極低出生體重早產兒以家庭為中心介入計畫的神經行為及神經生理功能療效

Abstract

背景：極低出生體重早產兒（出生體重小於1500克）是發展障礙的高危險群。早產兒之早期介入融入以家庭為中心的理論基礎於認知、動作發展上之介入成效多維持在嬰幼兒時期，於學齡前期及學齡期的療效並不明顯。有少數研究應用神經生理評估探討早產兒住院期早期介入的療效機制，發現會改變腦波連結相關性，唯腦波連結相關性的結果並不一致。目的：本研究探討極低出生體重早產兒從住院期持續至出院後的以家庭為中心之早期介入在神經生理功能及神經行為表現的療效，並探討神經生理功能及神經行為表現之間的關聯性。方法：本實驗於臺大、馬偕及成大醫院徵召極低出生體重早產兒，隨機分派至介入組與常規組，分別接受從住院期持續至矯齡1歲的以家庭為中心及常規性早期介入。兩組於矯齡1及4個月進行神經生理功能檢查，於睡眠狀態測量其腦波連結相關性，以及於新異刺激法下測量聽覺事件相關電位，並於矯齡6及12個月接受第三版貝萊氏嬰幼兒發展測驗。結果：269名個案中129名為介入組，140名為常規組。6及12個月的動作、認知與語言發展分數無組間差異。連結相關性於矯齡1至4月的變化，介入組在delta頻率帶的左右半球內從額葉至頂葉、顳葉及枕葉之腦波連結相關性皆顯著高於常規組（p值皆小於經錯誤發現率校正後之顯著水準）。此外，介入組theta頻率帶的左半球內從額葉至頂葉、枕葉及兩半球間的額葉之腦波連結同調性亦高於常規組（p值皆小於經錯誤發現率校正後之顯著水準）。聽覺事件相關電位生理參數於適重早產兒次族群中，介入組於F3電極之P150與N250尖峰潛伏期明顯快於常規組（p=0.01）。前額葉至頂葉與顳葉之腦波連結相關性於矯齡1至4月的變化與12個月動作分數達顯著相關（β=4.0~12.3, p <0.05），P150於F3之尖峰潛伏期與12個月認知功能達邊緣相關（β= −0.04, p=0.1）。結論：極低出生體重早產兒實施以家庭為中心之介入計畫在6及12個月的神經行為表現上無顯著療效，但明顯提高矯齡1至4個月額葉至其他腦部區域之腦波連結相關性，而且部分的神經生理參數與12個月的動作及認知功能有關。

Background: Preterm infants with very low birth weight (VLBW) are at high risk of developmental disorders in their lifetime. Previous studies on family-centered care for preterm infants showed short- to medium-term neurobehavioral benefit. Few studies have explored the neurophysiological changes underlying effective in-hospital intervention in preterm infants, however differences existed in the patterns of spectral coherence as measured by using electroencephalography (EEG). Purposes: This study was aimed to examine the effects of a family-centered intervention program (FCIP) on the neurophysiological function and neurobehavioral performance in VLBW preterm infants in the first year compared to a usual care program (UCP), and to investigate the relationships between neurophysiological function and neurobehavioral outcome. Methods: VLBW preterm infants from three medical centers in Taiwan were recruited and were randomly allocated to the FCIP and UCP to receive interventions from hospitalization to 12 months of corrected age (CA). Infants were assessed neurophysiological function using the EEG in sleep and EEG/event-related potentials (ERPs) in an auditory oddball paradigm at 1 and 4 months CA, followed by neurobehavioral assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 6 and 12 months CA. Results: This study included 269 VLBW preterm infants (129 in the FCIP and 140 in the UCP). Cognitive, language, and motor composite scores at 6 and 12 months were comparable between groups. The FCIP showed greater increase in the EEG coherence in bilateral intra-hemispheric pairs in the frontal-to-parietal, temporal, and occipital regions from 1 to 4 months CA than the UCP (all p< significant level adjusted by false discovery rate). Among preterm infants with appropriate for gestational age, the peak latencies of P150 and N250 at F3 electrode in auditory oddball procedure were shorter in the FCIP group than in the UCP group (all p=0.01). The coherence pairs in prefrontal-to-temporal and parietal regions from 1 to 4 months were correlated with motor score at 12 months (β=4.0~12.3, all p <0.05); the peak latency of P150 was marginally correlated with cognitive score at 12 months (β=−0.04, p=0.1) in all preterm infants. Conclusions: The FCIP yielded changes in on the brain connectivity between 1 and 4 months CA but showed no obvious neurobehavioral effect at 6 and 12 months CA in VLBW preterm infants. Furthermore, certain electrophysiological measures were associated with subsequent motor and cognitive outcome in VLBW preterm infants.