‘Praemonitus, praemunitus’: Engaging with late effects

Forewarned is forearmed. Having rich information with regard to the trajectory of childhood conditions provides practitioners with ammunition to help children and their families in dealing with long-term and/or late-onset sequelae. Moreover, having this knowledge could lead to attempts to prevent or minimize the consequences of illness, impairments, experiences, and treatments. This philosophy aligns with contemporary models of health care and education that promote broader preventative programs rather than waiting to treat the unexpected sequelae. Furthermore, monitoring the trajectory of childhood conditions might inform us about many conditions that became apparent in adulthood. Although childhood neurodevelopmental conditions often resolve, some with treatment and others without, many are lifelong. In addition, the increasing survival of children following medical treatment and/or rehabilitation calls for researchers and clinicians to engage more with long-term sequelae. In most cases, we have little information about the trajectory of childhood conditions.

Fortunately there is a growing literature that informs us about long-term effects, the pervasive, sometimes changing, but persisting symptomatology of childhood conditions that persist into adolescence and adulthood. More elusive are ‘late effects’, those symptoms that manifest later – sometimes decades later – in life. Not only do we have little knowledge of what the late effects are, but even less to inform our theories as to why they appear, and why they appear later. Although central to the definition of late effects is that the symptoms are absent earlier, it is also possible that effects could be present earlier, but are sub-clinical or unrecognized. Some late effects are visible, while many require testing to become apparent.

Research on children at risk of developmental delays has demonstrated an array of consequences that appear later in life. Unfortunately, many studies are limited by their short-term follow-up intervals. Furthermore, it is difficult to disentangle the variables in retrospective or long-term prospective studies because their interactions are multi-faceted. Consider, for example, the identification of the late effects of otitis media with effusion (OME). OME results in a temporary mild conductive hearing loss. For decades researchers have tried to determine whether OME in childhood leads to late effects in language development and other developmental domains [1]. Methodological threats are posed by tangled variables. The disease is extremely variable; research has not determined who is at risk of OME, or how often children get OME. Little research tracks the severity of the disease through its trajectory, and treatment protocols vary in different contexts. The conductive hearing loss fluctuates, sometimes leading to other auditory or vestibular complications, and as well as variability in the disease itself, many children who have a history of OME are also at the risk of other factors such as low birthweight or spending significant hours in child care settings [2]. The critical gaps in our knowledge about the late effects of OME should point us in a direction in which we must develop comprehensive, multidisciplinary long-term follow-up protocols for all children with complex childhood conditions such as OME, in which we describe the disease or impairments, the treatments, the contexts of the children's lives, and their outcomes.

The research on childhood cancer has yielded lessons with regard to the study of late effects. Not only has this research demonstrated what the late effects are [3], but has informed medical practice such that treatment protocols and options for childhood cancer treatment can be better negotiated and more informed decisions can be made [4]. These studies have also demonstrated the need for multi-disciplinary, long-term follow-up and the need for life-long risk-based care for all survivors of childhood cancer [3]. A number of researchers who have engaged with the late effects of childhood cancer have recommended that follow-up protocols are flexible, quick, economical, standardized, and free from theoretical constraints and ambiguous terminology.

We might be well served by following these recommendations to develop purposeful long-term tracking of childhood conditions. We will have to urge parents, professionals, and later the children themselves to buy into follow-up protocols. Examples can be taken from the swelling reservoir of data that has shown that the late effects of childhood traumatic brain injury can be significant and persistent and can have deleterious effects on a range of developmental outcomes [5]. The information gleaned can lead to the development of theory – consider, for example, the theories pertaining to the development of the frontal lobe in children who have sustained a TBI where understanding the late effects of TBI has contributed to the understanding of the development of executive functions in children [6].

Similar to the follow-up protocols, the understanding of late effects calls for retrospective studies. It is sometimes extremely difficult to ascribe a relationship between the childhood condition and the adult symptomatology. Post-polio syndrome, in which many adult survivors of childhood polio experience a range of symptoms that appear decades after the childhood illness, is well recognized today, but it was not without skepticism that this conclusion was drawn and it took quite some time for post-polio syndrome to become a recognized entity. Even today the research is neither unequivocal nor conclusive [7]. Similarly, the late effects of Wilson's disease that arise from abnormal copper accumulation that begins at birth are fairly well recognized, but the symptoms are not always easy to link to copper metabolism [8].

In some conditions, the relationship is especially obscure. Consider, for instance, some of the research in psychiatry in which childhood and adulthood variables are knotted. It is often exceptionally difficult to relate the adults’ symptomatology of schizophrenia to childhood conditions [9]. Similarly, it is exceptionally difficult to relate the adult's psychosocial outcomes to early childhood experiences of living with mothers who have psychiatric disorder [10]. Clearly, there is a need for us to move beyond trying to disentangle the knots, and the ineffectual attempts to control for all variables, and rather examine associations and correlations critically. Rusby and Tasker [11] whose fascinating work investigated the late effects of separation from parents during World War II, demonstrated “the importance of knowledge of childhood history in the clinical treatment of older adults”.

Even so, childhood history is not always crystal clear. Sometimes effects are not recognized by clinicians and researchers as being related to a childhood condition because development in children, particularly young children, is rapid, always changing, and variable. There are also some effects that remain unrecognized in children because of our lack of understanding of normal developmental processes. One such example is depression in children which was unrecognized for many years as it was thought that those sections of the mind only developed in late childhood or adolescence, and hence it was presumed that children could not suffer from depressive mood disorders until they were older. In addition, depression may be unrecognized in younger children because it can have an insidious onset, be less apparent in children because they have less of a “role burden” than adults have [12], be related to other childhood conditions, and the symptoms can be variable. Effects like this are not latent, they are unrecognized.

If we are to be forewarned, we have much work to do. As researchers and clinicians, we must recalibrate our approaches to the assessment and management of childhood neurodevelopmental conditions such that we look to the future of the children, and re-examine the earlier lives of adults. And, as the childhood cancer literature has shown, we have to be sensitive to forewarning parents and children about their future. Getting through childhood with an illness or a disability is an achievement and knowing what is still to come might not be easy to live with. It is a challenge to neurodevelopmental rehabilitation to bring together humanities and sciences to ensure that the information about late effects is reliable and worthwhile.