Prenatal metal levels and congenital anomalies of the kidney and urinary tract: The Japan Environment and Children's Study.

BACKGROUND: Prenatal exposure to metal elements has been reported as a potential risk factor for congenital malformation. However, studies on the relationship with congenital anomalies of the kidney and urinary tract (CAKUT) are very scarce. METHODS: Participants of a prospective cohort from the Japan Environment and Children's Study, conducted at 15 research centers, were recruited between January 2011 and March 2014. The exposure factors were concentrations of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn) measured from maternal whole blood in the second or third trimester. The primary outcome was CAKUT diagnosed during the first three years of life, which was classified into isolated cases and complicated cases accompanied by extrarenal congenital defects. To conduct a nested case-control design within the cohort, we selected 351 isolated cases with 1404 matched controls, and 79 complicated cases with 316 matched controls. RESULTS: A logistic regression model was used to examine the associations between individual metal concentrations and each subtype of CAKUT. A higher level of Se was associated with an increased risk of isolated CAKUT (adjusted odds ratio [95 % confidence interval]: 3.22 [1.33-7.77]). Meanwhile, higher levels of Pb and Mn were associated with a reduced risk of the complicated subtype (0.46 [0.24-0.90] and 0.33 [0.15-0.73], respectively). A Bayesian kernel machine regression model accounting for mixed effects of multiple metals further demonstrated that a higher level of Mn alone was significantly associated with a reduced occurrence of the complicated subtype. CONCLUSIONS: Using a stringent statistical approach, the present study demonstrated that a higher Mn concentration in the maternal blood was associated with a lower risk of complicated CAKUT in offspring. Further cohort and experimental studies are needed to verify the clinical impact of this finding.

Critical vitamin deficiencies in autism spectrum disorder: Reversible and irreversible outcomes.

Vitamin deficiencies are an emerging concern in the management of children with autism spectrum disorder (ASD). Particular attention is required for recognizing the variable signs caused by unbalanced food intakes. We herein report two patients with multiple vitamin deficiencies who needed critical care showing different prognoses. Patient 1 with 'Shoshin' beriberi presenting with cardiac arrest had thiamine deficiency developed severe neurological sequelae despite rapid vitamin supplementation. Patient 2, who had leg pain and a limping gait, showed a rapid recovery with intravenous infusion and tube feeding after being diagnosed with scurvy. A literature search revealed several children with ASD with critically ill thiamine deficiency, but few reports documented a life-threatening condition in the form of cardiac arrest at the onset. Considering the high observation rate of food selectivity in children with ASD, early intervention is required to prevent the exacerbation of vitamin deficiencies to severe neurological disabilities.

Vitamin A deficiency-associated corneal perforation in a boy with autism spectrum disorder: A case report and literature review.

BACKGROUND: Malnutrition and vitamin deficiency are growing concerns in the clinical management of children with autism spectrum disorder (ASD). This case report presents a boy with ASD who developed vitamin A deficiency during follow-up. CASE REPORT: A 7-y-old boy had been diagnosed with ASD and developmental delay at age 18 mo. He developed convulsions associated with hypocalcemia and vitamin D deficiency at 3 y of age. Although vitamin D supplementation was continued, he was only able to eat rice, green tea, and fried potatoes from 3 y of age to age 7 y. He had started rubbing his eyes and had refused to open his eyes 9 mo before. An ophthalmologic examination showed bilateral corneal ulcers and right corneal perforation. Vitamin A was immediately supplemented with a nasogastric tube; however, his right eye was surgically enucleated against the persistent infection. LITERATURE REVIEW: A search of the relevant literature from 1993 to 2020 identified 11 cases of patients with ASD (5-17 y of age) who developed vitamin A deficiency owing to malnutrition. Only 4 cases (36%) had a full recovery in visual acuity. CONCLUSION: Vitamin A deficiency frequently causes irreversible visual impairment in children with ASD. Vigilant monitoring of vitamin levels prevents unfavorable outcomes in children with ASD and difficulty in food intake.

Association of aortic valve calcification with carotid artery lesions and peripheral artery disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis. METHODS: In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC. RESULTS: AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43-7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10-2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02-1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72-0.95). CONCLUSIONS: AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.