Sleep-disordered breathing, craniofacial development, and neurodevelopment in premature infants: a 2-year follow-up study

Highlights

• Premature infants present a clear higher frequency of sleep problems at two years of age.

• Abnormal breathing during sleep is an important cause of these sleep problems.

• Abnormal breathing during sleep is also associated with developmental delays.

• The abnormal orofacial growth in premature infant plays a role in the abnormal breathing during sleep.

Abstract

Introduction

Sleep problems, neuro-developmental development, and sleep-disordered-breathing (SDB), are reported as more prevalent in premature infants than in full-term infants. We investigated the relationship between neuro-development, and SDB in preterm infants at 24 months corrected age (CA) with a narrow palatal presentation over time.

Methods

We enrolled infants 40 weeks or younger at birth collecting obstetric and birth data. Participants were followed up at 6, 12, 18, and 24 months CA. We evaluated craniofacial development by inspecting and photo documenting hard palate; sleep using sleep diary, actigraphy and night-time polysomnography-PSG-; and development using Bayley- Scales-of-Infant-Development and Denver-Developmental-Screening-Test (DDST) at each visit and comparing results at six months and two years.

Results

244 premature infants [139 (57.0%) boys, [at birth: mean gestational age-GA- 31.5 ± 3.2 weeks, 1691.9 ± 593.9 g, 40.2 ± 5.2 cm], and 30 full term infants (50% boys), [mean GA 39.3 ± 1.0 weeks, 3131.0 ± 390.0 g, and 49.38 ± 2.0 cm] were enrolled in the study. At 6 and 24 months, 65.2% premature infants had a narrow hard palate (NHP). At 24 months, 79% had an apnea–hypopnea- index (AHI) > 1 events/hour at PSG, with a mean AHI of 3.00 ± 2.95. Only 10% of full term infants had NHP at birth and the mean AHI was 0.5 ± 0.2 event/hour at 24 months.

Conclusion

Preterm infants have a higher occurrence of NHP at birth. At two years of age they have more sleep problems, most commonly associated with obstructive-SDB, and a higher rate of development delays. Frequency of NHP is still abnormally high, suggesting not only abnormal orofacial growth over-time, but also impact of this abnormal growth in the genesis of the obstructive-SDB.

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.