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Introduction of complementary foods and obesity: an international perspective
February 2015 Volume 166 Number 2
Focusing on nutrition in the medically fragile — Denise M. Goodman, MD, MS
Biological basis for feeding readiness in the preterm — Alan H. Jobe, MD, PhD
Copyright ª 2015 by Elsevier Inc.
C
hildren with medical complexity represent the most fragile of children with special health care needs. The group is heterogeneous, with both acquired and congenital disease, and includes those with a broad array of diagnoses including neurologic impairment, metabolic disorders, and complex cardiovascular or gastrointestinal conditions. The prevalence of this group is growing, as is the subgroup of those who require chronic invasive mechanical ventilation. Both the content of care for these children and the manner in which it is delivered differs from that of healthy ambulatory children. With this in mind, the article by Martinez et al in this issue of The Journal is a welcome addition to the literature. Using a sample of 20 children from the home ventilator program of Boston Children’s Hospital, they performed a comprehensive assessment of their nutritional status and metabolic state using portable equipment in the home setting. The accompanying editorial adds context and caveats to the findings. The importance of this work is three-fold. First, this group of children on home chronic ventilation exhibited unique metabolic profiles; if confirmed these data will permit individualized nutritional prescriptions aimed at optimizing health. Second, the work underscores that even something as fundamental as nutrition merits rigorous evaluation equivalent to that expected of innovative new drugs and devices, and nutrition needs to be precisely titrated to metabolic needs. Finally, these evaluations were performed during home visits. When a visit to a tertiary care center is difficult, whether due to limited mobility, socioeconomic issues, or geography, this study demonstrates that high quality care can be delivered in alternative settings. Article page 350< Editorial page 228<
A
ssessing oral feeding readiness in the neonatal intensive care unit for preterm infants is a nursing art and skill that depends on signs from the infant. The determination of when an infant can feed successfully is an imprecise clinical determination that varies widely depending on customs and local traditions. At one extreme, very preterm infants are fed successfully in low resource environments with droppers, spoons, and other devices before nippling is initiated. At the other extreme, gastric tube feeding may be continued beyond a developmental stage when oral feeding can be achieved with care and persistence. Clearly, feeding is a skill dependent on the maturation and coordination of multiple systems. In an innovative application of the salivary analysis of gene expression and systems biology, Maron et al report that 5 genes that plausibly related to maturation of feeding behavior (signals for hunger, energy homeostasis, olfactory neurogenesis, visual behavior, and facial development) change expression from before to after successful feeding in preterm infants. Although the expression levels can be combined as a biomarker to predict feeding readiness, the currently used empiric assessments and a bit of trial and error are adequate for most infants. However, this research has identified opportunities to better delineate the components of feeding behavior, their maturation, and developmental abnormalities in infants with feeding difficulties. This report is a provocative demonstration of how systems biology can be applied to routine clinical care interventions. Article page 282< 215
Introduction of complementary foods and obesity: an international perspective — Stephen R. Daniels, MD, PhD
Autistic disorder and cancer risk — Paul G. Fisher, MD
D-dimers to detect traumatic brain injury — Paul G. Fisher, MD
216
T
he relationship of breastfeeding, timing of introduction of complementary foods and other early feeding practices, and the risk of obesity is an important area for study. In this issue of The Journal, Zheng et al evaluate these relationships in a large cohort study in mainland China. It is interesting to see that the complementary foods introduced early in life in China are fish liver oil, rice cereal, egg yolk, fish paste, liver paste, tofu, animal blood, bread/fine dried noodle, ground meat/soy, and pureed noodle/cookies. This emphasizes the cultural differences in the kinds of foods that are first introduced into the diet of infants. They found no association between timing of complementary feeding and obesity. However, they did find that early introduction of fish liver oil was associated with higher BMI at 4-5 years of age. This suggests that early introduction of certain types of food may be important in increasing the risk of obesity development. It also raises the question regarding whether important lessons might be learned by comparing infant feeding practices across cultures. Article page 326<
A
utism and neuropsychiatric disorders have been linked to an increasing number of genes, some developmental and others cancer predisposition loci. Autism also has been related to abnormal neural development with macrocephaly and differences in brain morphology. Thus, it is natural to consider whether autism and cancer might share a common link because of dys-regulation of loss of growth. Chiang et al approach this topic with their Taiwanese national cohort study examining 8,438 children diagnosed with cancer from 1997 to 2011. Cancer developed nearly twice as often as suspected in children with autistic disorder, with a standardized incidence ratio of 1.94 (95% CI 1.18-2.99). Although these data are significant, we should exercise caution when interpreting their results. The study findings are based upon 20 individuals diagnosed with cancer, when only about 10 were expected. Although the study sample here is larger than prior works, the number of children with overlapping autistic disorder and cancer remains small. Children with autistic disorder overwhelmingly still did not develop cancer. More work is needed to explore the biological underpinnings of this relationship. Article page 418<
I
s there a biomarker to help identify children at risk for traumatic brain injury, particularly mild abusive head trauma, who might then benefit from additional screening with head computed tomography (CT)? Berger et al examine serum d-dimer concentration first retrospectively among a discovery cohort of children less than age 4 years, assessing 93 controls without traumatic brain injury and 102 cases with traumatic brain injury suspected to be abuse. Significantly higher levels were seen in the cases, who had a median level of 0.43 mg/L. Then prospectively among a validation cohort of 24 prospective normal controls and 20 cases with abnormal head CT demonstrating brain injury, and using a cutoff of 0.59 mg/L, the sensitivity and specificity for identification of a cases by d-dimer concentration was 90% and 75%, respectively. At a cutoff of 1.0 mg/L positive predictive value and negative predictive values were 87% and 88%, respectively. Serum d-dimer level might identify children who would benefit from neuroimaging to evaluate for possibility of brain injury. Additional study will be needed to delineate better the validity and utility of this and other markers. Article page 383<
Vol. 166, No. 2
Pulmonary hypertension with diaphragmatic hernia — Alan H. Jobe, MD, PhD
February 2015
A
s care practices have evolved to target the complex pulmonary abnormalities in newborns with diaphragmatic hernia, survival has increased greatly. However, mortality and prolonged pulmonary morbidity remains high. Pulmonary hypertension is uniformly present soon after birth for the infant with a significant diaphragmatic hernia and much of the acute care is directed toward treating the pulmonary hypertension while trying to minimize lung injury. But the natural history of the resolution of the pulmonary hypertension has not been described. Although imperfect, echocardiography is the only practical technique for repetitive evaluations of pulmonary hypertension. In this issue of The Journal, Lusk et al report that for a group of 140 infants with diaphragmatic hernia, 70% resolved their pulmonary hypertension prior to death or discharge, with a mean time of resolution of 18 days. Not surprisingly, the use of extracorporeal membrane oxygenation, death, and duration of ventilation correlated with persistence of pulmonary hypertension. The encouraging news is that the hypoplastic vasculature in the lungs of infants with diaphragmatic hernia can remodel and grow quite rapidly despite the need for ventilatory support and supplemental oxygen. Article page 251<
217
Focusing on nutrition in the medically fragile — Denise M. Goodman, MD, MS
Biological basis for feeding readiness in the preterm — Alan H. Jobe, MD, PhD
Copyright ª 2015 by Elsevier Inc.
C
hildren with medical complexity represent the most fragile of children with special health care needs. The group is heterogeneous, with both acquired and congenital disease, and includes those with a broad array of diagnoses including neurologic impairment, metabolic disorders, and complex cardiovascular or gastrointestinal conditions. The prevalence of this group is growing, as is the subgroup of those who require chronic invasive mechanical ventilation. Both the content of care for these children and the manner in which it is delivered differs from that of healthy ambulatory children. With this in mind, the article by Martinez et al in this issue of The Journal is a welcome addition to the literature. Using a sample of 20 children from the home ventilator program of Boston Children’s Hospital, they performed a comprehensive assessment of their nutritional status and metabolic state using portable equipment in the home setting. The accompanying editorial adds context and caveats to the findings. The importance of this work is three-fold. First, this group of children on home chronic ventilation exhibited unique metabolic profiles; if confirmed these data will permit individualized nutritional prescriptions aimed at optimizing health. Second, the work underscores that even something as fundamental as nutrition merits rigorous evaluation equivalent to that expected of innovative new drugs and devices, and nutrition needs to be precisely titrated to metabolic needs. Finally, these evaluations were performed during home visits. When a visit to a tertiary care center is difficult, whether due to limited mobility, socioeconomic issues, or geography, this study demonstrates that high quality care can be delivered in alternative settings. Article page 350< Editorial page 228<
A
ssessing oral feeding readiness in the neonatal intensive care unit for preterm infants is a nursing art and skill that depends on signs from the infant. The determination of when an infant can feed successfully is an imprecise clinical determination that varies widely depending on customs and local traditions. At one extreme, very preterm infants are fed successfully in low resource environments with droppers, spoons, and other devices before nippling is initiated. At the other extreme, gastric tube feeding may be continued beyond a developmental stage when oral feeding can be achieved with care and persistence. Clearly, feeding is a skill dependent on the maturation and coordination of multiple systems. In an innovative application of the salivary analysis of gene expression and systems biology, Maron et al report that 5 genes that plausibly related to maturation of feeding behavior (signals for hunger, energy homeostasis, olfactory neurogenesis, visual behavior, and facial development) change expression from before to after successful feeding in preterm infants. Although the expression levels can be combined as a biomarker to predict feeding readiness, the currently used empiric assessments and a bit of trial and error are adequate for most infants. However, this research has identified opportunities to better delineate the components of feeding behavior, their maturation, and developmental abnormalities in infants with feeding difficulties. This report is a provocative demonstration of how systems biology can be applied to routine clinical care interventions. Article page 282< 215
Introduction of complementary foods and obesity: an international perspective — Stephen R. Daniels, MD, PhD
Autistic disorder and cancer risk — Paul G. Fisher, MD
D-dimers to detect traumatic brain injury — Paul G. Fisher, MD
216
T
he relationship of breastfeeding, timing of introduction of complementary foods and other early feeding practices, and the risk of obesity is an important area for study. In this issue of The Journal, Zheng et al evaluate these relationships in a large cohort study in mainland China. It is interesting to see that the complementary foods introduced early in life in China are fish liver oil, rice cereal, egg yolk, fish paste, liver paste, tofu, animal blood, bread/fine dried noodle, ground meat/soy, and pureed noodle/cookies. This emphasizes the cultural differences in the kinds of foods that are first introduced into the diet of infants. They found no association between timing of complementary feeding and obesity. However, they did find that early introduction of fish liver oil was associated with higher BMI at 4-5 years of age. This suggests that early introduction of certain types of food may be important in increasing the risk of obesity development. It also raises the question regarding whether important lessons might be learned by comparing infant feeding practices across cultures. Article page 326<
A
utism and neuropsychiatric disorders have been linked to an increasing number of genes, some developmental and others cancer predisposition loci. Autism also has been related to abnormal neural development with macrocephaly and differences in brain morphology. Thus, it is natural to consider whether autism and cancer might share a common link because of dys-regulation of loss of growth. Chiang et al approach this topic with their Taiwanese national cohort study examining 8,438 children diagnosed with cancer from 1997 to 2011. Cancer developed nearly twice as often as suspected in children with autistic disorder, with a standardized incidence ratio of 1.94 (95% CI 1.18-2.99). Although these data are significant, we should exercise caution when interpreting their results. The study findings are based upon 20 individuals diagnosed with cancer, when only about 10 were expected. Although the study sample here is larger than prior works, the number of children with overlapping autistic disorder and cancer remains small. Children with autistic disorder overwhelmingly still did not develop cancer. More work is needed to explore the biological underpinnings of this relationship. Article page 418<
I
s there a biomarker to help identify children at risk for traumatic brain injury, particularly mild abusive head trauma, who might then benefit from additional screening with head computed tomography (CT)? Berger et al examine serum d-dimer concentration first retrospectively among a discovery cohort of children less than age 4 years, assessing 93 controls without traumatic brain injury and 102 cases with traumatic brain injury suspected to be abuse. Significantly higher levels were seen in the cases, who had a median level of 0.43 mg/L. Then prospectively among a validation cohort of 24 prospective normal controls and 20 cases with abnormal head CT demonstrating brain injury, and using a cutoff of 0.59 mg/L, the sensitivity and specificity for identification of a cases by d-dimer concentration was 90% and 75%, respectively. At a cutoff of 1.0 mg/L positive predictive value and negative predictive values were 87% and 88%, respectively. Serum d-dimer level might identify children who would benefit from neuroimaging to evaluate for possibility of brain injury. Additional study will be needed to delineate better the validity and utility of this and other markers. Article page 383<
Vol. 166, No. 2
Pulmonary hypertension with diaphragmatic hernia — Alan H. Jobe, MD, PhD
February 2015
A
s care practices have evolved to target the complex pulmonary abnormalities in newborns with diaphragmatic hernia, survival has increased greatly. However, mortality and prolonged pulmonary morbidity remains high. Pulmonary hypertension is uniformly present soon after birth for the infant with a significant diaphragmatic hernia and much of the acute care is directed toward treating the pulmonary hypertension while trying to minimize lung injury. But the natural history of the resolution of the pulmonary hypertension has not been described. Although imperfect, echocardiography is the only practical technique for repetitive evaluations of pulmonary hypertension. In this issue of The Journal, Lusk et al report that for a group of 140 infants with diaphragmatic hernia, 70% resolved their pulmonary hypertension prior to death or discharge, with a mean time of resolution of 18 days. Not surprisingly, the use of extracorporeal membrane oxygenation, death, and duration of ventilation correlated with persistence of pulmonary hypertension. The encouraging news is that the hypoplastic vasculature in the lungs of infants with diaphragmatic hernia can remodel and grow quite rapidly despite the need for ventilatory support and supplemental oxygen. Article page 251<
217