The “7 Great Achievements in Pediatric Research” campaign noted discoveries in the past 40 years that have improved child and adult health in the United States and around the globe. This article predicts the next 7 great pediatric research advancements, including new immunizations, cancer immunotherapy, genomic discoveries, identification of early antecedents of adult health, impact of specific social–environmental influences on biology and health, quality improvement science, and implementation and dissemination research to reduce global poverty. It is an extraordinary time of new research tools that include electronic health records, technological ability to manage big data and measure “omics,” and new functional and structural imaging modalities. These tools will discern mechanisms leading to health and disease with new prevention targets and cures. This article further discusses the challenges and opportunities to accelerate these exciting pediatric research discoveries to improve the lives of children and the adults they will become.

There are far more good historians than there are good prophets. It is extraordinarily difficult to predict scientific discovery, which is often propelled by seminal insights coming from unexpected directions…Any extrapolation of history into the future presupposes an environment of static discovery—an oxymoron.

Richard Klausner, NCI Director, 1997, in The Emperor of All Maladies by Siddhartha Mukherjee1 

Advances in pediatric research have improved the lives of infants, children, adolescents, and society at large. The American Academy of Pediatrics Committee on Pediatric Research’s “7 Great Achievements in Pediatric Research” campaign identified research achievements in the past 40 years that have reduced morbidity and mortality and increased the quality of life worldwide.2 These 7 success stories were chosen from responses in an open-ended survey of pediatric professional organization board members on the greatest successes in pediatric research and future opportunities (Table 1): preventing disease with life-saving immunizations, reducing sudden infant death with the Back to Sleep campaign, finding a cure for acute lymphoblastic leukemia, helping premature infants breathe with surfactant therapy, preventing HIV transmission from mother to infant, increasing the life expectancy for children with sickle cell anemia and cystic fibrosis, and saving lives with car seats and seat belts. These achievements, and many more beyond these 7, would not have been possible without pediatric research.

TABLE 1

Seven Great Achievements in Pediatric Research in the Past 40 Years1 

Preventing disease with life-saving immunizations 
Reducing sudden infant death with the Back to Sleep campaign 
Curing a common childhood cancer 
Saving premature infants by helping them breathe 
Preventing HIV transmission from mother to infant 
Increasing life expectancy for children with chronic diseases 
Saving lives with car seats and seat belts 
Preventing disease with life-saving immunizations 
Reducing sudden infant death with the Back to Sleep campaign 
Curing a common childhood cancer 
Saving premature infants by helping them breathe 
Preventing HIV transmission from mother to infant 
Increasing life expectancy for children with chronic diseases 
Saving lives with car seats and seat belts 

Despite these success stories, health threats remain, leading some to predict that American children today may for the first time face a shorter life span than their parents.3 Emerging risks to children such as new infections (eg, Zika) or continued epidemics of obesity and exposure to adverse childhood experiences highlight the need for continued investment and progress. However, research studies in children lag behind research focused on adults in quantity and quality.4 Growing evidence demonstrates that there are childhood antecedents to adult disease necessitating research and programmatic investment early in the life course.5 While applauding and learning from past achievements, what are the next 7 great research achievements we will honor 40 years from now? We again drew from and expanded on ideas from the previous survey. Although predicting the future is always risky business, the present article discusses 7 promising areas of science on the verge of breakthroughs that will impact the health of children, adolescents, adults, and communities (Table 2).

TABLE 2

Predicting the Next 7 Great Achievements in Pediatric Research

More pediatric immunizations prevent emerging and persistent diseases 
Cancer immunotherapy in pediatrics shows promise 
Genomic discoveries predict, prevent, and more effectively treat disease 
Big life course data recognizes fetal and childhood origins of adult health and disease, resulting in effective early interventions 
Knowledge of the interaction of biology and the physical and social environment leads to effective prevention for individual and population health 
Quality improvement science creates safe, efficient systems of care 
Implementation and dissemination research reduces global poverty 
More pediatric immunizations prevent emerging and persistent diseases 
Cancer immunotherapy in pediatrics shows promise 
Genomic discoveries predict, prevent, and more effectively treat disease 
Big life course data recognizes fetal and childhood origins of adult health and disease, resulting in effective early interventions 
Knowledge of the interaction of biology and the physical and social environment leads to effective prevention for individual and population health 
Quality improvement science creates safe, efficient systems of care 
Implementation and dissemination research reduces global poverty 

Immunizations were one of the previous “7 Great Achievements” highlighting the success of Haemophilus influenzae type B and rotavirus vaccines. In the next 40 years, it is likely that vaccines will prevent emerging diseases such as Zika or Ebola, cancers (eg, human papillomavirus vaccine), and persistent causes of worldwide morbidity and mortality (eg, tuberculosis, influenza, malaria). Although the dangers of Zika virus have only recently emerged, there has been rapid progress in understanding its biology, pathogenesis, immunity, and potential targets for candidate vaccines.6 For influenza infection, there is a need to develop new vaccines with improved safety, efficacy, and ease of administration compared with conventional influenza vaccines. Advances in influenza vaccine development include live attenuated, cell-based, genomic, and synthetic peptide vaccines.7 Childhood immunization not only prevents disease for the individual child but also provides herd immunity to protect the community. Speeding new vaccine development will require the steps of basic discovery and epidemiologic research, clinical trials, and implementation and dissemination research.

It has long been known that cancer cells develop the ability to evade, or hide from, the immune system. The mainstays of cancer therapy for decades have been surgery, radiation, and chemotherapy. These approaches attack the cancer directly but are not well targeted and kill healthy as well as malignant cells. The promise of cancer immunotherapy lies in the fact that the therapy uses each patient’s own immune system, is targeted to cancer cells that express aberrant proteins, and can have long-lasting effects. Several approaches include the following: (1) dendritic cell therapy (eg, cancer vaccines); (2) antibody therapy, in particular monoclonal antibodies to specific proteins on cancer cells (eg, checkpoint blockade); and (3) engineered T cells, a process in which T cells are genetically modified to express chimeric antigen receptors or engineered T-cell receptors. Although what works in adult cancers may not work for children, and even though drug companies often focus more on adults, immunotherapy is showing promise in childhood cancer. For example, chimeric antigen receptor T-cell therapy offers hope for relapsed or refractory acute lymphoblastic leukemia.8 As with any therapy that alters the immune system, some of these therapies have serious adverse effects due to activation of the immune response and some off-target effects. In addition, the financial costs are sizable. However, these therapies may be the “moonshot” for pediatric cancers that have been difficult to treat. Success depends on continued basic science discovery combined with clinical trials through pediatric oncology collaborative research networks.

Elias Zerhouni, a previous director of the National Institutes of Health, noted that because of increasing knowledge about the genetic origin of disease, 4 “Ps” will characterize medical care in the future: predictive, preemptive, participatory, and personalized. It has been suggested that 2 additional “Ps”—prenatal and pediatrics—should be added because an individual’s genome will be known early in life.9 Next-generation sequencing will lead to 3 exciting advances. First, the number of diseases for which we find single-gene mutations will rapidly increase. It is likely that the number of core conditions in the newborn recommended screening panel10 will continue to grow. New genome-editing technologies based on programmable nucleases that induce double-strand DNA breaks in a site-specific sequence have led to the ability to correct specific genetic sequences that lead to single-gene mutations. These techniques, along with improved ability to isolate, propagate, and reintroduce corrected stem cells, offer the promise for gene therapy for single gene disorders without the side effects caused by random off-site insertions of new genetic material, which have led to malignant transformation of stem cells.11,12 

Second, lessons from large genome-wide association studies have shown that most common disorders are either multigenic in origin or have significant modifier genes that can profoundly affect the severity of a single gene mutation. These modifiers will offer new therapeutic targets. One example of this principle is the demonstration that 2 genes (BCL11A and LRF), not linked to the mutation of the βS Globin gene, are associated with inhibition of fetal hemoglobin production postnatally. Targeted inhibition of these genes increases fetal hemoglobin levels and decreases sickle hemoglobin levels, thereby potentially modifying the severity of the disease.13 

Third, acquired somatic gene mutations found in some forms of cancer, for example, will be detected by using highly sensitive analysis, perhaps in single cells circulating in the blood or other fluids (ie, stool, saliva). Mass spectrometry of emerging aberrant proteins from these “second hits” may be screened in individuals who have a family history of cancer or germline mutations making them more susceptible.

Genomic and proteomics/metabolomics screening prenatally, at birth, and throughout the life course will greatly enhance the role of the clinician in predicting, diagnosing, and preventing diseases early.

It is now clear that adaptive responses of the fetus to environmental factors affecting the mother can contribute to the emergence of adult-onset disorders, including obesity, type 2 diabetes, hypertension, and cardiovascular disease.14,16 Baseline matching of genomic and epigenomic mapping at birth (along with changes in epigenetic markers during early childhood) will identify children who will be at risk for common adolescent and adult-onset disorders and perhaps even psychiatric disorders and some forms of cancer. Genomic/epigenomic/metabolomic patterns at birth,17 monitoring postnatal growth velocities (ie, timing of adipose rebound18), early childhood levels of inflammatory cytokines,19 and other biomarkers will lead to pediatric interventions to prevent or forestall these conditions later in life.

Early studies have now shown patterns of epigenetic changes in newborn DNA associated with maternal exposure to environmental toxins, especially heavy metals.20 Evidence is mounting but still inconsistent as to the effect of exposure to heavy metals in utero and development of small-for-gestational-age infants, a known risk factor for adult-onset cardiovascular disease.21 Prenatal exposure to heavy metals (arsenic, cadmium, mercury, and lead) predisposes to adverse birth outcomes and neuropsychological/cognitive disorders in children and adolescents.22 Monitoring and preventing maternal, paternal, and early childhood exposure to these and other environmental toxins will be as important as lead prevention efforts in avoiding decrements in IQ23 and other neurologic and psychologic disorders.24 Finally, any environmental factor that leads to a stress response (eg, maternal deprivation, malnutrition, exposure to violence, adverse childhood experiences) can clearly re-program a variety of gene interactions that can be identified according to epigenetic patterns.25 Monitoring for genomic sequences that predispose to environmental stressor sensitivity, changes in epigenomic patterns, and subsequent presence of biologic markers will allow public health and individualized interventions.

In 1999, the Institute of Medicine released a book called To Err Is Human: Building a Safer Health System, a landmark report on patient safety and medical error.26 In that report, it was estimated that medical errors in the United States accounted for 44 000 to 98 000 deaths per year. A revised estimate in 2013 found that medical error was the third most common cause of death in the United States, with ∼251 000 deaths attributable to medical errors.27 These statistics highlight the magnitude of this problem and the need to address it in a comprehensive and systematic way. Since the 1999 Institute of Medicine report, there has been increased focus on quality improvement and the development of safe and efficient systems of care. That focus, as well as the development of important new approaches to quality, has yielded valuable results in areas such as reducing hospital-acquired bloodstream infections and prevention of venous thromboembolism. A report issued by the Department of Health and Human Services in 2015 estimated that from 2010 to 2014, there were 87 000 fewer patient deaths in hospitals and nearly $20 billion in health care costs that were saved as a result of a reduction in the number of hospital-acquired conditions.28 Much of this success has been among adults, in whom quality measurement has been driven by Medicare. Fortunately, the Children’s Health Insurance Program Reauthorization Act established the Pediatric Quality Measures Program to increase the portfolio of evidence-based pediatric quality measures. Clearly, continued progress in quality improvement science and access to electronic medical record databases will improve the health and welfare of children.

Dissemination and implementation research and the social sciences have an important role in translating scientific and technological advances to practice and policy, particularly in settings that face challenges of poor infrastructure, poverty, and limited governmental capacity. Despite the tremendous impact of vaccines, nearly 1 in 5 children worldwide have not received routine immunizations for vaccine-preventable illnesses.29 According to the World Health Organization, 38% of health care facilities surveyed in a sample of 54 low-income countries lacked access to “even rudimentary levels of water,” particularly in primary health facilities.30 Scientific and technological innovations in the development of decentralized and “off-grid” techniques for decontaminating water have made significant progress. Research is required on the social determinants of effectiveness, including evidence-based knowledge about behavioral interventions, the costs and benefits of different approaches, and optimizing technological designs and approaches for ease of use, cultural appropriateness, and sustainability.31 

Examples of effective dissemination and implementation science include efforts of the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunisation) and the Bill & Melinda Gates Foundation, which have saved lives through equitable dissemination of vaccines in lower income countries.32 Guinea worm (dracunculiasis) eradication led by the Carter Center and the Centers for Disease Control and Prevention is another example. Guinea worm disease is poised to be the next disease after smallpox to be eradicated by identifying and addressing the political, structural, logistic, and attitudinal barriers to infection control and by using core public health practices of surveillance, case containment, and evidence-based intervention.

We are on the edge of exciting discoveries and initiatives to improve the lives of children and the adults they will become. It is an extraordinary time of new research tools, including electronic health records, technological ability to gather and manage big data and measure “omics,” and new functional and structural imaging modalities. These tools will discern mechanisms leading to health and disease, with new prevention targets and cures. The 7 achievements discussed are not exhaustive, and we welcome discussion of these 7 and more in Pediatrics’ online reader comments.

The inclusion of children and adolescents in clinical research is essential to ensure that these individuals benefit from important scientific discoveries. Furthermore, studying child health across the stages of development is critical for understanding the pathophysiology of disease into adulthood and is the basis for developing preventive and curative treatments for chronic adult illnesses. As a start, it is important to collect reliable data and report on the number of ongoing pediatric studies in different age groups and the number of children enrolled. National Institutes of Health (NIH) funding is the backbone of the research enterprise at US academic medical centers. Since 2001, pediatric departments have had decreased success rates for NIH funding compared with other departments,33 and the proportion of the NIH budget devoted to the pediatric research portfolio has reportedly declined.34 

Conducting pediatric research presents unique challenges and requires special support. The relative rarity of serious child health problems reflects the success of previous research but also presents challenges in conducting clinical trials with large enough sample sizes. Also, child research often requires longer time frames to assess outcomes. Pediatric clinical drug trials are an example. Because of the scientific, ethical, and operational challenges of drug trials in children, many drugs and devices are brought to market without pediatric indications and pediatric-specific labeling. A median of 9 years passes from approval of adult-use drugs and the inclusion of pediatric data in product labels.35 Reasons for this disparity include the smaller pool of patients available for trials in children, thus requiring a larger number of sites to achieve a sufficient sample size; another reason for this disparity, from a business perspective, is the higher fixed and marginal costs for drug companies to develop new drugs with less potential downstream profit.36 Uniting key stakeholders, including children and their families, academia, industry, and government agencies, in a public–private partnership for clinical trials could foster faster development of new drugs, devices, and biomedical innovation. Support of infrastructure for this type of network and expansion (eg, more sites, longer term outcome studies) of other collaborative pediatric research networks for drug trials or other research (eg, Pediatric Trials Network,37 Children’s Oncology Group38) are essential to address the barriers to pediatric research progress.

The need for more longitudinal cohort studies with longer time frames to assess outcomes will be assisted by the use of electronic medical records and research investments such as the Environmental Influences on Child Health Outcomes (ECHO) program, which supports multiple, synergistic, longitudinal studies by using existing study populations.39 In the Federation of Pediatric Organization's Visioning Summit on the Future of the Workforce in Pediatrics, a key research recommendation was to “create common data systems to support child health research and education that link to patient outcomes.”40 Electronic health records will assist in longitudinal data collection but must also link families across generations and must include genetic and social factors for optimal clinical and research impact. Linking electronic health records to biologic specimens for research and to other system databases such as birth records and education or social services data could enhance efforts to understand the mechanisms of poor health and development.

Finally, augmenting the researcher pipeline in pediatric and life course research must be a priority. This approach will require training programs starting in college and professional school and spanning a research career. With fewer physicians choosing and sustaining research careers, partnerships between the NIH, other public and private institutions, academic medical centers, and other stakeholders must inspire the next generation of scholars.33 

Research in child health is a proven investment in adult health, with societal payoff. Underinvestment puts our next generation of research gains and our next generation of children at risk. We often take for granted the research progress of the past. Continued progress requires heightened focus on pediatric research and investment in our future: children.

     
  • NIH

    National Institutes of Health

All authors conceptualized and drafted the manuscript, and all authors approved the final manuscript as submitted.

FUNDING: No external funding.

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: Dr Cheng was past Chair of the American Academy of Pediatrics Committee on Pediatric Research, and Dr Bogue is the current Chair. Dr Dover has indicated he has no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.