Cytokines and parturition: investigating adiponectin, TNF-α, and IL-6 in mother-newborn pairs.

OBJECTIVE: Cytokines are reported to be associated with various pregnancy complications and health outcomes of the offspring. However, reference values during pregnancy have not been established, effects of clinical and obstetric factors have not been examined, and interactions between different cytokines have not yet been reported. METHODS: In this cross-sectional study, we recruited 120 mother-newborn pairs. Maternal venous blood samples (6 mL) were taken on admission to the labor ward; newborn venous blood samples (6 mL) were drawn from the placental part of the umbilical cord (UC). Adiponectin, TNF-α, and IL-6 serum concentrations were measured by commercial immunoassays. Clinical and obstetric variables were analyzed for their association with maternal and UC cytokine concentrations. RESULTS: Forty-six adiponectin pairs, 55 TNF-α pairs, and 14 IL-6 pairs were available for analysis. Correlation between UC and maternal adiponectin-, IL-6-, and TNF-α levels was low. We found a significant correlation of UC adiponectin with maternal brain-derived neurotrophic factor (BDNF) and maternal adiponectin, and between maternal leptin and maternal TNF-α. CONCLUSIONS: Clinical and obstetric variables as well as interactions between cytokines may have an impact on serum concentrations of the respective cytokines in maternal and UC blood. Further studies are required to confirm our findings.

Pregnancy in women with hypertrophic cardiomyopathy: data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: We report the maternal and foetal outcomes at birth and after 6 months in a cohort of pregnant women with hypertrophic cardiomyopathy (HCM). Although most women with HCM tolerate pregnancy well, there is an increased risk of obstetric and cardiovascular complications. METHODS AND RESULTS: All pregnant women with HCM entered into the prospective worldwide Registry of Pregnancy and Cardiac disease (ROPAC) were included in this analysis. The primary endpoint was a major adverse cardiovascular event (MACE), which included death, heart failure (HF), thrombo-embolic event, and arrhythmia. Baseline and outcome data were analysed and compared for patients with MACE vs. without MACE and for patients with obstructive HCM vs. non-obstructive HCM. Sixty pregnant women (mean age 30.4 ± 6.0 years) with HCM (41.7% obstructive) were included. No maternal mortality occurred in this cohort. In 14 (23%) patients at least one MACE occurred: 9 (15.0%) HF and 7 (12%) an arrhythmia (6 ventricular and 1 atrial fibrillation). MACE occurred most commonly during the 3rd trimester and postpartum period. In total, 3 (5.0%) women experienced foetal loss. Women with MACE had a higher rate of emergency Caesarean delivery for cardiac reasons (21.4% vs. 0%, P = 0.01). No significant differences in pregnancy outcome were found between women with obstructive and non-obstructive HCM. NYHA functional class of ≥II and signs of HF before pregnancy, were associated with MACE. CONCLUSION: Although most women with HCM tolerated pregnancy well, cardiovascular complications were not uncommon and predicted by pre-pregnancy status facilitating pre-pregnancy counselling and targeted antenatal care.

Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays a fundamental role in brain development; additionally, it is involved in various aspects of cerebral function, including neurodegenerative and psychiatric diseases. Involvement of BDNF in parturition has not been investigated. The aim of our study was to analyze determinants of umbilical cord BDNF (UC-BDNF) concentrations of healthy, term newborns and their respective mothers. METHODS: This cross-sectional prospective study was performed at a tertiary referral center. Maternal venous blood samples were taken on admission to labor ward; newborn venous blood samples were drawn from the umbilical cord (UC), before delivery of the placenta. Analysis was performed with a commercially available immunoassay. Univariate analyses and stepwise multivariate regression models were applied. RESULTS: 120 patients were recruited. UC-BDNF levels were lower than maternal serum concentrations (median 641 ng/mL, IQR 506 vs. median 780 ng/mL, IQR 602). Correlation between UC- and maternal BDNF was low (R=0.251, p=0.01). In univariate analysis, mode of delivery (MoD), gestational age (GA), body mass index at delivery, and gestational diabetes were determinants of UC-BDNF (MoD and smoking for maternal BDNF, respectively). Stepwise multivariate regression analysis revealed a model with MoD and GA as determinants for UC-BDNF (MoD for maternal BDNF). CONCLUSIONS: MoD and GA at delivery are determinants of circulating BDNF in the mother and newborn. We hypothesize that BDNF, like other neuroendocrine factors, is involved in the neuroendocrine cascade of delivery. Timing and mode of delivery may exert BDNF-induced effects on the cerebral function of newborns and their mothers.

Clinical spectrum of fetal long QT syndrome: a single-center experience.

OBJECTIVE: A considerable proportion of unexplained intrauterine fetal deaths are attributed to long QT syndrome (LQTS) susceptibility. Additionally, the estimated prevalence of LQTS in newborns is 1 in 2000. Still, prenatal diagnosis of LQTS is very rare. The aim of this study was to assess the frequency of prenatal diagnosis of LQTS at our institution, present the cases, compare our findings with the existing literature and propose a possible screening approach. METHODS: We searched our fetal database between 2006 and 2013 for cases with suspected diagnosis of LQTS. RESULTS: During the investigation period around 26 000 fetuses were evaluated and three cases of suspected fetal LQTS identified. Two cases of familial LQTS had no or mild intrauterine manifestation of the condition, the third fetus had a de-novo mutation with severe, early-onset disease. CONCLUSIONS: LQTS continues to be a challenging prenatal diagnosis. In fetuses who present with complex arrhythmias, a high degree of suspicion is required, and close surveillance and timely delivery in the presence of a multidisciplinary team are necessary. For asymptomatic cases or screening purposes, routine fetal heart rate registration and detailed assessment of cases with a low for gestational age baseline may be an option.

[Speckle tracking--a new ultrasound tool for the assessment of fetal myocardial function]. / Speckle tracking--ein neues Ultraschallverfahren zur Beurteilung der fetalen Myokardfunktion.

Speckle tracking is a new ultrasound tool to assess 2D ventricular global and segmental myocardial velocity and deformation (strain, strain rate). Multiple factors such as fetal motion, high heart rates, low blood pressure, small size of the heart, physiological cardiac translation, filling and maturational changes of myocardium, polyhydramnion, maternal obesity and aortic pulsation can degrade the image quality and result in artifacts and measurement errors which may have an impact on the final analysis. Therefore deformation indices such as strain and strain rate offer a quantitative technique for the estimation of global and segmental myocardial function and contractility. At present longitudinal peak systolic strain is the most commonly applied deformation parameter used to analyse segmental and global myocardial contractility in adults. When obtained using Doppler methods, these measurements are angle dependent, whereas speckle tracking techniques overcome the limitations of Doppler echocardiography which is a particular advantage in foetal echocardiography. Nevertheless, the time and training necessary to acquire high-quality video clips limit the implementation of speckle tracking into clinical routine. It is not yet clear whether this new technique will identify subclinical myocardial impairment earlier than with current techniques or allow for better discrimination between healthy fetuses and fetuses with congenital heart disease. The clinical use of speckle tracking will have to be demonstrated in larger groups of complicated pregnancies.

[Preconception and contraceptive counselling of women with cardiovascular diseases]. / Präkonzeptionelle und kontrazeptive Beratung von Frauen mit kardiovaskulären Erkrankungen.

Thanks to progress in cardiothoracic surgery, an increasing number of women with complex congenital heart diseases enter adulthood. Additionally, demographic and lifestyle changes result in the manifestation of acquired cardiac diseases during child-bearing years. Some 0.5-4% of all pregnancies occur in women with cardiovascular diseases. In the developed countries cardiovascular complications are the leading cause of maternal mortality. In pregnancies with cardiac conditions obstetric complication rates are raised. Up to 50% result in miscarriages or terminations; perinatal morbidity and mortality is increased. Contraceptive counselling should accordingly be offered to adolescents with congenital cardiac malformations and to patients with acquired cardiac diseases. Various contraceptive methods are available with different efficacies. International guidelines aid in the choice of the most appropriate method. Before contemplating pregnancy, preconception counselling by an interdisciplinary team should take place. This includes an assessment of the cardiac complication risk during pregnancy, delivery and post-partum. Cardiac function should be optimized and the medication evaluated with respect to teratogenicity. Special aspects of antenatal care, genetic factors of the cardiac disease and perinatal outcome should also be addressed. This review discusses the relevance of cardiovascular disease in the context of female reproduction. It presents currently available risk scores and the various topics to be covered in preconception counselling. This includes an overview of drugs commonly prescribed and genetic factors of congenital malformations. Furthermore, indications and contraindications of contraceptive methods are reviewed; this includes special aspects in the prescription of contraceptives for this particular group of women.

High-risk pregnancy management in women with hypopituitarism.

Pregnancy after complete loss of pituitary function is uncommon. However, advances in fertility treatment have led to increased pregnancy rates in hypopituitary women. We hereby present a literature review of pregnancies affected by hypopituitarism, including a comparison with published controls; further, we add one case report of severe hypopituitarism where third-trimester oxytocin supplementation was performed. As only limited information is available on management and outcome, our purpose was to determine obstetric complications associated with deficiency of pituitary hormones. The analysis of 31 pregnancies in 27 women revealed that hypopituitary women are at increased risk: postpartum hemorrhage occurred in 8.7%, transverse lie in 16%; 42.4% of the newborns were small for gestational age. These findings are supposedly the result of uterine dysfunction caused by hormone deficiency. Oxytocin supplementation was performed with the aim to establish physiologic conditions and to prevent postpartum uterine inertia. In this case substitution may have contributed to correct fetal presentation but did not prevent postpartum hemorrhage. Further investigations into both oxytocin-dependent and -independent mechanisms regulating uterine contractions and contractility are necessary to develop strategies for prevention of uterine inertia in oxytocin-deficient pregnancies.

Diagnosis, treatment and application of color Doppler in conservative management of abnormally adherent placenta.

PURPOSE: Placenta ac-, in-, percreta is rare, but associated with high maternal morbidity. We report the results of diagnosis and management of patients with this condition at our institution. Serial color Doppler examinations were performed to investigate the pattern and duration of perfusion to abnormally adherent placenta after conservative treatment. The influence of these results on management decisions was evaluated. MATERIALS AND METHODS: Women with placenta ac-, in-, percreta delivering within a three-year interval were included. Diagnosis was established by ultrasound, color Doppler, MRI, and histology specimen. B-mode ultrasound and color Doppler were applied post-operatively. RESULTS: Fifteen cases of placenta ac-, in-, percreta occurred (0.29% of deliveries). 73.3% were associated with placenta previa, 66.6% had > or = 1 previous uterine surgery. Abnormal placentation was diagnosed antenatally in 5/15 cases; in these women complication rate (0/5 vs. 8/10, p = 0.12) and blood loss was significantly lower (mean 1.140 vs. 3.080 ml, p < 0.01). 8/15 women underwent Cesarean hysterectomy, 2 after embolization of uterine arteries. 7/15 women had conservative management. In 3 of these cases complete removal of the placenta was achieved; in the remaining 4 the entire (n = 2) or parts (n = 2) of the placenta were left in place, methotrexate was administered postoperatively, and close clinical and laboratory controls were performed. Serial color Doppler examinations revealed cessation of blood flow to the adherent tissue 9 - 13 weeks postoperatively, followed by complete resorption (n = 1)/expulsion (n = 1) of placental fragments. In two cases (placenta previa percreta) curettage was performed without major complications after negative blood flow. CONCLUSION: The high maternal morbidity of placenta ac-, in-, percreta can be reduced with antenatal diagnosis and elective delivery. Conservative management of placenta percreta may be considered in selected cases, with embolization and/or methotrexate as an adjuvant therapy. Serial examinations of the perfusion in the retained placental tissue allow conclusions about the degree of involution and aid in determining the appropriate timing of curettage if necessary.

Human chorionic gonadotropin (hCG) in the male reproductive tract.

Normal hypothalamic-pituitary testicular and prostatic functions are essential for maintenance of male fertility, whereby glycoprotein hormones (GPH) as well as androgens are major endocrine and local regulators. We have investigated whether the GPH human chorionic gonadotropin (hCG) and the free alpha and beta subunits thereof are produced in the target organs themselves and potentially act as auto/paracrine modulators of fertility. Immunofluorometric assays (IFMAs) based on our panel of highly selective monoclonal antibodies, immunohistochemistry (IHC), confocal laser scanning microscopy (CLSM) and 1- and 2D gel electrophoreses with subsequent western blotting have been utilized for the detection of hCGalpha, hCGbeta and its metabolite hCGbeta core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGalpha and hCGbeta, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n=17): hCGalpha 2630+/-520 ng/mL (mean+/-S.E.M.), hCGbeta 2+/-0.28 ng/mL, hCGbetacf and hCG 0.19+/-0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGalpha, in serum of young men (n=20): hCGalpha 0.142+/-0.054 ng/mL (mean+/-S.E.M.), hCGbeta 0.05 ng/mL and hCG 0.004+/-0.003 ng/mL. Levels of these markers were not correlated with sperm counts. Of all body fluids including those of pregnant women seminal plasma is the richest physiological source for genuine free i.e. non-dissociated GPHalpha (M(r,app) 23k) which may even appear as di- or tetramers. Its concentration is similar to that observed in maternal serum (weeks 10-12 of gestation) and in extra-embryonic coelomic fluid. In contrast to those fluids where ratios of free subunits to hCG are in the range of 1:100 highly inverse ratios in the range of 10.000:1.000:1 were observed for hCGalpha:hCGbeta:hCG in seminal plasma. hCGalpha is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGalpha and hCGbeta in male and female fertility.

Infection in a neonate caused by Pichia fabianii: importance of molecular identification.

Pichiafabianii, an uncommon yeast species recovered from clinical specimens, was documented as the cause of an infection in a 5-week-old female twin delivered at 25 and 3/7 weeks. She developed respiratory distress syndrome and necrotizing enterocolitis. At the time of the infection, she was febrile, thrombocytopenic, and still was requiring minimal ventilatory support. Blood cultures drawn on two consecutive days were positive for a germ tube negative yeast. Phenotypic methods including carbohydrate fermentations and assimilations (API 20C AUX) did not identify the yeast. Sequencing of D1/D2 domain of the large subunit rDNA was performed in one laboratory and sequencing a subunit of D2 performed in a second laboratory identified the yeast as P. fabianii. The organism was susceptible in vitro to amphotericin B, fluconazole and 5-fluorocytosinc. The patient responded to amphotericin B and removal of her vascular catheter. This case illustrates that there are an increasing number of fungi that may be pathogenic. Phenotypic tests may fail to identify them, emphasizing the need for commercially available, molecular based assays for identification.

Comparison of an automated repetitive sequence-based PCR microbial typing system to pulsed-field gel electrophoresis for analysis of outbreaks of methicillin-resistant Staphylococcus aureus.

Rapid and sensitive methods for accurate strain delineation are essential for monitoring and preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA). Pulsed-field gel electrophoresis (PFGE) has been the standard technique for strain typing most bacterial species including MRSA. The goal of this study was to compare the performance of the DiversiLab microbial typing system (Bacterial BarCodes, Inc., Houston, TX) (rep-PCR) to that of PFGE for typing MRSA isolates from five well-defined outbreaks. The DiversiLab rep-PCR assay is a rapid, semiautomated method based on PCR amplification of specific regions between noncoding repetitive sequences in the bacterial genome. rep-PCR was performed according to the manufacturer's recommendations, and the results were analyzed and dendrograms were generated using the DiversiLab analysis software (version 2.1.66 a). PFGE was performed and interpreted according to published procedures. rep-PCR results using similarity indices (SI) of 80%, 85%, and 90% were compared to PFGE analysis. In addition, intra- and interrun reproducibility was determined for rep-PCR. Overall, correct assignment to outbreak versus nonoutbreak clusters occurred for 91 of 109 isolates (85% agreement) when using a SI of 85%. For each specific outbreak, concordance between rep-PCR and PFGE ranged from 73% to 100%. There were 18 discrepant results (17%). Fourteen isolates were unique by PFGE, but they were placed in clusters by rep-PCR; the other 4 were placed in clusters different from those assigned by PFGE. Intra- and interrun reproducibility was excellent. Times to results were 12 to 24 h for rep-PCR compared to 2 to 4 days for PFGE. Rapid, standardized results and excellent reproducibility make rep-PCR a valuable tool for use in MRSA investigations. However, since rep-PCR was less discriminatory than PFGE, we recommend that it be used to screen isolates, followed by testing isolates which share the same rep-PCR pattern with a more sensitive method, such as PFGE or multilocus sequence typing.

Methicillin-resistant Staphylococcus caprae in a neonatal intensive care unit.

Staphylococcus caprae, a hemolytic coagulase-negative staphylococcus that is infrequently associated with humans, was initially detected in specimens from six infants in our neonatal intensive care unit due to phenotypic characteristics common to methicillin-resistant Staphylococcus aureus. These isolates were subsequently identified as S. caprae by the Automated RiboPrinter microbial characterization system. This prompted an 8-month retrospective investigation in our neonatal intensive care unit. S. caprae was the cause of 6 of 18 episodes of coagulase-negative staphylococcal bacteremia, was the most common coagulase-negative staphylococcus recovered from the nares of 6 of 32 infants surveyed in a methicillin-resistant S. aureus surveillance program, and was isolated from 1 of 37 health care providers' hands. Of 13 neonatal intensive care unit isolates tested, all were methicillin resistant and positive for the mecA gene. All 21 isolates were found to be a single strain by Automated RiboPrinter and pulsed-field gel electrophoresis with ApaI or SmaI digestion; ApaI was more discriminating in analyzing epidemiologically unrelated strains than Automated RiboPrinter or electrophoresis with SmaI. These findings extend the importance of S. caprae, emphasize its similarities to methicillin-resistant S. aureus, and demonstrate its ability to persist in an intensive care unit setting.

Vancomycin resistance, esp, and strain relatedness: a 1-year study of enterococcal bacteremia.

The prevalence of esp, a gene associated with infection-derived and outbreak strains, in enterococcal blood isolates from 2002 was determined. Fifty-five of 137 (40.1%) Enterococcus faecalis isolates, 30 of 58 (51.7%) E. faecium isolates, 1 of 1 E. raffinosus isolate, 0 of 4 E. gallinarum isolates, and 0 of 1 E. casseliflavus isolate were positive. esp wasn't associated with vancomycin resistance (VR) or clinical service. VR E. faecium isolates were less genetically diverse than vancomycin-susceptible strains. A large cluster of VR isolates, belonging to esp-positive E. faecium, was revealed. These data support the hypothesis that esp and VR may contribute to dissemination of particular clones.

[Hormone replacement therapy and the risk of developing breast cancer]. / Risiken der Hormonersatztherapie. Wie sind aktuelle Studien zu bewerten?

The Million Women Study (MWS) and the Women's Health Initiative (WHI) Study reveal an increased breast cancer risk and a higher relative risk for cardiovascular diseases in women on hormone replacement therapy (HRT) in comparison with control groups. For this reason, the WHI study was terminated prematurely. From the point of view of the internist, it would appear that, on the basis of the results of these studies, prophylactic treatment with estrogens and progesterone is no longer indicated. It must, however, be noted that numerous aspects are still unclear. This therefore means that in patients with severe menopausal symptoms giving rise to a high level of distress, HRT continues to be justified over the short term after a current cardiovascular risk or relevant tumor disease has been excluded.

Otitis caused by Scedosporium apiospermum in an immunocompetent child.

Scedosporium apiospermum (Pseudallescheria boydii) is a ubiquitous saprophytic mold. It is considered an infrequent but important and emerging human pathogen, mostly in immunocompromised hosts. Otomycosis secondary to S. apiospermum is extremely rare. We report an 8-year-old immunocompetent male who developed otitis media and otitis externa from S. apiospermum, which was successful treated with combination of surgical debridement and topical clotrimazole therapy. A brief literature review of infections caused by S. apiospermum follows the case presentation.

Prevalence of yeast among children in Nigeria and the United States.

Fungal infections have gained considerable importance over the last decade as a result of significant increase in the incidence of opportunistic and systemic candidosis. Although Candida albicans is the predominant causative agent of candidosis, particularly oral disease, recently an epidemiological trend has been observed where other less pathogenic species of Candida, including the newly characterized species Candida dubliniensis, are emerging as significant opportunistic pathogens. The present study aimed to screen for the presence of C. dubliniensis and to compare the recovery of yeast species from 30 seemingly healthy and 30 HIV-positive children in the United States, as well as from 64 malnourished Nigerian children. Oral samples were cultured for fungal growth, and all germ tube and chlamydospore positive isolates were tested for ability to grow at 45 degrees C to differentiate between C. albicans and C. dubliniensis. All isolates were speciated based on colony color production on CHROMagar medium and sugar assimilation profiles. Among the 30 HIV-positive children, 15 (50%) were positive for fungus; 12 were positive for C. albicans, with one of the latter also positive for Candida glabrata, and three were found to harbor C. dubliniensis. Among the 30 non-HIV-positive children, five C. albicans and four C. dubliniensis isolates were recovered. No C. dubliniensis isolates were recovered from the Nigerian group. However, eight other different yeast species were recovered from 31 (48.4%) of the 64 Nigerian children sampled, with six of them growing a combination of species. In comparing the data from the Nigerian and United States children, the frequency of yeasts in the malnourished Nigerian group was considerably higher. The most striking difference between the two groups was in the variety of the usually less encountered and less pathogenic yeast species recovered from the Nigerian population. The findings support previously reported observations that there may be intrinsic differences between different populations sampled and that malnutrition might favor the presence of yeast species other than C. albicans.

Recovery of Candida dubliniensis and other yeasts from human immunodeficiency virus-associated periodontal lesions.

Oral and subgingival samples from periodontal lesions were collected from 54 human immunodeficiency virus (HIV)-positive and 20 HIV-negative patients and cultured for yeast species. Of the 54 samples cultured from HIV-positive patients, 44 (82%) were positive for yeast species, of which 29 (66%) were subgingival. A total of 19 (48%) patients were positive for Candida dubliniensis, of which 15 (79%) were colonized in subgingival sites. Seven isolates of Candida glabrata, two isolates of Candida parapsilosis, and one isolate of Saccharomyces cerevisiae were recovered. This study reports for the first time the recovery of C. dubliniensis from subgingival intraoral sites and confirms the presence of Candida species in sites of periodontal disease associated with HIV.