Cellular immune responses in amniotic fluid of women with preterm labor and intra-amniotic infection or intra-amniotic inflammation.

PROBLEM: Preterm birth is commonly preceded by preterm labor, a syndrome that is causally linked to both intra-amniotic infection and intra-amniotic inflammation. However, the stereotypical cellular immune responses in these two clinical conditions are poorly understood. METHOD OF STUDY: Amniotic fluid samples (n = 26) were collected from women diagnosed with preterm labor and intra-amniotic infection (amniotic fluid IL-6 concentrations ≥2.6 ng/mL and culturable microorganisms, n = 10) or intra-amniotic inflammation (amniotic fluid IL-6 concentrations ≥2.6 ng/mL without culturable microorganisms, n = 16). Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. Amniotic fluid concentrations of classical pro-inflammatory cytokines, type 1 and type 2 cytokines, and T-cell chemokines were determined using immunoassays. RESULTS: Women with spontaneous preterm labor and intra-amniotic infection had (a) a greater number of total leukocytes, including neutrophils and monocytes/macrophages, in amniotic fluid; (b) a higher number of total T cells and CD4+ T cells, but not CD8+ T cells or B cells, in amniotic fluid; and (c) increased amniotic fluid concentrations of IL-6, IL-1ß, and IL-10, compared to those with intra-amniotic inflammation. However, no differences in amniotic fluid concentrations of T-cell cytokines and chemokines were observed between these two clinical conditions. CONCLUSION: The cellular immune responses observed in women with preterm labor and intra-amniotic infection are more severe than in those with intra-amniotic inflammation, and neutrophils, monocytes/macrophages, and CD4+ T cells are the main immune cells responding to microorganisms that invade the amniotic cavity. These findings provide insights into the intra-amniotic immune mechanisms underlying the human syndrome of preterm labor.

The immunophenotype of decidual macrophages in acute atherosis.

PROBLEM: Acute atherosis is a uteroplacental arterial lesion that is associated with pregnancy complications such as preeclampsia and preterm birth, the latter being the leading cause of perinatal morbidity and mortality worldwide. However, the immunobiology of acute atherosis is poorly understood. METHOD OF STUDY: Placental basal plate samples were collected from women who delivered with (n = 11) and without (n = 31) decidua basalis lesions of acute atherosis. Multicolor flow cytometry was used to quantify M1- and M2-like macrophage subsets and the expression of iNOS and IL-12 by decidual macrophages. Multiplex fluorescence staining and phenoptics were performed to localize M1-, MOX-, and Mhem-like macrophages in the decidual basalis. RESULTS: Macrophages displayed diverse phenotypes in the decidua basalis with acute atherosis. M2-like macrophages were the most abundant subset in the decidua; yet, this macrophage subset did not change with the presence of acute atherosis. Decidual M1-like macrophages were increased in acute atherosis, and such macrophages displayed a pro-inflammatory phenotype, as indicated by the expression of iNOS and IL-12. Decidual M1-like pro-inflammatory macrophages were localized near both transformed and non-transformed vessels in the decidua basalis with acute atherosis. MOX and Mhem macrophages were also identified near transformed vessels in the decidua basalis with acute atherosis. Finally, monocyte-like cells were present on the vessel wall of non-transformed decidual vessels, indicating a possible intravascular source for macrophages in acute atherosis. CONCLUSION: Decidual macrophages display different phenotypes, namely M1-like, M2-like, MOX, and Mhem subsets. Yet, pro-inflammatory macrophages are enriched in the decidua basalis with acute atherosis. These findings provide a molecular foundation for future mechanistic inquiries about the role of pro-inflammatory macrophages in the pathogenesis of acute atherosis.

The immunophenotype of amniotic fluid leukocytes in normal and complicated pregnancies.

PROBLEM: The immune cellular composition of amniotic fluid is poorly understood. Herein, we determined: 1) the immunophenotype of amniotic fluid immune cells during the second and third trimester in the absence of intra-amniotic infection/inflammation; 2) whether amniotic fluid T cells and ILCs display different phenotypical characteristics to that of peripheral cells; and 3) whether the amniotic fluid immune cells are altered in women with intra-amniotic infection/inflammation. METHOD OF STUDY: Amniotic fluid samples (n = 57) were collected from 15 to 40 weeks of gestation in women without intra-amniotic infection/inflammation. Samples from women with intra-amniotic infection/inflammation were also included (n = 9). Peripheral blood mononuclear cells from healthy adults were used as controls (n = 3). Immunophenotyping was performed using flow cytometry. RESULTS: In the absence of intra-amniotic infection/inflammation, the amniotic fluid contained several immune cell populations between 15 and 40 weeks. Among these immune cells: (i) T cells and ILCs were greater than B cells and natural killer (NK) cells between 15 and 30 weeks; (ii) T cells were most abundant between 15 and 30 weeks; (iii) ILCs were most abundant between 15 and 20 weeks; (iv) B cells were scarce between 15 and 20 weeks; yet, they increased and were constant after 20 weeks; (v) NK cells were greater between 15 and 30 weeks than at term; (vi) ILCs expressed high levels of RORγt, CD161, and CD103 (ie, group 3 ILCs); (vii) T cells expressed high levels of RORγt; (viii) neutrophils increased as gestation progressed; and (ix) monocytes/macrophages emerged after 20 weeks and remained constant until term. All of the amniotic fluid immune cells, except ILCs, were increased in the presence of intra-amniotic infection/inflammation. CONCLUSION: The amniotic fluid harbors a diverse immune cellular composition during normal and complicated pregnancies.

Prenatal Diagnosis of Dextrocardia with Complex Congenital Heart Disease Using Fetal Intelligent Navigation Echocardiography (FINE) and a Literature Review.

Fetal dextrocardia is a type of cardiac malposition where the major axis from base to apex points to the right side. This condition is usually associated with a wide spectrum of complex cardiac defects. As a result, dextrocardia is conceptually difficult to understand and diagnose on prenatal ultrasound. The advantage of four-dimensional sonography with spatiotemporal image correlation (STIC) is that this modality can facilitate fetal cardiac examination. A novel method known as fetal intelligent navigation echocardiography (FINE) allows automatic generation of nine standard fetal echocardiography views in normal hearts by applying intelligent navigation technology to STIC volume datasets. In fetuses with congenital heart disease, FINE is also able to demonstrate abnormal cardiac anatomy and relationships when there is normal cardiac axis and position. However, this technology has never been applied to cases of cardiac malposition. We report herein for the first time, a case of fetal dextrocardia and situs solitus with complex congenital heart disease in which the FINE method was invaluable in diagnosing multiple abnormalities and defining complex anatomic relationships. We also review the literature on prenatal sonographic diagnosis of dextrocardia (with an emphasis on situs solitus), as well as tricuspid atresia with its associated cardiac features.

Signaling by two-component system noncognate partners promotes intrinsic tolerance to polymyxin B in uropathogenic Escherichia coli.

Bacteria use two-component systems (TCSs) to react appropriately to environmental stimuli. Typical TCSs comprise a sensor histidine kinase that acts as a receptor coupled to a partner response regulator that coordinates changes in bacterial behavior, often through its activity as a transcriptional regulator. TCS interactions are typically confined to cognate pairs of histidine kinases and response regulators. We describe two distinct TCSs in uropathogenic Escherichia coli (UPEC) that interact to mediate a response to ferric iron. The PmrAB and QseBC TCSs were both required for proper transcriptional response to ferric iron. Ferric iron induced the histidine kinase PmrB to phosphotransfer to both its cognate response regulator PmrA and the noncognate response regulator QseB, leading to transcriptional responses coordinated by both regulators. Pretreatment of the UPEC strain UTI89 with ferric iron led to increased resistance to polymyxin B that required both PmrA and QseB. Similarly, pretreatment of several UPEC isolates with ferric iron increased tolerance to polymyxin B. This study defines physiologically relevant cross talk between TCSs in a bacterial pathogen and provides a potential mechanism for antibiotic resistance of some strains of UPEC.

Intensive Care Admissions in Pregnancy: Analysis of a Level of Support Scoring System.

OBJECTIVES: Development of a validated triaging system that can be used by obstetric providers to identify obstetric patients at risk of developing severe morbidity during an admission is urgently required. Maternal Critical Care Working Group (MCCWG) recommended a "level of care" strategy that based patient acuity needs on number of individual organ systems requiring support. The objective of this study was to apply the MCCWG level of support for critical care (MCCWG LOC) scoring to pregnant women admitted to an intensive care unit (ICU) to predict maternal outcomes and to compare it to the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system. METHODS: In this retrospective study, we applied the MCCWG LOC scoring to pregnant women admitted to an ICU at the Detroit Medical Center, between January 2006 and December 2010. The MCCWG LOC was scored on admission to the ICU, and patients were subsequently divided into two groups (Group 1, patients requiring Level 1 and 2 support and Group 2, patients requiring level 3a and 3b support) and their outcome variables were compared. The MCCWG LOC scores were also compared to APACHE II scoring, an ICU scoring system, to test if an alignment of the two systems existed, and if they were able to predict outcomes such as death, hospital and intensive care stay. RESULTS: Sixty-nine pregnant women (0.25% of deliveries) required admission to the ICU and 3 maternal deaths were reported. Sixty-four (92.7%) patients had pre-existing medical problems. Fifty-eight (84%) of admissions were secondary to a medical diagnosis. Mean APACHE II score (p < 0.018) and APACHE II predicted mortality rate were significantly higher in Group 2 (p < 0.018). The hospital length of stay (LOS) (p < 0.017) and ICU LOS (p < 0.0001) were significantly longer in Group 2 as compared to Group 1. Group 2 patients required more interventions while in the ICU (p < 0.0001). All the patients who died were classified as Group 2. CONCLUSIONS FOR PRACTICE: In a cohort of women requiring intensive care admission during pregnancy, MCCWG LOC, a simplified organ system based, triaging scoring system, predicted maternal outcomes and correlated with APACHE II score. Our data support initiatives for further development and testing of global obstetric triaging scoring systems for the purposes of risk stratification, monitoring of quality and resource allocation.

Outcomes following intra-amniotic instillation with indigo carmine to diagnose prelabor rupture of membranes in singleton pregnancies: a single center experience.

OBJECTIVE: To evaluate clinical outcomes of women with singleton pregnancies that underwent intra-amniotic dye instillation (amniodye test) following equivocal diagnosis of prelabor rupture of membranes (PROM). METHOD: Records of 34 pregnant women who underwent amniodye test for equivocal PROM were reviewed. Comparisons of characteristics, amniotic fluid (AF) cultures, AF interleukin (IL)-6 concentrations, and placenta pathology results between women who tested positive and those who tested negative were performed. A sub-analysis of women who were amniodye test-negative was also performed. RESULTS: (1) Commonest indication for amniodye test was a typical history of PROM with positive conventional tests and persistently normal AF volume, (2) amniodye test-positive women had a shorter procedure-to-delivery interval (p = 0.008), and a greater proportion of histologic acute chorioamnionitis (p = 0.04) and funisitis (p = 0.01) than amniodye-negative women, and (3) in addition to similarities to women with amniodye-positive test, amniodye test-negative women who delivered <34 weeks, had a greater proportion of women with risk for preterm birth (p = 0.04), than their counterparts who delivered between 34 0/7 and 36 6/7 weeks. CONCLUSION: Equivocal diagnosis of PPROM should warrant an amniodye test to avoid iatrogenic intervention in women with intact amniotic membranes. AF analysis should be performed in amniodye test-negative women.

Racial disparities in the optimal for induction of labor in low-risk term pregnancies: a national population-based study.

OBJECTIVE: The recommendation for elective induction of labor (IOL) is to await ≥ 39 weeks. Studies show earlier maturity of Blacks compared to Whites. The objective was to examine the effect of the Black race on the risk of intrapartum and neonatal complications after IOL. METHODS: Black women with non-indicated IOL at 37-42 weeks were selected from the CDC-Birth Cohorts 2007-2010. Congenital anomalies, hypertension/diabetes, low-birth weight, breech presentation, previous cesarean and premature rupture of membranes were excluded. Intrapartum/neonatal complications were analyzed. Logistic regression was used to calculate adjusted odds ratios, using 39 weeks as reference. RESULTS: 311,264 black were compared with 2,451,774 deliveries of other races. For Blacks, the risks of cesarean delivery and intrapartum complications were lower at 38 weeks. Chance of vaginal delivery was greater at 38 weeks. Risks of neonatal complications was not increased at 38 compared to 39 weeks. CONCLUSIONS: Intrapartum complications were lower at 38 than at 39 weeks in Blacks with no increased risk of neonatal complications. Meconium staining and fetal distress were higher as early as at 40 weeks, perhaps due to accelerated maturation. While a 39-week goal is simple and benefits many patients, a more "personalized medicine" approach may benefit even more mothers and babies.

Optimal visualization of the fetal four-chamber and outflow tract views with transabdominal ultrasound in the morbidly obese: Are we there yet?

BACKGROUND: To compare optimal visualization of the four-chamber and outflow-tract views of the fetal heart on sonographic examination between morbidly obese (body mass index [BMI] ≥ 40 kg/m(2) ) and nonobese (BMI < 25 kg/m(2) ) pregnant women. METHODS: In this retrospective cohort study, we included records and images from 509 pregnant women who had first undergone sonographic examination between 18 and 36 weeks' fetal gestational age. RESULTS: Compared with the nonobese women, morbidly obese women had lower optimal visualization of the four-chamber and outflow-tract heart views: four-chamber view, morbidly obese, 83/186 (44.6%), versus nonobese, 283/323 (87.6%), and outflow-tract view, morbidly obese, 80/186 (43%) versus nonobese, 258/290 (89%); p < 0.0001 for each comparison. Similar outcomes were observed when the results from each subcategory of morbidly obese women (ie, BMI 40-49.9, 50-59.9, and ≥60 kg/m(2) ) were compared with that from nonobese women; p < 0.0001 for each comparison. These outcomes remained the same regardless of whether this comparison was made among those who had their examination before or at 19 weeks' or more gestational age. Among the morbidly obese women, there was no difference in optimal visualization of the four-chamber or outflow-tract views regardless of whether the examination was performed at <23 weeks' or at ≥23 weeks' gestational age: four-chamber view <23 weeks, 44.8% (78/174), versus four-chamber view ≥23 weeks, 41.7% (5/12); p = 0.8, and outflow-tract view <23 weeks, 43.1% (75/174), versus outflow-tract view ≥23 weeks, 41.7% (5/12); p = 0.9. After controlling for maternal age and race, the odds of visualizing the four-chamber and outflow-tract views in the morbidly obese were reduced compared with those in their nonobese counterparts: odds ratio (OR) for four-chamber, 0.13; 95% confidence interval (CI), 0.08-0.21, and OR for outflow-tract, 0.11; 95% CI, 0.07-0.17. CONCLUSIONS: Optimal visualization of the fetal four-chamber and outflow-tract views was achieved in less than 50% of morbidly obese women, compared with almost 90% in nonobese women.