以家庭為中心介入對於極低出生體重早產兒在學齡前期的神經發展及神經生理功能之療效

Abstract

背景與目的：極低出生體重早產兒(出生體重小於1,500公克)為發展障礙之高危險群。過去研究報告早期介入對於早產兒具有短期療效，然而有關長期的神經發展及神經生理的改變與兩者之間的關係探討則相當有限。因此，本研究目的為探討臺灣極低出生體重早產兒實施以家庭為中心之早期介入相對於常規照護在4歲時之神經發展和神經生理功能療效，以及檢驗早期神經生理功能的改變是否中介4歲之神經發展及神經生理療效。方法: 本研究追蹤251位極低出生體重早產兒4歲時的神經發展及神經生理功能，這些早產兒於出生後以隨機分配方式，分別接受從住院開始為期一年的以家庭為中心介入與常規照護，曾於矯正年齡1及4個月使用睡眠腦波檢查以及事件相關電位之聽覺特異刺激評估神經生理功能，並於4歲時接受神經行為評估 (包括認知的魏氏幼兒智力量表修訂版、動作的兒童動作ABC 評量表第二版、以及行為的兒童行爲量表1.5-5歲版)及神經生理功能評估 (腦波及事件相關電位測量休息、聽覺特異與執行功能抑制控制任務)。結果：兩組分別有102位孩童於4歲時回來接受神經發展及神經生理功能評估。兩組之動作表現(7.4±2.4 vs. 7.4±2.1)、智商分數(96.8±14.4 vs. 94.3±16.7)及行為表現(53.9±11.4 vs. 55.0±10.5)相當。而在執行功能抑制控制測驗的形狀反應/不反應任務中，以家庭為中心介入組比常規照護組呈現較高的正確率(83% vs. 77%, p=0.03)及N2於不反應試驗中在frontocentral 電極有較短的潛時(357.94 毫秒 vs. 389.75 毫秒, p=0.04)；而在顏色反應/不反應任務中，以家庭為中心介入組之P3於反應及不反應試驗中在frontal, frontocentral, central和parietal 電極呈現較短的潛時(489.95~586.75 毫秒 vs. 587.04~676.33 毫秒, 所有 P值<0.05)、P3於不反應試驗中在central 電極有較大的振幅(16.92 微伏 vs. 5.29 微伏, p=0.04)及P3於反應試驗中在parietal 電極有較大的振幅(9.76 微伏 vs. -1.18 微伏, p=0.04)。至於4歲之休息時腦區聯結相關性及聽覺特異任務的神經生理參數均無顯著組間差異。中介因素分析顯示，早期神經生理因子和4歲之神經發展預後間並無明顯相關。 結論：以家庭為中心介入對於極低出生體重早產兒之4歲認知功能，尤其是抑制控制表現，比常規照護具較佳的療效。

Background and purpose: Preterm infants with very low birth weight (VLBW, birth weight < 1,500 g) are at risk of developmental disabilities. Although meta-analyses revealed short-term developmental effect of early intervention for preterm infants, the long-term neurobehavioral and neurophysiological changes and their relationship has rarely been examined. The purposes of this study were therefore to examine the long-term effectiveness of a family-centered intervention program (FCIP) on neurobehavioral and neurophysiological function in VLBW preterm infants in Taiwan at 4 years of age compared with a usual care program (UCP), and to assess if early neurophysiological changes mediated the effects on the 4-year outcomes. Methods: This study prospectively examined the neurobehavioral and neurophysiological function in 251 VLBW preterm infants at 4 years of age who were randomly allocated for FCIP (N=122) and UCP (N=129) from hospitalization to 12 months of corrected age (CA). Infants were assessed neurophysiological function using the electroencephalography (EEG) in sleep and EEG/event-related potentials (ERP) in an auditory oddball task at 1 and 4 months CA, followed by neurobehavioral (cognition: Wechsler Preschool and Primary Scale of Intelligence-Revised; motor function: Movement Assessment Battery for Children-2nd Edition; behavior: Child Behavioral Check List for Ages 1.5-5) and neurophysiological assessment (EEG/ERPs in resting, auditory oddball task and inhibitory control tasks) at 4 years of age. Results: A total of 102 FCIP group children and 102 UCP group children returned for assessment at 4 years of age. The FCIP and UCP groups were comparable in the motor score (7.4±2.4 vs. 7.4±2.1), full scale IQ score (96.8±14.4 vs. 94.3±16.7) and total behavior score (53.9±11.4 vs. 55.0±10.5). As for the executive function, the FCIP group children manifested significantly higher correct rate (83% vs. 77%, p=0.03) and shorter N2 latency at the Fcz channel (357.94 ms vs. 389.75 ms, p=0.04) and shorter P3 peak latency at the Pz channel (499.16 ms vs. 553.47 ms, p=0.02) in the go trials during the shape Go/Nogo task; the FCIP group children had significantly shorter P3 peak latency at the Fz, Fcz, Cz and Pz channels in the nogo and go trials (489.95~586.75 ms vs. 587.04~676.33 ms, all P<0.05), larger P3 mean amplitudes at the Cz channel in the nogo trials (16.92 μV vs. 5.92 μV, p=0.04) and larger P3 mean amplitudes at the Pz channel in the go trials (9.76 μV vs. -1.18 μV, p=0.04) during the color Go/Nogo task than the UCP group children. There was no difference between groups in the resting EEG coherence, and peak amplitude and latency variables in the auditory oddball task at 4 years of age, however. Neither was the early neurophysiological variables related to later neurodevelopmental outcome. Conclusions: The FCIP yielded beneficial effect on cognitive function, specifically inhibitory control in executive function, in VLBW preterm children at preschool age than the UCP.