Original ArticleSleep-disordered breathing, craniofacial development, and neurodevelopment in premature infants: a 2-year follow-up study
Introduction
Since obstructive-sleep-apnea-OSA-was first identified in full-term children by Guilleminault et al. in 1976 [1], sleep-disordered-breathing-SDB- and OSA have been associated with many morbidities such as cardiovascular and metabolic (eg, hypertension) [2], growth (eg, failure to thrive) [3], neurocognitive (eg, low academic performance) [4], [5], and neurobehavioral (eg, inattention, hyperactivity, impulsivity, aggressivity, and poor executive functions, communication, and adaptive skills) [5], [6] during childhood or adolescence.
Recently, preterm birth has been recognized as a risk factor for both SDB (at age 8–11) [7] and OSA (at age 2.5–6) [8] in prepubertal children. Our previous prospective studies have reported that premature infants are at a great risk of developing SDB [9]. Meanwhile, OSA has been reported not only to be more severe in adults with a past history of prematurity, but also to be associated with a clear narrow hard palate-NHP- and a very narrow upper airway [10]. How does this risk develops, what is the frequency of such risk, is there an association between SDB and poor sleep, is there an association between early SDB and early development of premature infants are questions incompletely resolved [10], [11], [12].
Adenotonsillar hypertrophy has been the first-line treatment target for childhood SDB and OSA [13]. However, craniofacial anomalies, not adenotonsillar hypertrophy, are the primary cause of OSA in syndromic infants [10], [13], [14]. These craniofacial anomalies include hypoplasia or displacement of the maxilla or mandible, such as midface hypoplasia, micrognathia, glossoptosis [15], Pierre Robin sequence [16], and changes associated with NHP [17]. However, orofacial dysfunction in non-syndromic infants such as present in premature infants may be associated with orofacial growth problem that may result in OSA [14], [17], [18], [19].
Currently, an abundant literature has also demonstrated the association of pediatric SDB and OSA with cognitive (mental) and behavioral (psychomotor) problems [4], [5], [6], [20], [21], [22], [23]. One study suggested that OSA may lead to neuronal damage in the hippocampus and prefrontal cortex, which could permanently alter the cognitive potential of a developing child [23]. We hypothesized that the presence of a NHP in premature infants and impairment of orofacial growth may play a major role in the development of SDB and thus, may play a role in the observed neurodevelopmental deficits. Our study aimed to further investigate the development of SDB in premature infants, its relations with the orofacial development based on clinical information, and the potential impact on neuro-development.
Section snippets
Method
This cohort study was approved by the institutional review board of Chang Gung Memorial Hospital.
Results
We recruited 30 full-term and 244 premature infants (see Table 1 for demographic and initial information at enrollment and differences between full-term and premature infants). With aging, four groups of premature infants could be identified from an initial NHP + group consisting of 152 (62.3%) children; and an initial NHP- group of 92 (37.7%). 181 children did not change their anatomic attribute between birth and six months of age, ie. stayed in Group NHP+ and NHP-. These 181 children were
Discussion
The study-results showed that the presence at birth, and persistence overtime, of a NHP in premature infants is associated with persistence of obstructive-SDB and sleep problems (Table 2a, Table 2ba and 2b) and may thus worsen neurodevelopmental deficits (Table 3). Although, the sample size of our premature infant group is not very large, in this prospective study, we observed in our premature infants, how narrow hard palates, sleep problems, and neurodevelopment evolved and interacted during
Conclusion
Our data have shown the following: Premature infants present with a NHP, more SDB-related sleep problems, and more neurodevelopmental deficits than full-term infants and premature infants without NHP. Until two years old, premature infants with continuous presence of NHP have more SDB-related sleep problems and more neurodevelopmental deficits than those without. These findings are in support our hypothesis that a NHP in premature infants participates in the development of SDB-related sleep
Acknowledgement
These data were presented at the “The International Pediatric Sleep Association”, Paris, April, 2018. This study was supported by Chang Gung Memorial Hospital grants CORPG 3F0771 and CORPG 3F0751 (Yu-Shu Huang).
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Jen-Fu Hsu and Yu-Shu Huang contributed equally to this article.