Risk of congenital anomalies in relation to the uptake of trihalomethane from drinking water during pregnancy.

OBJECTIVES: Congenital anomalies have been inconsistently associated with maternal crude estimated exposure to drinking water trihalomethane (THM). We investigated the relationship between individual THM uptake during the first trimester of pregnancy and congenital anomalies. METHODS: We estimated maternal THM uptake for 3074 live births using residential tap water concentrations, drinking water ingestion, showering and bathing, and uptake factors of THM in the blood. Multiple logistic regression was used to investigate the association of THM exposure with congenital anomalies. RESULTS: We observed no statistically significant relationships between congenital anomalies and the total THM internal dose. We found little indication of a dose-response relationship for brominated THM and congenital heart anomalies. The relationship was statistically significant for bromodichloromethane (BDCM) (OR=2.16, 95% CI 1.05 to 4.46, highest vs lowest tertile) during the first month of pregnancy. During the first trimester of pregnancy, the probability of developing heart anomalies increased for every 0.1 µg/d increase in the BDCM and for every 0.01 µg/d increase in the internal dibromochloromethane (DBCM) dose (OR 1.70, 95% CI 1.09 to 2.66, and OR 1.25, 95% CI 1.01 to 1.54, respectively). A dose-response relationship was evident for musculoskeletal anomalies and DBCM exposure during the first and second months of pregnancy, while BDCM exposure tended to increase the risk of urogenital anomalies. CONCLUSIONS: This study shows some evidence for an association between the internal dose of THM and the risk of congenital anomalies. In particular, increased prenatal exposure to brominated THM might increase the risk of congenital heart and musculoskeletal anomalies.

Changing composition of renal calculi in patients with musculoskeletal anomalies.

BACKGROUND AND PURPOSE: Calculi from patients with musculoskeletal (MS) anomalies who are largely immobile and prone to urinary infections have been traditionally composed primarily of struvite and carbonate apatite. Because of substantial improvements in the care of these patients in recent decades, stone etiology may have shifted from infectious to metabolic. We assessed the composition of renal calculi and metabolic characteristics in a contemporary cohort of patients with MS anomalies who underwent percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Retrospective analysis of patients who underwent PCNL between April 1999 and June 2009 and had follow-up 24-hour urine studies was performed. Patients with MS anomalies included spinal cord injury, myelomeningocele, muscular dystrophy, multiple sclerosis, cerebral palsy, or other clinical syndromes causing kyphoscoliosis and contractures. RESULTS: Our cohort included 33 patients with MS anomalies and 334 consecutive patients as a control group who underwent PCNL and had metabolic workup. Stones were infectious in etiology in 18.4% and 6.2% in MS and control groups, respectively. Thus, most patients harbored stones of metabolic origin. Metabolic stones in the MS group were composed of 52.7% hydroxyapatite, 10.5% calcium oxalate, 7.9% brushite, 2.6% uric acid, 0% cystine, and 7.9% other. Metabolic stones in the control group were 50.5% calcium oxalate, 16.4% hydroxyapatite, 11.5% brushite, 10.8% uric acid, 4.3% cystine, and 0.3% other. Mean 24-hour urine values for patients with metabolic stones in MS/control groups were volume 2.18/1.87 L/d, pH 6.78/6.05, calcium to creatinine ratio 220/151 mg/g, and oxalate 44.8/39.5 mg/d. CONCLUSIONS: Although patients with MS anomalies are traditionally thought to harbor infection-related calculi, most will be found to have calculi of metabolic etiology. The incidence of calcium phosphate stones is high in this group of patients, perhaps reflecting their high urinary pH.

Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome).

A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.