Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort.

INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. RESULTS: Eight metabolites were associated with amyloid ß and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. DISCUSSION: PFAMs have been found increased and associated with amyloid ß burden in CSF and clinical measures.

Baseline serum magnesium concentrations and neurodevelopmental outcomes of extremely low birth weight premature infants.

AIM: To test the hypothesis that, in ELBW infants who did not receive antenatal MgSO4, lower baseline serum Mg is associated with poorer neurodevelopmental outcomes (NDO). STUDY DESIGN: The study was conducted in two phases: phase 1-- retrospective, and phase 2--prospective. SUBJECTS: Extremely low birth weight infants. OUTCOME MEASURES: Mortality and adverse NDO were assessed in relation to initial serum Mg measured in the first 12 hours of age. RESULTS: We studied 156 ELBW infants. In phase 1 (n=102): initial serum Mg (median [IQ range]) was greater in the infants who died compared to those who survived (1.7 [1.5-2.2] mg/dL vs. 1.6 [1.4-1.7] mg/dL, p=0.034). In phase 2 (n=54): initial serum Mg was greater in infants who died or had adverse NDO at 9 months when compared to those who survived with better NDO (1.7 [1.55-2.1] mg/dL vs. 1.5 [1.4-1.68] mg/dL, p=0.008). Using receiver operating characteristic (ROC) curve, increased Mg concentration in the first 12 hours>1.6 mg/dL was associated with unfavorable outcomes with sensitivity of 73%, specificity of 67%, and odds ratio of 5.5 (CI=1.2-24.8, p=0.037). CONCLUSIONS: In a cohort of preterm infants without antenatal exposure to MgSO4, initial serum Mg concentrations associated positively with poor outcomes. Further studies are needed in ELBW infants with poor NDO to determine whether they have a dysfunctional transport system that prevents Mg from entering into cells, or they have an active process that excretes Mg extracellularly.

Racial disparities in maternal hemoglobin concentrations and pregnancy outcomes.

OBJECTIVE: To examine the association of maternal hemoglobin (Hb) concentrations with preterm and low birth weight (LBW) deliveries in African Americans compared to Caucasians. METHODS: We conducted a retrospective analysis of perinatal data on 17,338 African-American and Caucasian pregnant women who delivered at the George Washington University Hospital (GWUH) between January 1990 and December 2003. We used univariate and logistic regression analyses to examine for associations. RESULTS: Compared to Caucasians (n=9432), African American mothers (n=7906) had a higher incidence of anemia (26.9% vs. 7.1%, P<0.001), preterm (22.1% vs. 12.8%, P<0.001) and LBW (18.6% vs. 9.7%, P<0.001) outcomes. This association increased with decreasing Hb concentrations in each race. Risk for preterm and LBW outcomes were higher in African Americans compared to Caucasians at Hb concentration ≥12 g/dL (P<0.007); however, there were no race-specific risk at Hb concentration <11 g/dL (P>0.05). CONCLUSIONS: The association of race with preterm and LBW outcomes relates to maternal Hb. Our findings suggest: a) anemia is a strong risk factor that masks the influence of race, b) African American race could be a surrogate for other factors that contribute to adverse outcomes, and c) Caucasian race could be less adaptive to anemia.

Maternal asthma, race and low birth weight deliveries.

BACKGROUND: Asthma during pregnancy may compromise the well-being of the fetus and potentially impact an infant's birth weight via different mechanisms. AIMS: 1) To assess the influence of asthma during pregnancy on the incidence of LBW outcomes in white non-Hispanic (WNH) and black non-Hispanic (BNH) women. 2) To identify other risk factors that affect low birth weight (LBW) (birth weight<2500g) outcomes among asthmatic women. DESIGN/SUBJECTS: We conducted a retrospective analysis of compiled perinatal data on 17,073 patients including 9348 WNH and 7725 BNH women delivering at the George Washington University Hospital between 1990 and 2003. Univariate and logistic regression analyses were used to examine associations. RESULTS: A total of 423 (2.5%) women had an asthma diagnosis, with a higher incidence in BNH women when compared to WNH women (3.4% vs. 1.7%, P<0.001). In the WNH population, asthmatic women had higher incidences of gravidity, thyroid disease, and illicit drug use, whereas in the BNH population, asthmatic women had higher incidences of increased body mass index (BMI), and use of alcohol, tobacco and illicit drugs. After controlling for confounders in multiple logistic regression analyses, there was an association between asthma and LBW outcomes in BNH women (OR: 1.7, CI: 1.1-2.6, p=0.01), but not in WNH women (OR=0.99, CI=0.5-2.2, p=0.97). CONCLUSIONS: Asthma during pregnancy is a risk factor for LBW outcomes in BNH but not WNH women. The increased alcohol and illicit drug use in BNH women with asthma is an unexpected finding that deserves further study.