Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.

Crystal structures of the components of the Staphylococcus aureus leukotoxin ED.

Staphylococcal leukotoxins are a family of ß-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins that Staphylococcus aureus produces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays in S. aureus pathogenesis and the identification of its protein receptors, combined with its presence in S. aureus methicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. The two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.

High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster).

Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism (SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred (F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies.

First insights into the transcriptome and development of new genomic tools of a widespread circum-Mediterranean tree species, Pinus halepensis Mill.

Aleppo pine (Pinus halepensis Mill.) is a relevant conifer species for studying adaptive responses to drought and fire regimes in the Mediterranean region. In this study, we performed Illumina next-generation sequencing of two phenotypically divergent Aleppo pine accessions with the aims of (i) characterizing the transcriptome through Illumina RNA-Seq on trees phenotypically divergent for adaptive traits linked to fire adaptation and drought, (ii) performing a functional annotation of the assembled transcriptome, (iii) identifying genes with accelerated evolutionary rates, (iv) studying the expression levels of the annotated genes and (v) developing gene-based markers for population genomic and association genetic studies. The assembled transcriptome consisted of 48,629 contigs and covered about 54.6 Mbp. The comparison of Aleppo pine transcripts to Picea sitchensis protein-coding sequences resulted in the detection of 34,014 SNPs across species, with a Ka /Ks average value of 0.216, suggesting that the majority of the assembled genes are under negative selection. Several genes were differentially expressed across the two pine accessions with contrasted phenotypes, including a glutathione-s-transferase, a cellulose synthase and a cobra-like protein. A large number of new markers (3334 amplifiable SSRs and 28,236 SNPs) have been identified which should facilitate future population genomics and association genetics in this species. A 384-SNP Oligo Pool Assay for genotyping with the Illumina VeraCode technology has been designed which showed an high overall SNP conversion rate (76.6%). Our results showed that Illumina next-generation sequencing is a valuable technology to obtain an extensive overview on whole transcriptomes of nonmodel species with large genomes.

Is vitamin D supplementation necessary in healthy full-term breastfed infants? A follow-up study of bone mineralization in healthy full-term infants with and without supplemental vitamin D.

AIM: The aim of the study is to establish whether healthy full-term breastfed infants require supplemental vitamin D for proper bone mineralization. METHODS: Bone mineralization was studied by performing ultrasound scans of 73 healthy full-term subjects at the age of 3 months. The infants were divided into three groups. Group A: breastfed without supplemental vitamin D (BF); group B: breastfed with supplement of 400 IU/day of vitamin D (BFD); group C: fed with formula (with and without supplemental vitamin D 400 IU/day) (FF). The values of mcSOS (m/sec) and mcBTT (µsec) were assessed in all subjects. RESULTS: A statistically significant difference has been found between group A vs group B both in mcSOS (P=0.03) and in mcBTT (P=0.01) values and also between group A vs group C both in mcSOS (P=0.012) and in mcBTT (P=0.003) values. Significant differences between group B vs group C were not found. In 75% of subjects of group A mcSOS and mcBTT values were ≤ the 10th percentile, while in group B they were between the 10th and 50th percentile. In FF infants given supplemental vitamin D mcSOS and mcBTT values were between the 25th and 75th percentile. CONCLUSION: Human breast milk is an appropriate source of nutrition for the growth of healthy full-term newborns, but is poor in vitamin D as demonstrated by the impaired bone mineralization in the breastfed infants without supplemental vitamin D. The results presented demonstrate that exclusively breastfed infants require at least 400 IU/day of supplemental vitamin D.

Deep sequencing in pre- and clinical vaccine research.

Vaccine research has experienced a quantum leap after the beginning of the genomics era. High-throughput sequencing techniques, unlimited computing resources, as well as new bioinformatic algorithms are now changing the way we perform genomic studies. Whole genome sequencing will soon become the gold standard for phylogenetic and epidemiology studies and is already shedding new light on the dynamics of bacterial evolution. We believe that deep sequencing projects, together with structural studies on vaccine candidates, will allow targeting constant epitopes and avoid vaccine failure due to antigenic variability. Systems biology, which is expected to revolutionize vaccine research and clinical studies, greatly relies on high-throughput technologies such as RNA-seq. Furthermore, genomics is a key element to develop safer vaccines, and the accuracy of deep sequencing will allow monitoring vaccine coverage after their introduction on the market.

ACTH and cortisol cord plasma concentrations in preterm and term infants.

OBJECTIVE: To measure the adrenocorticotropic hormone (ACTH) and cortisol (F) cord plasma levels in preterm and term infants in relation to their mode of delivery. STUDY DESIGN: We studied 180 newborns appropriate for gestational age (GA) with birth weights between 365 and 4380 g and GAs between 21 and 41 weeks divided into three groups: born by vaginal delivery (VD), elective cesarean section (ECS) and emergency cesarean section (EMCS). ACTH and F levels were valued with enzyme-linked immunosorbent assay testing. Median concentrations were compared between groups by Student's T-test for independent and paired data. Multiple regression analysis was used to investigate the effect of GA on F and ACTH concentrations. RESULT: A significant positive correlation between GA and plasma concentrations of ACTH (P<0.05) was found in the whole population, but not between GA and F (P=NS). A significant positive correlation was found between GA and plasma concentrations of both ACTH (P=0.01) and F (P=0.03) in VD. In those born by ECS, we demonstrated a positive correlation not only between plasma concentrations of ACTH (P=0.0000) and F (P=0.00002), respectively, with GA, but also a correlation between ACTH and F (P=0.0004). No significant correlations were found in the EMCS group (P=NS). CONCLUSION: Our results suggest simultaneous pituitary-adrenal maturation, which is complete only at term. The responsiveness of preterm babies to different stressful stimulations is similar to the terms' but quantitatively lower, and the secretion of ACTH and F may not suffice in severe pathological circumstances.

Increased risk of brain injury in IVF babies.

AIM: The aim of this paper was to assess brain injury occurrence among in vitro fertilization (IVF) babies. METHODS: We examined all babies born in our hospital in the triennium 2004-2006, comparing the presence of brain injuries between IVF babies and the rest of the population. RESULTS: In IVF group (180 babies), brain injury was present in 4 babies, while in the rest of population (n=3602) it was present in 23 babies (P=0.042, RR: 3.18). IVF babies have a higher risk of being born with a birthweight less than 2 500 grams (P<0.0001; RR: 5.133). When we considered only babies born with a birth weight less than 2 500 grams, the difference of brain injury between the two groups was not significant. CONCLUSION: In IVF babies, brain injury occurred more frequently than in the rest of population. This is probably due to a higher rate of premature births and low birth weight in IVF population. Anyway, this data should be disclosed to future parents to make an informed decision.

Aminoterminal B-type natriuretic peptide (NT-proBNP) in the therapy of patent ductus arteriosus.

BACKGROUND: NT-proBNP is a reliable index in case of cardiac diseases. OBJECTIVE: To evaluate the diagnostic usefulness of NT-proBNP as index of the closure of patent ductus arteriosus (PDA) in ELBW. METHODS: Considered 73 ELBW (mGA 26+3 weeks; mBW 789 g) with echocardiographical diagnosis of PDA. The closure of the duct was spontaneous in 22%, pharmacological in 49.3% and by surgical ligation in 28.7%. Plasma NT-proBNP levels were measured on day 3 in 35 preterm infants; in 20 of them concentrations of the peptide were assayed on day 3 and on closure of the duct. RESULTS: On day 3 the median of NT-proBNP levels was 13718 pg/ml (range 1918-70000). Peptide concentrations did not differ between pharmacological treatment and surgical ligation (respectively 13718 and 12342 pg/ml; p = 0.33). Concentrations of NT-proBNP were significantly lower on the closure of the duct (p < 0.0001) compared to concentrations on day 3 (median 12666 at day 3 versus 2443.5 pg/ml at closure), with a decrease of 80.71%. CONCLUSIONS: ELBW showed high variability of NT-proBNP concentrations both on day 3 and on closure of PDA. Although NT-proBNP high levels were indicative of the presence of hsPDA, due to the extreme heterogeneity of the values it was not possible to determine an absolute cut-off concentration of NT-proBNP below which closure of the duct occurred, while a decrease of NT-proBNP > or =80% was a reliable index of PDA closure.

[Influence of prolonged treatment with octreotide on GH, IGF I, insulin, ACTH, cortisol, T3, T4 and TSH secretion in a case of congenital chylothorax]. / Influenza del trattamento prolungato con octreotide sulla secrezione di GH, IGFI, insulina, ACTH, cortisolo, T3, T4 e TSH in un caso di chilotorace congenito.

Congenital chylothorax is a rare condition characterized by the accumulation of lymph fluid in the pleural space that causes respiratory and circulatory dysfunctions, immune deficiencies, hypoalbuminemia, electrolyte imbalance and alterations of the coagulation. Mortality rates are elevated and can rise to 50%. Therapy consists in conservative treatment based on thoracic drainage combined with total parenteral nutrition or use of low-fat high-protein diet supplemented with medium chain triglycerides. In case of failure surgical intervention may be considered. During the last years some authors have experienced the use of octreotide with doubtful results. In no case the drug impact on insulin, GH and cortisol secretion in neonatal age has been investigated and only in one case the effect on thyroid hormones has been assessed. We report the case of a 36-week baby with congenital chylothorax treated with octreotide for 42 days. The drug was well tolerated but hormonal level measurements showed a deep depression of insulin secretion unaccompanied by alterations of glucose levels. Levels of GH and TSH showed only a transitory decrease. ACTH and cortisol remained normal. At 5 months, the measurements of hormonal levels did not show significant alterations. It is not possible to determine if such a drug played an essential role in the solution of the pleural effusion, but it is important to emphasize that a prolonged treatment with octreotide has not caused, in our case, persistent hormonal alterations.

[Quantitative ultrasound for the assessment of bone in the preterm infant]. / Utilizzo dell'ultrasonografia quantitativa nella valutazione dello stato minerale osseo del neonato pretermine.

AIM: Preterm infants are at risk of osteopathy of prematurity (OP). The present study aims to assess quantitative ultrasound as a safe and non-invasive method in evaluating bone mineral status in the critically ill preterm infant. METHODS: Sixty preterm infants (27 females) have been evaluated in the Neonatal Intensive Care Unit of the University Hospital of Siena. Gestational age was between 22 and 36 weeks and birth weight ranged between 610 and 3240 g. A single operator did all the measurements on the second metacarpus by the DBM Sonic BP (IGEA). Ultrasound parameters were bone transmission time (BTT, micros) and speed of sound (SOS, m/s). RESULTS: BTT positively increased with birth gestational age (r=0.72, P<0.001, F-Ratio=62.4428), birth weight (r=0.7827, P<0.001, F-Ratio=91.7274) and birth length (r=0.7729, P<0.001, F-Ratio=86.0748). SOS was also related with gestational age (r=0.2937, P<0.023, F-Ratio=5.4768), birth weight (r=0.2634, P<0.042, F-Ratio=4.3250) and birth length (r=0.3252, P<0.011, F-Ratio=6.8596). Small infants for gestational age showed BTT values lower then infants with appropriate size for gestational age (P<0.03). There was no difference between male and female infants. CONCLUSION: Quantitative ultrasound is a non-invasive method, which is easy to perform in a Neonatal Intensive Unit, safe, harmless and gentle. This method detects subtle differences in bone mineral status, according to gestational age, weight and length. Quantitative ultrasound is a useful screening tool for early detection of bone status in newborns and a valid method for the longitudinal assessment of bone in growing children.

[Survival rates in a single neonatal intensive care unit (period 2002-2007). Neuro-developmental outcome and survival for infants born at 23-25 weeks of gestation]. / Sopravvivenza in una unità di terapia intensiva neonatale (periodo 2002-2007). Outcome neurologico e sopravvivenza dei nati di età gestazionale 23-25 settimane.

AIM: The aim of this study was to evaluate survival rates in a single Neonatal Intensive Care Unit (NICU) (period 2002-2007), with a special focus on the survival data and outcome at one-year of corrected age for infants born at 23-25 weeks of gestation. METHODS: All infants who had evidence of heart activity at birth were actively resuscitated, regardless of birth weight or gestational age. Survival rate was calculated as a function of the following variables: birth weight and gestational category; gender in infants of birth weight < or = 1000 g ; appropriate (AGA) or small (SGA) weight for gestational age; inborn or outborn. Twenty-eight newborns (23-25 weeks of gestation) completed follow-up at one-year of corrected age. RESULTS: During the examined period, no infants died in the delivery room; 833 newborns were admitted to the NICU. Overall survival rates were as following: <500 g (37%), 501-750 g (59%), 751-1,000 g (82%), 1,001-1,250 g (96%), 1251-1,500 g (97%), 1,501-2,000 g (100%), 2,001-2,500 g (98%), >2,500 g (99%); 23-25 weeks of gestation (50%); 26-27 weeks (77%), 28-32 weeks (90%); males < or = 1,000 g (68%), females < or = 1,000 g (68%); AGA < or = 1,000 g (63%), SGA < or = 1,000 g (79%), AGA < or =28 weeks (63%), SGA < or = 28 weeks (67%); inborn (54%), outborn (25%). A fraction of 64% (infants of 23-25 weeks of gestation) did not show handicap at one-year of corrected age, while 25% presented severe, 7% moderate, and 4% mild handicaps. CONCLUSION: High rate of survival without handicap at one-year of corrected age at extremely low gestational age and the chance of improvements in neonatal care for newborn < or = 24 weeks, indicate the appropriateness for our strategy of resuscitating all newborns with evidence of heart activity in the delivery room.

[Insulin and glucagon plasma levels in very low birth weight preterm infants of appropriate weight for gestational age]. / Livelli plasmatici di insulina e glucagone in neonati pretermine di peso molto basso appropriato per l'eta gestazionale.

OBJECTIVES: Prematurity is a known risk factor for hypoglycaemia, hyperglycemia, neonatal sepsis and other common neonatal complications, possibly associated with glucoregolatory hormone (insulin and glucagon) alterations. Insulin and glucagon levels change also in relation to gender, mode of delivery and postnatal clinical severity. Because of the lack of reference range in literature, the aim of this study is to assess plasma insulin and glucagon levels in preterm appropriate for gestational age (AGA) infants of birth weight <1500 g (very low birth weight, VLBW) as a function of gestation, birth weight, gender and mode delivery. METHODS: The authors examined 48 preterm AGA infants (mean birth weight 1 163+/-286 g, mean gestational age 28.2+/-2.4 weeks). The infant population was subdivided in relation to gestational age, weight, gender, mode of delivery and assisted ventilation at 5-7(th) days. Plasma glucose, insulin and glucagon levels were assessed in all newborns at birth and at 5-7(th) days of life. Data were analyzed using t-test. RESULTS: A negative correlation between insulin and gestational age was observed (P<0.05). At birth, no significant differences regarding plasma glucose, insulin and glucagon levels were observed as a function of the examined category variables. At the 5-7(th) days of life, insulin levels were significantly higher in newborns with gestational age =or<27 weeks (P<0.02), in the female gender (P<0.02) and in the infants born to emergency Cesarean delivery (P<0.05). CONCLUSIONS: These findings indicate potentially useful reference range values for plasma insulin and glucagon in the VLBW population.

Is Cupressus sempervirens native in Italy? An answer from genetic and palaeobotanical data.

This study represents the first large-scale analysis using nuclear molecular markers to assess genetic diversity and structure of Cupressus sempervirens L.. Genetic and fossil data were combined to infer the possible role of human activity and evolutionary history in shaping the diversity of cypress populations. We analysed 30 populations with six polymorphic nuclear microsatellite markers. Dramatic reductions in heterozygosity and allelic richness were observed from east to west across the species range. Structure analysis assigned individuals to two main groups separating central Mediterranean and eastern populations. The two main groups could be further divided into five subgroups which showed the following geographical distributions: Turkey with the Greek islands Rhodes and Samos, Greece (Crete), Southern Italy, Northern Italy, Tunisia with Central Italy. This pattern of genetic structure is also supported by SAMOVA and Barrier analyses. Palaeobotanical data indicated that Cupressus was present in Italy in the Pliocene, Pleistocene and Holocene. Furthermore, our molecular survey showed that Italian cypress populations experienced bottlenecks that resulted in reduced genetic diversity and allelic richness and greater genetic differentiation. Recent colonization or introduction may also have influenced levels of diversity detected in the Italian populations, as most individuals found in this range today have multilocus genotypes that are also present in the eastern range of the species. The data reveal a new interpretation of the history of cypress distribution characterized by ancient eastern populations (Turkey and Greek islands) and a mosaic of recently introduced trees and remnants of ancient, depauperate populations in the central Mediterranean range.

Molecular and cellular signatures of human vaccine adjuvants.

Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.

Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth-weight infants with small thymus at birth.

BACKGROUND: An acute thymic involution in human fetuses and newborns has been described in very-low-birth-weight (VLBW) infants with histological chorioamnionitis. However, the mechanisms of thymic involution remain to be clarified. Here, we tested the hypothesis that an activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution at birth. METHODS: A total of 180 randomly selected VLBW newborns (28.8 +/- 3.15 wk gestation; 1093 +/- 305 g) entered the study. Thymic size was measured on standard chest radiographs at birth, and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina (CT) and that of the thorax (T). CT/T < 0.28 was considered to indicate a small thymic size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total of 66 (36.7%) newborns had CT/T < 0.28. Infants with small thymus had significantly increased cortisol on d-1 ( approximately 5.2-folds) [median: 18.95 (95% CI: 11.20-39.4) microg/dl vs. 3.66 (1.94-6.82) microg/dl, p < 0.0001)] and d-7( approximately 1.7-folds) [12.0 (4.39-22.97) microg/dl vs. 7.8 (3.63-12.8) microg/dl, p = 0.0384)], as compared with those with normal thymic size, together with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 ( approximately 1.9-folds) [28 (15.6-61.07) pg/ml vs. 14.9 (9.0-23.42) pg/ml, p = 0.0005)], while no significant differences for cortisol at mo-1 or ACTH concentrations on d-7 and mo-1 were evidenced (p > 0.50). From a multivariate logistic regression analysis, a small thymus at birth was a significant independent predictor of plasma cortisol concentrations in the top-quartile (OR = 14.4; 95% CI: 6.079-34.11), and plasma ACTH concentrations in the top-quartile (OR = 4.40 (95% CI: 1.99-9.74) on d-1 (results adjusted for variables significant at univariate analysis). CONCLUSIONS: Our data indicated the presence of a previously unrecognized, early activation of the HPA axis in VLBW newborns with a small thymus at birth.

RrgA is a pilus-associated adhesin in Streptococcus pneumoniae.

Adherence to host cells is important in microbial colonization of a mucosal surface, and Streptococcus pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits, RrgA, RrgB and RrgC. We sought to determine which subunit(s) confers adherence. Bacteria deficient in RrgA are significantly less adherent than wild-type organisms, while overexpression of RrgA enhances adherence. Recombinant monomeric RrgA binds to respiratory cells, as does RrgC with less affinity, and pre-incubation of epithelial cells with RrgA reduces adherence of wild-type piliated pneumococci. Non-adherent RrgA-negative, RrgB- and RrgC-positive organisms produce pili, suggesting that pilus-mediated adherence is due to expression of RrgA, rather than the pilus backbone itself. In contrast, RrgA-positive strains with disrupted rrgB and rrgC genes exhibit wild-type adherence despite failure to produce pili by Western blot or immunoelectron microscopy. The density of bacteria colonizing the upper respiratory tract of mice inoculated with piliated RrgA-negative pneumococci was significantly less compared with wild-type; in contrast, non-piliated pneumococci expressing non-polymeric RrgA had similar numbers of bacteria in the nasopharynx as piliated wild-type bacteria. These data suggest that RrgA is central in pilus-mediated adherence and disease, even in the absence of polymeric pilus production.

Umbilical cord serum activin A levels are increased in pre-eclampsia with impaired blood flow in the uteroplacental and fetal circulation.

The aims of the present study were to evaluate the umbilical cord serum activin A concentrations in complicated pregnancies and also to explore the relationship between activin A levels and blood flow velocity in fetal arteries. Umbilical cord blood samples were obtained postpartum after a full term uneventful gestation (control group, n=40), and from pregnancies complicated by gestational diabetes (n=13), preterm labour (n=18), or pre-eclampsia (n=19). Cord serum activin A levels were three-fold higher in pregnancies complicated by pre-eclampsia (1.17+/-0.14 ng/ml, p<0.01) than in the control group (0.43+/-0.03 ng/ml), but were unaltered in the diabetes and preterm labour groups. The pre-eclampsia group had a marked increase of umbilical artery pulsatility index (PI) and also a decrease of middle cerebral artery PI (p<0.01). Furthermore, activin A concentration correlated directly with the umbilical artery PI (r=0.540, p=0.021), with the length of stay in the Neonatal Intensive Care Unit (r=0.857, p<0.001) and also with cord blood pH (r=-0.886, p<0.001). In conclusion, umbilical cord serum activin A levels are increased in the presence of pre-eclampsia and provide an indirect marker of impaired blood flow in the uteroplacental and fetal circulation.