Increased calcium supplementation is associated with morbidity and mortality in the infant postoperative cardiac patient.

OBJECTIVE: The purpose of this study was to assess the association of calcium replacement therapy with morbidity and mortality in infants after cardiac surgery involving cardiopulmonary bypass. DESIGN: Retrospective chart review. SETTING: The cardiac intensive care unit at a tertiary care children's hospital. PATIENTS: Infants undergoing cardiac surgery involving cardiopulmonary bypass between October 2002 and August 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total calcium replacement (mg/kg calcium chloride given) for the first 72 postoperative hours was measured. Morbidity and mortality data were collected. The total volume of blood products given during the first 72 hrs was recorded. Infants with confirmed chromosomal deletions at the 22q11 locus were noted. Correlation and logistic regression analyses were used to generate odds ratios and 95% confidence intervals, with p < .05 being significant. One hundred seventy-one infants met inclusion criteria. Age was 4 +/- 3 months and weight was 4.9 +/- 1.7 kg at surgery. Six infants had deletions of chromosome 22q11. Infants who weighed less required more calcium replacement (r = -.28, p < .001). Greater calcium replacement correlated with a longer intensive care unit length of stay (r = .27, p < .001) and a longer total hospital length of stay (r = .23, p = .002). Greater calcium replacement was significantly associated with morbidity (liver dysfunction [odds ratio, 3.9; confidence interval, 2.1-7.3; p < .001], central nervous system complication [odds ratio, 1.8; confidence interval, 1.1-3.0; p = .02], infection [odds ratio, 1.5; confidence interval, 1.0-2.2; p < .04], extracorporeal membrane oxygenation [odds ratio, 5.0; confidence interval, 2.3-10.6; p < .001]) and mortality (odds ratio, 5.8; confidence interval, 5.8-5.9; p < .001). Greater calcium replacement was not associated with renal insufficiency (odds ratio, 1.5; confidence interval, 0.9-2.3; p = .07). Infants with >1 sd above the mean of total calcium replacement received on average fewer blood products than the total study population. CONCLUSIONS: Greater calcium replacement is associated with increasing morbidity and mortality. Further investigation of the etiology and therapy of hypocalcemia in this population is warranted.

A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort.

PURPOSE: The aim of the study was to determine the actual GJB2 and GJB6 mutation frequencies in North America after several years of generalized testing for autosomal recessive nonsyndromic sensorineural hearing loss to help guide diagnostic testing algorithms, especially in light of molecular diagnostic follow-up to universal newborn hearing screening. METHODS: Mutation types, frequencies, ethnic distributions, and genotype-phenotype correlations for GJB2 and GJB6 were assessed in a very large North American cohort. RESULTS: GJB2 variants were identified in 1796 (24.3%) of the 7401 individuals examined, with 399 (5.4%) homozygous and 429 (5.8%) compound heterozygous. GJB6 deletion testing was performed in 12.0% (888/7401) of all cases. The >300-kb deletion was identified in only nine individuals (1.0%), all of whom were compound heterozygous for mutations in GJB2 and GJB6. Among a total of 139 GJB2 variants identified, 53 (38.1%) were previously unreported, presumably representing novel pathogenic or benign variants. CONCLUSIONS: The frequency and distribution of sequence changes in GJB2 and GJB6 in North America differ from those previously reported, suggesting a considerable role for loci other than GJB2 and GJB6 in the etiology of autosomal recessive nonsyndromic sensorineural hearing loss, with minimal prevalence of the GJB6 deletion.