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Inositol supplementation in premature infants with respiratory distress syndrome
The Journal of Pediatrics Volume 122, Number 3
This study provides the first evidence from a double-blind, placebo-controlled trial that methotrexate has benefit in the treatment of JRA. Similar short-term studies of hydroxychloriquine and penicillamine showed no therapeutic effect. This study did not address the issue of whether the drug can induce remission and prevent the erosion and subsequent destruction of joints, nor did it provide direct measures of functional impairment and health. The latter is important in that correlation between functional impairment and indexes of joint involvement is generally poor. The short-term nature of this study also limited its ability to assess the long-term risk/benefit ratio of therapy with methotrexate. Further studies will be needed to evaluate optimal dosing, appropriate monitoring, and the value of longer-term therapy. Patience H. White, MD Children's National Medical Center George Washington University Washington, DC 20010 9/34/44295
Predictive value of the human immunodeficiency virus I antigen test in children born to infected mothers. Andiman WA, Silva T J, Shapiro ED, O'Connor T, Olson B. Pediatr Infect Dis J 1992;11:436-40. Objective: To examine the utility of the human immunodeficieney virus type I ( H I V - I ) antigen test as an early predictor of HIV-I infection among children born to HIV-infected mothers. Design: Blind comparison of the HIVAG-1 Enzyme Immunoassay (Abbott Laboratories, Abbott Park, II1.) with HIV infection as defined by the Centers for Disease Control (Atlanta, Ga.) Setting:. Urban tertiary care hospital. Patients: Eighty-five infants enrolled in a prospective study of vertically acquired HIV infection. All were born to HIV-infected mothers and followed for the development of disease. A total of 228 serum samples were obtained at visits from birth to 50 months of age in this population. Main outcome measure: Performance of the commercial antigen test against the criterion standard of eventual clearing of antibody or development of definite HIV infection. Results: Of the 85 infants, 22 (26%) were classified as infected and 63 (74%) as having had seroreversion (by definition, these children were > 15 months of age). The sensitivity of the test (positive test results among infected children) ranged from 47% to 77% at 6 to 15 months of age, with confidence intervals of 21% to 73% by 6 months and 55%
Abstracts from the literature
495
to 92% by 15 months. The specificity (negative test results among noninfected children) ranged from 96% to 98%. In this population, with a prevalence of 26%, the positive and negative predictive values ranged from 85% to 92%. Both of the two tests showing false-positive results were the first test in young infants. Conclusions: This test, if positive, provides good evidence that infection is present; however, a negative test does not rule out disease. The test is least sensitive and specific during the first few months of life.
Comment: This study provides estimates of the characteristics of an inexpensive and widely available test for HIV infection, compared with the only available gold s t a n d a r d - eventual infection or antibody clearing in the patient. Other tests (polymerase chain reaction, viral culture) may be more accurate but are highly technical and not available to most practitioners. It should be remembered that the predictive values are dependent on the likelihood that a patient is inf e c t e d - t h e lower the prevalence of disease, the lower the positive predictive value and the higher the negative predictive value. This test is unlikely to be of any value in a general nursery population, but it may be useful in deciding on early treatment of infants of infected mothers. Virginia A. Moyer, MD, M P H University o f Texas )~ledical School at Houston Hottston, T X 77030 9/34/44294
Inositol supplementation in premature infants with respiratory distress syndrome Hallman M, Bry K, Hoppu K, Lappi M, Pohjavuori M. New Engl J Med 1992;326:1233-9. Objective: To determine whether administering inositol to premature infants in the quantities present in human milk alleviates respiratory failure and increases survival without bronchopulmonary dysplasia and without retinopathy of prematurity, and whether the serum concentration of inositol can be used to predict outcome. Design: Placebo-controlled, randomized, double-blind trial with stratification by gestational age and surfactant use. Setting: Neonatal intensive care unit in a university-based children's hospital. Patients: Infants born weighing less than 2000 gm at 24 to 31.9 weeks of gestational age, with respiratory distress evidenced by the need for at least 40% inspired oxygen and mechanical ventilation at 2 to 10 hours of age, and by the need for parenteral nutrition. Intervention: Inositol, 80 mg/kg per day, or glucose placebo was given intravenously starting at 4 to 12 hours of age and
496
Abstracts f r o m the literature
The Journal of Pediatrics March 1993
every 12 hours thereafter for 5 days. This regimen was repeated for infants who remained ventilator dependent on day 10 or 20 or both. Inositol or placebo was discontinued if oliguria or severe hyperglycemia occurred, or if enteral feeding exceeded 80 ml/kg per day. Main otttcome measures: The primary outcomes were survival at 28 days without bronchopulmonary dysplasia, and death before 28 days. Secondary outcomes were respiratory requirements during hospitalization and the presence of retinopathy of prematurity and neural development at 1 year of age. The frequencies of various complications of prematurity were also measured. Results: Both survival and survival without bronchopulmonary dysplasia were greater in the inositol group (89% vs 76%, and 71% vs 55%; p = 0.005). In addition, oxygen and mean airway pressure requirements during the first 6 days of life were lower in infants who received inositol than in those who received placebo. At 1 year of age (follow-up 99%), retinopathy of prematurity was less common (12% vs 27%) in the inositol group, and no grade IV disease occurred in the inositol group, compared with six cases (8%) in the placebo group. There were no significant differences in neural development between the groups. Conclusions: Inositol supplementation during the early neonatal period appears to increase survival and decrease bronchopulmonary dysplasia as well as retinopathy of prematurity. Comment: Inositol, a component of human milk, has received increasing attention as an essential part of the infant's diet; evidence from animal studies demonstrates abnormalities associated with deficiency. Although oral infant feedings contain inositol, intravenous preparations do not. This study provides evidence that inositol added to intravenous feedings for ill premature infants increases survival and decreases the rate of bronchopulmonary dysplasia and retinopathy of prematurity in premature infants who are ventilator dependent. All these children went on to enteral feedings of human milk. It is possible that some differences between the two groups might have been obscured by these high-inositol enteral feedings. Further studies will be needed to define the optimal intravenous dose and optimal duration of therapy. John Sparks, biD Virginia A. Moyer, MD, M i l l University o f Texas Medical School at Houston Houston, T X 77030
9/34/44293
ALSO NOTED
Renal transplantation In children: A report of the North American Pediatric Renal Transplant Cooperative Study McEnery PT, Stablein DM, Arbus G, Tejani A. New Engl J Med 1992;326:1727-32. The authors report on transplant results for 1550 children at 73 transplant centers, with data on survival, rejection, and growth.
Controlled study of linear growth In asthmatic children during treatment with inhaled corticosteroids Wolthers OD, Pedersen S. Pediatrics 1992;89:839-42. In a randomized, blinded, placebo-controlled trial, the authors show little difference in very short term growth rate between patients given placebo and those receiving up to 400/~g of inhaled budesonide per day. The study lacked power to demonstrate small to moderate differences in rate and did not address longer-term alterations in growth.
Efficacy of myringotomy with and without tympanostomy tubes for chronic otitis media with effusion Mandel EM, Rockette HE, Bluestone CD, Paradise JL, Nozza RJ. Pediatr Infect Dis J 1992;11:270-7. In a stratified, randomized trial including 111 children, tympanostomy tube placement resulted in fewer months with middle ear effusion, but even in this group, 52% met treatment failure criteria at 3 years.
Midazolam versus fentanyl as premedication for painful procedures in children with cancer Sandier ES, Weyman C, Connor K. Pediatrics 1992; 89:63 I-4. This randomized, blinded, crossover trial in 27 patients demonstrated a preference by patients for sedation with midazolam.
This study provides the first evidence from a double-blind, placebo-controlled trial that methotrexate has benefit in the treatment of JRA. Similar short-term studies of hydroxychloriquine and penicillamine showed no therapeutic effect. This study did not address the issue of whether the drug can induce remission and prevent the erosion and subsequent destruction of joints, nor did it provide direct measures of functional impairment and health. The latter is important in that correlation between functional impairment and indexes of joint involvement is generally poor. The short-term nature of this study also limited its ability to assess the long-term risk/benefit ratio of therapy with methotrexate. Further studies will be needed to evaluate optimal dosing, appropriate monitoring, and the value of longer-term therapy. Patience H. White, MD Children's National Medical Center George Washington University Washington, DC 20010 9/34/44295
Predictive value of the human immunodeficiency virus I antigen test in children born to infected mothers. Andiman WA, Silva T J, Shapiro ED, O'Connor T, Olson B. Pediatr Infect Dis J 1992;11:436-40. Objective: To examine the utility of the human immunodeficieney virus type I ( H I V - I ) antigen test as an early predictor of HIV-I infection among children born to HIV-infected mothers. Design: Blind comparison of the HIVAG-1 Enzyme Immunoassay (Abbott Laboratories, Abbott Park, II1.) with HIV infection as defined by the Centers for Disease Control (Atlanta, Ga.) Setting:. Urban tertiary care hospital. Patients: Eighty-five infants enrolled in a prospective study of vertically acquired HIV infection. All were born to HIV-infected mothers and followed for the development of disease. A total of 228 serum samples were obtained at visits from birth to 50 months of age in this population. Main outcome measure: Performance of the commercial antigen test against the criterion standard of eventual clearing of antibody or development of definite HIV infection. Results: Of the 85 infants, 22 (26%) were classified as infected and 63 (74%) as having had seroreversion (by definition, these children were > 15 months of age). The sensitivity of the test (positive test results among infected children) ranged from 47% to 77% at 6 to 15 months of age, with confidence intervals of 21% to 73% by 6 months and 55%
Abstracts from the literature
495
to 92% by 15 months. The specificity (negative test results among noninfected children) ranged from 96% to 98%. In this population, with a prevalence of 26%, the positive and negative predictive values ranged from 85% to 92%. Both of the two tests showing false-positive results were the first test in young infants. Conclusions: This test, if positive, provides good evidence that infection is present; however, a negative test does not rule out disease. The test is least sensitive and specific during the first few months of life.
Comment: This study provides estimates of the characteristics of an inexpensive and widely available test for HIV infection, compared with the only available gold s t a n d a r d - eventual infection or antibody clearing in the patient. Other tests (polymerase chain reaction, viral culture) may be more accurate but are highly technical and not available to most practitioners. It should be remembered that the predictive values are dependent on the likelihood that a patient is inf e c t e d - t h e lower the prevalence of disease, the lower the positive predictive value and the higher the negative predictive value. This test is unlikely to be of any value in a general nursery population, but it may be useful in deciding on early treatment of infants of infected mothers. Virginia A. Moyer, MD, M P H University o f Texas )~ledical School at Houston Hottston, T X 77030 9/34/44294
Inositol supplementation in premature infants with respiratory distress syndrome Hallman M, Bry K, Hoppu K, Lappi M, Pohjavuori M. New Engl J Med 1992;326:1233-9. Objective: To determine whether administering inositol to premature infants in the quantities present in human milk alleviates respiratory failure and increases survival without bronchopulmonary dysplasia and without retinopathy of prematurity, and whether the serum concentration of inositol can be used to predict outcome. Design: Placebo-controlled, randomized, double-blind trial with stratification by gestational age and surfactant use. Setting: Neonatal intensive care unit in a university-based children's hospital. Patients: Infants born weighing less than 2000 gm at 24 to 31.9 weeks of gestational age, with respiratory distress evidenced by the need for at least 40% inspired oxygen and mechanical ventilation at 2 to 10 hours of age, and by the need for parenteral nutrition. Intervention: Inositol, 80 mg/kg per day, or glucose placebo was given intravenously starting at 4 to 12 hours of age and
496
Abstracts f r o m the literature
The Journal of Pediatrics March 1993
every 12 hours thereafter for 5 days. This regimen was repeated for infants who remained ventilator dependent on day 10 or 20 or both. Inositol or placebo was discontinued if oliguria or severe hyperglycemia occurred, or if enteral feeding exceeded 80 ml/kg per day. Main otttcome measures: The primary outcomes were survival at 28 days without bronchopulmonary dysplasia, and death before 28 days. Secondary outcomes were respiratory requirements during hospitalization and the presence of retinopathy of prematurity and neural development at 1 year of age. The frequencies of various complications of prematurity were also measured. Results: Both survival and survival without bronchopulmonary dysplasia were greater in the inositol group (89% vs 76%, and 71% vs 55%; p = 0.005). In addition, oxygen and mean airway pressure requirements during the first 6 days of life were lower in infants who received inositol than in those who received placebo. At 1 year of age (follow-up 99%), retinopathy of prematurity was less common (12% vs 27%) in the inositol group, and no grade IV disease occurred in the inositol group, compared with six cases (8%) in the placebo group. There were no significant differences in neural development between the groups. Conclusions: Inositol supplementation during the early neonatal period appears to increase survival and decrease bronchopulmonary dysplasia as well as retinopathy of prematurity. Comment: Inositol, a component of human milk, has received increasing attention as an essential part of the infant's diet; evidence from animal studies demonstrates abnormalities associated with deficiency. Although oral infant feedings contain inositol, intravenous preparations do not. This study provides evidence that inositol added to intravenous feedings for ill premature infants increases survival and decreases the rate of bronchopulmonary dysplasia and retinopathy of prematurity in premature infants who are ventilator dependent. All these children went on to enteral feedings of human milk. It is possible that some differences between the two groups might have been obscured by these high-inositol enteral feedings. Further studies will be needed to define the optimal intravenous dose and optimal duration of therapy. John Sparks, biD Virginia A. Moyer, MD, M i l l University o f Texas Medical School at Houston Houston, T X 77030
9/34/44293
ALSO NOTED
Renal transplantation In children: A report of the North American Pediatric Renal Transplant Cooperative Study McEnery PT, Stablein DM, Arbus G, Tejani A. New Engl J Med 1992;326:1727-32. The authors report on transplant results for 1550 children at 73 transplant centers, with data on survival, rejection, and growth.
Controlled study of linear growth In asthmatic children during treatment with inhaled corticosteroids Wolthers OD, Pedersen S. Pediatrics 1992;89:839-42. In a randomized, blinded, placebo-controlled trial, the authors show little difference in very short term growth rate between patients given placebo and those receiving up to 400/~g of inhaled budesonide per day. The study lacked power to demonstrate small to moderate differences in rate and did not address longer-term alterations in growth.
Efficacy of myringotomy with and without tympanostomy tubes for chronic otitis media with effusion Mandel EM, Rockette HE, Bluestone CD, Paradise JL, Nozza RJ. Pediatr Infect Dis J 1992;11:270-7. In a stratified, randomized trial including 111 children, tympanostomy tube placement resulted in fewer months with middle ear effusion, but even in this group, 52% met treatment failure criteria at 3 years.
Midazolam versus fentanyl as premedication for painful procedures in children with cancer Sandier ES, Weyman C, Connor K. Pediatrics 1992; 89:63 I-4. This randomized, blinded, crossover trial in 27 patients demonstrated a preference by patients for sedation with midazolam.