieved competence, the cumulative summation analyses suggest that more than 100 repetitions would be needed if the goal was for the entire class of students to achieve competence. LEVEL OF EVIDENCE: II.

Longitudinal modulation of immune system cytokine profile during pregnancy.

OBJECTIVE: To characterize immune modulation as expressed by cytokine assays at three time-points in human pregnancy. STUDY DESIGN: This is a prospective, longitudinal study of a broad panel of cytokine expression during singleton pregnancies resulting in an uncomplicated, full-term, live births. Peripheral blood was obtained at 8-14, 18-22, and 28-32 weeks gestation. Six cytokines - IFN-γ, IL-4, TNF-α, IL-1ß, IL-6, and IL-10 - were measured in supernatants obtained from whole blood stimulations with PHA or LPS and were compared to unstimulated controls. Samples were processed by Luminex-100 MAP®. We used Generalized Linear Models (GLM) to evaluate cytokine trajectories. RESULTS: Complete data were obtained for 45 uncomplicated pregnancies. Overall, peripheral blood WBC's demonstrated dampened cytokine responses. However, over the course of pregnancy, we found enhanced counter-regulatory cytokine expression (e.g., shown by increased IL-10). CONCLUSION: The overall decrease in pro-inflammatory cytokines and increase in counter-regulatory cytokines as uncomplicated pregnancy progresses supports the evolving concepts of immunoregulation for the maintenance of a viable pregnancy.

Morbidity and discharge timing of late preterm newborns.

Late preterm newborns (LPNs), those with gestational ages (GAs) between 34 weeks and 36 weeks 6 days, account for 70% of preterm births. Because they have a mature appearance and are often cared for in a well baby nursery (WBN), parents may anticipate that the nursery course will be similar to that of a term infant and that their newborn will be discharged with his/her mother. How frequently their hospitalizations are prolonged beyond that of their mothers and the morbidities associated with prolonged hospitalization (PH) have not been well described. The objectives of the study were to (1) determine the proportion of LPNs with a PH and (2) describe the most common morbidities in LPNs and identify those associated with PH. The authors conducted retrospective chart reviews of the neonatal courses of LPNs born between December 2002 and April 2007 at the University of Utah Hospital. They compared maternal and newborn discharge dates to determine the proportion of LPNs with a PH and calculated frequencies of conditions and interventions indicating morbidity and identified associations between each of the conditions/interventions and PH. Of 235 LPNs, 94 (40%) had a PH; 75% of 34-week LPNs had a PH compared with 50% of those with GAs of 35 weeks and 25% of those with GAs of 36 weeks. The most common conditions/interventions were an oxygen need, phototherapy for jaundice, and hypothermia requiring an isolette. A need for nasogastric feeding and antibiotic administration for >3 days was consistently associated with a PH. LPNs whose only intervention was phototherapy for jaundice or IV antibiotics for <3 days did not have a PH. As a group, two thirds of LPNs experienced one or more conditions/interventions indicating morbidity, and 40% had a PH. Both were much more common in LPNs with GAs of 34 weeks compared with LPNs with GAs of 36 weeks. Nursery clinicians should counsel parents of LPNs regarding the likely possibility of morbidity and PH.

Prevention of preterm birth.

The preterm birth rate in the USA is nearing 13%. The recent rise has been attributed to increased indicated preterm births and multiple births following artificial conceptions. There are few obstetrical interventions that successfully delay or prevent spontaneous preterm birth or reduce the risk factors leading to indicated preterm birth. On the other hand, there are many strategies that have improved outcomes for those infants who are born preterm. These include the use of corticosteroids for fetal maturation and regionalization of perinatal care for high-risk mothers and their infants. Several interventions, including progesterone use and cerclage, demonstrate promise in reducing spontaneous preterm births. The most pressing need is to better define the populations of pregnant women for whom these and other interventions will effectively reduce preterm birth.