Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. Objectives We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. Methods A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p\0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not. Conclusion High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation

Metal-on-Metal Hip Prostheses and Systemic Health: A Cross-Sectional Association Study 8 Years after Implantation

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8 years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR) versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total body bone mineral density was 5% higher (mean difference 0.05 g/cm2 , P = 0.02) and bone turnover was 14% lower (TRAP 5b, mean difference 20.56IU/L, P = 0.006; osteocalcin, mean difference 23.08 ng/mL, P = 0.03) in the hip resurfacing versus conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference 25%, P = 0.04) and left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%, chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference in neuropsychological, renal tubular, hepatic or endocrine function between groups (P.0.05). Our findings of differences in bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate the risk of clinical disease

Recruitment flow chart.

<p>MoMHR  =  metal-on-metal hip resurfacing, THA  =  conventional hip replacement using a non-metal-on-metal bearing.</p

Serum markers of renal, hepatic, and endocrine function and injury.

<p>Values are mean ± standard deviation or median (interquartile range). Analysis is MoMHR versus THA by paired-t test or Wilcoxon test. P>0.05 all comparisons. ^‡Marker assayed in men only (n = 31 per group).</p

Neuropsychological and psychological endpoints.

<p>All test results were adjusted for by pre-morbid Intelligence Quotient using the Wechsler test for adult reading (WTAR). Values are mean±standard deviation or median (interquartile range). Analysis is MoMHR versus THA by paired t-test or Wilcoxon test; P>0.05, all comparisons.</p

Cardiac endpoints.

<p>Normally distributed data are presented as mean ±SD, and non-normally distributed data as median (IQR). Analysis is MoMHR versus THA. Continuous data were analyzed by paired t-test or Wilcoxon test; categorical data were analyzed by either Chi-squared test. *P<0.05, **P<0.01, P>0.05 for all other comparisons.</p

Patient characteristics and metal levels.

<p>Normally distributed data are presented as mean ±SD, and non-normally distributed data as median (IQR). Analysis is MoMHR versus THA. Continuous data were analyzed by paired t-test or Wilcoxon test; categorical data were analyzed by either Chi-squared test. *P<0.0001, P>0.05 for all other comparisons.</p

Urinary fractional excretion of cobalt and chromium versus plasma metal level in MoMHR patients.

<p>Line represents regression slope and dotted line represents 95% confidence interval. Comparison is fractional excretion of cobalt versus fractional excretion of chromium by linear regression analysis (P<0.0001).</p