Neurodevelopmental and neurofunctional outcomes in children with congenital diaphragmatic hernia

Abstract

The objective of this review was to provide a critical overview of our current understanding on the neurocognitive, neuromotor, and neurobehavioral development in congenital diaphragmatic hernia (CDH) patients, focusing on three interrelated clinical issues: (1) comprehensive outcome studies, (2) characterization of important predictors of adverse outcome, and (3) the pathophysiological mechanism contributing to neurodevelopmental disabilities in infants with CDH. Improved survival for CDH has led to an increasing focus on longer-term outcomes. Neurodevelopmental dysfunction has been recognized as the most common and potentially most disabling outcome of CDH and its treatment. While increased neuromotor dysfunction is a common problem during infancy, behavioral problems, hearing impairment and quality of life related issues are frequently found in older children and adolescence. Intelligence appears to be in the low normal range. Patient and disease specific predictors of adverse neurodevelopmental outcome have been defined. Imaging studies have revealed a high incidence of structural brain abnormalities. An improved understanding of the pathophysiological pathways and the neurodevelopmental consequences will allow earlier and possibly more targeted therapeutic interventions. Continuous assessment and follow-up as provided by an interdisciplinary team of medical, surgical and developmental specialists should become standard of care for all CDH children to identify and treat morbidities before additional disabilities evolve and to reduce adverse outcomes.

Introduction

Congenital diaphragmatic hernia (CDH), a developmental defect of the diaphragm, occurs in approximately 1 in 2500 live births (Fig. 1). CDH presents with a broad spectrum of severity dependent upon components of pulmonary hypoplasia and pulmonary hypertension [1]. Over the past 2 decades, advances in prenatal diagnosis, surgical technique and neonatal care have led to a decline in mortality. As survival has improved, ranging now from 60 to 80% even in more severely affected CDH children (liver-up, and a lung-to-head ratio < 1.0) [2], [3], [4], [5], long-term disabilities are now considered a key outcome measure for these children. Ongoing problems in CDH survivors include respiratory insufficiency, pulmonary hypertension, gastroesophageal reflux, failure to thrive, hernia recurrence, chest wall and orthopedic deformities as well as complications attributable to associated congenital abnormalities [6], [7], [8], [9], [10], [11], [12].

Adverse neurodevelopmental outcome has been identified as one of the most significant morbidities among CDH survivors. Thus, neurocognitive outcomes after surgical intervention for CDH are the focus of great clinical interest. There is a concerning incidence of significant impairments in widespread neurodevelopmental domains: fine and gross motor skills, visuospatial skills, and cognition, attention and behavioral skills, and speech and language skills [6], [7], [12], [13], [14], [15], [16], [17], [18]. Alone or in combination, these findings may significantly decrease quality of life for CDH children and their families, as well as result in significant costs to society. Despite the importance of these functional impairments, the underlying basis of these deficits remains poorly understood.

The objective of this review is to provide a critical overview of our current understanding on the neurocognitive, neuromotor, and neurobehavioral development in CDH patients, focusing on three interrelated clinical issues: (1) comprehensive outcome studies, (2) characterization of important predictors of adverse outcome, and (3) the pathophysiological mechanism contributing to neurodevelopmental disabilities in infants with CDH.