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Oxygenation during transition from birth
August 2013 Volume 163 Number 2
No association between the number of vaccine antigens and risk of autism spectrum disorders — Sarah S. Long, MD
Relationship between adolescent binge drinking and childhood alcohol use — Robert W. Wilmott, MD
Oxygenation during transition from birth — Alan H. Jobe, MD, PhD
Copyright ª 2013 by Mosby Inc.
M
any well-meaning parents have unfounded fears that their young children are exposed to too much immunologic stimulation through vaccines. Some then take real risks of underimmunizing their children or insisting on schedules that are unstudied for efficacy or safety. In this issue of The Journal, DeStefano et al performed a secondary analysis of the robust database from a case-control study evaluating potential risks of thimerosal exposure from vaccines. They sought to test the hypothesis that increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines was associated with risk of autism spectrum disorder (ASD). They repeatedly found aORs of 0.999 (with narrow CIs) for association of ASD diagnosed by 6-13 years of age with incremental increases in total antigens received, as well as with decreasing ages at receipt. The authors also found no association between the maximum number of antigens that a child was exposed to on a single day and ASD. This analysis adds rigorous study results that bolster findings of the 2004 comprehensive review by the Institute of Medicine, which concluded that evidence favors rejection of a possible causal association between vaccines (with or without thimerosal) and autism. The findings also are in step with the Institute of Medicine’s reassuring report released on January 16, 2013, entitled, “The Childhood Immunization Schedule and Safety: Stakeholder Concerns, Scientific Evidence, and Future Studies.” Pediatricians should be informed. Parents should be informed. When science “speaks,” it is loud and clear and should trump the fear of the unknown. Article page 561<
I
n this issue of The Journal, Sanchez et al from the Universidade Federal de S~ao Paulo have evaluated the hypothesis that childhood alcohol use may predict adolescent binge drinking in more than 17 000 high school students in Brazil. Logistic regression testing was used to evaluate the relationship between the first alcohol use and adolescent binge drinking. Adolescents who first used alcohol during childhood, as compared with those who only used alcohol at later stages, were more likely to engage in binge-drinking behaviors. They also had a pattern of heavy alcohol use and recent use of illegal drugs. The authors conclude that childhood alcohol use is a risk factor for the most dangerous patterns of alcohol use in adolescence, also noting an association with parental alcohol use. Article page 363<
N
ormal vaginal birth is a stressful event characterized by low and variable oxygenation of the fetus. The initiation of breathing after birth is a low point for oxygen saturation that then increases toward normal values over the first 10 or more minutes of life in normal term infants. An unresolved issue is how oxygen saturation of blood best can be targeted for infants needing resuscitation. Another level of sophistication is to ask questions about oxygen delivery to tissues. Oxygen delivery can be estimated with near infrared spectroscopy to measure oxygen extraction by the brain and peripheral tissues. In this issue of The Journal, Binder reported the time-saturation and timecerebral tissue oxygen extraction curves for late-preterm infants delivered by cesarean over the first 15 minutes of life. One-half the infants needed some respiratory 309
assistance. The saturation and oxygen extraction curves were quite different for the two groups, with the respiratory assistance group having lower cerebral oxygen delivery. These physiologic observations point to the complexity of neonatal cardiopulmonary adaptation at birth. How this information can be used is unclear. The use of such routine monitoring is unrealistic. These differences in oxygen extraction are unlikely to change outcomes, except at the extremes from normal. Article page 394<
Negative behaviors and events during pregnancy impact neonates’ birth characteristics — Sarah S. Long, MD
Central nervous system infection due to tick-borne encephalitis virus results in neurocognitive sequelae — Sarah S. Long, MD
Pharmacologic adrenal suppression — Thomas R. Welch, MD
310
A
growing body of literature identifies the negative impact of certain maternal behaviors (eg, smoking, substance abuse) on neonatal health (eg, preterm birth, low birth rate, smallness for gestational age). Smallness for gestational age is in turn associated with childhood developmental and behavioral problems, as well as excessive rates in adults of cardiovascular disease, stroke, non-insulin dependent diabetes mellitus, adiposity, and metabolic syndrome. In this issue of The Journal, Alhusen et al reported 166 highly vulnerable, poor, urban, predominantly African American, pregnant women in Baltimore, Maryland, and found that experiencing intimate partner violence during pregnancy (which had the extraordinary occurrence rate of 19%) and marijuana use each was associated with 4-fold and 5-fold odds, respectively, for delivering a neonate who was small for gestational age. The authors discuss the interwoven, extraordinary morbidities of this group of women and the need to mitigate each one to improve the lifelong outcomes for their offspring (and themselves). There also is a lesson for pediatricians that history of smallness for gestational age at birth should lead to screening for household violence and substance abuse, both of which have attendant future risks for the child. Article page 471<
T
ick-borne encephalitis (TBE) is a vector-borne disease due to TBE virus (TBEv) and is endemic in areas throughout Europe and Asia. An effective vaccine is available. Burden of sequelae following central nervous system TBEv infection is unknown in children. Knowledge would inform optimal vaccination strategy. In this issue of The Journal, Fowler et al in Sweden reported follow-up of 55 children 2 to 7 years post-TBE using parent and teacher questionnaires and Wechsler Intelligence Scales for Children (WISC-IV). Two-thirds of children had one or more residual problems and one-third were reported by parents or teachers to have problems with executive functioning, primarily in initiating and organizing activities and in working memory. WISC-IV testing showed significantly lower working memory index compared with reference norms. These data show that, when followed and studied carefully, children have substantial rates of sequlae following TBE that are similar to adults. Article page 555<
M
ost medical students are familiar with the ability of supraphysiologic doses of corticosteroids to suppress endogenous adrenal cortisol synthesis, with potentially disastrous consequences. Yet, experienced physicians sometimes forget this lesson when caring for children who are receiving treatment with glucocorticoids. A retrospective study in this issue of The Journal, by Wildi-Runge et al in Montreal, is a timely reminder of this principle of therapy. The authors examined the cortisol response to low-dose adrenocorticotropic hormone stimulation in 103 children who had received steroid therapy for an array of conditions. Although most children had a normal response, some did not. The authors examined a number of clinical variables (eg, underlying disease, growth failure, obesity) and found no good predictors of subnormal response to stimulation. Although catastrophic adrenal insufficiency following corticosteroid therapy in children is not seen often today, this report reminds us both that biochemical evidence Vol. 163, No. 2
of adrenal dysfunction is common and that it cannot easily be predicted. The authors provide some recommendations with which not everyone will agree, but which deserve consideration. Article page 484<
Genetics of primary ciliary dyskinesia in Amish and Mennonite communities — Robert W. Wilmott, MD
Pediatric spontaneous intracranial hypotension — Robert W. Wilmott, MD
I
n a study of primary ciliary dyskinesia in the Amish and Mennonite community in the US, Ferkol et al have shown that Amish and Mennonite subjects from geographically dispersed and socially isolated communities have the same DNAH5 mutation because of the common heritage of these populations. However, disease-causing mutations also were found in other genes associated with primary ciliary dyskinesia in affected individuals in the Amish and Mennonite community, underscoring the genetic heterogeneity that exists in this consanguineous population. Article page 383<
S
pontaneous intracranial hypotension is a rarely diagnosed cause of headache in children. However, Schievink et al at Cedars-Sinai Medical Center in Los Angeles have identified 24 children with this condition evaluated between 2001 and 2012. They usually presented with orthostatic headaches and 54% had a generalized connective tissue disorder. Magnetic resonance imaging showed typical changes of spontaneous intracranial hypotension in 79%. A cerebrospinal fluid leak was identified with or without associated meningeal diverticula in 42%. Twenty-three patients underwent epidural blood patching, 8 patients were treated with percutaneous injections of fibrin glue, and 11 patients eventually required surgical correction of the cerebrospinal fluid leak. Morbidity and mortality were low, but 5 patients required acetazolamide for rebound intracranial hypertension. Overall, outcome was good in 92% of patients. The authors conclude that most patients with this rare condition can be treated effectively with a combination of epidural blood patching and percutaneous injection of fibrin glue, and would reserve surgical treatment for refractory cases. Article page 504<
Magnetic resonance myelograms showing B, dural ectasia and C-F, numerous variations of meningeal diverticula. Compare to A, normal magnetic resonance myelogram. August 2013
311
No association between the number of vaccine antigens and risk of autism spectrum disorders — Sarah S. Long, MD
Relationship between adolescent binge drinking and childhood alcohol use — Robert W. Wilmott, MD
Oxygenation during transition from birth — Alan H. Jobe, MD, PhD
Copyright ª 2013 by Mosby Inc.
M
any well-meaning parents have unfounded fears that their young children are exposed to too much immunologic stimulation through vaccines. Some then take real risks of underimmunizing their children or insisting on schedules that are unstudied for efficacy or safety. In this issue of The Journal, DeStefano et al performed a secondary analysis of the robust database from a case-control study evaluating potential risks of thimerosal exposure from vaccines. They sought to test the hypothesis that increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines was associated with risk of autism spectrum disorder (ASD). They repeatedly found aORs of 0.999 (with narrow CIs) for association of ASD diagnosed by 6-13 years of age with incremental increases in total antigens received, as well as with decreasing ages at receipt. The authors also found no association between the maximum number of antigens that a child was exposed to on a single day and ASD. This analysis adds rigorous study results that bolster findings of the 2004 comprehensive review by the Institute of Medicine, which concluded that evidence favors rejection of a possible causal association between vaccines (with or without thimerosal) and autism. The findings also are in step with the Institute of Medicine’s reassuring report released on January 16, 2013, entitled, “The Childhood Immunization Schedule and Safety: Stakeholder Concerns, Scientific Evidence, and Future Studies.” Pediatricians should be informed. Parents should be informed. When science “speaks,” it is loud and clear and should trump the fear of the unknown. Article page 561<
I
n this issue of The Journal, Sanchez et al from the Universidade Federal de S~ao Paulo have evaluated the hypothesis that childhood alcohol use may predict adolescent binge drinking in more than 17 000 high school students in Brazil. Logistic regression testing was used to evaluate the relationship between the first alcohol use and adolescent binge drinking. Adolescents who first used alcohol during childhood, as compared with those who only used alcohol at later stages, were more likely to engage in binge-drinking behaviors. They also had a pattern of heavy alcohol use and recent use of illegal drugs. The authors conclude that childhood alcohol use is a risk factor for the most dangerous patterns of alcohol use in adolescence, also noting an association with parental alcohol use. Article page 363<
N
ormal vaginal birth is a stressful event characterized by low and variable oxygenation of the fetus. The initiation of breathing after birth is a low point for oxygen saturation that then increases toward normal values over the first 10 or more minutes of life in normal term infants. An unresolved issue is how oxygen saturation of blood best can be targeted for infants needing resuscitation. Another level of sophistication is to ask questions about oxygen delivery to tissues. Oxygen delivery can be estimated with near infrared spectroscopy to measure oxygen extraction by the brain and peripheral tissues. In this issue of The Journal, Binder reported the time-saturation and timecerebral tissue oxygen extraction curves for late-preterm infants delivered by cesarean over the first 15 minutes of life. One-half the infants needed some respiratory 309
assistance. The saturation and oxygen extraction curves were quite different for the two groups, with the respiratory assistance group having lower cerebral oxygen delivery. These physiologic observations point to the complexity of neonatal cardiopulmonary adaptation at birth. How this information can be used is unclear. The use of such routine monitoring is unrealistic. These differences in oxygen extraction are unlikely to change outcomes, except at the extremes from normal. Article page 394<
Negative behaviors and events during pregnancy impact neonates’ birth characteristics — Sarah S. Long, MD
Central nervous system infection due to tick-borne encephalitis virus results in neurocognitive sequelae — Sarah S. Long, MD
Pharmacologic adrenal suppression — Thomas R. Welch, MD
310
A
growing body of literature identifies the negative impact of certain maternal behaviors (eg, smoking, substance abuse) on neonatal health (eg, preterm birth, low birth rate, smallness for gestational age). Smallness for gestational age is in turn associated with childhood developmental and behavioral problems, as well as excessive rates in adults of cardiovascular disease, stroke, non-insulin dependent diabetes mellitus, adiposity, and metabolic syndrome. In this issue of The Journal, Alhusen et al reported 166 highly vulnerable, poor, urban, predominantly African American, pregnant women in Baltimore, Maryland, and found that experiencing intimate partner violence during pregnancy (which had the extraordinary occurrence rate of 19%) and marijuana use each was associated with 4-fold and 5-fold odds, respectively, for delivering a neonate who was small for gestational age. The authors discuss the interwoven, extraordinary morbidities of this group of women and the need to mitigate each one to improve the lifelong outcomes for their offspring (and themselves). There also is a lesson for pediatricians that history of smallness for gestational age at birth should lead to screening for household violence and substance abuse, both of which have attendant future risks for the child. Article page 471<
T
ick-borne encephalitis (TBE) is a vector-borne disease due to TBE virus (TBEv) and is endemic in areas throughout Europe and Asia. An effective vaccine is available. Burden of sequelae following central nervous system TBEv infection is unknown in children. Knowledge would inform optimal vaccination strategy. In this issue of The Journal, Fowler et al in Sweden reported follow-up of 55 children 2 to 7 years post-TBE using parent and teacher questionnaires and Wechsler Intelligence Scales for Children (WISC-IV). Two-thirds of children had one or more residual problems and one-third were reported by parents or teachers to have problems with executive functioning, primarily in initiating and organizing activities and in working memory. WISC-IV testing showed significantly lower working memory index compared with reference norms. These data show that, when followed and studied carefully, children have substantial rates of sequlae following TBE that are similar to adults. Article page 555<
M
ost medical students are familiar with the ability of supraphysiologic doses of corticosteroids to suppress endogenous adrenal cortisol synthesis, with potentially disastrous consequences. Yet, experienced physicians sometimes forget this lesson when caring for children who are receiving treatment with glucocorticoids. A retrospective study in this issue of The Journal, by Wildi-Runge et al in Montreal, is a timely reminder of this principle of therapy. The authors examined the cortisol response to low-dose adrenocorticotropic hormone stimulation in 103 children who had received steroid therapy for an array of conditions. Although most children had a normal response, some did not. The authors examined a number of clinical variables (eg, underlying disease, growth failure, obesity) and found no good predictors of subnormal response to stimulation. Although catastrophic adrenal insufficiency following corticosteroid therapy in children is not seen often today, this report reminds us both that biochemical evidence Vol. 163, No. 2
of adrenal dysfunction is common and that it cannot easily be predicted. The authors provide some recommendations with which not everyone will agree, but which deserve consideration. Article page 484<
Genetics of primary ciliary dyskinesia in Amish and Mennonite communities — Robert W. Wilmott, MD
Pediatric spontaneous intracranial hypotension — Robert W. Wilmott, MD
I
n a study of primary ciliary dyskinesia in the Amish and Mennonite community in the US, Ferkol et al have shown that Amish and Mennonite subjects from geographically dispersed and socially isolated communities have the same DNAH5 mutation because of the common heritage of these populations. However, disease-causing mutations also were found in other genes associated with primary ciliary dyskinesia in affected individuals in the Amish and Mennonite community, underscoring the genetic heterogeneity that exists in this consanguineous population. Article page 383<
S
pontaneous intracranial hypotension is a rarely diagnosed cause of headache in children. However, Schievink et al at Cedars-Sinai Medical Center in Los Angeles have identified 24 children with this condition evaluated between 2001 and 2012. They usually presented with orthostatic headaches and 54% had a generalized connective tissue disorder. Magnetic resonance imaging showed typical changes of spontaneous intracranial hypotension in 79%. A cerebrospinal fluid leak was identified with or without associated meningeal diverticula in 42%. Twenty-three patients underwent epidural blood patching, 8 patients were treated with percutaneous injections of fibrin glue, and 11 patients eventually required surgical correction of the cerebrospinal fluid leak. Morbidity and mortality were low, but 5 patients required acetazolamide for rebound intracranial hypertension. Overall, outcome was good in 92% of patients. The authors conclude that most patients with this rare condition can be treated effectively with a combination of epidural blood patching and percutaneous injection of fibrin glue, and would reserve surgical treatment for refractory cases. Article page 504<
Magnetic resonance myelograms showing B, dural ectasia and C-F, numerous variations of meningeal diverticula. Compare to A, normal magnetic resonance myelogram. August 2013
311