Lifelong Impact Research Articles

Successful transition from pediatric to adult care in inflammatory bowel disease: what is the key?

The incidence of pediatric-onset inflammatory bowel disease (IBD) is on the rise, accounting for up to 25% of IBD cases. Pediatric IBD often has extensive bowel involvement with aggressive and rapidly progressing behavior compared to adult IBD. Because IBD has a high morbidity rate and can have a lifelong impact, successful transition from pediatric to adult care is important to maintain the continuity of care. Furthermore, successful transition facilitates appropriate development and psychosocial well-being among patients, as well as comprehensive and harmonious healthcare delivery amongst stakeholders. However, there are various obstacles related to patients, family, providers, and organizations that interfere with successful transition. Successful transition requires a flexible and tailored plan that is made according to the patient’s developmental abilities and situation. This plan should be established through periodic interviews with the patient and family and through close collaboration with other care providers. Through a stepwise approach to the transition process, patients’ knowledge and self-management skills can be improved. After preparation for the transition is completed and the obstacles are overcome, patients can be gradually moved to adult care. Finally, successful transition can increase patients’ adherence to therapy, maintain the appropriate health status, improve patients’ self-management, and promote self-reliance among patients.

Yo-Yo Dieting is Better than None.

See accompanying article, pg. 1733.

Oxygen therapy of the newborn from molecular understanding to clinical practice

Oxygen is one of the most critical components of life. Nature has taken billions of years to develop optimal atmospheric oxygen concentrations for human life, evolving from very low, peaking at 30% before reaching 20.95%. There is now increased understanding of the potential toxicity of both too much and too little oxygen, especially for preterm and asphyxiated infants and of the potential and lifelong impact of oxygen exposure, even for a few minutes after birth. In this review, we discuss the contribution of knowledge gleaned from basic science studies and their implication in the care and outcomes of the human infant within the first few minutes of life and afterwards. We emphasize current knowledge gaps and research that is needed to answer a problem that has taken Nature a considerably longer time to resolve.

Refractive Error and Ocular Findings Among Infants and Young Children With Severe Problem Behavior and Developmental Disabilities

ABSTRACTThe prevalence of refractive error and ocular disorders among infants and young children with severe behavioral problems and developmental disorders is not well defined, particularly in developing countries. We performed a retrospective review of ophthalmic examinations performed during a National Institutes of Health–funded cohort study of very young children in Peru with behavioral problems and at risk for developmental disorders. Two-hundred twenty-two children between the ages of 0 and 4 years (mean 2.2 ± 0.9 years) were examined and 100 (45.0%) had an abnormal ocular exam. Overall, the prevalence of refractive error was 33.3%, nystagmus was 12.2%, and strabismus was 10.9%. Among children with Down syndrome, refractive error ranged from 46.2% at age 2 to 85.7% at age 4. Refractive error and ocular disorders are highly prevalent even at a young age in children with behavioral problems and developmental disorders. Much of the visual impairment in this population is treatable; early identification and intervention can have a lifelong positive impact on neurodevelopment.

Nutrition and Lung Growth.

Experimental evidence from animal models and epidemiology studies has demonstrated that nutrition affects lung development and may have a lifelong impact on respiratory health. Chronic restriction of nutrients and/or oxygen during pregnancy causes structural changes in the airways and parenchyma that may result in abnormal lung function, which is tracked throughout life. Inadequate nutritional management in very premature infants hampers lung growth and may be a contributing factor in the pathogenesis of bronchopulmonary dysplasia. Recent evidence seems to indicate that infant and childhood malnutrition does not determine lung function impairment even in the presence of reduced lung size due to delayed body growth. This review will focus on the effects of malnutrition occurring at critical time periods such as pregnancy, early life, and childhood, on lung growth and long-term lung function.

Reducing age bias in decision analyses of anticoagulation for patients with nonvalvular atrial fibrillation - A microsimulation study.

BackgroundAnticoagulation decreases a patient’s risk of ischemic stroke and increases the risk of hemorrhage. Decision analyses regarding anticoagulation therefore require that different outcomes be weighted in comparison to one another. Most decision analyses to date have weighted intracranial hemorrhage (ICH) as 1.5 times worse than ischemic stroke, but because death and disability have lifelong impact, the expected impact should vary by life expectancy. Therefore, a fixed weighting ratio leads to age-related bias decision analyses of anticoagulation. We aimed to quantify the relative impact of ICH and ischemic stroke and derive a ratio that allows decision analysis without microsimulation.MethodsWe created a microsimulation model to predict QALYs lost due to ICH and ischemic stroke. We then applied a meta-model to predict the ratio of QALYs lost from ICH relative to ischemic stroke.ResultsPreviously-used weighting ratios (1.5) are close to our derived mean weighting ratio (1.60). However, the weighting ratio of QALYs lost from ICH relative to ischemic stroke is sensitive to age and discount rate. Patients at younger ages have higher mean weighting ratios, as do patients with higher discount rates.ConclusionsThe ratio of QALYs lost to ICH relative to ischemic stroke varies with age and discount rate. We present a set of such ratios here for use in decision analyses that do not incorporate full microsimulation models. Use of weighting ratios that vary with age, rather than the current fixed ratios, has the potential to reduce age-based bias in decision-making regarding events with lifelong implications. In this case, use of dynamic ratios may change anticoagulation recommendations for patients with nonvalvular atrial fibrillation at relatively low stroke risk.

The BabySeq project: implementing genomic sequencing in newborns

BackgroundThe greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The “BabySeq Project” is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.MethodsFamilies of newborns are enrolled from Boston Children’s Hospital and Brigham and Women’s Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.DiscussionThe BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns.Trial registrationThe study is registered in ClinicalTrials.gov Identifier: NCT02422511. Registration date: 10 April 2015.

Discussing the impact of air pollution on heart disease

Discussing the impact of air pollution on heart disease

The lifelong impact of fetal growth restriction on cardiac development.

BackgroundMaternal nutrient restriction (MNR) is a widespread cause of fetal growth restriction (FGR), an independent predictor of heart disease and cardiovascular mortality. Our objective was to examine the developmental and long-term impact of MNR-induced FGR on cardiac structure in a model that closely mimics human development.MethodsA reduction in total caloric intake spanning pre-gestation through to lactation in guinea pig sows was used to induce FGR. Proliferation, differentiation, and apoptosis of cardiomyocytes were assessed in late-gestation fetal, neonatal, and adult guinea pig hearts. Proteomic analysis and pathway enrichment were performed on fetal hearts.ResultsCardiomyocyte proliferation and number of mononucleated cells was enhanced in the MNR-FGR fetal and neonatal heart, suggesting a delay in cardiomyocyte differentiation. In fetal hearts of MNR-FGR animals, apoptosis was markedly elevated and the total number of cardiomyocytes reduced, the latter remaining so throughout neonatal and into adult life. A reduction in total cardiomyocyte number in adult MNR-FGR hearts was accompanied by exaggerated hypertrophy and a disorganized architecture. Pathway analysis identified genes related to cell proliferation, differentiation, and survival.ConclusionsFGR influences cardiomyocyte development during critical windows of development, leading to a permanent deficiency in cardiomyocyte number and compensatory hypertrophy in a rodent model that recapitulates human development.

Loss of myogenic potential and fusion capacity of muscle stem cells isolated from contractured muscle in children with cerebral palsy.

Cerebral palsy (CP) is the most common cause of pediatric neurodevelopmental and physical disability in the United States. It is defined as a group of motor disorders caused by a nonprogressive perinatal insult to the brain. Although the brain lesion is nonprogressive, there is a progressive, lifelong impact on skeletal muscles, which are shorter, spastic, and may develop debilitating contractures. Satellite cells are resident muscle stem cells that are indispensable for postnatal growth and regeneration of skeletal muscles. Here we measured the myogenic potential of satellite cells isolated from contractured muscles in children with CP. When compared with typically developing (TD) children, satellite cell-derived myoblasts from CP differentiated more slowly (slope: 0.013 (SD 0.013) CP vs. 0.091 (SD 0.024) TD over 24 h, P < 0.001) and fused less (fusion index: 21.3 (SD 8.6) CP vs. 81.3 (SD 7.7) TD after 48 h, P < 0.001) after exposure to low-serum conditions that stimulated myotube formation. This impairment was associated with downregulation of several markers important for myoblast fusion and myotube formation, including DNA methylation-dependent inhibition of promyogenic integrin-β 1D (ITGB1D) protein expression levels (-50% at 42 h), and ~25% loss of integrin-mediated focal adhesion kinase phosphorylation. The cytidine analog 5-Azacytidine (5-AZA), a demethylating agent, restored ITGB1D levels and promoted myogenesis in CP cultures. Our data demonstrate that muscle contractures in CP are associated with loss of satellite cell myogenic potential that is dependent on DNA methylation patterns affecting expression of genetic programs associated with muscle stem cell differentiation and muscle fiber formation.

Translational insights on developmental origins of metabolic syndrome: Focus on fructose consumption

Metabolic syndrome (MetS) is a highly prevalent complex trait despite recent advances in pathophysiology and pharmacological treatment. MetS can begin in early life by so-called the developmental origins of health and disease (DOHaD). The DOHaD concept offers a novel approach to prevent MetS through reprogramming. High fructose (HF) intake has been associated with increased risk of MetS. HF diet becomes one of the most commonly used animal model to induce MetS. This review discusses the maternal HF diet induced programming process and reprogramming strategy to prevent MetS of developmental origin, with an emphasis on: (1) an overview of metabolic effects of fructose consumption on MetS; (2) insight from maternal HF animal models on MetS-related phenotypes; (3) impact of HF consumption induces organ-specific transcriptome changes; and (4) application of reprogramming strategy to prevent maternal HF consumption-induced MetS. Research into the preventions and treatments of MetS that begin early in life will have a lifelong impact and profound savings in disease burden and financial costs.

Avoidant personality disorder: current insights.

Avoidant personality disorder (AVPD) is a relatively common disorder that is associated with significant distress, impairment, and disability. It is a chronic disorder with an early age at onset and a lifelong impact. Yet it is underrecognized and poorly studied. Little is known regarding the most effective treatment. The impetus for research into this condition has waxed and waned, possibly due to concerns regarding its distinctiveness from other disorders, especially social anxiety disorder (SAD), schizoid personality disorder, and dependent personality disorder. The prevailing paradigm subscribes to the “severity continuum hypothesis”, in which AVPD is viewed essentially as a severe variant of SAD. However, areas of discontinuity have been described, and there is support for retaining AVPD as a distinct diagnostic category. Recent research has focused on the phenomenology of AVPD, factors of possible etiological significance such as early parenting experiences, attachment style, temperament, and cognitive processing. Self-concept, avoidant behavior, early attachments, and attachment style may represent points of difference from SAD that also have relevance to treatment. Additional areas of research not focused specifically on AVPD, including the literature on social cognition as it relates to attachment and personality style, report findings that are promising for future research aimed at better delineating AVPD and informing treatment.

Common childhood illnesses: Febrile seizures

Febrile seizures are a common symptom in a child with a feverish illness. They are usually uncomplicated, with no lifelong impact on a child's health and development. However, they can often be a frightening experience for parents who worry that the seizure is a sign that the child may be seriously unwell.

Psychosis Risk Syndrome: What Now?

Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify "high-risk" patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce "psychosis risk syndrome" as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, "attenuated psychosis syndrome" was included in section III of the newly published manual as a condition for further studies. The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms ("prodrome" and "psychosis-risk syndrome") and concerning available therapeutic options, both psychosocial and pharmacological. "Attenuated psychosis syndrome" is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.

A project to improve the way in which complementary feeding advice is issued to families

Complementary feeding (CF) is seen as one of the most significant milestones for the developing infant and one that has a lifelong impact on health and wellbeing ( Scientific Advisory Committee on Nutrition (SACN), 2011 ). This article describes a project that looked at the issuing of CF advice, to undertake a service improvement with the aim of improving the timing, consistency and quality of CF advice to infants under 6 months of age and their families. In the current financial climate it is important to implement a change without increasing staff levels or caseloads. The change consisted of issuing CF advice universally at the already established 6–8 week contact, enabling parents to better understand the rationale behind current guidelines to make informed choices about when to start solid food and what food to offer.

CDC Grand Rounds: Addressing Health Disparities in Early Childhood.

Research suggests that many disparities in overall health and well-being are rooted in early childhood (1,2). Stressors in early childhood can disrupt neurologic, metabolic, and immunologic systems, leading to poorer developmental outcomes (1). However, consistent, responsive caregiving relationships and supportive community and health care environments promote an optimal trajectory (3,4). The first 8 years of a child's life build a foundation for future health and life success (5-7). Thus, the cumulative and lifelong impact of early experiences, both positive and negative, on a child's development can be profound. Although the health, social service, and education systems that serve young children and their families and communities provide opportunities to support responsive relationships and environments, efforts by these systems are often fragmented because of restrictions that limit the age groups they can serve and types of services they can provide. Integrating relationship-based prevention and intervention services for children early in life, when the brain is developing most rapidly, can optimize developmental trajectories (4,7). By promoting collaboration and data-driven intervention activities, public health can play a critical role in both the identification of at-risk children and the integration of systems that can support healthy development. These efforts can address disparities by reducing barriers that might prevent children from reaching their full potential.

Maanasa: An early individualized remedial educational intervention model for scholastic backwardness among upper primary students

Background: Scholastic backwardness is called as the learning achievement which is below the expected for a given age, cognitive skills, and schooling. Early identification and remedial measures are to be initiated at school level to control its lifelong impact. Objective: The objective of this study is to evolve an early individualized, remedial educational intervention model for the scholastic backwardness among upper primary students at the school level by the resource teachers. Materials and Methods: Whole upper primary students of the four government schools of the South Maararikkulam Grama Panchayath constituted the study population. The scholastic backwardness among them was identified and referred to specially trained resource teachers who were appointed in the schools under Maanasa project. They were graded as mild, moderate and severe category based on the level of scholastic backwardness. Children were given 1 academic year of individualized educational intervention along with inclusive education. Apart from these interventions, families of the identified students were given psychosocial interventions to create a learningfriendly atmosphere in their families. Learning skills of the scholastically backward students were re-assessed at the end of academicyear. Results: Out of total 629 students, 147 had scholastic backwardness (23.7%). Among these, 68 had mild, 60 moderate, and 19 had severe scholastic backwardness on reading skill grading. Psychosocial problems including alcoholism, domestic violence, quarrelsome events, and abandoned family were noticed among 48.7% of the parents of scholastically backward students. Reassessment at the end of academic year showed improvement of scholastic skill among 52.38% of the students. Conclusion: The present study proves that scholastic backwardness can be successfully approached and intervened at school level itself by impartingindividualized educational interventions by trained resource teachers. The parents should be taken into confidence for successful intervention.

Assessment of treatment patterns and healthcare costs associated with probable Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a chronic and severe form of epilepsy characterized by intractable seizures, cognitive impairment, and abnormal electroencephalogram findings with slow spike-wave complexes. It typically presents before age 8, but symptoms continue into adulthood and require lifelong treatment associated with significant clinical burden. Data on LGS-associated healthcare utilization and costs are limited. In this study we use a claims-based LGS classifier based on random forest methodology to identify patients with probable LGS from the a Medicaid multi-state database and assess its prevalence across the age spectrum, healthcare utilization, treatment patterns, costs, and comorbid conditions. The classifier identified patients with probable LGS across all ages, with up to 8% of 10-year-old patients with epilepsy identified as having probable LGS. The prevalence of probable LGS was lower in older age cohorts, indicating that it may be under-recognized in older patients. Our analysis showed that probable LGS is associated with considerably higher total healthcare and medical costs than non-LGS patients. The costs were generally consistent between age cohorts, suggesting that the cost burden extends beyond childhood and has a lifelong impact. Analysis of treatment patterns suggest that while the majority of probable LGS patients in this study received widest-spectrum AEDs, a considerable proportion did not and therefore may have been inadequately treated. Further, usage of clobazam and rufinamide was decreased in older compared to younger patient cohorts, indicating that older patient cohorts are less likely to be receiving optimum treatment for LGS. These findings indicate the need for increased clinical attention to LGS beyond pediatric years, with a focus on optimization of treatment for LGS patients of all ages with widest-spectrum AEDs. Timely recognition and adequate treatment of LGS are likely to result in improved outcomes and less costly management of this condition.

Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability’ may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.

Connecting the Dots: An Ecological Lens to Preventive Measures for Adverse Childhood Experiences

ABSTRACTAdversity in early childhood may have a profound impact on physical and mental health as well as general well-being later in life. Despite increasing research evidence on the lifelong impact of adverse experiences, one of the key questions that motivated this research was how to translate this knowledge into preventive measures. This article presents data from an exploratory study aimed to explore strategies and effective practices to prevent adverse experiences in early childhood. An ecological framework organized participants’ suggested actions, highlighting the importance of proactive, multifaceted approaches and interventions that connect the child to the background environment where adversity takes place.