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The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study
Journal of Pediatric Surgery xxx (2015) xxx–xxx
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Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study☆,☆☆ Emma L. Harris a,b,c, Susannah J. Hart c,d, Corrado Minutillo b,⁎, Madur Ravikumara b, Teresa M. Warner a,d, Yvette Williams b, Elizabeth A. Nathan c,d, Jan E. Dickinson c,d a
Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women, Perth, WA, Australia Neonatal Intensive Care Unit, Princess Margaret Hospital for Children, Perth, WA, Australia Biostatistics Unit, Women and Infants Research Foundation, Perth, WA, Australia d School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia b c
a r t i c l e
i n f o
Article history: Received 11 May 2015 Received in revised form 26 August 2015 Accepted 30 August 2015 Available online xxxx Key words: Gastroschisis Outcome studies Questionnaires Infant Child Adolescent Congenital Surgery Neurodevelopment Intellect Psychology
a b s t r a c t Objectives: Previous gastroschisis specific neurodevelopmental studies have focused on the first 3 years of life. The aim of this study was to assess the intellectual, behavioral and neurological outcomes of older children and adolescents born with gastroschisis. Study design: Of 99 gastroschisis survivors born in Western Australia, 1992 to 2005, and who were at least 5 years old, 42 agreed to take part in this study. The study assessed: intellectual ability, with age appropriate Wechsler intelligence scales; neurological status; hearing; vision; behavioral status with the Strengths and Difficulties Questionnaire (SDQ); and parenting style with the Parenting Relationship Questionnaire (PRQ). All results were compared to normative means. Results: Median age at follow-up was 10 years (range 5–17). No child had evidence of cerebral palsy or hearing loss; 1 child had amblyopia. Psychometric tests were completed in 39 children: mean full scale IQ was 98.2 (standard deviation [SD] 10.7); the working memory index was the only subscale to show a significant decrease from the normative mean (mean 95.5, SD 12.4, p = 0.038). The mean SDQ behavioral scores were significantly lower for 3 of 5 domains and the Total Difficulties score. PRQ scores were significantly abnormal for 4 of 7 domains: Communication, Discipline, Satisfaction with School and Relational Frustration. Conclusions: Overall intellectual abilities were within a normal range. The decrease in working memory index and the behavioral and parenting relationship impairments could be an effect of perinatal factors, gastroschisis management and complications or the complexity of the socio-economic environment. Crown Copyright © 2015 Published by Elsevier Inc. All rights reserved.
1. Background Gastroschisis is a relatively common and serious congenital structural anomaly of the abdominal wall and bowel. Most countries report an increasing incidence [1–4], currently 2.4/10,000 births in Western Australia [5], with survival over 90% [6]. Children born with gastroschisis are frequently exposed Abbreviations: WISC IV, Wechsler Intelligence Scale for Children; WPPSI III, Wechsler Preschool and Primary Scale of Intelligence; FSIQ, Full Scale Intelligence Quotient; SDQ, Strengths and Difficulties Questionnaire; PRQ, Parenting Relationship Questionnaire; IUGR, intrauterine growth restriction; SD, standard deviation; SEIFA, Socio-Economic Index for Advantage. ☆ Disclosure: The study was funded by a research grant obtained from Channel 7 Telethon, Western Australia. ☆☆ The authors declare no conflict of interest, real or perceived by the study sponsor or authors in: (1) study design; (2) the collection, analyfcsis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. Dr Emma Harris wrote the first draft of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. ⁎ Corresponding author at: Princess Margaret Hospital for Children, GPO Box D184, Perth, Western Australia 6840, Australia. Tel.: +61 8 93408672; fax: +61 8 93407852. E-mail address: [email protected] (C. Minutillo).
to known risk factors for abnormal neuro-psycho-developmental outcome: for example, born to young, single mothers; exposed to maternal vasoactive and illicit drug use, both antenatally and postnatally [7,8]; are frequently delivered preterm and/or growth restricted [9,10]; and exposed to proinflammatory cytokines [11–15]. Even late preterm delivery, 34–36 weeks' gestation, confers a small risk of an adverse neurodevelopmental outcome compared with a term delivery [16–18]. In addition, recent animal and human studies have raised concerns about the neurodevelopmental effects of anesthesia [19] and surgery in young infants [20]. There is ample evidence of suboptimal neurodevelopmental outcomes following early cardiac surgery in infants [21] and increasing evidence of adverse neurodevelopmental outcomes following noncardiac, neonatal surgery [22–26]. Gastroschisis specific neurodevelopmental follow-up studies have been relatively reassuring, although these studies have been limited to children less than three years of age [6,27–29]. This study was designed and conducted with the primary aim to assess the neurocognitive and behavioral outcomes and the parent–child relationship of a state-wide population cohort of children and adolescents born with gastroschisis; children were at least five years old in order to give a longer term view of outcome.
http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062 0022-3468/Crown Copyright © 2015 Published by Elsevier Inc. All rights reserved.
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
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E.L. Harris et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx
2. Methods
decile of 10 [35]. The mother's postcode was that at the time of birth of her child with gastroschisis.
2.1. Data 2.2. Statistical methods All children and adolescents born with gastroschisis in Western Australia between 1992 and 2005 inclusive were identified through the Maternal Fetal Medicine Service Database at King Edward Memorial Hospital for Women (KEMH) and the Princess Margaret Hospital for Children neonatal database (Neobase). These two hospitals are the only tertiary obstetric and children's hospitals in Western Australia. All neonatal gastroschisis cases in Western Australia are managed at Princess Margaret Hospital, enabling complete case ascertainment. The medical records of each case were reviewed and relevant clinical data documented onto a preformed data sheet. Supplementary clinical, socio-economic and demographic data were collected at the time of the case examination for this study. The majority of neonates were managed with complete primary closure (90%), the preferred method during the study period. Details of the initial neonatal course and associated morbidities and the longer term surgical and growth outcomes of this cohort have been published previously [30]. An assessment of intellectual ability was made with either the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI), if less than 6 years old, or the Wechsler Intelligence Scale for Children IV (WISC), Australian Standardized Editions [31,32] by a trained psychologist (YW). The WISC-IV and WPPSI-III each has a mean of 100 and a standard deviation (SD) of 15 and each test has a set of sub scales, each with a mean of 10 and an SD of 3. These are internationally recognized tools commonly used in both medical practice and research. Parents or guardians completed the Strengths and Difficulties Questionnaire (SDQ); this is a commonly used behavioral screening questionnaire for 4–17 year old children [33]. The SDQ asks about 25 attributes; five questions in each of five domains: emotional symptoms; conduct problems; hyperactivity/inattention; peer relationship problems; and prosocial behavior. Scores from the first four attributes can be added together to generate a Total Difficulties Score. Normative data for the SDQ questionnaire have been reported for many nations including for Australian (7–17 years) and American (4–17 years) children. The study group means for each domain were compared to both the American and Australian population means. The SDQ manual categorizes each domain into four bands; the Very High (abnormal) band comprises the top 5% for all domains except for the Prosocial domain, and Very Low (abnormal) comprises the bottom 5%. The Parenting Relationship Questionnaire (PRQ) is designed to capture a parent's perspective of their parent–child relationship for children 2–18 years of age. Parents are asked 71 questions, which require a Never, Sometimes, Often and Almost Always response, which are scored 0, 1, 2, and 3 respectively. Each question relates to one of seven subscales: attachment, discipline practices, involvement, parenting confidence and relational frustration in the 2–5 year old group and, in addition, communication and satisfaction with school in children 6–18 years of age. Normative values for each of the subscales have been developed and are referred to as T scores, each with a mean and an SD of 50 and 10 respectively. T scores of two or more SDs below the mean (two or more above the mean, in the case of relational frustration) suggest significant relationship problems [34]. The children were also physically examined for signs of cerebral palsy and, if present, classified with the Gross Motor General Classification System. Eye and ear examinations were performed and visual acuity was completed with Snellen charts. All parents reported previous normal hearing tests. The Australian Bureau of Statistics' Socio-Economic Indexes for Advantage (SEIFA) and Disadvantage was used to assess each child's relative advantage (high values) or disadvantage (low values), which were derived from 2006 Census variables, such as household income and tertiary education by post code. These values are expressed as deciles and range from 1 to 10, i.e., the lowest scoring 10% of areas (post codes) are given a decile of one and the highest scoring 10% of areas are given a
Descriptive summaries were represented by frequency distributions for categorical data and mean and standard deviation or median and interquartile range for continuous data, depending on data normality. Comparisons between study group and nonstudy group characteristics were made using the Mann–Whitney and the chi-square test for continuous and categorical data respectively. Neurodevelopmental and behavioral outcomes were assessed against standardized norms using the One-sample t-test for continuous data and the Binomial test for categorical data. The association between FSIQ and neonatal factors such as gestational age, birth weight and length of stay was assessed using linear regression analysis. IBM SPSS version 20.0 statistical software (Armonk, NY) was used for data analysis. p-Values b0.05 were considered statistically significant. 2.3. Ethics The KEMH and Princess Margaret Hospital Scientific Ethics Committees granted ethical approval for the conduct of this study. Written consent was obtained from a parent or guardian and child (where possible). 3. Results 3.1. Demographic characteristics The study cohort consisted of 103 live born children. There were four postnatal deaths resulting in a 96% survival. Gastroschisis was diagnosed antenatally in 93/99 (94%) neonates. All of the study children were born at KEMH and in all of these the gastroschisis was diagnosed antenatally. We were able to locate 89 of the 99 surviving children and recruit 42 to the study. The median age of the study group was 10 years with a range of 5–17 years. Forty-two children underwent a physical examination and 39 were tested with either the WISC-IV (n = 35) or WPPSI-III (n = 4); and 38 completed the SDQ and the PRQ. Table 1 compares the neonatal characteristics of the study and nonstudy survivors who underwent psychometric testing. Maternal age was similar between the two groups; including the number of teenage mothers at the time of birth, 10/39 (25.6%) in the study group versus 11/60 (18.3%) in the nonstudy group, p = 0.385. The proportion of teenage mothers in the general Western Australian population in 1996 to 1998, approximately midway through our study, was 5.9% [36]. More female than male children agreed to take part in this follow-up study and the median gestational age of the study group was 1 week earlier than the nonstudy group; both these characteristics were statistically different between the two groups. Otherwise there were no significant differences between the two groups. Table 1 Neonatal characteristics of study and nonstudy groups.
Birth weight (g)a Gestation (weeks)a Female:Male Apgar 5 minutesa Neonatal length of stay (days)a Complex gastroschisis Number neonatal laparotomiesa Maternal age (y)a SEIFAb decile a b
Study (n = 39)
Nonstudy (n = 60)
p Value
2530 (1990, 2735) 36 (34, 37) 22:17 9 (9, 9) 24 (19, 31) 7 (18%) 1 (1, 1)
2565 (2112, 2760) 37 (36, 37) 20:40 9 (8, 9) 23 (17, 32) 8 (13%) 1 (1, 2)
0.749 0.024 0.023 0.386 0.386 0.531 0.683
23 (19, 23) 6 (5, 8)
24 (20, 27) 7 (5.5, 8)
0.844 0.302
Median (interquartile range). Socio-economic index for areas (see Statistical methods).
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
E.L. Harris et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx Table 2 Psychometric analysis with WISC-IV or WIPPSI-III (n = 39).
Full scale IQ Verbal comprehension Perceptual reasoning Working memorya Processing speed a
Table 4 Parenting Relationship Questionnaire—T scores.
Mean
SD
p Value
N (%), ≥1SD below mean
98.2 99.3 98.0 95.5 101.0
10.7 12.3 9.7 12.4 14.4
0.290 0.718 0.198 0.038 0.667
4 (10) 4 (10) 2 (5) 5 (14) 6 (15)
The WPPSI does not contain a Working Memory index (n = 35).
Attachment Communication Discipline Involvement Parenting confidence Satisfaction with school Relationship frustration
Mean
SD
p Valuea
50.6 48.5 45.9 47.2 46.2 49.6 55.3
10.82 12.34 9.48 9.44 10.29 12.40 11.42
0.720 0.381 0.013 0.082 0.021 0.824 0.003
Numbers = 38 for each scale except for Communication and Satisfaction with school which are 34 each. a p Values are for study group means against standardized mean T score 50.
3.2. Physical examination No child had clear evidence of cerebral palsy, although two young children had delayed gross motor milestones; both these children, at six and eight years of age, had significant ongoing problems with malabsorption from short gut syndrome resulting in frequent hospital admissions, poor growth and limited physical activity. No child had hearing loss; one child had developed amblyopia in one eye from strabismus. 3.3. Psychometric analysis The results from the WISC-IV and WPPSI-III analysis are shown in Table 2. The mean Full Scale Intelligence Quotient (FSIQ) of the study group was 98.2 (SD 10.7); this was not statistically different from the Australian normative mean. No child met the accepted criterion for Intellectual Disability (FSIQ of b70, i.e., N2 SDs below the general population mean). However, three children were in the ‘low average’ range (80–89) and one child was in the ‘borderline’ range (70–79), as categorized by the Wechsler manual. One of these four (10%) children (FSIQ 81) had suffered a complicated neonatal course and had significant, ongoing problems with short bowel syndrome; the other three children had not suffered a complicated neonatal course. Subscale scores were not significantly different to the Australian normative mean, except for a lower mean working memory index, mean 95.5 (SD 12.4), p = 0.038. No subscale scores were more than 2 SDs below the normative means except for 1 child in the Verbal Comprehension scale; this child had English as her second language. There were no significant gender differences in FSIQ and sub scale scores except that girls had a significantly higher mean score for Processing Speed, 105.1 v 95.6, p = 0.039). There was no significant correlation between FSIQ and each of birth weight, gestational age, birth weight Z score, number of laparotomies or anesthetics in the neonatal period or length of neonatal stay. Multivariable analysis was not conducted as the authors considered the small sample size, absence of a control group and other socio-demographic data inadequate to be able to draw any meaningful conclusions. 3.4. Psychological analysis Table 3 compares the results of the 38 parent completed SDQs for the study group compared with American (4–17 year old) population means. The study group means were significantly lower for 3/5 domains
Table 3 Parent/guardian reported Strength and Difficulties Questionnaire results.
Emotional symptoms Conduct problems Hyperactivity inattention Peer problems Prosocial behavior Total difficulties
3
Study, mean (SD)
American, mean (SD)
p Valuea
Australian, mean (SD)
2.8 (2.2) 1.9 (2.1) 4.5 (3.0) 1.7 (1.9) 7.8 (2.0) 10.9 (6.5)
1.6 (1.8) 1.3 (1.6) 2.8 (2.5) 1.4 (1.5) 8.6 (1.8) 7.1 (5.7)
0.002 0.086 0.001 0.337 0.018 b0.001
2.1 (2.0) 1.5 (1.6) 3.1 (2.4) 1.6 (1.9) 8.3 (1.7) 8.2 (6.1)
Numbers for each row = 38. American means are for 4–17 year old children. Australian means are for 7–17 year old children. a p Value is for the study group mean compared to American population mean.
(excepting Peer and Conduct Problems) and for the Total Difficulties score compared to the normative means. Published SDQ results for Australian children cover a slightly different age group (7–17 year old) [37]; 29 study children fell into this age range. The SDQ analysis for these 29 children, showed a similar pattern to the comparison with the American population (means, SDs and p values for each of Emotional Symptoms 3.1, 2.25, p = 0.03; Conduct 1.7, 1.5, p = 0.5; Hyperactivity 4.4, 3.2, p = 0.037); Peer Problems 1.5, 1.5, p = 0.86; Prosocial 7.8, 1.9, p = 0.16; and Total Difficulties score 10.7, 5.53, p = 0.02). The SDQ manual categorizes scores in the top 5% (or bottom 5% for Prosocial behavior) as an abnormal result. Nine of 38 (24%) children scored in the abnormal range, in at least 1 domain (range 1–5) and the proportions of children with abnormal results in each domain were: Emotional Symptoms 2/38 (5.3%, p = 0.50); Conduct 1/38 (2.6%, p = 0.38); Hyperactivity 5/38 (13.2%, p = 0.03); Peer Problems 3/38 (7.9%, p = 0.33); Prosocial 5/38 (13.2%, p = 0.03); and Total Difficulties score 2/38 (5.3%, p = 0.50). Results of the PRQ are shown in Table 4. The study group had significantly lower mean T-score values for Discipline and Parenting Confidence and a significantly higher mean T-score for Relationship Frustration. The proportion of children in the “lower extreme” (i.e., N2 SDs below mean) T score range (“upper extreme” for Relational Frustration) were: Attachment 1/38 (2.6%, p = 0.500); Communication 3/34 (8.8%, p = 0.025); Discipline 3/38 (7.9%, p = 0.039); Involvement 1/38 (2.6%, p = 0.500); Parenting Confidence 2/38 (5.3%, p = 0.249); Satisfaction with School 3/34 (8.8%, p = 0.025); Relational Frustration 4/38 (10.5%, p = 0.002), as compared with the approximately 2.3% expected in a normally distributed population. 4. Discussion This is the only study to date to report a comprehensive assessment of neurodevelopmental and behavioral outcomes in older children and adolescents born with gastroschisis. The intellectual abilities of the children and adolescents in this cohort were substantially similar to the normative population; no child had evidence of intellectual delay (as defined by an IQ b 70); none had evidence of cerebral palsy or hearing loss and only 1 child had a visual defect in the form of amblyopia. These results are reassuring and in keeping with the only other 3 gastroschisis specific studies to have reported neurodevelopmental outcomes using formal developmental tests [6,27,29]. These latter studies were all in much younger children, approximately 12–44 months; only 3 (2.4%) of the combined 123 young children to have psychometric testing had an intellectual score of b70, consistent with intellectual delay. One other study found that approximately a quarter of children born with simple gastroschisis failed various developmental screening tests at 2 years of age and 15% of the overall group were accepted into early intervention services; this was not significantly more than a matched, non-syndromic, non-surgical neonatal intensive group but 5–7 times more than the local general population [28]. Earlier neurodevelopmental studies were less reassuring, but these studies grouped gastroschisis and omphalocele together, usually not reporting results separately or they were short on detail [38–41]. Perhaps the
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
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E.L. Harris et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx
best and most reassuring of these studies, was that by Ginn-Pease et al. [40], which detailed the intellectual and psychological outcomes of 56 children, average age 10.6 years (range 6–16), born with anorectal and anterior abdominal wall defects (22); this latter group had a mean FSIQ 101.1 (using an earlier version of the WISC, Revised). All children in this study had IQs in the normal range, although the original cohort of 59 was reduced to 56 because 3 children with “severe mental retardation”, underlying condition unspecified, could not be tested. The generally reassuring results of the current study and those of younger children born with gastroschisis outlined above, need to be set against the less reassuring neurodevelopmental outcomes found in young children following cardiac [42,43] and noncardiac surgery [22–26,44,45] in neonates or infants. The series of studies on the progressive neuro-developmental outcomes of a cohort of 1 year old, 3 year old and adolescent children after neonatal surgery by Ludman et al. [22,23,26], showed that while their cognitive abilities were within the normal range, their abilities significantly lagged those of a control group; even in early adolescence, they performed less well in core academic subjects than their peers, although none were considered delayed [46]. Laing et al. [24] assessed the neurodevelopmental outcome of 46 children, at a mean age of 24 months, who had undergone a wide range of noncardiac neonatal surgery and reported a high prevalence of mild and significant delay (Bayley scores: 16% and 9% had Mental and Psychomotor Developmental indices b70, respectively). One in five children had global developmental delay; a similar finding to a Japanese study [44]. Walker et al. [25] reported the neurodevelopmental outcomes, at one year of age, of a population-based cohort of 127 infants born at term that had undergone noncardiac surgery in the first 90 days of life, and compared their outcomes to a cohort of healthy controls, using the Bayley-III scales. The surgical infants were significantly behind the healthy controls in each of the five Bayley subscales, except expressive language. The biggest difference was in the gross motor subscale, where 38% of the surgical infants were delayed compared with 20% of the healthy controls (odds ratio 0.41; 95% CI, 0.26–0.63). However, it is important to appreciate that the mean values for each of the Bayley subscales of the surgical infants, were all within 1SD of the general, normalized population values. In summary, most of these studies, including the present study, show that gastroschisis and general surgical children are performing within the normal range, however they perform less well than their peers in those studies using control groups. Child psychiatric disorders are relatively common in the general community and the Strengths and Difficulties Questionnaire has been shown to be a screening tool with good sensitivity and specificity for screening these disorders; in one study identifying over 70% of individuals with conduct, hyperactivity, depressive and some anxiety disorders [47]. Although the children and adolescents in our study had, as a group and as reported by their parents or guardians, significantly abnormal means in most domains on the SDQ, compared with the general population, the actual numbers with abnormal scores were within the expected range except for the Hyperactivity–Inattention and Prosocial domains. The study by Ginn-Pease et al. [40] found that approximately a quarter of children had behavioral dysfunction in the internalizing, externalizing and social competence subscales of the Achenbach Child Behavior Checklist in their follow-up of anterior abdominal wall defects and anorectal anomalies. Children recovering from other forms of neonatal surgery have also been found to have higher levels of various behavioral problems [42,44,48,49]. In general, the parent–child relationship in our study seemed suboptimal compared to published norms, especially in the areas of communication, discipline, satisfaction with school and relational frustration. Unfortunately, this study was not powered to study the causes of the sub optimal parent child relationship, or behavioral problems as found with the SDQ, and there are likely to be many factors at work beside gastroschisis, such as the high teenage parenting. However, the negative impact of neonatal illness on the parent–child relationship has also been observed in other studies of neonates requiring intensive care and in
children with major birth defects requiring newborn surgery [50]. Mothers of infants with developmental delay are most at risk of interaction difficulties and may benefit from early identification and timely intervention [51]. Authoritative parenting is considered by psychologists to be the optimal form of parenting and requires a democratic relationship between parent and child and encourages independence in the child; implementing this form of parenting has been found to be highly stressful for parents of children with health problems, resulting in relational frustration [52].
5. Limitations We recognize that there are some limitations to this study. We could only recruit and evaluate 42% of the cohort. It is possible that children from families of higher socio-economic status would be more likely to participate in the study. However, there was no difference in the Socio-Economic Index for Advantage and Disadvantage between the study and nonstudy group, p = 0.302, according to the Australian Bureau of Statistics' data [35]. Recall bias may mean that those children with ongoing medical needs are more likely to participate in the study. The use of population norms rather than a prespecified control group could be a limitation. Controlling for important factors, such as maternal age, education and socio-economic status, prematurity and the complexities of gastroschisis and its management would have been very difficult. The study group had significantly more female participants and the median gestational age of the study group was 1 week earlier than the nonstudy group, factors known to affect developmental outcomes, although in different directions. Additionally, ongoing changes in the prenatal, medical and surgical management of gastroschisis could be expected to alter the long-term outcomes of affected children. Many units now manage abdominal wall defects with conservative treatment by silo reduction and avoid general anesthesia: therefore, it will be important to monitor the outcomes of the new generation of surviving neonates with gastroschisis. However, within these limitations, this is the only published cohort of older children born with gastroschisis with psychometric and psychological data which should prove useful to clinicians when counselling parents.
6. Conclusions School aged children and adolescents born with gastroschisis are overall of normal intellect with a small but significant decrease in working memory index. There were no children with cerebral palsy or significant visual or hearing deficits. Of concern however, the children seemed at increased risk for the common pediatric behavioral problems and the parent–child relationship was impaired in many domains. These latter concerns are likely caused by the complex inter relationship between socio-economic status, perinatal factors, the disease itself and the effects of treatment and any resulting complications which will require much larger studies to unravel. Simple, robust psychosocial strategies need to be developed to support families with children with long term health problems.
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Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
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[30] Harris EL, Minutillo C, Hart S, et al. The long term physical consequences of gastroschisis. J Pediatr Surg 2014;49:1466–70. [31] Wechsler D. Wechsler Intelligence Scale for Children - Fourth Edition Australian Standardised Edition (WISC-IV Australian). Pearson; 2005. [32] Wechsler D. Wechsler Preschool & Primary Scale of Intelligence–Third Edition Australian Standardised Edition (WPPSI-III Australian). Pearson; 2004. [33] YouthinMind: Strengths and Difficulties Questionnaire; 2012. [34] Kamphaus RW, CR. R. Parenting Relationship Questionnaire Manual. NCS Pearson, Inc.; 2006 [35] Index of relative socio-economic advantage and disadvantage. Australian Bureau of Statistics; 2006, [Canberra]. [36] Gee V, O'Neil MT. Perinatal, infant and maternal mortality in Western Australia, 1996–1998. http://www.health.wa.gov.au/publications/documents/perinatal/Perinatal% 20Infant%20Maternal%20Mortality%20Cohort%20in%20WA%201996-1998%20combined. pdf. [37] Mellor D. Normative data for the Strengths and Difficulties Questionnaire in Australia. Aust Psychol 2005;40:215–22. [38] Berseth CL, Malachowski N, Cohn RB, et al. Longitudinal growth and late morbidity of survivors of gastroschisis and omphalocele. J Pediatr Gastroenterol Nutr 1982;1:375–9. [39] Boyd PA, Bhattacharjee A, Gould S, et al. Outcome of prenatally diagnosed anterior abdominal wall defects. Arch Dis Child Fetal Neonatal Ed 1998;78:F209–13. [40] Ginn-Pease ME, King DR, Tarnowski KJ, et al. Psychosocial adjustment and physical growth in children with imperforate anus or abdominal wall defects. J Pediatr Surg 1991;26:1129–35. [41] Henrich K, Huemmer HP, Reingruber B, et al. Gastroschisis and omphalocele: treatments and long-term outcomes. Pediatr Surg Int 2008;24:167–73. [42] Schaefer C, von Rhein M, Knirsch W, et al. Neurodevelopmental outcome, psychological adjustment, and quality of life in adolescents with congenital heart disease. Dev Med Child Neurol 2013;55:1143–9. [43] Majnemer A, Limperopoulos C, Shevell M, et al. Developmental and functional outcomes at school entry in children with congenital heart defects. J Pediatr 2008; 153:55–60. [44] Kubota A, Nose K, Yamamoto E, et al. Psychosocial and cognitive consequences of major neonatal surgery. J Pediatr Surg 2011;46:2250–3. [45] Gischler SJ, Mazer P, Duivenvoorden HJ, et al. Interdisciplinary structural follow-up of surgical newborns: a prospective evaluation. J Pediatr Surg 2009;44:1382–9. [46] Ludman L. Re: psychosocial and cognitive consequences of major neonatal surgery. J Pediatr Surg 2012;47:1303–4 [author reply 1304–1305]. [47] Goodman R, Ford T, Simmons H, et al. Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample. Br J Psychiatry 2000;177:534–9. [48] Ludman L, Spitz L, Tsuji H, et al. Hirschsprung's disease: functional and psychological follow up comparing total colonic and rectosigmoid aganglionosis. Arch Dis Child 2002;86:348–51. [49] Bellinger DC, Newburger JW. Neuropsychological, psychosocial, and quality-of-life outcomes in children and adolescents with congenital heart disease. Prog Pediatr Cardiol 2010;29:6. [50] Kratochvil MS, Robertson CM, Kyle JM. Parents' view of parent–child relationship eight years after neonatal intensive care. Soc Work Health Care 1991;16:95–118. [51] Laing S, McMahon C, Ungerer J, et al. Mother-child interaction and child developmental capacities in toddlers with major birth defects requiring newborn surgery. Early Hum Dev 2010;86:793–800. [52] Woolfson L, Grant E. Authoritative parenting and parental stress in parents of preschool and older children with developmental disabilities. Child Care Health Dev 2006;32:177–84.
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study☆,☆☆ Emma L. Harris a,b,c, Susannah J. Hart c,d, Corrado Minutillo b,⁎, Madur Ravikumara b, Teresa M. Warner a,d, Yvette Williams b, Elizabeth A. Nathan c,d, Jan E. Dickinson c,d a
Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women, Perth, WA, Australia Neonatal Intensive Care Unit, Princess Margaret Hospital for Children, Perth, WA, Australia Biostatistics Unit, Women and Infants Research Foundation, Perth, WA, Australia d School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia b c
a r t i c l e
i n f o
Article history: Received 11 May 2015 Received in revised form 26 August 2015 Accepted 30 August 2015 Available online xxxx Key words: Gastroschisis Outcome studies Questionnaires Infant Child Adolescent Congenital Surgery Neurodevelopment Intellect Psychology
a b s t r a c t Objectives: Previous gastroschisis specific neurodevelopmental studies have focused on the first 3 years of life. The aim of this study was to assess the intellectual, behavioral and neurological outcomes of older children and adolescents born with gastroschisis. Study design: Of 99 gastroschisis survivors born in Western Australia, 1992 to 2005, and who were at least 5 years old, 42 agreed to take part in this study. The study assessed: intellectual ability, with age appropriate Wechsler intelligence scales; neurological status; hearing; vision; behavioral status with the Strengths and Difficulties Questionnaire (SDQ); and parenting style with the Parenting Relationship Questionnaire (PRQ). All results were compared to normative means. Results: Median age at follow-up was 10 years (range 5–17). No child had evidence of cerebral palsy or hearing loss; 1 child had amblyopia. Psychometric tests were completed in 39 children: mean full scale IQ was 98.2 (standard deviation [SD] 10.7); the working memory index was the only subscale to show a significant decrease from the normative mean (mean 95.5, SD 12.4, p = 0.038). The mean SDQ behavioral scores were significantly lower for 3 of 5 domains and the Total Difficulties score. PRQ scores were significantly abnormal for 4 of 7 domains: Communication, Discipline, Satisfaction with School and Relational Frustration. Conclusions: Overall intellectual abilities were within a normal range. The decrease in working memory index and the behavioral and parenting relationship impairments could be an effect of perinatal factors, gastroschisis management and complications or the complexity of the socio-economic environment. Crown Copyright © 2015 Published by Elsevier Inc. All rights reserved.
1. Background Gastroschisis is a relatively common and serious congenital structural anomaly of the abdominal wall and bowel. Most countries report an increasing incidence [1–4], currently 2.4/10,000 births in Western Australia [5], with survival over 90% [6]. Children born with gastroschisis are frequently exposed Abbreviations: WISC IV, Wechsler Intelligence Scale for Children; WPPSI III, Wechsler Preschool and Primary Scale of Intelligence; FSIQ, Full Scale Intelligence Quotient; SDQ, Strengths and Difficulties Questionnaire; PRQ, Parenting Relationship Questionnaire; IUGR, intrauterine growth restriction; SD, standard deviation; SEIFA, Socio-Economic Index for Advantage. ☆ Disclosure: The study was funded by a research grant obtained from Channel 7 Telethon, Western Australia. ☆☆ The authors declare no conflict of interest, real or perceived by the study sponsor or authors in: (1) study design; (2) the collection, analyfcsis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. Dr Emma Harris wrote the first draft of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. ⁎ Corresponding author at: Princess Margaret Hospital for Children, GPO Box D184, Perth, Western Australia 6840, Australia. Tel.: +61 8 93408672; fax: +61 8 93407852. E-mail address: [email protected] (C. Minutillo).
to known risk factors for abnormal neuro-psycho-developmental outcome: for example, born to young, single mothers; exposed to maternal vasoactive and illicit drug use, both antenatally and postnatally [7,8]; are frequently delivered preterm and/or growth restricted [9,10]; and exposed to proinflammatory cytokines [11–15]. Even late preterm delivery, 34–36 weeks' gestation, confers a small risk of an adverse neurodevelopmental outcome compared with a term delivery [16–18]. In addition, recent animal and human studies have raised concerns about the neurodevelopmental effects of anesthesia [19] and surgery in young infants [20]. There is ample evidence of suboptimal neurodevelopmental outcomes following early cardiac surgery in infants [21] and increasing evidence of adverse neurodevelopmental outcomes following noncardiac, neonatal surgery [22–26]. Gastroschisis specific neurodevelopmental follow-up studies have been relatively reassuring, although these studies have been limited to children less than three years of age [6,27–29]. This study was designed and conducted with the primary aim to assess the neurocognitive and behavioral outcomes and the parent–child relationship of a state-wide population cohort of children and adolescents born with gastroschisis; children were at least five years old in order to give a longer term view of outcome.
http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062 0022-3468/Crown Copyright © 2015 Published by Elsevier Inc. All rights reserved.
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
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E.L. Harris et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx
2. Methods
decile of 10 [35]. The mother's postcode was that at the time of birth of her child with gastroschisis.
2.1. Data 2.2. Statistical methods All children and adolescents born with gastroschisis in Western Australia between 1992 and 2005 inclusive were identified through the Maternal Fetal Medicine Service Database at King Edward Memorial Hospital for Women (KEMH) and the Princess Margaret Hospital for Children neonatal database (Neobase). These two hospitals are the only tertiary obstetric and children's hospitals in Western Australia. All neonatal gastroschisis cases in Western Australia are managed at Princess Margaret Hospital, enabling complete case ascertainment. The medical records of each case were reviewed and relevant clinical data documented onto a preformed data sheet. Supplementary clinical, socio-economic and demographic data were collected at the time of the case examination for this study. The majority of neonates were managed with complete primary closure (90%), the preferred method during the study period. Details of the initial neonatal course and associated morbidities and the longer term surgical and growth outcomes of this cohort have been published previously [30]. An assessment of intellectual ability was made with either the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI), if less than 6 years old, or the Wechsler Intelligence Scale for Children IV (WISC), Australian Standardized Editions [31,32] by a trained psychologist (YW). The WISC-IV and WPPSI-III each has a mean of 100 and a standard deviation (SD) of 15 and each test has a set of sub scales, each with a mean of 10 and an SD of 3. These are internationally recognized tools commonly used in both medical practice and research. Parents or guardians completed the Strengths and Difficulties Questionnaire (SDQ); this is a commonly used behavioral screening questionnaire for 4–17 year old children [33]. The SDQ asks about 25 attributes; five questions in each of five domains: emotional symptoms; conduct problems; hyperactivity/inattention; peer relationship problems; and prosocial behavior. Scores from the first four attributes can be added together to generate a Total Difficulties Score. Normative data for the SDQ questionnaire have been reported for many nations including for Australian (7–17 years) and American (4–17 years) children. The study group means for each domain were compared to both the American and Australian population means. The SDQ manual categorizes each domain into four bands; the Very High (abnormal) band comprises the top 5% for all domains except for the Prosocial domain, and Very Low (abnormal) comprises the bottom 5%. The Parenting Relationship Questionnaire (PRQ) is designed to capture a parent's perspective of their parent–child relationship for children 2–18 years of age. Parents are asked 71 questions, which require a Never, Sometimes, Often and Almost Always response, which are scored 0, 1, 2, and 3 respectively. Each question relates to one of seven subscales: attachment, discipline practices, involvement, parenting confidence and relational frustration in the 2–5 year old group and, in addition, communication and satisfaction with school in children 6–18 years of age. Normative values for each of the subscales have been developed and are referred to as T scores, each with a mean and an SD of 50 and 10 respectively. T scores of two or more SDs below the mean (two or more above the mean, in the case of relational frustration) suggest significant relationship problems [34]. The children were also physically examined for signs of cerebral palsy and, if present, classified with the Gross Motor General Classification System. Eye and ear examinations were performed and visual acuity was completed with Snellen charts. All parents reported previous normal hearing tests. The Australian Bureau of Statistics' Socio-Economic Indexes for Advantage (SEIFA) and Disadvantage was used to assess each child's relative advantage (high values) or disadvantage (low values), which were derived from 2006 Census variables, such as household income and tertiary education by post code. These values are expressed as deciles and range from 1 to 10, i.e., the lowest scoring 10% of areas (post codes) are given a decile of one and the highest scoring 10% of areas are given a
Descriptive summaries were represented by frequency distributions for categorical data and mean and standard deviation or median and interquartile range for continuous data, depending on data normality. Comparisons between study group and nonstudy group characteristics were made using the Mann–Whitney and the chi-square test for continuous and categorical data respectively. Neurodevelopmental and behavioral outcomes were assessed against standardized norms using the One-sample t-test for continuous data and the Binomial test for categorical data. The association between FSIQ and neonatal factors such as gestational age, birth weight and length of stay was assessed using linear regression analysis. IBM SPSS version 20.0 statistical software (Armonk, NY) was used for data analysis. p-Values b0.05 were considered statistically significant. 2.3. Ethics The KEMH and Princess Margaret Hospital Scientific Ethics Committees granted ethical approval for the conduct of this study. Written consent was obtained from a parent or guardian and child (where possible). 3. Results 3.1. Demographic characteristics The study cohort consisted of 103 live born children. There were four postnatal deaths resulting in a 96% survival. Gastroschisis was diagnosed antenatally in 93/99 (94%) neonates. All of the study children were born at KEMH and in all of these the gastroschisis was diagnosed antenatally. We were able to locate 89 of the 99 surviving children and recruit 42 to the study. The median age of the study group was 10 years with a range of 5–17 years. Forty-two children underwent a physical examination and 39 were tested with either the WISC-IV (n = 35) or WPPSI-III (n = 4); and 38 completed the SDQ and the PRQ. Table 1 compares the neonatal characteristics of the study and nonstudy survivors who underwent psychometric testing. Maternal age was similar between the two groups; including the number of teenage mothers at the time of birth, 10/39 (25.6%) in the study group versus 11/60 (18.3%) in the nonstudy group, p = 0.385. The proportion of teenage mothers in the general Western Australian population in 1996 to 1998, approximately midway through our study, was 5.9% [36]. More female than male children agreed to take part in this follow-up study and the median gestational age of the study group was 1 week earlier than the nonstudy group; both these characteristics were statistically different between the two groups. Otherwise there were no significant differences between the two groups. Table 1 Neonatal characteristics of study and nonstudy groups.
Birth weight (g)a Gestation (weeks)a Female:Male Apgar 5 minutesa Neonatal length of stay (days)a Complex gastroschisis Number neonatal laparotomiesa Maternal age (y)a SEIFAb decile a b
Study (n = 39)
Nonstudy (n = 60)
p Value
2530 (1990, 2735) 36 (34, 37) 22:17 9 (9, 9) 24 (19, 31) 7 (18%) 1 (1, 1)
2565 (2112, 2760) 37 (36, 37) 20:40 9 (8, 9) 23 (17, 32) 8 (13%) 1 (1, 2)
0.749 0.024 0.023 0.386 0.386 0.531 0.683
23 (19, 23) 6 (5, 8)
24 (20, 27) 7 (5.5, 8)
0.844 0.302
Median (interquartile range). Socio-economic index for areas (see Statistical methods).
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
E.L. Harris et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx Table 2 Psychometric analysis with WISC-IV or WIPPSI-III (n = 39).
Full scale IQ Verbal comprehension Perceptual reasoning Working memorya Processing speed a
Table 4 Parenting Relationship Questionnaire—T scores.
Mean
SD
p Value
N (%), ≥1SD below mean
98.2 99.3 98.0 95.5 101.0
10.7 12.3 9.7 12.4 14.4
0.290 0.718 0.198 0.038 0.667
4 (10) 4 (10) 2 (5) 5 (14) 6 (15)
The WPPSI does not contain a Working Memory index (n = 35).
Attachment Communication Discipline Involvement Parenting confidence Satisfaction with school Relationship frustration
Mean
SD
p Valuea
50.6 48.5 45.9 47.2 46.2 49.6 55.3
10.82 12.34 9.48 9.44 10.29 12.40 11.42
0.720 0.381 0.013 0.082 0.021 0.824 0.003
Numbers = 38 for each scale except for Communication and Satisfaction with school which are 34 each. a p Values are for study group means against standardized mean T score 50.
3.2. Physical examination No child had clear evidence of cerebral palsy, although two young children had delayed gross motor milestones; both these children, at six and eight years of age, had significant ongoing problems with malabsorption from short gut syndrome resulting in frequent hospital admissions, poor growth and limited physical activity. No child had hearing loss; one child had developed amblyopia in one eye from strabismus. 3.3. Psychometric analysis The results from the WISC-IV and WPPSI-III analysis are shown in Table 2. The mean Full Scale Intelligence Quotient (FSIQ) of the study group was 98.2 (SD 10.7); this was not statistically different from the Australian normative mean. No child met the accepted criterion for Intellectual Disability (FSIQ of b70, i.e., N2 SDs below the general population mean). However, three children were in the ‘low average’ range (80–89) and one child was in the ‘borderline’ range (70–79), as categorized by the Wechsler manual. One of these four (10%) children (FSIQ 81) had suffered a complicated neonatal course and had significant, ongoing problems with short bowel syndrome; the other three children had not suffered a complicated neonatal course. Subscale scores were not significantly different to the Australian normative mean, except for a lower mean working memory index, mean 95.5 (SD 12.4), p = 0.038. No subscale scores were more than 2 SDs below the normative means except for 1 child in the Verbal Comprehension scale; this child had English as her second language. There were no significant gender differences in FSIQ and sub scale scores except that girls had a significantly higher mean score for Processing Speed, 105.1 v 95.6, p = 0.039). There was no significant correlation between FSIQ and each of birth weight, gestational age, birth weight Z score, number of laparotomies or anesthetics in the neonatal period or length of neonatal stay. Multivariable analysis was not conducted as the authors considered the small sample size, absence of a control group and other socio-demographic data inadequate to be able to draw any meaningful conclusions. 3.4. Psychological analysis Table 3 compares the results of the 38 parent completed SDQs for the study group compared with American (4–17 year old) population means. The study group means were significantly lower for 3/5 domains
Table 3 Parent/guardian reported Strength and Difficulties Questionnaire results.
Emotional symptoms Conduct problems Hyperactivity inattention Peer problems Prosocial behavior Total difficulties
3
Study, mean (SD)
American, mean (SD)
p Valuea
Australian, mean (SD)
2.8 (2.2) 1.9 (2.1) 4.5 (3.0) 1.7 (1.9) 7.8 (2.0) 10.9 (6.5)
1.6 (1.8) 1.3 (1.6) 2.8 (2.5) 1.4 (1.5) 8.6 (1.8) 7.1 (5.7)
0.002 0.086 0.001 0.337 0.018 b0.001
2.1 (2.0) 1.5 (1.6) 3.1 (2.4) 1.6 (1.9) 8.3 (1.7) 8.2 (6.1)
Numbers for each row = 38. American means are for 4–17 year old children. Australian means are for 7–17 year old children. a p Value is for the study group mean compared to American population mean.
(excepting Peer and Conduct Problems) and for the Total Difficulties score compared to the normative means. Published SDQ results for Australian children cover a slightly different age group (7–17 year old) [37]; 29 study children fell into this age range. The SDQ analysis for these 29 children, showed a similar pattern to the comparison with the American population (means, SDs and p values for each of Emotional Symptoms 3.1, 2.25, p = 0.03; Conduct 1.7, 1.5, p = 0.5; Hyperactivity 4.4, 3.2, p = 0.037); Peer Problems 1.5, 1.5, p = 0.86; Prosocial 7.8, 1.9, p = 0.16; and Total Difficulties score 10.7, 5.53, p = 0.02). The SDQ manual categorizes scores in the top 5% (or bottom 5% for Prosocial behavior) as an abnormal result. Nine of 38 (24%) children scored in the abnormal range, in at least 1 domain (range 1–5) and the proportions of children with abnormal results in each domain were: Emotional Symptoms 2/38 (5.3%, p = 0.50); Conduct 1/38 (2.6%, p = 0.38); Hyperactivity 5/38 (13.2%, p = 0.03); Peer Problems 3/38 (7.9%, p = 0.33); Prosocial 5/38 (13.2%, p = 0.03); and Total Difficulties score 2/38 (5.3%, p = 0.50). Results of the PRQ are shown in Table 4. The study group had significantly lower mean T-score values for Discipline and Parenting Confidence and a significantly higher mean T-score for Relationship Frustration. The proportion of children in the “lower extreme” (i.e., N2 SDs below mean) T score range (“upper extreme” for Relational Frustration) were: Attachment 1/38 (2.6%, p = 0.500); Communication 3/34 (8.8%, p = 0.025); Discipline 3/38 (7.9%, p = 0.039); Involvement 1/38 (2.6%, p = 0.500); Parenting Confidence 2/38 (5.3%, p = 0.249); Satisfaction with School 3/34 (8.8%, p = 0.025); Relational Frustration 4/38 (10.5%, p = 0.002), as compared with the approximately 2.3% expected in a normally distributed population. 4. Discussion This is the only study to date to report a comprehensive assessment of neurodevelopmental and behavioral outcomes in older children and adolescents born with gastroschisis. The intellectual abilities of the children and adolescents in this cohort were substantially similar to the normative population; no child had evidence of intellectual delay (as defined by an IQ b 70); none had evidence of cerebral palsy or hearing loss and only 1 child had a visual defect in the form of amblyopia. These results are reassuring and in keeping with the only other 3 gastroschisis specific studies to have reported neurodevelopmental outcomes using formal developmental tests [6,27,29]. These latter studies were all in much younger children, approximately 12–44 months; only 3 (2.4%) of the combined 123 young children to have psychometric testing had an intellectual score of b70, consistent with intellectual delay. One other study found that approximately a quarter of children born with simple gastroschisis failed various developmental screening tests at 2 years of age and 15% of the overall group were accepted into early intervention services; this was not significantly more than a matched, non-syndromic, non-surgical neonatal intensive group but 5–7 times more than the local general population [28]. Earlier neurodevelopmental studies were less reassuring, but these studies grouped gastroschisis and omphalocele together, usually not reporting results separately or they were short on detail [38–41]. Perhaps the
Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062
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best and most reassuring of these studies, was that by Ginn-Pease et al. [40], which detailed the intellectual and psychological outcomes of 56 children, average age 10.6 years (range 6–16), born with anorectal and anterior abdominal wall defects (22); this latter group had a mean FSIQ 101.1 (using an earlier version of the WISC, Revised). All children in this study had IQs in the normal range, although the original cohort of 59 was reduced to 56 because 3 children with “severe mental retardation”, underlying condition unspecified, could not be tested. The generally reassuring results of the current study and those of younger children born with gastroschisis outlined above, need to be set against the less reassuring neurodevelopmental outcomes found in young children following cardiac [42,43] and noncardiac surgery [22–26,44,45] in neonates or infants. The series of studies on the progressive neuro-developmental outcomes of a cohort of 1 year old, 3 year old and adolescent children after neonatal surgery by Ludman et al. [22,23,26], showed that while their cognitive abilities were within the normal range, their abilities significantly lagged those of a control group; even in early adolescence, they performed less well in core academic subjects than their peers, although none were considered delayed [46]. Laing et al. [24] assessed the neurodevelopmental outcome of 46 children, at a mean age of 24 months, who had undergone a wide range of noncardiac neonatal surgery and reported a high prevalence of mild and significant delay (Bayley scores: 16% and 9% had Mental and Psychomotor Developmental indices b70, respectively). One in five children had global developmental delay; a similar finding to a Japanese study [44]. Walker et al. [25] reported the neurodevelopmental outcomes, at one year of age, of a population-based cohort of 127 infants born at term that had undergone noncardiac surgery in the first 90 days of life, and compared their outcomes to a cohort of healthy controls, using the Bayley-III scales. The surgical infants were significantly behind the healthy controls in each of the five Bayley subscales, except expressive language. The biggest difference was in the gross motor subscale, where 38% of the surgical infants were delayed compared with 20% of the healthy controls (odds ratio 0.41; 95% CI, 0.26–0.63). However, it is important to appreciate that the mean values for each of the Bayley subscales of the surgical infants, were all within 1SD of the general, normalized population values. In summary, most of these studies, including the present study, show that gastroschisis and general surgical children are performing within the normal range, however they perform less well than their peers in those studies using control groups. Child psychiatric disorders are relatively common in the general community and the Strengths and Difficulties Questionnaire has been shown to be a screening tool with good sensitivity and specificity for screening these disorders; in one study identifying over 70% of individuals with conduct, hyperactivity, depressive and some anxiety disorders [47]. Although the children and adolescents in our study had, as a group and as reported by their parents or guardians, significantly abnormal means in most domains on the SDQ, compared with the general population, the actual numbers with abnormal scores were within the expected range except for the Hyperactivity–Inattention and Prosocial domains. The study by Ginn-Pease et al. [40] found that approximately a quarter of children had behavioral dysfunction in the internalizing, externalizing and social competence subscales of the Achenbach Child Behavior Checklist in their follow-up of anterior abdominal wall defects and anorectal anomalies. Children recovering from other forms of neonatal surgery have also been found to have higher levels of various behavioral problems [42,44,48,49]. In general, the parent–child relationship in our study seemed suboptimal compared to published norms, especially in the areas of communication, discipline, satisfaction with school and relational frustration. Unfortunately, this study was not powered to study the causes of the sub optimal parent child relationship, or behavioral problems as found with the SDQ, and there are likely to be many factors at work beside gastroschisis, such as the high teenage parenting. However, the negative impact of neonatal illness on the parent–child relationship has also been observed in other studies of neonates requiring intensive care and in
children with major birth defects requiring newborn surgery [50]. Mothers of infants with developmental delay are most at risk of interaction difficulties and may benefit from early identification and timely intervention [51]. Authoritative parenting is considered by psychologists to be the optimal form of parenting and requires a democratic relationship between parent and child and encourages independence in the child; implementing this form of parenting has been found to be highly stressful for parents of children with health problems, resulting in relational frustration [52].
5. Limitations We recognize that there are some limitations to this study. We could only recruit and evaluate 42% of the cohort. It is possible that children from families of higher socio-economic status would be more likely to participate in the study. However, there was no difference in the Socio-Economic Index for Advantage and Disadvantage between the study and nonstudy group, p = 0.302, according to the Australian Bureau of Statistics' data [35]. Recall bias may mean that those children with ongoing medical needs are more likely to participate in the study. The use of population norms rather than a prespecified control group could be a limitation. Controlling for important factors, such as maternal age, education and socio-economic status, prematurity and the complexities of gastroschisis and its management would have been very difficult. The study group had significantly more female participants and the median gestational age of the study group was 1 week earlier than the nonstudy group, factors known to affect developmental outcomes, although in different directions. Additionally, ongoing changes in the prenatal, medical and surgical management of gastroschisis could be expected to alter the long-term outcomes of affected children. Many units now manage abdominal wall defects with conservative treatment by silo reduction and avoid general anesthesia: therefore, it will be important to monitor the outcomes of the new generation of surviving neonates with gastroschisis. However, within these limitations, this is the only published cohort of older children born with gastroschisis with psychometric and psychological data which should prove useful to clinicians when counselling parents.
6. Conclusions School aged children and adolescents born with gastroschisis are overall of normal intellect with a small but significant decrease in working memory index. There were no children with cerebral palsy or significant visual or hearing deficits. Of concern however, the children seemed at increased risk for the common pediatric behavioral problems and the parent–child relationship was impaired in many domains. These latter concerns are likely caused by the complex inter relationship between socio-economic status, perinatal factors, the disease itself and the effects of treatment and any resulting complications which will require much larger studies to unravel. Simple, robust psychosocial strategies need to be developed to support families with children with long term health problems.
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Please cite this article as: Harris EL, et al, The long-term neurodevelopmental and psychological outcomes of gastroschisis: A cohort study, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.08.062