Research Update: 8- to 13-Year Study of Neurodevelopmental Outcomes in Children with Pulmonary Hypoplasia

Pulmonary hypoplasia — or small, underdeveloped lungs — occurs in patients with congenital diaphragmatic hernia, lung lesion and giant omphalocele. Advances in prenatal and neonatal treatment have significantly improved the outcomes of these patients. However, these patients are left with neurodevelopmental, cardiopulmonary, gastrointestinal and surgical morbidities that require long-term follow-up.

The Pulmonary Hypoplasia Program (PHP) at The Children’s Hospital of Philadelphia is committed to prospectively tracking perinatal and follow-up outcomes of children with pulmonary hypoplasia in an effort to improve understanding and care. The program recently completed a review of neurodevelopmental outcomes at 5 years of age in 36 CDH patients enrolled in the PHP between June 2004 and September 2014. A key finding from this review is that CDH survivors are at increased risk for developing emotionally reactive and pervasive developmental problems.

The neurodevelopmental outcomes assessed at a median of 5 years included cognition (Wechsler Preschool and Primary Scale of Intelligence), visual-motor integration, academic achievement (Woodcock-Johnson Tests of Achievement) and behavior problems (Child Behavior Checklist). Scores were grouped as average, borderline or extremely low by standard deviation intervals. The majority of CDH children had average neurodevelopmental outcomes at 5 years of age. However, rates of borderline and extremely low IQ scores were significantly higher than in the general population. Prolonged N/IICU stay, prolonged intubation, tracheostomy placement, pulmonary hypertension, autism, hearing impairment and developmental delays identified during infancy were significantly associated with worse performances (P<0.05).

Based on these results, our team has developed a study to re-evaluate these children at ages 8 to 13 to determine long-term neurodevelopmental, cardiac, pulmonary and quality of life outcomes in this patient population. Led by principal investigator Holly L. Hedrick, MD, Attending Pediatric and Fetal Surgeon and PHP Director, this customized assessment will include tests in academic knowledge and fluency; verbal and visual memory and reasoning; processing speed; executive functioning; and pulmonary function. The study will also measure quality of life and parental stress, and will include a limited echocardiogram and a chest X-ray.

This information currently does not exist in the medical literature and no other center has reviewed the outcomes of PHP children at 8 to 13 years of age. Our team hopes that findings from the study will deepen the amount of information we can provide families and referring physicians during prenatal counseling about how children will ultimately perform in school.

Long-term follow-up studies such as these are difficult to carry out, as they require funding to support staff time and study-related procedures, as well as travel and lodging costs for participating families, some of whom may be financially burdened and/or may live a great distance from our hospital. Dr. Hedrick and her team would not be able to advance this vital work without support from philanthropic patient families.

Other recent PHP studies of note have found:

• Lung functions of survivors of CDH remain abnormal throughout the first 3 years of life. The degree of pulmonary function impairment correlated both with markers of the initial degree of pulmonary hypoplasia and the duration of mechanical ventilation. Understanding the relationship between the phenotypic presentation of CDH and the potential for subsequent lung growth will help refine both pre- and postnatal therapies to optimize lung growth in CDH infants.
• Improved outcomes in CDH patients undergoing surgical repair following ECMO with significantly increased survival, lower rates of surgical bleeding, and decreased total duration of ECMO therapy compared to patients repaired on ECMO. In patients who can be successfully weaned from ECMO, this study supports a role for delayed repair off ECMO with reduced operative morbidity and increased survival.