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Young Adult Patients with a History of Pediatric Disease: Impact on Course of Life and Transition into Adulthood

      Abstract

      Purpose

      To assess the course of life of young adults who grew up with a chronic or life-threatening disease, and to compare their course of life with that of peers from the general population. Optimal transition from pediatric to adult health care requires knowledge of the psychosocial history of patients grown up with a pediatric disease.

      Methods

      A total of 508 young adults from the general Dutch population and 650 patients, aged 18–30 years, participated: 348 survivors of childhood cancer, 93 patients with anorectal malformations, 72 patients with Hirschsprung’s disease, 61 patients with oesophageal atresia, 76 patients with end-stage renal disease. They completed the Course of Life Questionnaire, which retrospectively assesses the achievement of developmental milestones (autonomy, psychosexual and social development), and risk behavior (antisocial behavior, substance use and gambling).

      Results

      The young adults grown up with a chronic or life-threatening disease proved to have achieved significantly fewer milestones, or at older age than their peers, in all course-of-life domains. The course of life of young adults grown up with esophageal atresia was not delayed compared with that of their peers, whereas that of survivors of childhood cancer and patients with end-stage renal disease was delayed most.

      Conclusions

      Health care providers should help to minimize the harm for children who grow up with a chronic or life-threatening disease by encouraging parents to stimulate social contacts and autonomy. Attention should especially be directed at children and adolescents growing up with childhood cancer or with end-stage renal disease.

      Keywords

      As the treatment of children with chronic or life-threatening disease (referred to as “chronic disease” from this point to improve readability) has dramatically improved over recent decades, more and more pediatric patients will reach adulthood. As a result, more and more physicians will be confronted with young adult patients having grown up with chronic diseases. Optimal transition from pediatric to adult health care requires physicians with knowledge of the psychosocial history of growing up with a chronic pediatric disease.
      Concern has risen about the implications of chronic pediatric disease later in life. Children with a chronic disease are somewhat more likely than healthy children to show maladjustment [
      • Eiser C.
      Psychological effects of chronic disease.
      ,
      • Lavigne J.V.
      • Faier-Routman J.
      Psychological adjustment to pediatric physical disorders a meta-analytic review.
      ,
      • Cadman D.
      • Boyle M.
      • Szatmari P.
      • et al.
      Chronic illness, disability and mental and social well-being findings of the Ontario Child health study.
      ]. They tend to suffer more than average from behavior problems, especially internalizing problems such as depression, anxiety, and social withdrawal [
      • Boekaerts M.
      • Röder I.
      Stress, coping, and adjustment in children with a chronic disease a review of the literature.
      ]. Children with both chronic illness and associated disability are at considerable risk for social adjustment problems [
      • Cadman D.
      • Boyle M.
      • Szatmari P.
      • et al.
      Chronic illness, disability and mental and social well-being findings of the Ontario Child health study.
      ]. The impact of chronic disease in childhood on the course of life is less well understood [
      • Gledhill J.
      • Rangel L.
      • Garralda E.
      Surviving chronic physical illness psychosocial outcome in adult life.
      ]. Fulfilling developmental tasks and achieving developmental milestones in youth (such as search for contacts outside the family, or acquisition of independence), referred to as the “course of life,” are of great importance to the adjustment in adult life [
      • Garber J.
      Classification of childhood psychopathology a developmental perspective.
      ,
      • Lewis M.
      • Miller S.M.
      ]. Chronic disease in children often increases dependence on caretakers, and decreases participation in peer- and school-based activities [
      • Calsbeek H.
      • Rijken M.
      • Bekkers M.J.T.M.
      • et al.
      Social position of adolescents with chronic digestive disorders.
      ,
      • Vannatta K.
      • Zeller M.
      • Noll R.B.
      • et al.
      Social functioning of children surviving bone marrow transplantation.
      ,
      • La Greca A.M.
      Social consequences of pediatric conditions fertile area for future investigation and intervention.
      ,
      • Miller B.D.
      • Wood B.L.
      Childhood asthma in interaction with family, school, and peer systems a developmental model for primary care.
      ], which may affect the achievement of developmental milestones. Furthermore, puberty may be delayed, depending on the illness. For example, patients with Crohn’s disease, cystic fibrosis, and chronic renal disease may enter puberty later than average [
      • Blum R.W.M.
      Chronic illness and disability in adolescence.
      ].
      From a developmental psychology point of view, risk behavior is also relevant because displaying risk behavior—in terms of trying out—is, to a certain extent, part of the development from being a teenager to becoming an adult. It is conceivable that chronically ill teenagers display less risk behavior than healthy peers because they are aware of just how vulnerable their health is [
      • Tyc V.L.
      • Hadley W.
      • Crockett G.
      Predictors of intentions to use tobacco among adolescent survivors of cancer.
      ,
      • Weinstein N.D.
      Testing four competing theories of health-protective behavior.
      ]. Moreover, increased parental involvement as a result of the chronic illness [
      • Miller B.D.
      • Wood B.L.
      Childhood asthma in interaction with family, school, and peer systems a developmental model for primary care.
      ,
      • Rait D.S.
      • Ostroff J.S.
      • Smith K.
      • et al.
      Lives in balance perceived family functioning and the psychosocial adjustment of adolescent cancer survivors.
      ], and treatment regimens that restricts a child’s physical activity may limit a child’s opportunities for unsupervised time with peers, which may decrease a child’s opportunities to engage in risk activities with peers [
      • La Greca A.M.
      Social consequences of pediatric conditions fertile area for future investigation and intervention.
      ]. On the other hand, we might expect chronically ill adolescents to display more risk behavior to compensate for the restrictions caused by the disease. Previous studies among survivors of childhood cancer showed inconsistent results about this matter [
      • Haupt R.
      • Byrne J.
      • Connelly R.R.
      • et al.
      Smoking habits in survivors of childhood and adolescent cancer.
      ,
      • Tao M.L.
      • Guo M.D.
      • Weiss R.
      • et al.
      Smoking in adult survivors of childhood acute lymphoblastic leukemia.
      ,
      • Verrill J.R.
      • Schafer J.
      • Vannatta K.
      • et al.
      Agression, antisocial behavior, and substance abuse in survivors of pediatric cancer possible protective effect of cancer an its treatment.
      ,
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ].
      All these implications of chronic diseases could be a threat to the accomplishment of developmental tasks, resulting in a delayed course of life. Retardation in development may have significant consequences for later functioning and quality of life (QoL), e.g., development of autonomy appeared to be positively related with both health outcomes and ego development [
      • DiNapoli P.P.
      • Murphy D.
      The marginalization of chronically ill adolescents.
      ].
      The main purpose of the study was to investigate the course of life of young adults grown up with a chronic disease, because, as far as we know, this has never been done before. An explorative study among diverse patient groups was designed, starting global with a large group (chronic conditions as a whole) and ending more detailed (results by disease group). Our first hypothesis was that the course of life of young adults having grown up with a chronic disease would be delayed. That means that we expected them to have fulfilled fewer milestones, or to have reached the milestones when they were older, than the general population (reference group). In addition, we expected differences between the young adults having grown up with a chronic disease and the reference group on the domains of risk behavior. Second, we hypothesized that differences in the course of life would be found among the several disease groups because of the diverse medical consequences of the diseases.

      Methods

      Procedures

      The course of life was examined in several patient groups participating in studies at the academic children’s hospitals in The Netherlands: survivors of childhood cancer (SCC), patients with anorectal malformations (ARM), patients with Hirschsprung disease (HD), patients with esophageal atresia (EA), and patients with end-stage renal disease (ESRD). Norm data of the Course of Life Questionnaire were available for young adults aged 18–30 years [
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ]. Therefore, patients either less than 18 years or over 30 years were excluded from analyses.
      Patients were invited to participate by letter and filled in an informed consent form. The study protocol was approved by the Medical Ethic Committee of the Academic Medical Centre Amsterdam. More information about the procedures of the studies is reported in the Appendix.

      Measures

      The Course of Life Questionnaire was used to assess the achievement of developmental milestones. This instrument was developed by the Psychosocial Department of the Emma Children’s hospital [
      • Grootenhuis M.A.
      • Stam H.
      • Destrée-Vonk A.
      • et al.
      Levensloop Vragenlijst voor Jong-Volwassenen [Course of life questionnaire for young adults].
      ] to be able to investigate the course of life of young adults who have grown up with a chronic or life-threatening disease, and to facilitate comparison with peers without a history of disease. The items concern behavior characteristics of certain age stages, developmental tasks, and the limitations children might face when they grow up with a chronic disease. Most questions ask retrospectively whether the respondent had achieved certain milestones or at what age the respondent achieved the milestones. The answers are dichotomized, if necessary, before being added up to the scale-score. The items are divided into five scales: autonomy development (6 items, autonomy at home and outside the home), psychosexual development (4 items, love and sexual relations), social development (12 items, contacts with peers), antisocial behavior (4 items, misbehavior at school and outside it), and substance use and gambling (12 items). In the current study, one item (“the use of hard drugs after finishing secondary school”) was left out because the answers were not reliably filled in owing to a mistake in the layout. A higher score on the first three scales indicates the accomplishment of more developmental milestones. Higher scores on antisocial behavior and on substance use and gambling mean that the respondent displays more risk behavior.
      The validity of the course-of-life scales is good. First, the items are based on the literature and clinical experience. Second, the results among a normative population of 508 young adults from the general Dutch population proved to be in line with several datasets of the Dutch population [
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ,
      • Grootenhuis M.A.
      • Stam H.
      • Destrée-Vonk A.
      • et al.
      Levensloop Vragenlijst voor Jong-Volwassenen [Course of life questionnaire for young adults].
      ]. The test-retest reliability is good (r ≥ .86) [
      • Last B.F.
      • Grootenhuis M.A.
      • Destrée-Vonk A.
      • et al.
      De ontwikkeling van een levensloopvragenlijst voor jong-volwassenen (LVJV) [The development of a course of life questionnaire for young adults].
      ]. The internal consistency of the scales is satisfactory, except of the autonomy scale, probably because the items concern diverging aspects of autonomy [
      • Grootenhuis M.A.
      • Stam H.
      • Destrée-Vonk A.
      • et al.
      Levensloop Vragenlijst voor Jong-Volwassenen [Course of life questionnaire for young adults].
      ]. The Cronbach alphas (α) in the populations under study were: autonomy development α = .43–.57; psychosexual development α = .68–.79; social development α = .59–.83; antisocial behavior α = .37–.75; substance use and gambling α = .70–.78. The Cronbach alpha for the antisocial behavior scale as found in the patients treated for ARM was bad (α = .37).
      Medical data of the SCC were obtained from the registry at the long-term follow-up clinic at The Emma Children’s Hospital AMC [
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ]. Medical information about the ARM or HD patients was obtained from the database constructed for the “NAHO study” that contained medical data of all children treated at the Pediatric Surgical Centre of the Netherlands [
      • Hartman E.E.
      • Oort F.J.
      • Aronson D.C.
      • et al.
      Critical factors affecting quality of life of adult patients with anorectal malformations or Hirschsprung’s disease.
      ]. Medical data of the EA patients were obtained from the database of patients treated for EA at the Pediatric Surgical Centre of Amsterdam [
      • Deurloo J.A.
      • Ekkelkamp S.
      • Schoorl M.
      • et al.
      Esophageal atresia historical evolution of management and results in 371 patients.
      ]. Medical data of the ESRD patients were derived from the ‘LERIC-study’, collected by chart review of all available charts in 37 hospitals in the Netherlands [
      • Groothoff J.W.
      • Grootenhuis M.A.
      • Offringa M.
      • et al.
      Quality of life in adults with end-stage renal disease since childhood is only partially impaired.
      ].

      Statistical analysis

      The Statistical Package for the Social Sciences (SPSS Inc., Chicago, Illinois) Windows version 11.5 was used for all analyses. Before conducting the final analyses, scales were constructed and their reliability was calculated. To detect confounders, differences between the demographics of the study groups were tested by applying ANOVA and chi-square tests. Furthermore, we formed a dummy variable for ‘group’ and took the reference group as reference for the analyses.
      After these preparatory analyses, chi-square tests, Mantel-Haenszel summary chi-square tests, and logistic regression analyses were conducted at the frequency distributions of the (dichotomous) items. The items scores of substance use and gambling, and antisocial behavior were calculated by gender, because of the known effect of gender [
      • Grootenhuis M.A.
      • Stam H.
      • Destrée-Vonk A.
      • et al.
      Levensloop Vragenlijst voor Jong-Volwassenen [Course of life questionnaire for young adults].
      ], and because of the lower percentage of women in the sample of HD than in the other samples. We used a significance level of p < .01 to compensate for the multiple testing.
      Furthermore, ANOVA was conducted on the scales with satisfactory internal consistency: Psychosexual development, social development, and substance use and gambling. The effect of disease was assessed, as well as the main effects for age and gender. In addition, we made post hoc comparisons (Bonferroni correction).
      Following Cohen [
      • Cohen J.
      ], effect sizes (d) of .2, .5, and .8 were considered small, medium, and large, respectively. Finally, to be sure about the results, we also performed nonparametric Mann-Whitney U tests and Kruskal-Wallis tests because the distributions of the scores of the course-of-life scales were not distributed quite normally.

      Results

      Patients

      The datasets provided information about the course of life of 1158 young adults aged 18–30 years: 348 SCC, 93 patients with ARM, 72 patients with HD, 61 patients with EA, 76 patients with ESRD (62 transplanted and 14 on chronic dialysis at the time of investigation), and 508 young adults from the general Dutch population (reference group). Four patients suffering from both HD and EA were included in both patient samples. The patients with ARM, HD, or ESRD represent a national sample.
      Mean ages in the samples were comparable but they differed with respect to gender. The characteristics of the patient samples and the reference group are listed in Table 1.
      Table 1Demographic and medical characteristics
      Childhood cancerAnorectal malformationsHirschsprungEsophageal atresiaRenal diseaseReference group
      Number of patients
      Medical data were not available for all patients.
      348
      Primary diagnosis: leukemia/lymphoma 49.7%, solid tumor 43.1%, brain tumor 7.2%; treatment: chemotherapy (with/without surgery) 56.3%, radiotherapy (with/without surgery) 4.0%, combination therapy (chemotherapy and radiotherapy, with/without surgery) 32.2%, surgery alone 7.5%.
      93726176
      18.4% on dialysis at time of investigation, 81.6% transplanted.
      508
      Female (%)50.347.316.745.948.753.0
      Mean age at study (years)24.3 (18.7–30.9)24.8 (20.1–30.7)24.1 (20.0–30.8)23.8 (18.0–30.8)25.3 (20.7–30.8)24.2 (18.0–30.9)
      Dutch origin (%)96.598.910010086.896.1
      Age at first diagnosis (years)7.3 (.0–17.0)At birthFirst year of lifeAt birth10.2 (1.9–14.4)
      Onset renal replacement therapy.
      NA
      Mean time since first diagnosis (years)17.0 (6.2–30.7)NANANANANA
      Mean time since end of last treatment (years)15.4 (5.0–30.3)NANANANANA
      Mean duration of treatment (years)1.0 (.0–6.0)NANANA3.4 (.0–19.9)
      Mean time on dialysis 3.4 (0.0–19.9), mean time with a renal graft 11.2 (0.0–23.0).
      NA
      Relapse or second malignancy (%)12.4NANANANANA
      Additional congenital malformations (%)NA64.513.941.0NANA
      Stoma (%)NA6.52.8NANANA
      Disabilities (%)
      Motor, visual or auditory disability.
      NANANANA14.5NA
      On dialysis at time of study (%)NANANANA18.4
      81.6% renal transplanted at time of study.
      NA
      Mean age at onset renal replacement therapy (years)NANANANA10.2 (1.9–14.4)NA
      NA = not applicable.
      a Medical data were not available for all patients.
      b Motor, visual or auditory disability.
      c Primary diagnosis: leukemia/lymphoma 49.7%, solid tumor 43.1%, brain tumor 7.2%; treatment: chemotherapy (with/without surgery) 56.3%, radiotherapy (with/without surgery) 4.0%, combination therapy (chemotherapy and radiotherapy, with/without surgery) 32.2%, surgery alone 7.5%.
      d 18.4% on dialysis at time of investigation, 81.6% transplanted.
      e Onset renal replacement therapy.
      f Mean time on dialysis 3.4 (0.0–19.9), mean time with a renal graft 11.2 (0.0–23.0).
      g 81.6% renal transplanted at time of study.

      Course of life of young adults grown up with a chronic disease versus the reference group

      The young adults who grew up with a chronic disease (as a whole) differed significantly from the reference group on one or more milestones in all developmental domains (Table 2). Furthermore, they turned out to display less antisocial behavior and their prevalence of substance use during secondary school was lower than among the reference group (Table 3).
      Table 2Autonomy, psychosexual and social development; young adults grown up with a chronic disease
      Chronic diseases included: survivors of childhood cancer (SCC), patients with anorectal malformations (ARM), patients with Hirschsprung’s disease (HD), patients with esophageal atresia (EA), and patients with end-stage renal disease (ESRD).
      versus reference group
      Chronic disease % (n)Reference group % (n)p Value
      Chi-square-test.
      Autonomy development
       Paid jobs, secondary school
        At the age of 18 or younger81.6 (528)87.4 (443).009
        At the age of 19 or older/never18.4 (119)12.6 (64)
       For the first time being on holiday without adults
        At the age of 17 or younger40.2 (259)52.9 (268)< .001
        At the age of 18 or older/never59.8 (385)47.1 (239)
      Psychosexual development
       First girlfriend/boyfriend
        At the age of 17 or younger58.2 (375)80.4 (407)< .001
        At the age of 18 or older/never41.8 (269)19.6 (99)
       For the first time sexual intimacy
        At the age of 18 or younger67.4 (430)83.4 (421)< .001
        At the age of 19 or older/never32.6 (208)16.6 (84)
       For the first time sexual intercourse
        At the age of 18 or younger43.1 (276)58.5 (296)< .001
        At the age of 19 or older/never56.9 (364)41.5 (210)
      Social development
       At least one year of membership in a sports club, primary school
        Yes71.9 (466)84.2 (427)< .001
        No28.1 (182)15.8 (80)
       At least one year of membership in a sports club, secondary school
        Yes58.9 (382)73.6 (373)< .001
        No41.1 (267)26.4 (134)
       Number of friends, secondary school
        < 441.7 (270)30.4 (154)< .001
        ≥ 458.3 (377)69.6 (352)
       Leisure time, mainly with ....., secondary school
        Friends78.7 (503)85.1 (430).006
        Brothers and/or sisters, parents, on your own21.3 (136)14.9 (75)
       At least 1 year of membership in a sports club, after secondary school
        Yes39.3 (252)48.9 (243).001
        No60.7 (390)51.1 (254)
      a Chronic diseases included: survivors of childhood cancer (SCC), patients with anorectal malformations (ARM), patients with Hirschsprung’s disease (HD), patients with esophageal atresia (EA), and patients with end-stage renal disease (ESRD).
      b Chi-square-test.
      Table 3Antisocial behavior and substance use and gambling; young adults grown up with a chronic disease
      Chronic diseases included: survivors of childhood cancer (SCC), patients with anorectal malformations (ARM), patients with Hirschsprung’s disease (HD), patients with esophageal atresia (EA), and patients with end-stage renal disease (ESRD).
      versus reference group, by gender
      Males % (n)Females % (n)p Value
      Mantel Haenszel summary chi-square-test.
      Chronic diseaseReference groupChronic diseaseReference group
      Antisocial behavior
       Ever been refused admission to lessons, secondary school
        Yes29.8 (105)44.5 (106)18.2 (54)25.3 (68)< .001
        No70.2 (247)55.5 (132)81.8 (242)74.7 (201)
      Substance and gambling
       Alcohol, secondary school
        Never/occasionally75.1 (265)62.2 (148)86.4 (255)82.1 (220).001
        Often/very often24.9 (88)37.8 (90)13.6 (40)17.9 (48)
       Smoking, secondary school
        No69.5 (244)66.2 (157)72.6 (215)55.0 (148)< .001
        Yes30.5 (107)33.8 (80)27.4 (81)45.0 (121)
       Soft drugs, secondary school
        Never76.9 (270)58.2 (138)85.1 (252)81.4 (219)< .001
        Occasionally/often/very often23.1 (81)41.8 (99)14.9 (44)18.6 (50)
       Smoking, after secondary school
        No59.1 (205)55.3 (126)67.7 (197)49.3 (132)< .001
        Yes40.9 (142)44.7 (102)32.3 (94)50.7 (136)
       Soft drugs, after secondary school
        Never70.0 (245)61.1 (140)84.9 (248)79.1 (212)< .001
        Occasionally/often/very often30.0 (105)38.9 (89)15.1 (44)20.9 (56)
      a Chronic diseases included: survivors of childhood cancer (SCC), patients with anorectal malformations (ARM), patients with Hirschsprung’s disease (HD), patients with esophageal atresia (EA), and patients with end-stage renal disease (ESRD).
      b Mantel Haenszel summary chi-square-test.
      Finally, the young adults grown up with a chronic disease had significantly lower (p < .001) scale scores, small to moderate effect sizes (d), meaning that they had achieved fewer milestones, or that they achieved the milestones when they were older than the reference group: psychosexual development F (1,1123) = 24.10, d = .50, social development F (1,1032) = 52.43, d = .27, and substance use and gambling F (1,1105) = 25.83, d = .25. The results were confirmed by nonparametric Mann-Whitney U tests.

      Course of life across disease categories

      Table 4, Table 5 present the milestones on which the several disease groups differed significantly from the reference group. The SCC as well as the ARM and ESRD patients reported fewer milestones with respect to autonomy development than the reference group. Except for the EA patients, all the disease groups differed from the reference group on most of the milestones of psychosexual development. The SCC and the ESRD and ARM patients reported having fulfilled fewer milestones on social development than the reference group, although this was not true for the HD and EA patients. The SCC and the ESRD patients were the only disease groups that displayed less antisocial behavior and substance use than the reference group.
      Table 4Autonomy, psychosexual and social development; young adults grown up with a chronic disease versus reference group
      CC % (n)ARM % (n)HD % (n)EA % (n)ESRD % (n)Ref % (n)p Value
      Significant for group according to logistic regression.
      Autonomy development
       Paid jobs, secondary school
        At the age of 18 or younger79.9
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (278)
      90.0 (81)91.7 (66)93.4 (57)60.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (46)
      87.4 (443)< .001
        At the age of 19 or older/never20.1 (70)10.0 (9)8.3 (6)6.6 (4)39.5 (30)12.6 (64)
       For the first time being on holiday without adults
        At the age of 17 or younger43.1
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (149)
      36.3
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (33)
      41.7 (30)40.7 (24)30.3
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (23)
      52.9 (268)< .001
        At the age of 18 or older/never56.9 (197)63.7 (58)58.3 (42)59.3 (35)69.7 (53)47.1 (239)
      Psychosexual development
       First girlfriend/boyfriend
        At the age of 17 or younger61.3
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (212)
      64.8
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (59)
      62.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (45)
      64.4
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (38)
      27.6
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (21)
      80.4 (407)< .001
        At the age of 18 or older/never38.7 (134)35.2 (32)37.5 (27)35.6 (21)72.4 (55)19.6 (99)
       For the first time falling in love
        At the age of 18 or younger87.4 (299)91.1 (82)83.1 (59)94.9 (56)76.0
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (57)
      91.7 (462)< .001
        At the age of 19 or older/never12.6 (43)8.9 (8)16.9 (12)5.1 (3)24.0 (18)8.3 (42)
       For the first time sexual intimacy
        At the age of 18 or younger69.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (237)
      67.8
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (61)
      69.4
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (50)
      71.2 (42)52.6
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (40)
      83.4 (421)< .001
        At the age of 19 or older/never30.5 (104)32.2 (29)30.6 (22)28.8 (17)47.4 (36)16.6 (84)
       For the first time sexual intercourse
        At the age of 18 or younger47.8
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (164)
      42.2
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (38)
      38.9
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (28)
      50.8 (30)21.1
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (16)
      58.5 (296)< .001
        At the age of 19 or older/never52.2 (179)57.8 (52)61.1 (44)49.2 (29)78.9 (60)41.5 (210)
      Social development
       At least 1 year of membership in a sports club, primary school
        Yes73.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (255)
      76.1 (70)75.0 (54)77.0 (47)52.6
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (40)
      84.2 (427)< .001
        No26.5 (92)23.9 (22)25.0 (18)23.0 (14)47.4 (36)15.8 (80)
       Number of friends in first–third grade, primary school
        < 435.3 (120)53.3 (49)30.4 (21)46.7 (28)23.7 (18)37.0 (187)< .001
        ≥ 464.7 (220)46.7
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (43)
      69.6 (48)53.3 (32)76.3 (58)63.0 (319)
       Number of friends in fourth–sixth grade, primary school
        < 434.7 (120)55.4 (51)29.6 (21)42.6 (26)27.6 (21)30.9 (156)< .001
        ≥ 465.3 (226)44.6
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (41)
      70.4 (50)57.4 (35)72.4 (55)69.1 (349)
       At least 1 year of membership in a sports club, secondary school
        Yes61.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (214)
      57.0
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (53)
      63.4 (45)68.9 (42)36.8
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (28)
      73.6 (373)< .001
        No38.5 (134)43.0 (40)36.6 (26)31.1 (19)63.2 (48)26.4 (134)
       Number of friends, secondary school
        < 441.0 (142)50.5 (47)37.5 (27)38.3 (23)40.8 (31)30.4 (154).002
        ≥ 459.0
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (204)
      49.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
       (46)
      62.5 (45)61.7 (37)59.2 (45)69.6 (352)
       Leisure time, mainly with ....., secondary school
        Friends77.5
      Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
       (265)
      80.2 (73)81.4 (57)85.0 (51)75.0 (57)85.1 (430).006
        Brothers and/or sisters, parents, on your own22.5 (77)19.8 (18)18.6 (13)15.0 (9)25.0 (19)14.9 (75)
      CC = childhood cancer; ARM = anorectal malformations; HD = Hirschsprung’s disease; EA = esophageal atresia; ESRD = endstage renal disease, Ref = reference group.
      a Significant for group according to logistic regression.
      b Disease group differed significantly from the reference group, according to logistic regression analyses: p < .01.
      c Disease group differed significantly from the reference group, according to logistic regression analyses: p < .001.
      Table 5Antisocial behavior and substance use and gambling; young adults grown up with a chronic disease versus reference group, by gender
      Males % (n)Females % (n)p Value
      Significance for group according to logistic regression by gender.
      CCARMHDEAESRDRefCCARMHDEAESRDREf
      Antisocial behavior
       Ever been refused admission to lessons, secondary school
      SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .001.
      ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
        Yes25.6 (44)34.7 (17)37.3 (22)33.3 (11)28.2 (11)44.5 (106)18.3 (32)27.3 (12)8.3 (1)21.4 (6)8.1 (3)25.3 (68).001
        No74.4 (128)65.3 (32)62.7 (37)66.7 (22)71.8 (28)55.5 (132)81.7 (143)72.7 (32)91.7 (11)78.6 (22)91.9 (34)74.7 (201)
      Substance use and gambling
       Alcohol, secondary school
      ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
      SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
        Never/occasionally73.4 (127)81.3 (9)68.3 (41)69.7 (23)89.7 (35)62.2 (148)88.5 (154)81.8 (36)75.0 (9)82.1 (23)89.2 (33)82.1 (220).003
        Often/very often26.6 (46)18.7 (39)31.7 (19)30.3 (10)10.3 (4)37.8 (90)11.5 (20)18.2 (8)25.0 (13)17.9 (5)10.8 (4)17.9 (48)
       Smoking, secondary school
      SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .001.
        No73.7 (126)70.8 (34)60.0 (36)75.8 (25)59.0 (23)66.2 (157)78.3 (137)54.5 (24)58.3 (7)71.4 (20)73.0 (27)55.0 (148)< .001
        Yes26.3 (45)29.2 (14)40.0 (24)24.2 (8)41.0 (16)33.8 (80)21.7 (38)45.5 (20)41.7 (5)28.6 (8)27.0 (10)45.0 (121)
       Soft drugs, secondary school
      SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
        Never74.3 (127)81.3 (39)73.3 (44)87.9 (29)79.5 (31)58.2 (138)86.3 (151)81.8 (36)83.3 (10)78.6 (22)89.2 (33)81.4 (219).001
        Occasionally/often/very often25.7 (44)18.7 (9)26.7 (16)12.1 (4)20.5 (8)41.8 (99)13.7 (24)18.2 (8)16.7 (2)21.4 (6)10.8 (4)18.6 (50)
       Gambling, secondary school
      ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
        Never72.1 (124)69.4 (34)58.3 (35)60.6 (20)84.6 (33)62.9 (149)94.9 (166)93.2 (41)91.7 (11)92.9 (26)94.6 (35)91.0 (244).02
        Occasionally/often/very often27.9 (48)30.6 (15)41.7 (25)39.4 (13)15.4 (6)37.1 (88)5.1 (9)6.8 (3)8.3 (1)7.1 (2)5.4 (2)9.0 (24)
       Alcohol, after secondary school
      ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .001.
        Never/occasionally41.7 (70)41.7 (20)31.7 (19)24.2 (8)82.1 (32)33.8 (76)67.6 (115)65.1 (28)50.0 (6)50.0 (14)86.5 (32)63.5 (169)< .001
        Often/very often58.3 (98)58.3 (28)68.3 (41)75.8 (25)17.9 (7)66.2 (149)32.4 (55)34.9 (15)50.0 (6)50.0 (14)13.5 (5)36.5 (97)
       Smoking, after secondary school
      SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .001.
        No65.1 (110)61.7 (29)41.7 (25)63.6 (21)52.6 (20)55.3 (126)75.4 (129)41.9 (18)66.7 (8)57.1 (16)70.3 (26)49.3 (132)< .001
        Yes34.9 (59)38.3 (18)58.3 (35)36.4 (12)47.4 (18)44.7 (102)24.6 (42)58.1 (25)33.3 (4)42.9 (12)29.7 (11)50.7 (136)
       Soft drugs, after secondary school
      ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
        Never67.5 (114)75.5 (37)71.7 (43)60.6 (20)79.5 (31)61.1 (140)86.5 (148)75.0 (33)75.0 (9)82.1 (23)94.6 (35)79.1 (212).02
        Occasionally/often/very often32.5 (55)24.5 (12)28.3 (17)39.4 (13)20.5 (8)38.9 (89)13.5 (23)25.0 (11)25.0 (3)17.9 (5)5.4 (2)20.9 (56)
      CC = childhood cancer; ARM = anorectal malformations; HD = Hirschsprung’s disease; EA = esophageal atresia; ESRD = endstage renal disease; Ref = reference group.
      a Significance for group according to logistic regression by gender.
      b SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .001.
      c ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
      d SCC differed significantly from the reference group, according to logistic regression analyses by gender: p < .01.
      e ESRD differed significantly from the reference group, according to logistic regression analyses by gender: p < .001.
      Finally, all disease groups except the EA patients reported significantly lower scale scores than the reference group on psychosexual development (p < .001). The SCC were the only young adults who scored significantly lower than the reference group on social development (p < .001), and the SCC as well as the ESRD patients scored significantly lower on substance use and gambling (p < .001).

      Discussion

      To achieve optimal transition from pediatric to adult health care, physicians should have knowledge of the medical as well as the psychosocial history of patients grown up with a chronic disease. Therefore, the course of life of young adults grown up with diverse diseases (CC, ARM, HD, EA, ESRD) was investigated and compared with that of a reference group of young adults from the general Dutch population.
      The young adults grown up with a chronic disease (as a whole) reported a delayed course of life compared with that of the reference group. They achieved fewer milestones in the developmental domains autonomy, psychosexual, and social development, or achieved the milestones when they were older than the reference group. A delayed course of life could be considered unfavorable because achieving developmental milestones in youth is of great importance in the adjustment to adult life [
      • Garber J.
      Classification of childhood psychopathology a developmental perspective.
      ,
      • Lewis M.
      • Miller S.M.
      ].
      The young adults grown up with a chronic disease reported less risk behavior—in terms of trying out—than the reference group. Although the latter finding could be indicative of a deviant course of life, the display of less antisocial behavior and less substance use and gambling are in themselves not unfavorable. In contrast, it could be indicative of protective health behavior, which is of utmost importance for young adults with histories of chronic disease.
      The disease groups turned out to differ with respect to the course of life. The course of life of EA patients was found to be as favorable as that reported by the reference group, in contrast to that of the SCC and the ESRD patients, who reported having achieved fewer milestones in all domains, risk-taking behavior included.
      The differences found in the course of life of the diverse patient groups could indicate that the medical consequences of several diseases influence the course of life to a certain extent. The favorable course of life of the EA patients could be expected because EA, a congenital malformation of the esophagus, is usually repaired in the first week after birth so that gastrointestinal continuity is restored. On the other hand, the operation does not ensure normal esophageal function; gastroesophageal reflux and disturbed motility of the esophagus are frequently occurring problems after correction of EA [
      • Deurloo J.A.
      • Ekkelkamp S.
      • Bartelsman J.F.W.M.
      • et al.
      Gastroesophageal reflux Prevalence in adults older than 28 years after correction of esophageal atresia.
      ,
      • Tovar J.A.
      • Diez Pardo J.A.
      • Murcia J.
      • et al.
      Ambulatory 24-hour manometric and pH metric evidence of permanent impairment of clearance capacity in patients with esophageal atresia.
      ]. Nevertheless, in general, patients perceive their generic and disease specific QoL to be good [
      • Deurloo J.A.
      • Ekkelkamp S.
      • Hartman E.E.
      • et al.
      Quality of life in adults after correction of oesophageal atresia.
      ]. The course of life of the ARM and HD patients was hampered in the psychosexual domain. This is not unexpected considering the location of the malformations. Patients who grew up with HD scored as favorable as the general population in the social and autonomy domains, so these patients showed that they were able to adjust to their illness and to participate in social activities. Apart from the psychosexual domain, young adults with ARM also reported a less favorable course of life in the social and autonomy domains. This suggests that ARM had a more negative impact on daily life in childhood than HD had. These results are in line with the findings of a study on the QoL in young adults with ARM or HD. Hartman et al [
      • Hartman E.E.
      • Oort F.J.
      • Aronson D.C.
      • et al.
      Critical factors affecting quality of life of adult patients with anorectal malformations or Hirschsprung’s disease.
      ] found that both patient groups encountered overall physical health problems, but that only patients with ARM reported additional pain and limitations in role functioning owing to physical problems.
      The negative impact of CC and ESRD on daily life in childhood is enormous in comparison with the consequences of EA, ARM and HD, probably owing to the life-threatening nature of the disease, and the duration and consequences of treatment. It is known that suffering from CC and the subsequent treatment often increases the child’s dependence on adults, and decreases participation in peer- and school-based activities [
      • Vannatta K.
      • Zeller M.
      • Noll R.B.
      • et al.
      Social functioning of children surviving bone marrow transplantation.
      ,
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ,
      • Pendley J.S.
      • Dahlquist L.M.
      • Dreyer Z.
      Body image and psychosocial adjustment in adolescent cancer survivors.
      ,
      • Spirito A.
      • Stark L.J.
      • Cobiella C.
      • et al.
      Social adjustment of children succesfully treated for cancer.
      ,
      • Vannatta K.
      • Gartstein M.A.
      • Short A.
      • et al.
      A controlled study of peer relationships of children surviving brain tumors teacher, peer, and self ratings.
      ]. The same also applied for children with ESRD [
      • Brownbridge G.
      • Fielding D.M.
      Psychosocial adjustment to end-stage renal failure comparing heamodialysis, continuous ambulatory peritoneal dialysis and transplantation.
      ]. It is not surprising that the ESRD patients reported even fewer developmental milestones than the SCC. Not all SCC suffer from (the consequences of) the disease after treatment ends, whereas all patients with ESRD have to deal with a continuing disease. For children with ESRD, the medical regime is a continuous burden; dialysis is very time consuming. Even after transplantation, the consequences of the disease, such as medication, continue to influence the daily functioning of these patients.
      The findings of the current study are clinically relevant. In general, knowledge about possible gaps in the course of life could be useful in clinical practice because it enables health care providers to aim for the most favorable course of life for their patients. The results stress the importance of directing attention, especially to children growing up with CC and children with ESRD. Physicians currently treating young adult patients with these conditions should pay attention to their social and independent functioning, especially during transition from childhood to adulthood. Furthermore, the role of the patients’ parents comes into focus. It is known that parents of chronically ill children tend to overprotect their sick child [
      • Rait D.S.
      • Ostroff J.S.
      • Smith K.
      • et al.
      Lives in balance perceived family functioning and the psychosocial adjustment of adolescent cancer survivors.
      ], but this does not help the child to develop the personal skills needed to cope with the challenges of growing up with a chronic disease. Therefore, health care providers should help the parents stimulate and encourage the independence of their child.
      In most disease groups the young adults had achieved fewer milestones than the reference group with respect to psychosexual and social development. This finding indicates that it is even more important to encourage children with a chronic disease to make friends and to participate in peer activities and, if applicable, to maintain the social contacts they had before they became ill. Social development seemed to be related to psychosexual development (Pearson’s correlation .41, p < .01), so that friendships in youth are probably important for later sexual relationships. Peer relationships are important for social development and self-esteem, especially in adolescents. Adolescents with chronic illnesses may become marginalized by peers, rejected for being different at a time when body image and identity so largely depend on conformity [
      • DiNapoli P.P.
      • Murphy D.
      The marginalization of chronically ill adolescents.
      ]. Chronic illness may complicate the transition to adulthood, characterized by transition from family life to independent living and transition from education to employment, and is closely related to positive social and emotional development earlier on [
      • Sinnema G.
      Youths with chronic illness and disabitlity on their way to social and economic participation a health-care perspective.
      ].
      This article offers insight into the course of life in young adults grown up with a chronic disease in The Netherlands, though the questionnaire and the study encountered some limitations. First, it should be realized that the results cannot be generalized to all chronic or life-threatening diseases in childhood. Although the results need to be viewed with caution, knowledge about the possible impact of chronic disease on the course of life of the patients was obtained, because five quite different patient groups were studied and appeared to differ from each other. Second, the concept ‘course of life’ is more comprehensive than the milestones covered by the Course of Life Questionnaire. The fact that the course of life is measured retrospectively limits the range of topics. To prevent bias caused by inadequate memory, the questions are factual and do not go further back than to primary school, but the occurrence of bias is not guaranteed. Third, the differences found among the patient groups could be due to other than medical factors, such as coping with the disease, family functioning, and social support. Further (longitudinal) research would be worthwhile on (a) protective and risk factors with regard to a delayed course of life, such as medical determinants and personal characteristics of the patient and the parents, (b) the consequences of a delayed course of life for the adjustment in young adulthood, e.g., Quality of Life and sociodemographic outcomes such as employment, educational status, and living situation, and (c) interventions with respect to the course of life.

      Acknowledgments

      The research reported in this article has been supported and financed by the Dutch Cancer Society, the Netherlands Digestive Diseases Foundation, and the Dutch Kidney Association. We thank Dr. D.C. Aronson, Prof. Dr. H.N. Caron, Dr. B.F. Last, and Prof. Dr. M.A.G. Sprangers for their supervision and counseling on the several studies.

      Appendix.

      Survivors of childhood cancer (SCC)

      The data were collected in the context of the “VOLG study,” conducted by the Psychosocial Department of The Emma Children’s Hospital AMC, and directed at QoL of SCC. In 2001 and 2002, 499 consecutive young adult SCC who attended the long-term follow-up clinic at The Emma Children’s Hospital AMC were asked to fill in questionnaires. A total of 355 (71.0%) questionnaires were returned, of which 348 could be used in the current study (Table 1). A comprehensive description of the SCC has been reported in Stam et al [
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ].

      Patients with anorectal malformations (ARM) or Hirschsprung disease (HD)

      The data were collected in the context of a longitudinal study examining QoL of patients with ARM or HD (“NAHO study”). Between December 1998 and January 1999, 534 patients (aged 17 to 54 years) with ARM or HD, who had been treated in one of the seven Dutch Pediatric Surgical Centers or known at the two patient societies for ARM or HD, received a set of questionnaires. In December 2001, the 341 (64%) patients who completed the first questionnaires also were sent a second set of questionnaires, which additionally included the Course of Life Questionnaire used in this article. Two hundred sixty-one patients (77%) also completed the second booklet. The data of 93 patients with ARM and 72 patients with HD could be used in the current study (Table 1). A comprehensive description of the patients has been reported in Hartman et al [
      • Hartman E.E.
      • Oort F.J.
      • Aronson D.C.
      • et al.
      Critical factors affecting quality of life of adult patients with anorectal malformations or Hirschsprung’s disease.
      ].

      Patients with esophageal atresia (EA)

      The data were collected in the context of a follow-up study of patients treated for EA at the Pediatric Surgical Center of Amsterdam (Emma Children’s Hospital AMC and Vrije Universiteit Medical Center). Besides the functional outcome, the QoL of adults born with EA was studied.
      In 2002, a questionnaire was sent to 119 consecutive patients treated for EA between 1947 and 1985. Ninety-seven (82%) of the questionnaires were completed. The data of 61 patients with EA could be used in the current study (Table 1).

      Patients with end-stage renal disease (ESRD)

      The data were collected in the context of a national long-term follow-up study evaluating late physical, social, and psychological effects of renal insufficiency in children (LERIC).
      The LERIC cohort comprised all Dutch patients who had started chronic renal replacement therapy at age 0–14 years between 1972 and 1992, and born before 1979. Pre-emptively transplanted patients were included. Patients were recruited from the database of The National Dutch Registry of patients on renal replacement therapy (RENINE, Rotterdam, The Netherlands) and the database of all centers for pediatric nephrology in The Netherlands. A 1-day visit to the Emma Children’s Hospital AMC for the cross-sectional part of the study included the completion of the Course of Life Questionnaire. The data of 76 patients with ESRD (62 transplanted and 14 on chronic dialysis) could be used in the current study (Table 1). A comprehensive description of the patients with ESRD has been reported in Groothoff et al [
      • Groothoff J.W.
      • Grootenhuis M.A.
      • Offringa M.
      • et al.
      Quality of life in adults with end-stage renal disease since childhood is only partially impaired.
      ].

      Reference group

      The data were collected in the context of the VOLG study to provide a reference group for the young adult SCC. At the end of 2000 and 2001, 264 general practitioners (GPs) were asked to recruit 10 patients from their lists whose surnames started with a given letter of the alphabet, and who were of a given gender and age. A total of 82 (31.0%) GPs participated, who we assumed to have recruited 820 patients. The investigators received 517 (63%) questionnaires, of which 508 could be used in the current study (Table 1). A comprehensive description of the reference group has been reported [
      • Stam H.
      • Grootenhuis M.A.
      • Last B.F.
      The course of life of survivors of childhood cancer.
      ].

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