Dietary determinants of aflatoxin B1-lysine adduct among infants in Nepal.

BACKGROUND: Aflatoxins are mycotoxins produced by naturally occurring fungi on food, and aflatoxin B1 (AFB1) is carcinogenic, immunotoxic and hepatotoxic. This study assesses the relationship between AFB1 in Nepali infants at 12 months of age and their diet at 9 and 12 months of age. METHODS: The study used data collected from 1329 infants enrolled in the AflaCohort Study. Aflatoxin exposure was assessed at 12 months using serum AFB1-lysine pg/mg albumin biomarker measured using high performance liquid chromatography-fluorescent detection. Dietary data were collected using food frequency questionnaire. We conducted ordinary least squares and quantile regression analyses with backward elimination to assess lagged (9-month diet and 12-month AFB1) and contemporaneous (12-month diet and 12-month AFB1) associations. RESULTS: Eighty-one percent of children at 12 months had detectable levels of serum AFB1-lysine (geometric mean: 0.79 pg/mg albumin, 95% CI: 0.74-0.83). The levels ranged from 0.4 to 85 pg/mg albumin. Dietary diversity at 9 and 12 months were not associated with serum AFB1-lysine levels. Consumption of fish and groundnuts at both 9 and 12 months and infant formula and cauliflower at 9 months were associated with higher serum AFB1-lysine while consumption of bananas and mangoes at 12 months were negatively associated with serum AFB1-lysine (p < 0.05). CONCLUSIONS: High prevalence of detectable AFB1-lysine among infants, and possible links to their dietary patterns argues for more urgent research into which foods in children's diets are most contaminated, and into optimal entry points in the food chain that would allow for effective actions to minimize exposure.

Exposure to multiple mycotoxins, environmental enteric dysfunction and child growth: Results from the AflaCohort Study in Banke, Nepal.

Evidence of the impact of exposure to multiple mycotoxins and environment enteric dysfunction (EED) on child growth is limited. Using data from a birth cohort study, the objectives of this study were to (a) quantify exposure to multiple mycotoxins (serum aflatoxin [AFB1 ] and ochratoxin A [OTA], urinary fumonisin [UFB1 ] and deoxynivalenol [DON]), as well EED (lactulose:mannitol [L:M] ratio); (b) examine the potential combined effects of multiple mycotoxin exposure and EED on growth. Multivariate regressions were used to identify associations between growth measurements (length, weight, anthropometric z-scores, stunting and underweight) at 24-26 months of age and exposure to mycotoxins and EED at 18-22 months (n = 699). Prevalence of AFB1 , DON, OTA and UFB1 exposure ranged from 85% to 100%; average L:M ratio was 0.29 ± 0.53. In individual mycotoxin models, AFB1 exposure was negatively associated with weight, WAZ, increased odds of stunting (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.08, 1.52; p = 0.004) and underweight (OR: 1.18, 95% CI: 1.00, 1.38; p = 0.046). Irrespective of other mycotoxin exposure and presence of EED, AFB1 was negatively associated with length, weight, head circumference, LAZ and WAZ, and with increased odds of stunting and underweight, UFB1 was associated with increased odds of underweight, and DON was negatively associated with head circumference. EED was associated with the impaired length and weight. These findings suggest that certain mycotoxins and EED may have independent impacts on different facets of growth and that aflatoxin dominates such impacts. Thus, programs reducing exposure to mycotoxin and EED through multi-sectoral nutrition-sensitive interventions have the potential to improve child growth.

Aflatoxin exposure and child nutrition: measuring anthropometric and long-bone growth over time in Nepal.

BACKGROUND: Naturally occurring aflatoxins may contribute to poor growth and nutritional statuses in children. OBJECTIVES: We analyzed the relationship between contemporary and lagged aflatoxin exposure and 1) length-for-age z-score (LAZ); and 2) length, knee-heel length, stunting, weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ). METHODS: We conducted a longitudinal birth cohort study involving 1675 mother-infant dyads in rural Nepal. Participants were repeatedly visited from pregnancy to 2 years of age (2015-2019). One blood sample was collected during pregnancy and 4 samples were collected from the children at 3, 6, 12, and 18-22 months of age to measure concentrations of aflatoxin B1 (AFB1)-lysine adduct. Multivariate linear fixed-effects and logistic models with generalized estimating equations were used to identify associations between child growth and aflatoxin exposure. RESULTS: AFB1-lysine adducts were detected in the majority of children (at 3 months, 80.5%; at 6 months, 75.3%; at 12 months, 81.1%; and at 18-22 months, 85.1%) and in 94.3% of pregnant women. Changes in contemporary ln child AFB1-lysine adduct concentrations were significantly associated with changes in LAZ (ß, -0.05; 95% CI, -0.09 to -0.02; P = 0.003), length (ß, -0.19; 95% CI, -0.29 to -0.10; P < 0.001), knee-heel length (ß, -0.09; 95% CI, -0.13 to -0.05; P < 0.001), and WAZ (ß, -0.04; 95% CI, -0.07 to -0.005; P = 0.022). Serum aflatoxin concentrations were associated with stunting (OR, 1.18; 95% CI, 1.05-1.32; P = 0.005). Similar results were found in the models using changes in contemporary ln AFB1 adjusted for changes in child weight, with significant associations with changes in WLZ (ß, -0.07; 95% CI, -0.10 to -0.03; P < 0.001). Changes in time-lagged ln AFB1 (unadjusted and adjusted for changes in child weight) were associated with changes in length and knee-heel length. CONCLUSIONS: Our results add to the growing body of evidence confirming chronic aflatoxin exposure and suggest that exposure is significantly correlated with various negative growth outcomes, which may vary by child weight status. This trial was registered at clinicaltrials.gov as NCT03312049.

Prophylactic warfarin therapy after primary percutaneous coronary intervention for anterior ST-segment elevation myocardial infarction.

OBJECTIVES: This study sought to determine the benefits of adding oral anticoagulation therapy in patients with anterior wall ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PCI). BACKGROUND: Guidelines suggest adding oral anticoagulation to dual-antiplatelet therapy in patients with STEMI when left ventricular apical akinesis or dyskinesis is present to prevent thromboembolic complications. The benefits of this triple therapy remain unknown. METHODS: We identified patients with anterior STEMI referred (PCI) between July 2004 and June 2010 with apical akinesis or dyskinesis on transthoracic echocardiography. We compared patients who were prescribed warfarin to patients who were not. We excluded patients with left ventricular thrombus, a separate need for oral anticoagulation, and previous intracranial bleeding. The primary outcome was a composite of net adverse clinical events (NACE) consisting of all-cause mortality, stroke, reinfarction, and major bleeding at 180 days. RESULTS: Among 460 patients who qualified, 131 were discharged on warfarin therapy and 329 without warfarin therapy. Dual-antiplatelet therapy was prescribed for 99.2% of the patients in the warfarin group and for 97.6% of the patients in the no warfarin group (p = 0.46). Compared with patients in the no warfarin group, patients in the warfarin group had higher rates of NACE (14.7% vs. 4.6%, p = 0.001), death (5.4% vs. 1.5%, p = 0.04), stroke (3.1% vs. 0.3%, p = 0.02), and major bleeding (8.5% vs. 1.8%, p < 0.0001). By propensity score analysis, allocation to warfarin therapy was an independent predictor of NACE (odds ratio [OR]: 4.01, 95% confidence interval: 2.15 to 7.50, p < 0.0001). In a separate multivariable analysis, the OR of NACE remained significantly higher compared with patients who were not prescribed warfarin (OR: 3.13, 95% confidence interval: 1.34 to 7.22, p = 0.007). CONCLUSIONS: Our results do not support the addition of warfarin therapy after primary PCI in patients with apical akinesis or dyskinesis.