Sleep-disordered breathing in infants with myelomeningocele

PROJECT SUMMARY
Spina bifida is the most common permanently disabling birth defect in the USA; myelomeningocele (MMC)
is the most severe form. Sleep-disordered breathing (SDB) is common in affected children and is a risk factor
for sudden death in this population. Abnormal sleep physiology is likely multifactorial for children with MMC,
related to the level of spinal defect, presence of congenital and acquired brainstem abnormalities,
musculoskeletal factors, and pulmonary abnormalities. Yet, systematic assessment for SDB is not routine.
Fetal surgery to close the spinal defect is a major advance in MMC therapy. Fetal surgery improves motor
development and can reduce the need for ventriculoperitoneal (VP) shunts by diminishing hindbrain herniation,
but cognitive outcomes are not improved compared with post-natal MMC repair (mean Bayley-II mental
development index scores ~1SD lower than normal controls at age 30 months) and persistent executive
function deficits are common later in childhood. The effect of fetal MMC repair on sleep pathophysiology
remains unknown. Meanwhile, emerging evidence suggests that for otherwise healthy children even mild
symptoms of SDB during infancy, such as parent-reported snoring, identify long-term risk for adverse
neurobehavioral consequences, including subtle cognitive deficits. Thus, the premise of this proposal is that
SDB is a potentially remediable contributor to the abnormal cognitive outcomes for children with MMC.
Innovative preliminary work by the investigators suggests that SDB is ubiquitous among newborns with
MMC regardless of the timing of surgical repair. We recruited twenty newborns with MMC for neonatal
polysomnography (5 fetal repair and 15 post-natal repair). All of these neonates had SDB, with no difference
between those who received fetal vs. post-natal repair. We now have a unique opportunity to leverage the
existing infrastructure of the North American Fetal Therapy Network (NAFTNet) for a multicenter observational
study that will have direct impact on clinical practice through the following specific aims – Aim 1: Determine
whether fetal vs. post-natal MMC repair at NAFTNet centers influences neonatal SDB; Aim 2: Define the
association between neonatal SDB, objective measures of sleep physiology, timing of MMC surgery, and
neurodevelopmental outcomes at age 2 years for patients with MMC; Aim 3: Assess whether fetal vs. post-
natal MMC repair influences the risk for persistent SDB at age 2 years.
Evaluation of sleep in neonates who require intensive care is an innovative, emerging opportunity with
potential for major impact on health and quality of life for affected children. This study will be the first of its kind
and could pave the way for a significant shift in clinical practice, to include routine screening of newborns with
MMC for SDB as part of a new standard of care. Results of this work will inform future intervention studies
designed to determine the most effective approach to treatment of SDB as a strategy to optimize long-term
medical and neurodevelopmental outcomes.

Grant Number: 5R01HL147261-05
NIH Institute/Center: NIH
Principal Investigator: JOHN BARKS