Maternal Vitamin D Status Linked to Fetal Outcomes

Maternal vitamin D status is independently associated with markers of physiological and pathological growth in term infants, including birth weight, placental-to-fetal weight ratio, and size for gestational age (J Clin Endocrinol Metabl 2013;98:398–404). According to the authors, the findings warrant adequately powered randomized controlled trials to evaluate whether maternal vitamin D supplementation might improve fetal growth.

The study involved 2,146 blood samples of women carrying only one fetus who did not have preexisting diabetes or hypertension and who entered prenatal care prior to week 26 of gestation. The investigators measured total serum 25(OH)D using liquid chromatography-tandem mass spectrometry. Mean 25(OH)D level was 51.3 nmol/L.

After confounder adjustment, the researchers found that women with 25(OH)D levels ≥37.5 nmol/L delivered babies with higher birth weight and larger head circumference than those with concentrations <37.5 nmol/L. Birth weight and head circumference rose with increasing maternal 25(OH)D levels up to 37.5 nmol/L, then leveled off. Maternal 25(OH)D levels ≥37.5 nmol/L in the first trimester were associated with half the risk of their babies being small for gestational age, in comparison to mothers with levels <37.5 nmol/L. However, this association did not hold during the second trimester.

Plasma Lactate an Independent Risk Factor for Death, Adverse Outcomes in Pulmonary Embolism

Italian researchers reported that patients with pulmonary embolism (PE) who also have elevated plasma lactate concentrations are at high risk of death and adverse outcome, independent of shock, hypotension, right-sided ventricular dysfunction, or injury markers (Ann Emerg Med 2012; The findings suggest that patients with characteristics similar to those in this study should be monitored closely.

The authors investigated the role of plasma lactate in PE because it is known to be a marker of the severity of tissue oxygen supply-to-demand imbalance, can be easily and rapidly assayed, and in at least one retrospective analysis was associated with high mortality in acute PE.

This observational study involved 270 consecutive adult patients who presented to the emergency department with suspected PE. PE was confirmed by either CT or lung scan. Plasma lactate and troponin I levels were assessed at baseline. The subjects' mean age was 73 years, and 56% were women.

The primary endpoint was all-cause mortality at any point within 30 days of presentation. Secondary endpoints included a composite of all-cause mortality, PE-related death, and clinical deterioration because of PE. The researchers defined high plasma lactate level as ≥2 mmol/L.

Overall, patients who died had significantly higher mean plasma lactate levels compared to survivors, 4.7 mmol/L versus 1.6 mmol/L. Mortality progressively increased with higher plasma lactate levels, so that the predefined cutoff value of 2 mmol/L showed a sensitivity of 82.4%, specificity of 73.5%, and derived positive-predictive and negative-predictive values of 17.3% and 98.4%, respectively.

The researchers suggested that the findings warrant a multicenter prospective study to confirm and extend knowledge about the prognostic value of plasma lactate level in PE.

Solid-Phase Assays Best for Identifying Donor-Specific Antibodies

A meta-analysis of studies examining rejection rates and graft outcomes in renal transplant recipients found a significantly elevated risk for early, acute antibody-mediated rejection and poor graft outcomes when patients had donor-specific antibodies detected by solid-phase assays (J Am Soc Nephrol 23:2061–71). The findings held even when flow cytometry crossmatch results were negative.

The authors conducted this study to further understand the relationship between donor-specific antibodies detected by different methods with overall graft outcomes. Complement-dependent cytotoxicity crossmatch by flow cytometry has been shown to be specific for detecting donor-specific antibodies and to be associated with poor short-term graft outcomes. However, the clinical significance of donor-specific antibodies detected by solid-phase assays is unclear.

The investigators pooled data from seven retrospective cohort studies involving 1,119 transplant recipients, of whom 145 had donor-specific antibodies detected by solid-phase assay. They risk-stratified the patients by reported flow cytometry crossmatch results to pool patients into groups based on similar immunologic risks.

The authors found that donor-specific antibodies detected by solid-phase assay, even when flow cytometry crossmatch results are negative, signal nearly double the risk for antibody-mediated rejection, with a 1.98 relative risk. In these same patients who had positive solid-phase assay results but negative flow cytometry crossmatch results, the authors found a 76% increased risk of graft failure.

The findings suggest the need for increased vigilance and enhanced immunosuppression regimens in patients with donor-specific antibodies detected by solid-phase assay, even if results from crossmatch testing are negative.

Filamin C, Meprin A Validated as Early Markers of Kawasaki Disease

A urine proteomic analysis of children with Kawasaki disease identified more than 190 candidate markers unique to this patient population (EMBO Mol Med 2012;4:1–11). The investigators went on to validate two of the markers, filamin C and meprin A, and found these proteins had receiver operating characteristic areas under the curve of 0.98. The findings suggest that these biomarkers may improve the diagnostic accuracy of clinical evaluations of children with suspected Kawasaki disease, lead to development of novel therapeutic targets, and enable improved biological classification of the disease.

Researchers at Boston Children's Hospital conducted the analysis because existing markers for Kawasaki disease, including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, have inadequate specificity and sensitivity for detecting the condition. In addition, algorithms to improve diagnosis have been proposed but their accuracy remains limited. Yet early diagnostics are needed to enable interventions that might forestall complications of Kawasaki disease.

The proteomics analysis involved 107 subjects with possible Kawasaki disease, of which 53 were ultimately diagnosed with the disease. The researchers used mass spectrometry to identify at least 190 proteins found exclusively in patients with Kawasaki disease. Of these, the researchers chose to validate filamin C, which is associated with endothelial and myocardial cell injury, and meprin A, which has immune-mediating properties, because of their biological functions thought to have relevancy in Kawasaki disease and because of the availability of commercial enzyme-linked immunosorbent assays (ELISA) to measure them. The researchers validated both filamin C and meprin A via ELISA using serum samples from separate cohorts of patients with confirmed Kawasaki disease and those without the condition. Both markers were significantly elevated in Kawasaki disease patients versus controls.