- 學位論文
極低出生體重早產兒於6至36個月齡間之動作與心智發展軌跡
Motor and Mental Developmental Trajectories in Preterm Children with Very Low Birth Weight during 6 to 36 Months of Age
摘要
背景與目的：極低出生體重早產兒(出生體重小於 1500g)為發展障礙之高危險群，因此亟需早期定時評估與介入。過去追蹤早產兒發展表現的文獻，多僅呈現群體的平均表現，而未考慮早產族群於發展歷程中的差異性及其潛在的影響因子。因此，本篇研究欲追溯先前長期追蹤之世代研究的臺灣極低出生體重早產兒個案，探討其於6個月至3歲間之心智與動作發展變化軌跡、與不同發展軌跡相關的影響因子以及3歲前發展軌跡與4歲動作、認知與行為發展預後之關聯性。方法: 本研究收錄之極低出生體重早產兒皆於父母同意參與研究後，皆先進行周產期與社會環境資料蒐集，於6、12、24及36個月時以貝萊氏嬰幼兒發展測驗第二版評估心智與動作發展，並於4歲時接受兒童動作評估、魏氏幼兒智力測驗及兒童行為檢核。統計部份將使用潛在成長曲線模式、群組化軌跡模式及混合成長模型檢驗具代表性的軌跡模型，並以邏輯式回歸分析探討發展軌跡與影響因子及發展預後之相關性。結果: 極低出生體重早產兒於6至36個月間呈現三種心智發展軌跡:持續正常(64%)、逐漸變差(31.4%)及持續遲緩(4.6%);以及四種動作發展軌跡:優於平均(6.3%)、持續正常(60%)、逐漸變差(28.5%)及持續遲緩(5.2%)。相對於心智正常發展軌跡，逐漸變差軌跡與嚴重視網膜病變(勝算比[95%信賴區間] = 3.6 [1.3-9.9])、較低的父親教育程度(勝算比[95%信賴區間] = 2.2 [1.3-3.8])、及較低的母親教育程度(勝算比[95%信賴區間] = 1.8 [1.2-2.8])有顯著相關(所有p<0.05);持續遲緩軌跡與較低出生體重(勝算比[95%信賴區間] = 0.3 [0.1-0.6])、住院天數較長(勝算比[95%信賴區間] = 3.3 [1.5-7.4])、嚴重腦傷(勝算比[95%信賴區間] =17.9 [1.7-488.2])、父親教育程度較低(勝算比[95%信賴區間] = 3.8 [1.1-12.7)、及母親教育程度較低(勝算比[95%信賴區間] = 2.7 [1.2-60.2])有顯著相關(所有p<0.05)。而相對於動作優於平均及正常發展軌跡，逐漸變差軌跡則與較低出生體重(勝算比[95%信賴區間] = 0.5 [0.3-0.7])及父親職業階級(勝算比[95%信賴區間] = 2.2 [1.1-4.3])有顯著相關(所有p<0.05); 持續遲緩軌跡與嚴重視網膜病變(勝算比[95%信賴區間] = 2.7[1.1-6.5])、嚴重腦傷(勝算比[95%信賴區間] =10.7 [2.2-50.7])、父親教育程度較低(勝算比[95%信賴區間] = 2.2 [1.0-4.8])、及母親職業階級較低(勝算比[95%信賴區間] = 16.7 [2.1-133.6])有顯著相關(p<0.05)。此外，逐漸變差之心智發展軌跡可預測早產兒4歲之認知發展遲緩(勝算比[95%信賴區間] = 11.3 [2.3-55.1]);持續遲緩之心智發展軌跡可預測早產兒4歲之認知發展遲緩(勝算比[95%信賴區間] = 130.6 [33.2-777.0])、動作發展遲緩(勝算比[95%信賴區間] = 18.3 [5.5-60.1])、及內隱性行為問題(勝算比[95%信賴區間] = 4.3 [1.4-12.6]) (所有p<0.05)。逐漸變差之動作發展軌跡可預測早產兒4歲之動作發展遲緩(勝算比[95%信賴區間] = 4.2 [1.8-9.8]);持續遲緩之動作軌跡則可預測早產兒4歲之認知發展遲緩(勝算比[95%信賴區間] = 24.6 [6.0-94.0])、動作發展遲緩(勝算比[95%信賴區間] = 53.4 [13.5-210.0])、及內隱性行為問題(勝算比[95%信賴區間] = 3.2 [1.2-8.8]) (所有p<0.05)。結論: 極低出生體重早產兒於6至36個月間呈現多種心智及動作發展軌跡，且該軌跡與部份周產期及社會環境因素具顯著相關性，並可預測於4歲時之認知、動作及行為發展預後表現。本項研究的結果能夠提供臺灣早產兒早期發展評估與預測之重要參考。
並列摘要
Background and purpose: Preterm children with very low birth weight (VLBW, birth weight < 1,500 g) are at risk of adverse developmental outcomes that require early identification and intervention of those who will have developmental disorder. Previous follow-up studies mostly examined the average developmental performance in preterm children and rarely explored the variations of developmental progress within population and the potential influencing factors. The purposes of this study were therefore to retrospectively abstract the longitudinal data of our previous cohort studies to examine the mental and motor development trajectories in VLBW preterm children in Taiwan during the first three years of age, to investigate the influencing factors for different trajectories, and to assess the relations of trajectories with developmental outcomes at four years of age. Methods: The perinatal and socio-environmental data were collected in all preterm infants with VLBW at baseline. Their mental and motor development were assessed by the Bayley Scales of Infant Development- Second Edition at 6, 12, 24 and 36 months of age; and the motor, cognitive and behavioral outcomes at 4 years of age were respectively examined using the Movement Assessment Battery for Children- Original or Second Edition, the Wechsler Preschool and Primary Scale of Intelligence, Revised and the Child Behavior Checklist for Ages 1.5-5. Developmental trajectories were examined by the latent growth curve modeling, group-based trajectory modeling and growth mixture modeling sequentially to select a representative model. The relations of developmental trajectories with influencing factors and subsequent outcomes were examined using logistic regression analysis. Results: Preterm children with VLBW showed three mental trajectories: stably normal (64.0%), deteriorating (31.4%) and persistently delayed patterns (4.6%); and four motor trajectories: above average (6.3%), stably normal (60.0%), deteriorating (28.5%) and persistently delayed patterns (5.2%) during 6 to 36 months of age. With respect to the stably normal pattern in mental development, the deteriorating pattern was associated with severe retinopathy of prematurity (ROP) (odds ratio [OR] [95% confidence interval (CI)] = 1.8 [1.3-3.1]), lower paternal educational level (OR [95% CI] = 2.2 [1.3-3.7]) and lower maternal educational level (OR [95% CI] = 1.8 [1.2-2.8]); whereas the persistently delayed pattern was associated with lower birth weight (OR [95% CI] = 0.3 [0.1-0.6]), longer hospital stay (OR [95% CI] = 3.3 [1.5-7.4]), major brain damage (OR [95% CI] = 17.9 [1.7-488.2]), lower paternal educational level (OR [95% CI] = 3.4 [1.5-7.8]) and lower maternal educational level (OR [95% CI] = 2.7 [1.2-60.2]) (all p<0.05). With respect to the above average and stably normal patterns in motor development, the deteriorating pattern was associated with lower birth weight (OR [95% CI] = 0.5 [0.3-0.7]) and paternal occupation status (OR [95% CI] = 2.2 [1.1-4.3]) (both p<0.05); the persistently delayed pattern was associated with severe ROP (OR [95% CI] = 2.7[1.1-6.5]), major brain damage (OR [95% CI] = 10.7 [2.2-50.7]), lower paternal education level (OR [95% CI] = 2.2 [1.0-4.8]) and lower maternal occupation status (OR [95% CI] = 16.7 [2.1-133.6]) (all p<0.05). Furthermore, the deteriorating mental pattern was predictive of mental delay (OR [95% CI] = 11.3 [2.3-55.1], p<0.05); whereas, the persistently delayed mental pattern was predictive of mental delay (OR [95% CI] = 130.6 [33.2-777.0]), motor delay (OR [95% CI] = 18.3 [5.5-60.1]) and internalizing behavioral problem at 4 years of age (OR [95% CI] = 4.3 [1.4-12.6]) (all p < 0.05). In contrast, the deteriorating motor pattern was predictive of mental delay (OR [95% CI] = 3.5 [1.1-11.7], p < 0.05) and motor delay at 4 years (OR [95% CI] = 4.2 [1.8-9.8]); whereas, the persistently delayed motor pattern was predictive of mental delay (OR [95% CI] = 24.6 [6.0-94.0], motor delay (OR [95% CI] = 53.4 [13.5-210.0], and internalizing problem at 4 years (OR [95% CI] = 3.2 [1.2-8.8]) (all p < 0.05). Conclusion: Preterm children with VLBW demonstrated various mental and motor trajectories during 6 to 36 months of age that were associated with certain perinatal and socio-environmental risk factors. Furthermore, the mental and motor trajectories were each predictive of 4-year mental, motor and behavioral outcomes. The study provides insightful information for planning early identification and intervention of preterm children with VLBW in Taiwan.