Neurodevelopmental impairment in children with congenital diaphragmatic hernia: Not an uncommon complication for survivors

doi:10.1016/j.jpedsurg.2019.05.021

Journal of Pediatric Surgery

Volume 55, Issue 4, April 2020, Pages 625-634

https://doi.org/10.1016/j.jpedsurg.2019.05.021 Get rights and content

Abstract

Purpose

To evaluate neurodevelopmental impairment (NDI) in children born with congenital diaphragmatic hernia (CDH).

Methods

Using a defined search strategy, a systematic review was conducted to define the incidence and types of NDI, to report abnormal neuroimaging findings and to evaluate possible NDI predictors. A meta-analysis was performed on comparative studies reporting risk factors for NDI, using RevMan 5.3.

Results

Of 3541 CDH children (33 studies), 829 (23%) had NDI, with a higher incidence in CDH survivors who received ECMO treatment (49%) vs. those who had no ECMO (22%; p < 0.00001). NDI included neuromuscular hypotonia (42%), hearing (13%) and visual (8%) impairment, neurobehavioral issues (20%), and learning difficulties (31%). Of 288 survivors that had postnatal neuroimaging, 49% had abnormal findings. The main risk factors for NDI were severe pulmonary hypoplasia, large defect size, ECMO use.

Conclusions

NDI is a relevant problem for CDH survivors, affecting 1 in 4. The spectrum of NDI covers all developmental domains and ranges from motor and sensory (hearing, visual) deficits to cognitive, language, and behavioral impairment. Further studies should be designed to better understand the pathophysiology of NDI in CDH children and to longitudinally monitor infants born with CDH to correct risk factors that can be modifiable.

Level of evidence

Level III.

Section snippets

Data sources and study selection

This study was registered on PROSPERO — international prospective register of systematic reviews (registration number: CRD42019121659) [15]. The systematic review was drafted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [16]. A systematic review of the literature was made using a defined search strategy (Table 1). Three investigators (GR, AR, and LM) independently searched scientific databases (PubMed, Medline, Cochrane Collaboration,

Study selection and characteristics

Of the initial 7281 abstracts screened following removal of duplicates, 241 full text articles were evaluated and 78 were eventually included in the final analysis [3], [5], [7], [8], [10], [11], [12], [13], [14], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68]

Discussion

The concept that some children born with CDH would have worse neurodevelopmental outcome than their peers has been under consideration for a couple of decades. The present review combines for the first time in a systematic approach all the studies evaluating NDI in this population of patients and outlines the different types of neurological deficits and imaging findings. The number of CDH survivors suffering from NDI is not negligible, with 1 in 4 children experiencing some degree of impaired

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Infants requiring high acuity care within a Paediatric Intensive Care Unit are at multifactorial risk of neurological injury to the immature brain, resulting in long-term developmental difficulties. In 2020, Queensland Children's Hospital implemented an individualised family-centred developmental care program, ‘Baby Liberation’, to address an identified service gap for critically unwell infants, aimed at optimising early neuroprotective strategies and minimising risk of suboptimal developmental outcomes.
To implement Baby Liberation for infants admitted to a quaternary paediatric intensive care referral centre. Secondary aims were to describe environmental changes, enablers and limitations related to implementation.
A single-centre, prospective implementation pilot study investigated the feasibility of implementing Baby Liberation. Subjects included infants less than six months of age admitted to Queensland Children's Hospital Paediatric Intensive Care Unit.
Primary measures comprised data collected during the implementation period, including number of eligible patients and number of developmental care plans provided. Environmental audit data were collected pre and post implementation to inform secondary outcomes.
Baby Liberation was feasibly implemented into the Queensland Children's Hospital Paediatric Intensive Care Unit. During implementation, 181 individualised care plans were provided to 313 eligible infants (57.8 %). Environmental audits showed improvements in all areas of developmental care, with greatest improvements noted in pain and stress management (+95 %) and staff support and development (+83.3 %).
Implementation of Baby Liberation was feasible within a large quaternary paediatric intensive care unit and has potential to be expanded into other clinical areas providing acute infant care.
Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic
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We compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy.
We conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay.
At one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6–86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (−13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1–89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (−3.0), p = 0.28] had declining scores.
These initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management.
III.
Prenatal Brain Maturation is Delayed in Neonates with Congenital Diaphragmatic Hernia
2024, Journal of Pediatrics
To assess brain development in fetuses with congenital diaphragmatic hernia (CDH) using a fetal Total Maturation Score (fTMS).
This is a retrospective cohort study using data from a single-center clinical registry. Neonates with an antenatal diagnosis of CDH between 2014 and 2020 and prenatal brain magnetic resonance imaging (MRI) (n = 48) were included. We compared our study sample with historical healthy controls (n = 48). The relationship between fTMS and gestational age (GA), as well as the association between fTMS and key prenatal variables and placental pathologic findings, were evaluated.
Compared with healthy controls, neonates with CDH had a significant delay in fTMS (P value <.001). Within the CDH cohort, there was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right vs left CDH, sex, presence of abnormal echocardiogram findings, treatment with extracorporeal membrane oxygenation (ECMO), or in-hospital mortality. Placentas of neonates with CDH had a high proportion of fetal vascular malperfusion (56%) and chronic inflammation (67%), and relatively large placentas had a protective effect on prenatal brain maturation (P value = .025).
Prenatal brain maturation in neonates with CDH is delayed. Placental pathology may influence fetal brain development. The etiology and clinical impact of prenatal brain immaturity in neonates with CDH warrant further investigation.
Transpyloric Tube Placement Shortens Time to Full Feeding in Left Congenital Diaphragmatic Hernia
2023, Journal of Pediatric Surgery
Nutritional complications have an impact in both short- and long-term morbidity of patients with congenital diaphragmatic hernia (CDH). We aimed to compare time to full enteral tube feeding depending on route -gastric (GT) or transpyloric (TPT)- in newborns with left CDH (L-CDH).
Retrospective cohort study of L-CDH patients admitted to a referral tertiary care NICU between January 2007 and December 2014. Lethal chromosomal abnormalities and death before initiation of enteral nutrition were exclusion criteria.
37 patients were fed through GT, 46 by TPT. TPT children took 11.0 (6.8) days to reach full enteral tube feeding and spent 16.6 (8.1) days on parenteral nutrition vs 16.8 (14.7) days (p = 0.041) and 22.7 (13.5) days (p = 0.020) of GT patients. TPT children had 3.9 (2.4) days of fasting due to GI issues and 20% had episodes of decreased rates of enteral nutrition for extra-GI complications vs 11.4 (11.1) days (p = 0.028) and 49% (p = 0.006). According to the best fitting model (R² 0.383, p < 0.001), the TPT-group achieved full enteral feeding 8.4 days earlier than the GT-group (95% CI -14.76 to - 2.02 days), after adjustment by severity of illness during the first days, o/e LHR_liver and class of diaphragmatic defect. There were no differences in growth outcomes and length of stay between survivors of GT and TPT groups.
TPT shortens time to full enteral nutrition, especially in the most severe L-CDH patients. We propose that placement of a TPT at the end of the surgical repair procedure should be considered, especially in higher-risk patients.
Treatment study, Level III. Retrospective comparative, case–control study.
All Care is Brain Care: Neuro-Focused Quality Improvement in the Neonatal Intensive Care Unit
2023, Clinics in Perinatology
Anti-reflux surgery in children with congenital diaphragmatic hernia: A prospective cohort study on a controversial practice
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Citation Excerpt :
It seems interesting to underline that children born with EA showed a catch-up growth at 5 years, whereas nutritional morbidity was still present in children born with CDH at this same age [35]. This persistent failure to thrive may participate in the high rates of neuro-developmental impairment (NDI), that affects 1 in 4 CDH survivors [35,38]. Recent studies have reported an association between poor growth during infancy and NDI during childhood [39].
Gastro-esophageal reflux disease (GERD) is the most frequent long-term morbidity of congenital diaphragmatic hernia (CDH) survivors. Performing a preventive fundoplication during CDH repair remains controversial. This study aimed to: (1) Analyze the variability in practices regarding preventive fundoplication; (2) Identify predictive factors for fundoplication.
(3) Evaluate the impact of preventive fundoplication on gastro-intestinal outcomes in children with a CDH patch repair;
This prospective multi-institutional cohort study (French CDH Registry) included CDH neonates born in France between January 1st, 2010-December 31st, 2018. Patch CDH was defined as need for synthetic patch or muscle flap repair. Main outcome measures included need for curative fundoplication, tube feed supplementation, failure to thrive, and oral aversion.
Of 762 CDH neonates included, 81 underwent fundoplication (10.6%), either preventive or curative. Median follow-up was 3.0 years (IQR: 1.0–5.0).
(1) Preventive fundoplication is considered in only 31% of centers. The rates of both curative fundoplication (9% vs 3%, p = 0.01) and overall fundoplication (20% vs 3%, p < 0.0001) are higher in centers that perform preventive fundoplication compared to those that do not.
(2) Predictive factors for preventive fundoplication were: prenatal diagnosis (p = 0.006), intra-thoracic liver (p = 0.005), fetal tracheal occlusion (p = 0.002), CDH-grade C-D (p < 0.0001), patch repair (p < 0.0001). After CDH repair, 8% (n = 51) required curative fundoplication (median age: 101 days), for which a patch repair was the only independent predictive factors identified upon multivariate analysis.
(3) In neonates with patch CDH, preventive fundoplication did not decrease the need for curative fundoplication (15% vs 11%, p = 0.53), and was associated with higher rates of failure to thrive (discharge: 81% vs 51%, p = 0.03; 6-months: 81% vs 45%, p = 0.008), tube feeds (6-months: 50% vs 21%, p = 0.02; 2-years: 65% vs 26%, p = 0.004), and oral aversion (6-months: 67% vs 37%, p = 0.02; 1-year: 71% vs 40%, p = 0.03).
Children undergoing a CDH patch repair are at high risk of requiring a curative fundoplication. However, preventive fundoplication during a patch repair does not decrease the need for curative fundoplication and is associated with worse gastro-intestinal outcomes in children.
II – Prospective Study.

View all citing articles on Scopus

^☆: Funding: This work was supported by the Canadian Institute of Health Research (CIHR)–SickKids Foundation New Investigator Research Grant (NI18-1270R)

^☆☆: Conflict of interest: The authors declare that they have no conflict of interest.

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Thoracic ConditionNeurodevelopmental impairment in children with congenital diaphragmatic hernia: Not an uncommon complication for survivors☆,☆☆

Abstract

Purpose

Methods

Results

Conclusions

Level of evidence

Section snippets

Data sources and study selection

Study selection and characteristics

Discussion

J Pediatr Surg

Semin Pediatr Surg

Early Hum Dev

Early Hum Dev

J Pediatr Surg

Int J Surg

A review and computer program Control Clin Trials

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr

J Pediatr Surg

Ann Thorac Surg

J Pediatr Surg

J Pediatr

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

Int J Pediatr Otorhinolaryngol

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

Early Hum Dev

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

Early Hum Dev

J Pediatr Surg

J Pediatr Surg

Early Hum Dev

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr

J Pediatr

Ann Thorac Surg

J Pediatr Surg

J Pediatr Surg

Trends, correlates, and survival of infants with congenital diaphragmatic hernia and its subtypes

Birth Defects Res

Thoracic Condition
Neurodevelopmental impairment in children with congenital diaphragmatic hernia: Not an uncommon complication for survivors☆,☆☆