BRIEF C L I N I C A L A N D LABORATORY OBSERVATIONS
Articles in this section should require less than three JOURNALpages: text, less than t,000 words; 1 or 2 illustrations and/or tables; up to 10 references.
Cord serum IgA in congenital cytomegalovirus infection Edward O. Mason, Jr., Ph.D.,* Mary Ann South, M.D., and John R. Montgomery, M.D., Houston, Texas
EVALUATION of cord serum concentrations of IgM has been reported as a useful but a nonspecific aid in the diagnosis of congenital infections caused by the TORCH agents (Toxoplasma, Rubella virus, Cytomegalovirus, Herpes virus)? Melish and Hanshaw ~reported that five of 19 (26%) infants with culture proved congenital cytomegalovirus infection had elevated cord IgM levels. It has been suggested that infants with congenital CMV infection may produce small amounts of IgA in response to antigenic stimulus by the virus2 McCracken and Shinefield a studied eight infants two to 11 days of age with clinical signs of CMV infection and found IgA present in all of the patients whereas age and weight-matched, noninfected control infants did not have detectable lgA. The concentrations of IgA and IgM in cord serum in congenitally infected and noninfected infants entered in a prospective study of congenital CMV infection are presented here.
From the Department of Pediatrics, Baytor College of Medicine and the Charles Thomas Parker Laboratory, Texas Children's Hospital. Supported by grant (A I-11111) from the National Institute of A llergy and Infectious Disease and RR00188 from the General Clinical Research Center, National Institutes of" Health. *Reprint address: Department of Pediatrics, Baylor College of Medicine, 1200 Moursund Ave., Houston, TX 77025.
Table I CMV(+)
Elevated IgM (%) IgA detected (%) Total infants
[
3 (33.3) 9 (100) 9
CMV( )
53 (12.0) 33 (7.5) 441
MATERIALS AND METHODS The study population consisted of 953 infants born to primiparous mothers over a 2 1/2-year period. All infants were screened for excretion of cytomegalovirus within 48 hours of birth using standard urine culture procedures. Blood was obtained at the time of delivery by gentle stripping of the cord after cleaning the severed end with a sterile gauze sponge. Abbreviations used Ig: immunoglobulin CMV: cytomegalovirus Four hundred and fifty cord sera were analyzed for IgM and IgA using low level radial immunodiffusion plates (Meloy Laboratories, Springfield, Va.). Cord sera with adult levels of IgA and IgM were considered to be contaminated by maternal blood and excluded from the study. A special screening IgA plate was prepared by placing extra wells in the agar of a standard low-level plate using a 14-gauge needle with the bevel removed. This allowed rapid economical screening for the presence of IgA since 80 to 100 sera could be tested on a single plate. Sera containing lgA on the screening plate were studied further using the stal~dard procedure for quantifying IgA. The minimum amount of IgA detectable with this system was 1.0 mg/dt. RESULTS None of the infected infants had overt signs of congenital CMV infection at birth. The average cord IgM level of the 441 noninfected infants was 14 mg/dl (SD = 7
The Journal of P E D I A T R t C S
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Brief cfinical and laboratory observations
mg/dl). An elevated cord IgM level was considered as the average value plus 1 SD (21 mg/dl). This value is similar to that used by other investigators.' Table I indicates that three (33.3%) of nine infants with culture proved CMV infection had elevated levels of IgM in cord serum whereas 53 (12.0%) of 441 noninfected infants had elevated levels of this globulin. IgA was present in cord serum of all nine of the CMV infected infants and in 33 (7.5%) of 441 infants without cultural evidence of CMV infection. DISCUSSION Because congenital infections may present as relatively mild and clinically inapparent disease, 4 elevated levels of IgM in cord serum are useful but nonspecific aids in screening for intrauterine infection? We found that cord serum IgA may also be of use, at least for screening for CMV infection, in that all infants in the series reported here who had this disease had IgA in the cord serum. Whereas 7.5% of non-CMV infected infants had IgA detected ha the cord serum, (we did not screen for other congenital infections), this is slightly less than the 12% of non-CMV infected infants who had elevated levels of cord IgM. Though the numbers of infants in this study are small,
Urinary cyclic AMP: High concentrations in vitamin D-deficient and -dependent rickets Oddmund Sovik, M.D.,* Lage Aksnes, Ph.D., and Jaran Apold, M.D., Bergen, Norway
TIIE ADVANCED STAGES of vitamin D-deficient rickets and vitamin D-dependent rickets are characterized by a renal tubular defect involving increased urinary loss of From the Department of Pediatrics, University of Bergen. Supported by grants'from the Norwegian Research Council for Science and the Humanities, Nordic lonsulin Fund, the Nansen foundation, and A ndssvakesakens forskningsfond. *Reprint address: Departmentof Pediatrics. Universityof Bergen, 5016 Haukeland,~ykehus, Bergen, Norway.
The Journal of Pediatrics December 1976
the correlation between the presence of IgA in cord serum and congenital CMV infection is statistically significant (p = less than 0.001). If this finding can be verified with larger numbers, demonstration of IgA in cord serum may provide a more sensitive method of rapid screening for congenital CMV infections. In addition, screening for lgA is a more convenient assay than that for IgM in that IgA was not detected in the cord serum of 92.5% of noninfected infants, making it an "all or nothing" test requiring no quantification. The modification of low-level IgA immunodiffusion plates to accommodate large numbers of specimens is also economical. REFERENCES
1. AlfordCA, Blankenship JV, Straumfjord JV and Cassaday G: The diagnostic significanceof IgM globulin elevations in newborn infants with chronic intrauterine infections, Birth Defects 4:5, 1968. 2. Melish ME, and Hanshaw JB: Congenital cytomegalovirus infection. Developmental progress of infants detected by routine screening, Am J Dis Child 126:190, 1973. 3. McCracken GH Jr, and Shinefield HR: Immunoglobulin concentrations in newborn infants with congenital cytomegalic inclusion disease, Pediatrics 36:933, 1965. 4. Hanshaw JB: Congenital cytomegalovirus infections, Birth Defects 4:39, 1968.
phosphate and amino acids. Although the pathogenesis of this tubulopathy is not yet well understood, elevated plasma levels of parathyroid hormone apparently play a major r o l e / ~ Lack of vitamin D metabolites m a y also play a role, since animal experiments have demonstrated a PTH-dependent action of 25-hydroxycholecalciferol on tubular reabsorption of phosphorus? The effect of PTH on tubular reabsorption of phosphate is probably mediated by adenosine 3',5'-monophosphate (cyclic AMP)~; we therefore investigated the urinary excretion of this nucleotide in two infants with severe rickets. Both infants showed a striking decrease of urinary cyclic AMP during treatment with vitamin D.~. Abbreviations used PTH: parathyroid hormone AMP: adenosine monophosphate CASE REPORTS Case 1. An eight-month-old boy was admitted to hospital for convulsions. Hypocalcemia (6.0 mg/dl) and radiologic signs of rickets were evident; he also had generalized hyperaminoaciduria and elevated concentration of serum alkaline phosphatase.
Articles in this section should require less than three JOURNALpages: text, less than t,000 words; 1 or 2 illustrations and/or tables; up to 10 references.
Cord serum IgA in congenital cytomegalovirus infection Edward O. Mason, Jr., Ph.D.,* Mary Ann South, M.D., and John R. Montgomery, M.D., Houston, Texas
EVALUATION of cord serum concentrations of IgM has been reported as a useful but a nonspecific aid in the diagnosis of congenital infections caused by the TORCH agents (Toxoplasma, Rubella virus, Cytomegalovirus, Herpes virus)? Melish and Hanshaw ~reported that five of 19 (26%) infants with culture proved congenital cytomegalovirus infection had elevated cord IgM levels. It has been suggested that infants with congenital CMV infection may produce small amounts of IgA in response to antigenic stimulus by the virus2 McCracken and Shinefield a studied eight infants two to 11 days of age with clinical signs of CMV infection and found IgA present in all of the patients whereas age and weight-matched, noninfected control infants did not have detectable lgA. The concentrations of IgA and IgM in cord serum in congenitally infected and noninfected infants entered in a prospective study of congenital CMV infection are presented here.
From the Department of Pediatrics, Baytor College of Medicine and the Charles Thomas Parker Laboratory, Texas Children's Hospital. Supported by grant (A I-11111) from the National Institute of A llergy and Infectious Disease and RR00188 from the General Clinical Research Center, National Institutes of" Health. *Reprint address: Department of Pediatrics, Baylor College of Medicine, 1200 Moursund Ave., Houston, TX 77025.
Table I CMV(+)
Elevated IgM (%) IgA detected (%) Total infants
[
3 (33.3) 9 (100) 9
CMV( )
53 (12.0) 33 (7.5) 441
MATERIALS AND METHODS The study population consisted of 953 infants born to primiparous mothers over a 2 1/2-year period. All infants were screened for excretion of cytomegalovirus within 48 hours of birth using standard urine culture procedures. Blood was obtained at the time of delivery by gentle stripping of the cord after cleaning the severed end with a sterile gauze sponge. Abbreviations used Ig: immunoglobulin CMV: cytomegalovirus Four hundred and fifty cord sera were analyzed for IgM and IgA using low level radial immunodiffusion plates (Meloy Laboratories, Springfield, Va.). Cord sera with adult levels of IgA and IgM were considered to be contaminated by maternal blood and excluded from the study. A special screening IgA plate was prepared by placing extra wells in the agar of a standard low-level plate using a 14-gauge needle with the bevel removed. This allowed rapid economical screening for the presence of IgA since 80 to 100 sera could be tested on a single plate. Sera containing lgA on the screening plate were studied further using the stal~dard procedure for quantifying IgA. The minimum amount of IgA detectable with this system was 1.0 mg/dt. RESULTS None of the infected infants had overt signs of congenital CMV infection at birth. The average cord IgM level of the 441 noninfected infants was 14 mg/dl (SD = 7
The Journal of P E D I A T R t C S
945
946
Brief cfinical and laboratory observations
mg/dl). An elevated cord IgM level was considered as the average value plus 1 SD (21 mg/dl). This value is similar to that used by other investigators.' Table I indicates that three (33.3%) of nine infants with culture proved CMV infection had elevated levels of IgM in cord serum whereas 53 (12.0%) of 441 noninfected infants had elevated levels of this globulin. IgA was present in cord serum of all nine of the CMV infected infants and in 33 (7.5%) of 441 infants without cultural evidence of CMV infection. DISCUSSION Because congenital infections may present as relatively mild and clinically inapparent disease, 4 elevated levels of IgM in cord serum are useful but nonspecific aids in screening for intrauterine infection? We found that cord serum IgA may also be of use, at least for screening for CMV infection, in that all infants in the series reported here who had this disease had IgA in the cord serum. Whereas 7.5% of non-CMV infected infants had IgA detected ha the cord serum, (we did not screen for other congenital infections), this is slightly less than the 12% of non-CMV infected infants who had elevated levels of cord IgM. Though the numbers of infants in this study are small,
Urinary cyclic AMP: High concentrations in vitamin D-deficient and -dependent rickets Oddmund Sovik, M.D.,* Lage Aksnes, Ph.D., and Jaran Apold, M.D., Bergen, Norway
TIIE ADVANCED STAGES of vitamin D-deficient rickets and vitamin D-dependent rickets are characterized by a renal tubular defect involving increased urinary loss of From the Department of Pediatrics, University of Bergen. Supported by grants'from the Norwegian Research Council for Science and the Humanities, Nordic lonsulin Fund, the Nansen foundation, and A ndssvakesakens forskningsfond. *Reprint address: Departmentof Pediatrics. Universityof Bergen, 5016 Haukeland,~ykehus, Bergen, Norway.
The Journal of Pediatrics December 1976
the correlation between the presence of IgA in cord serum and congenital CMV infection is statistically significant (p = less than 0.001). If this finding can be verified with larger numbers, demonstration of IgA in cord serum may provide a more sensitive method of rapid screening for congenital CMV infections. In addition, screening for lgA is a more convenient assay than that for IgM in that IgA was not detected in the cord serum of 92.5% of noninfected infants, making it an "all or nothing" test requiring no quantification. The modification of low-level IgA immunodiffusion plates to accommodate large numbers of specimens is also economical. REFERENCES
1. AlfordCA, Blankenship JV, Straumfjord JV and Cassaday G: The diagnostic significanceof IgM globulin elevations in newborn infants with chronic intrauterine infections, Birth Defects 4:5, 1968. 2. Melish ME, and Hanshaw JB: Congenital cytomegalovirus infection. Developmental progress of infants detected by routine screening, Am J Dis Child 126:190, 1973. 3. McCracken GH Jr, and Shinefield HR: Immunoglobulin concentrations in newborn infants with congenital cytomegalic inclusion disease, Pediatrics 36:933, 1965. 4. Hanshaw JB: Congenital cytomegalovirus infections, Birth Defects 4:39, 1968.
phosphate and amino acids. Although the pathogenesis of this tubulopathy is not yet well understood, elevated plasma levels of parathyroid hormone apparently play a major r o l e / ~ Lack of vitamin D metabolites m a y also play a role, since animal experiments have demonstrated a PTH-dependent action of 25-hydroxycholecalciferol on tubular reabsorption of phosphorus? The effect of PTH on tubular reabsorption of phosphate is probably mediated by adenosine 3',5'-monophosphate (cyclic AMP)~; we therefore investigated the urinary excretion of this nucleotide in two infants with severe rickets. Both infants showed a striking decrease of urinary cyclic AMP during treatment with vitamin D.~. Abbreviations used PTH: parathyroid hormone AMP: adenosine monophosphate CASE REPORTS Case 1. An eight-month-old boy was admitted to hospital for convulsions. Hypocalcemia (6.0 mg/dl) and radiologic signs of rickets were evident; he also had generalized hyperaminoaciduria and elevated concentration of serum alkaline phosphatase.
