臺灣博碩士論文加值系統

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。

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.

口試委員會審定書 i
致謝 ii
中文摘要 iii
English Abstract v
Contents viii
Chapter I. Introduction 1
1.1 Epidemiology and lifelong consequences of preterm birth with VLBW 1
1.2 Longitudinal development among VLBW preterm children 2
1.3 Influencing factors for development 4
1.4 Prediction of outcome by early development 6
1.5 Statistical methods to assess the developmental trajectories 7
1.6 Rationale of the study 9
1.7 Study purposes and hypotheses 9
Chapter II. Methods 11
2.1 Participants 11
2.2 Testing procedure 12
2.3 Outcome measurements 13
2.3.1 Bayley Scales of Infant Development- 2nd edition (BSID-II) and Bayley Scales of Infant and Toddler Development- 3rd edition (Bayley-III) 13
2.3.1 Movement Assessment Battery for Children- Original and Second Edition (MABC & MABC-II) 15
2.3.2 Wechsler Preschool and Primary Scale of Intelligence, Revised (WPPSI-R) 16
2.3.3 The Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5) 16
2.4 Statistical analysis 17
Chapter III. Results 20
3.1 Participants 20
3.2 Selection of trajectory model in mental and motor development 20
3.3 Mental and motor development in VLBW preterm children in first three years of age 22
3.4 Influencing factors for mental and motor developmental trajectories in VLBW preterm children during 6 to 36 months of age 23
3.5 Prediction of outcomes at four years of age by early developmental trajectories 25
Chapter IV. Discussion 27
4.1 Developmental trajectories at 6 to 36 months of age 27
4.2 Influencing factors for developmental trajectories 28
4.3 Relations of developmental trajectories with subsequent outcomes 32
4.4 Limitations 33
Chapter V. Conclusion 34

Tables and Figures 34
Table 1. Characteristics of preterm children who received two or more assessments and those who received one or no assessment 35
Table 2. Illustration of the BSID-II mental and motor scores for preterm children whose data were included for trajectory analysis 36
Table 3. Illustration of model fit indices for the mental and motor scores in preterm children with the linear, quadratic and cubic LGCM 37
Table 4. Illustration of model fit indices for the mental and motor scores in preterm children with the linear, quadratic and cubic GBTM 38
Table 5. Illustration of model fit indices for the mental and motor scores in preterm children with the linear, quadratic and cubic GMM 39
Table 6. Trajectories of the mental and motor scores in preterm children during the first three years of age 40
Table 7. Illustration of the perinatal and socio-environmental characteristics of preterm children among the three mental trajectories 41
Table 8. Illustration of the perinatal and socio-environmental characteristics of preterm children among the three motor trajectories 42
Table 9. Illustration of the perinatal and socio-environmental characteristics of preterm children in three developmental status 43
Table 10. Characteristics of preterm children who returned and did not return for assessments at 4 years of age 44
Table 11. Prediction of 4-year mental, motor and behavioral outcomes by early mental and motor trajectories in preterm children 45
Figure 1. The number of preterm children in the three cohort studies enrolled and administered the Bayley assessment at 6 to 36 months of age 46
Figure 2. The estimated means and trajectories of mental scores in preterm children at 6, 12, 24 and 36 months of age 47

Figure 3. The estimated means and trajectories of motor scores in preterm children at 6, 12, 24 and 36 months of age 48
References 49
Appendix 54

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