Umbilical cord characteristics and their association with adverse pregnancy outcomes: A systematic review and meta-analysis.

OBJECTIVE: Current data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes. METHODS: MEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA. RESULTS: This review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37). CONCLUSIONS: True umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.

Age dependence of in vitro survival of meningococci in whole blood during childhood.

OBJECTIVES: To determine the association between the ability of a different strains of meningococci to survive in whole blood and the age of the donor. METHODS: A panel of serogroup B and a serogroup C strain of Neisseria meningitidis was tested in an ex vivo whole blood model. Blood from 81 healthy children and 20 adults and from children during convalescence from serogroup B (55 patients) or serogroup C (43 patients) meningococcal infection was assessed. RESULTS: Age-dependent acquisition of whole blood killing of serogroup B and C bacterial isolates was demonstrated in healthy children with an inverse relationship to the reported incidence of disease. After infection with serogroup B or C meningococci, evidence of whole blood killing of the bacteria was found even in blood from children <2 years of age, the survival of a serogroup B strain, MC58, being reduced compared with that in healthy children (median, 64% compared with 194.5% survival at 90 min). In both affected children and controls, there was a significant correlation between whole blood killing of strain MC58 and of other serogroup B and C meningococci. CONCLUSIONS: The whole blood model measures both humoral and cellular mechanisms responsible for the bactericidal activity of blood. The model was first described 80 years ago, but this is the first description of its age dependency. Acquisition of bactericidal activity was more rapid in children infected and is directed at various strains of meningococci, indicating the presence of a cross-reactive antigen(s).

Streptococcus sanguis secretes CD14-binding proteins that stimulate cytokine synthesis: a clue to the pathogenesis of infective (bacterial) endocarditis?

Streptococcus sanguis is the major causative organism of infective (bacterial) endocarditis but, surprisingly, almost nothing is known about how it induces endocardial inflammation. In earlier studies we have shown that many bacteria secrete potent cytokine-inducing or -inhibiting proteins. We have therefore isolated the material secreted by S. sanguis grown on blood agar or in broth culture and have tested its ability to induce human peripheral blood monocytes to synthesize pro-inflammatory cytokines. The activation of monocytes by the secreted components of S. sanguis was almost totally blocked by heat and trypsin treatment but not by the lipopolysaccharide-inactivating antibiotic, polymyxin B, suggesting that activity is due to secreted proteins. The activity of the secreted material was significantly reduced by anti-CD14 monoclonal antibodies suggesting that the active protein (or proteins) was binding to the CD14/Toll-like receptor (TLR)4 complex. Fractionation of the secreted proteins by high performance liquid chromatography (HPLC) identified two proteins as being responsible for the majority of the cytokine induction: a manganese-dependent superoxide dismutase and a 190 kDa protein, which could not be sequenced, but which was neither CshA nor the PI/II proteins. These proteins, or the receptors to which they bind, may be therapeutic targets and may allow the development of adjunctive therapies to prevent endocardial damage during the often prolonged treatment of infective endocarditis with antibiotics. In addition, blocking of CD14 may have some therapeutic benefit.