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Original Articles: Nutrition

Neonatal Intestinal Failure Is Independently Associated With Impaired Cognitive Development Later in Childhood

Gunnar, Riikka J.∗,†; Kanerva, Kaisa; Salmi, Silja§; Häyrinen, Taru||; Haataja, Leena; Pakarinen, Mikko P.†,#; Merras-Salmio, Laura∗,†

Author Information
Journal of Pediatric Gastroenterology and Nutrition: January 2020 - Volume 70 - Issue 1 - p 64-71
doi: 10.1097/MPG.0000000000002529

Abstract

What Is Known

  • During the neonatal period, patients with intestinal failure are subject to various risk factors for adverse neurodevelopment.
  • Previous studies have shown mild to moderate cognitive and motor impairment in this patient group during the first years of life.

What Is New

  • We investigated the cognitive and motor function of pediatric patients with intestinal failure after infancy. Adverse outcomes in cognitive and motor development were common.
  • Cognitive impairment was associated with neonatal short bowel syndrome, the number of laparotomies and anesthesia, and the length of hospitalization.
  • We recommend standardized neurodevelopmental follow-up for children with history of intestinal failure.

Pediatric intestinal failure (IF) is defined as the reduction of functional gut mass under the level that is required to maintain normal growth and fulfill daily energy and fluid requirements through enteral nutrition (EN) (1). The etiology of neonatal and pediatric IF varies from short bowel syndrome (SBS) due to extensive bowel resection to severe primary dysmotility disorders and rare enteropathies (2). During the last decade, the prognosis of pediatric IF has greatly improved (3,4). Still, these patients face many risk factors for developmental delay during their illness including the underlying disease, multiple operations, repeated general anesthesia, infections, and prolonged hospitalization. In addition, development may also be further compromised due to inadequate nutrition (5–10). Although slow growth interferes with normal neurological development, prolonged parenteral nutrition (PN) is a recognized risk factor for white matter injuries among preterm babies (7,8).

Prematurity and low birth weight are well-known risk factors of necrotizing enterocolitis (NEC), which has been repeatedly shown to impair neurological outcomes (6,11–14). Nevertheless, also term children with SBS due to midgut volvulus, gastroschisis, small bowel atresia, or Hirschsprung disease are subject to prolonged hospitalization, multiple laparotomies, and general anesthesia during the vulnerable neonatal period. Major surgeries during the first months of life have been associated with developmental delay, whereas the role of general anesthesia on cognitive outcome remains debated (15–20). Furthermore, long hospitalization interferes with normal child-parent interaction (21,22).

Children with neonatal and pediatric onset dysmotility syndromes and congenital enteropathies are more likely to be born full term and are hence spared from the risks a prematurity brings. They are also, however, subject to prolonged PN and hospitalization and may require early surgical treatment (23–25).

Along with improved survival, the long-term neurological development of pediatric patients with IF has become an important area of growing interest. Therapeutic interventions can alleviate problems associated with developmental delay (26). There are, however, no systematic studies published to date among pediatric patients with a history of IF investigating their developmental profile beyond infancy. In this study, we sought to assess cognitive and motor impairment among children between 3 and 16 years with a history of IF and to depict underlying risk factors associated with adverse neurodevelopmental outcomes. We expected neurodevelopmental problems to be more common among children with IF than in the normal population.

MATERIALS AND METHODS

Study Setting

We conducted this prospective cross-sectional single-center study in the Helsinki University Children's Hospital between August 2017 and April 2018. Our hospital serves as a nationwide referral center for children with IF with an intestinal transplantation program (4).

Patients

We invited all eligible patients with IF due to SBS, primary dysmotility disorders, or enteropathies to participate. Inclusion criteria were a requirement of PN for >60 consecutive days at the onset of IF and, for SBS patients, <50% of age-adjusted small bowel remaining after surgical resection. The age requirement was from 3 to 16 years at the time of the examination (27). We excluded patients with known genetic syndromes or congenital central nervous system (CNS) malformations affecting neurodevelopment, patients with grade III to IV intracerebral hemorrhage during neonatal period or hydrocephalus, and patients currently hospitalized due to acute illness (Fig. 1). Differences in patient characteristics between the participants and eligible nonparticipants were analyzed. Written informed consent was signed by the parents of the attending children and by all children older than 6 years before study. Children who spoke Finnish as a second language were evaluated for their linguistic skills only when adequately mastered Finnish language was in daily use.

F1
FIGURE 1:
Flow chart of the patient selection process. Reasons for not finishing the cognitive tests were severe neurocognitive impairment (n = 1), inadequate language skills (n = 1), and inadequate cooperation (n = 2). The neurocognitive development of the 3 latter patients was estimated to be mildly abnormal (n = 1) or within normal limits (n = 2).

Methods

We assessed the cognitive and motor skills using validated tests with established normal population reference values. Psychological testing was carried out in 2 hours with a break in between 2 sessions and motor testing in 1-hour session. Psychological testing was conducted by one of the 2 study psychologists and motor testing by a certified pediatric physiotherapist. They were blinded to the patients’ medical history. Wechsler Preschool and Primary Scale of Intelligence for Children between 3 and 6 years old and Wechsler Intelligence Scale for Children between 7 and 16 years old covered Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), and intelligence quotient (IQ) (28,29). The scores are classified as follows: extremely low ≤69 (standard deviation [SD] ≤−2.01), borderline 70 to 79 (SD −2.00 to −1.34), low average 80 to 89 (SD −1.33 to −0.68), average 90 to 110 (SD −0.67–0.67), high average 111 to 120 (0.68–1.33), very high 121 to 130 (1.88–2.0), and extremely high ≥131 (SD ≥2.01).

Motor development was examined with the Movement Assessment Battery for Children, version 2 (Movement ABC-2 test). The examination included domains assessing manual dexterity, aiming and catching, and balance. Significant moving difficulty was considered when the test score was ≤56 (≤5th percentile), whereas score between 57 and 67 (6th–16th percentile) was indicative of risk of having moving difficulty. Scores ≥67 (≥16th percentile) were perceived as normal.

An Internet-based questionnaire assessing socioeconomic status was sent to all participants. The questions covered learning difficulties of siblings and an open question about parents’ worries over child's general development. Patients’ medical history was collected from patient records and our IF registry.

Statistical Methods

Cognitive test results were compared to VCI, PRI, and IQ score distributions of the general background population and Movement ABC-2 test percentiles were calculated (28–30). To assess possible risk factors for severe cognitive impairment, we divided the patients into 2 groups: those who had an IQ ≥66 or were estimated to have normal or mildly impaired cognitive function and those who had an IQ <66 or had serious neurocognitive impairment (31). The IQ score <66 was chosen as an indication of severe cognitive impairment because all these children need further investigations for the differential diagnosis of intellectual disability. If the IQ test result was available, that was used for the grouping. The children who were unable to complete all the neuropsychological tests were investigated for their recent clinical assessments.

In a separate analysis, we compared the IQ results of the following groups: children whose PN was started within first 45 days of life with those whose PN was started after the age of 12 months and, among children with SBS, those who had NEC with a group that had undergone surgical resection for other reasons. We also compared children who were currently on PN with those who had been rehabilitated to EN.

To assess risk factors for adverse motor development, children with abnormal motor development (Movement ABC-2 tests percentiles between 0.1 and 16) were compared to those with normal motor development (Movement ABC-2 tests percentiles ≥16th percentile).

The data are presented as medians with interquartile ranges (IQRs) unless stated otherwise. GraphPad Prism version 7.00 was used for statistical analysis except for multiple regression. Analyses comparing the groups described above were performed using 2-tailed Mann-Whitney test. IBM SPSS version 22.0 was used to calculate multiple linear regression to test the effect of low birth weight, number of laparotomies, and length of PN on IQ scores. P value ≤0.05 was considered significant.

The Strengthening the Reporting of Observational studies in Epidemiology for cross sectional studies guidelines were used in the process of writing the article.

The ethical committee of Helsinki University Hospital approved this study (Study number 1881/2017).

RESULTS

The selection process of patients is outlined in Figure 1. All 30 patients who participated in psychological testing were included in the study. Most children (24, 80%) had developed the illness leading to IF during the neonatal period. There were, however, 6 children whose PN was initiated after the first year of life.

Detailed patient characteristics are described in Table 1. Comparison of baseline patient characteristics between participants (n = 30) and nonparticipants (n = 10) revealed no significant differences except for greater percentage of girls among nonparticipants (60% vs 20%, P = 0.0249) (Supplementary Table, Supplemental Digital Content, https://links.lww.com/MPG/B728).

T1
TABLE 1:
Patient characteristic of all patients with intestinal failure and comparison of patients with normal or mildly impaired cognition and severe cognitive impairment

Twenty-four (80%) patients spoke Finnish as a first language. Of the 6 (20%) children with Finnish as their second language 4 spoke Finnish in day care, in school or with 1 parent. Three of them underwent successful psychological testing (Fig. 1).

Distribution of Intelligence Quotient, Verbal Comprehension Index, and Perceptual Reasoning Index Scores

The entire psychological assessment was completed by 26 patients. The distribution of VCI, PRI, and IQ scores compared to normative test reference scores is shown in Figure 2. The median IQ was 78 (IQR 65–91), median VCI score 74 (IQR 60–92), and median PRI score 79 (IQR 67–91). Of all patients, 15 (56%) scored <80, and 10 (35%) patients had an IQ <70 (−2 SD) compared to 7% and 2.2%, respectively, in these categories in the normal population.

F2
FIGURE 2:
Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), and intelligence quotient (IQ) distribution of pediatric intestinal failure (IF) patients (n = 26) completing the neurocognitive assessment study, compared with the score distribution in general population. The scores are described as follows: extremely low ≤69, very low 70–79, low average 80–89, average 90–110, high average 111–120, very high 121–130, extremely high ≥131.

Risk Factors for Severe Neurocognitive Impairment

To evaluate possible risk factors for severe neurocognitive impairment, children who had IQ <66 or serious neurocognitive impairment (n = 8, 27%) were compared to those who had IQ ≥66 or were estimated to have normal or mildly abnormal cognitive function (n = 22, 73%). The children with severe neurocognitive impairment had less small bowel remaining (P = 0.005), they had undergone a greater number of laparotomies (P = 0.007) and general anesthesia (P = 0.010), and a longer hospitalization after birth (P = 0.047) than those with normal or mildly abnormal cognitive function (Table 1).

In a multiple linear regression model (R2 = 0.577, P < 0.001), IQ increased 0.9 points for each additional 100 g in birth weight (95% confidence interval [CI] 0.4–1.4, P = 0.001), decreased 0.25 points for each additional month on PN (95% CI 0.12–0.38, P < 0.001), and decreased 1.47 points for each additional laparotomy (95% CI 0.036–2.9, P = 0.045).

Children whose PN was started after the age of 12 months (6, 20%) had normal median IQ of 96 (86–105). Most of these children (80%) had dysmotility syndrome as a cause of IF. The difference was significant when compared to IQ of 74 (IQR 60–85) in children (24, 80%) whose PN was started during the neonatal period (P = 0.005). Within the SBS group, IQ scores were similar when NEC patients (74, IQR 60–92) were compared to other surgical etiologies (70, IQR 55–94, P = 0.276).

Children who were on PN during the time of the testing had significantly lower IQ scores (65, IQR 55–77) when compared to children who had weaned off PN (86, IQR 68–100, P = 0.0223).

Motor Development and Movement ABC-2 Test Results

Twenty-eight patients completed the Movement ABC-2 test. The median percentile was 9 (IQR 2–34). The median percentile for manual dexterity was 13 (IQR 4–28), for aiming and catching 37 (IQR 13–50), and for balance 16 (IQR 5–50). Results of 10 patients (36%) fell into low percentiles between 0.1 and 5 indicating a significant impairment in motor skills. An additional 8 patients (28%) had percentiles between 9 and 16, indicating a risk of abnormal motor development. Ten (36%) patients had normal percentiles between 25 and 99.9. There were 5 patients who had both a significant motor impairment and a severe neurocognitive impairment.

To assess risk factors for impaired motor development, we compared children with low percentiles ≤16 with those whose motor development was normal (Table 2). An impaired motor development was associated with prematurity (P = 0.029), lower birth weight (P = 0.024), and lower IQ scores (P = 0.020).

T2
TABLE 2:
Comparison of pediatric intestinal failure patients with normal and abnormal motor development according to Movement Assessment Battery for Children, 2nd edition, test results

Socioeconomical Factors

Parents of 23 children (77%) answered the questionnaire covering socioeconomical factors and parental concern. Parents’ income or educational level or learning difficulties of first-degree relatives were not associated with neurocognitive impairment (data not shown).

DISCUSSION

Our study suggests that, among children with a history of neonatal IF, neurocognitive and motor impairment are alarmingly common even when comorbidities affecting the CNS are excluded. The risk for adverse outcome is highest among neonatal patients with. Of the study patients, one third had IQ scores >−2 SD and half scored >−1 SD when compared to normative reference values. Difficulties in motor functions were equally common, as more than one third of the patients had abnormal motor development and another third were considered at risk. The major underlying factors associated with severe cognitive impairment included shorter remaining small bowel, increased number of laparotomies, and general anesthesia procedures and prolonged hospitalization after birth, whereas difficulties in motor function associated with prematurity and low birth weight. These findings are in line with those reported recently among younger children with IF (32,33).

Chesley et al studied 17 children with IF at a mean age of 17 months. Four children (27%) had developmental impairment as defined by the Mental Developmental Index <70 (≤2.01 SD). Mental Developmental Index scores between −1 SD and −2 SD were found in additional 40% of the children. In the study adverse developmental outcome associated with an increased number of surgical procedures, longer hospitalization, and prematurity (33). These findings are comparable to our distribution of IQ scores later in childhood, and also to our associated risk factors except for the prematurity, which seemed not to be a major factor for cognitive weakening in our study.

The association of cognitive impairment with neonatal surgery has been addressed in several previous studies and is well established for NEC (6,11–14). Major surgery in term and near-term neonates for other indications also carries a risk for later cognitive problems (13,16–18,34–36). In longitudinal follow-up studies, any major surgery during the neonatal period was associated with developmental delay at 1 and 3 years when compared to healthy peers (17,18). Another study evaluating MRI scans within 10 days after neonatal surgery found white matter abnormalities indicative of hypoxic injury in 75% of the preterm and 58% of the term babies (34). The need for early surgical intervention may reflect underlying harmful systemic pathology hampering brain development during the neonatal period (34). The surgery itself, together with the inflammatory response it provokes, may, however, be equally destructive to the developing CNS during this vulnerable period. This is supported by our observation that children with late-onset IF after 12 months of age showed no remarkable cognitive impairment. Most of them had dysmotility syndrome as a cause of IF.

Both low birth weight and poor pre- and post-natal growth are known to adversely affect cognitive performance (7,37,38). The regression analysis showed the effect of low birth weight on cognitive results in our study as well. Systemic inflammation and poor nutrition during the neonatal period affect growth and hence have a negative effect on neurological development (7). IF children with more severe disease forms require longer PN, are at risk for repeat infections, and are more likely to develop nutritional deficiencies during enteral rehabilitation (10). The adverse effect of prolonged PN is also shown in our study where children who continued on PN during the study period had lower IQ scores than children who had rehabilitated to EN. In group comparisons, longer duration of PN in children with severe neurocognitive impairment was also apparent, although it remained statistically insignificant.

When preterm children are compared to those born full term, IQ scores lower than average are generally reported (39,40). However, in the Finnish PIPARI study extremely preterm children performed reassuringly well in cognitive tests. Compared to the IF patients of our study, the cognitive performance among the PIPARI preterm cohort was better (37). Although both birth weight and prolonged PN were associated with cognitive impairment in our regression analysis, 4 out of the 8 severely impaired children were born after 36 gestation weeks and only 2 before 28 weeks, indicating that prematurity was not the major culprit.

Movement difficulties and risk for motor development delay are associated with extreme prematurity and low birth weight, as demonstrated also in our study (41,42). In previous studies, major surgery has also been associated with motor delay. This delay in motor function might be reversible, although previous studies on the matter have presented controversial results (16,17,43). In our study, patients’ Movement ABC percentiles were similar in all age groups. Although the number of surgeries was not associated with adverse motor development in this study, in a previous study by So et al with 33 children with IF at the corrected age of 12 to 15 months it was one of the associated risk factors. Comparable to our study, the adverse neuromotor development, however, mainly associated with prematurity and low birth weight. Other risk factors included comorbidities of the CNS, hyperbilirubinemia, NEC, and longer intensive care stay (32).

There are limitations to this study. As pediatric IF is a rare disease, the number of patients examined was too small to allow for definitive analysis of underlying factors. Also, there is possible bias, as 25% of the eligible patients did not attend the study. We could not analyze the socioeconomical factors in the nonattending group, which also had a greater percentage of girls compared to the attending group. As it is possible that non-native Finnish speakers could receive lower scores in verbal tests, the patients who were suspected of having linguistic challenges were excluded from the VCI and IQ score analyses, further reducing the number of patients included in the analyses.

However, this study reached a representative portion of our patients. The strengths of this study include that our center follows a strict follow-up protocol, ensuring that all the children receive equal and standardized care. Most importantly, this study brings new information about the neurological development of children with a history of IF.

In our hospital, children born before 30 weeks GA or weighing >1500 g at birth are routinely checked for neurological development at a pediatric neurologist appointment, whereas children born at later gestational age are referred to a neurologist only when neurodevelopmental problems are suspected. During this study, children with IF were found to have both severe and milder neurocognitive and motor impairments that had gone unnoticed by general health practitioners and pediatricians, even though parental worry and problems at school or preschool had arisen. It is possible that due to somatic problems, developmental issues are overlooked. We recommend early neurological follow-up for all children with a history of IF. As these children encounter different problems in several areas of development, their rehabilitation, for example, physiotherapy, occupational therapy, and speech therapy, is always individualized. All interventions should have measurable goals mutually agreed with the child and caregivers, and the intervention should apply methods which activate and motivate the child in their natural environment (eg, home, day care, school).

CONCLUSIONS

Children with neonatal IF, and especially with neonatal SBS, are at significant risk of neurocognitive and motor impairment. It is likely that developmental problems are underdiagnosed in this patient group. Timely intervention can both improve neurodevelopmental outcomes and alleviate the associated problems (26). We strongly recommend systematic longitudinal neurological assessment of all children with a history of IF.

REFERENCES

1. Goulet O, Ruemmele F, Lacaille F, et al. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 2004; 38:250–269.
2. Squires RH, Duggan C, Teitelbaum DH, et al. Natural history of pediatric intestinal failure: initial report from the pediatric intestinal failure consortium. J Pediatr 2012; 161:723.e2–728.e2.
3. D’Antiga L, Goulet O. Intestinal failure in children: the European view. J Pediatr Gastroenterol Nutr 2013; 56:118–126.
4. Merras-Salmio L, Mutanen A, Ylinen E, et al. Pediatric intestinal failure: the key outcomes for the first 100 patients treated in a national tertiary referral center during 1984–2017. JPEN J Parenter Enteral Nutr 2018; 42:1304–1313.
5. Beers SR, Yaworski JA, Stilley C, et al. Cognitive deficits in school-age children with severe short bowel syndrome. J Pediatr Surg 2000; 35:860–865.
6. Hickey M, Georgieff M, Ramel S. Neurodevelopmental outcomes following necrotizing enterocolitis. Semin Fetal Neonatal Med 2018; 23:426–432.
7. Pfister KM, Ramel SE. Linear growth and neurodevelopmental outcomes. Clin Perinatol 2014; 41:309–321.
8. Barnett ML, Tusor N, Ball G, et al. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI. Neuroimage Clin 2017; 17:596–606.
9. Hukkinen M, Merras-Salmio L, Pakarinen MP. Health-related quality of life and neurodevelopmental outcomes among children with intestinal failure. Semin Pediatr Surg 2018; 27:273–279.
10. Gunnar R, Lumia M, Pakarinen MP, et al. Children with intestinal failure undergoing rehabilitation are at risk for essential fatty acid deficiency. JPEN J Parenter Enteral Nutr 2018; 42:1203–1210.
11. Hintz SR, Kendrick DE, Stoll BJ, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005; 115:969–703.
12. Schulzke SM, Deshpande GC, Patole SK. Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing enterocolitis: a systematic review of observational studies. Arc Pediatr Adolesc Med 2007; 161:583–590.
13. Roze E, Ta BD, Van der Ree MH, et al. Functional impairments at school age of children with necrotizing enterocolitis or spontaneous intestinal perforation. Pediatr Res 2011; 70:619–625.
14. Volpe JJ. Postnatal sepsis, necrotizing enterocolitis, and the critical role of systemic inflammation in white matter injury in premature infants. J Pediatr 2008; 153:160–163.
15. Allendorf A, Dewitz R, Weber J, et al. Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants—match control study after 2 years. J Pediatr Surg 2018; 53:1573–1577.
16. Morriss FH Jr, Saha S, Bell EF, et al. Surgery and neurodevelopmental outcome of very low-birth-weight infants. JAMA Pediatr 2014; 168:746–754.
17. Dwyer GM, Walker K, Baur L, et al. Developmental outcomes and physical activity behaviour in children post major surgery: an observational study. BMC Pediatr 2016; 16:123.
18. Walker K, Badawi N, Halliday R, et al. Early developmental outcomes following major noncardiac and cardiac surgery in term infants: a population-based study. J Pediatr 2012; 161:748.e1–752.e1.
19. Wang X, Xu Z, Miao CH. Current clinical evidence on the effect of general anesthesia on neurodevelopment in children: an updated systematic review with meta-regression. PLoS One 2014; 9:e85760.
20. O’Leary JD, Janus M, Duku E, et al. Influence of surgical procedures and general anesthesia on child development before primary school entry among matched sibling pairs. JAMA Pediatr 2019; 173:29–36.
21. Flacking R, Lehtonen L, Thomson G, et al. Closeness and separation in neonatal intensive care. Acta Paediatr 2012; 101:1032–1037.
22. Parsons CE, Young KS, Murray L, et al. The functional neuroanatomy of the evolving parent-infant relationship. Prog Neurobiol 2010; 91:220–241.
23. Pakarinen MP, Koivusalo AI, Rintala RJ. Outcomes of intestinal failure—a comparison between children with short bowel and dysmotile intestine. J Pediatr Surg 2009; 44:2139–2144.
24. Diamanti A, Fusaro F, Caldaro T, et al. Pediatric intestinal pseudo-obstruction: impact of neonatal and later onset on clinical and nutritional outcomes. J Pediatr Gastroenterol Nutr 2019; 69:212–217.
25. Jo SC, McCallum Z, Shalley H, et al. Outcomes of children with chronic intestinal failure: experience over two decades at a tertiary paediatric hospital. J Pediatr Gastroenterol Nutr 2019; 69:e79–e87.
26. Spittle A, Orton J, Anderson PJ, et al. Early developmental intervention programs provided post hospital discharge to prevent motor and cognitive impairment in preterm infants. Cochrane Database Syst Rev 2015. CD005495.
27. Struijs MC, Diamond IR, de Silva N, et al. Establishing norms for intestinal length in children. J Pediatr Surg 2009; 44:933–938.
28. Wechsler D. Wechsler Preschool and Primary Scale of Intelligence—Third Edition (WPPSI-III). Helsinki, Finland: Hogrefe Psykologien Kustannus Oy; 2009.
29. Wechsler D. Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV). Helsinki, Finland: Hogrefe Psykologien Kustannus Oy; 2010.
30. Harcourt Assessment, Henderson SE, Sugden DA, Barnett A. Movement Assessment Battery for Children—Second Edition (MOVEMENT ABC–2). 2nd ed2007.
31. Kamphaus RW, Winsor AP, Rowe EW. Flanagan DP, McDonough EM, et al. The history of intelligence test interpretation. Contemporary Intellectual Assessment: Theories, Tests, and Issues. New York, NY: Guilford Publications; 2018. 56–72.
32. So S, Patterson C, Gold A, et al. Early neurodevelopmental outcomes of infants with intestinal failure. Early Hum Dev 2016; 101:11–16.
33. Chesley PM, Sanchez SE, Melzer L, et al. Neurodevelopmental and cognitive outcomes in children with intestinal failure. J Pediatr Gastroenterol Nutr 2016; 63:41–45.
34. Trivedi A, Walker K, Loughran-Fowlds A, et al. The impact of surgery on the developmental status of late preterm infants—a cohort study. J Neonatal Surg 2015; 4:2.
35. Lap CC, Bolhuis SW, Van Braeckel KN, et al. Functional outcome at school age of children born with gastroschisis. Early Hum Dev 2017; 106-107:47–52.
36. Stolwijk LJ, Keunen K, De Vries LS, et al. Neonatal surgery for noncardiac congenital anomalies: neonates at risk of brain injury. J Pediatr 2017; 182:335.e1–341.e1.
37. Nyman A, Korhonen T, Munck P, et al. Factors affecting the cognitive profile of 11-year-old children born very preterm. Pediatr Res 2017; 82:324–332.
38. Guellec I, Lapillonne A, Marret S, et al. Effect of intra- and extrauterine growth on long-term neurologic outcomes of very preterm infants. J Pediatr 2016; 175:93.e1–99.e1.
39. Bhutta AT, Cleves MA, Casey PH, et al. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002; 288:728–737.
40. Doyle LW, Anderson PJ, Battin M, et al. Long term follow up of high-risk children: who, why and how? BMC Pediatr 2014; 14: 279-2431-14-279.
41. Zwicker JG, Yoon SW, Mackay M, et al. Perinatal and neonatal predictors of developmental coordination disorder in very low birthweight children. Arch Dis Child 2013; 98:118–122.
42. Synnes A, Anderson PJ, Grunau RE, et al. Predicting severe motor impairment in preterm children at age 5 years. Arch Dis Child 2015; 100:748–753.
43. Ballantyne M, Benzies KM, McDonald S, et al. Risk of developmental delay: comparison of late preterm and full-term Canadian infants at age 12 months. Early Hum Dev 2016; 101:27–32.
Keywords:

intelligence quotient; neonatal surgery; neurological development; parenteral nutrition; short bowel syndrome

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