107/10/26 小兒科聯合病例討論會：談嬰兒之骨質評估

評估成長的另一個指標： 談嬰兒之骨質評估 (Bone Status) 高醫大 醫學院呼吸治療學系 副教授

高醫附設醫院 小兒科部 新生兒科 主治醫師

陳秀玲 E-mail: 840062@ms.kmuh.org.tw

Outline • Current assessment of bone status for neonates: Quantitative ultrasound (QUS) • QUS studies in neonates – Calcium Intake during pregnancy & bone status in healthy full-term newborn infants – Assisted exercise improves bone strength in very low birth weight infants by bone QUS – The “normal range” at birth – Postnatal growth during the first year 1071026

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Physical growth 1. Body weight 2. Body height 3. Head circumference 4. ???

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Current assessment of bone status for neonates • Dual-energy x-ray absorptiometry (DEXA) – 雙能量X光吸收儀

• Quantitative computed tomography (QCT) – 定量電腦斷層掃描

• Quantitative ultrasound (QUS) – 定量超音波

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Quantitative Ultrasound (QUS) • QUS: develop in 1984 • As a noninvasive method of assessment, but with varying conclusions was reached • Advantages: – Non-ionising – Portable – Low cost Bone speed of sound 1071026

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Quantitative ultrasound (QUS) • The speed of sound (SOS) measurement can indicate the stiffness of a substance, the broadband ultrasound attenuation measures how much energy of the sound wave is lost from bone attenuation. • The measurement of SOS by QUS could be used to assess bone status (strength) in newborn infants.

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Sunlight OmnisenseÂŽ 7000SP for SOS assessment

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Sunlight OmnisenseÂŽ 7000SP

Bone speed of sound (SOS, m/s)

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QUS studies in neonates Calcium Intake during pregnancy & bone status in healthy full-term newborn infants Assisted exercise improves bone strength in very low birth weight infants by bone QUS The “normal range� at birth dependent on different gestational age Postnatal growth during the first year

97.4.26 兒科醫學會口頭報告

孕婦膳食之鈣質對健康足月新生兒 骨質密度之影響-初步報告 Calcium Intake during Pregnancy and Bone Mass Measured with Sound of Speed (SOS) in Healthy Full-term Newborn Infants --- preliminary report 陳秀玲 楊政憲1 胡淑惠1 曾馨誼 呂志忠 楊生湳 高雄醫學大學附設中和紀念醫院小兒部 高雄醫學大學生物醫學檢驗學系1

Factors affecting in utero mineral accretion • • • •

Effects of maternal vitamin D Intrauterine growth retardation Maternal insulin-dependent diabetes mellitus Maternal ethanol, smoking, and caffeine intake » Clinica Chimica Acta 333 (2003) 1-11

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Aim • The purpose of this study is to determine the effect of maternal calcium intake during pregnancy on bone status measured with quantitative ultrasound (QUS) measurement of bone speed of sound (SOS) in healthy full term newborn infants.

Maternal • Maternal Diet calcium intake Questionnaire Bone status of • Bone SOS neonates 1071026

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Maternal characteristics of study group All N=103 Maternal age (mean ± SD) , y

31.3± 3.9

Maternal height (mean ± SD) , cm

159.46 ± 5.40

Body weight increase during pregnancy (mean ± SD), kg

14.34 ± 4.36

First born

65%

Maternal smoking

1%

Alcohol consumption

1%

Coffee consumption

11.8%

Tea consumption

55.9%

Calcium intake (mean ± SD), mg/week

1771.2 ± 1495.9

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Neonatal characteristics of study group All N=103 Sex, male Gestational age (mean ± SD) , wk Birth body weight (mean ± SD), gm

54.9% 38.5 ± 1.0 3135.3 ± 350.9

Birth height (mean ± SD) , cm

50.5 ± 2.3

Head circumference (mean ± SD) , cm

33.4 ± 1.3

SOS at birth (mean ± SD) , m/s

2960.6 ± 109.6

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The frequency of SOS in full term newborn at birth in study group (N=103) SOS at birth 14 12 10 8 6

Frequency

4 Std. Dev = 109.56 2

Mean = 2960.6

0

N = 103.00 .0 75 32 0 .

25 3 2 .0 75 3 1 .0 25 31 0 .

75 3 0 .0 25 3 0 .0 75 29 0 .

25 2 9 .0 75 2 8 .0 25 28 0 .

75 2 7 .0 25 27

SOS at birth 1071026

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Pearson correlation Variable

by Variable

Correlation

P value

SOS at birth (m/s)

weekly calcium intake (mg/week)

0.186

0.030*

Gestational age (week)

0.024

0.814

Birth height (cm)

0.061

0.542

Head circumference (cm)

-0.011

0.913

Birth body weight (kg)

-0.068

0.501

0.028

0.780

Maternal age (y)

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Linear Regression SOS at birth (m/s)

Pearson correlation 0.186, P value=0.03

SOS = 2936.39 + 0.01 * weekly total calcium intake

weekly total calcium intake during pregnancy (mg/week) 1071026

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Conclusion • The preliminary result may provide information about the appropriate diet suggestion about calcium intake for pregnant mother and bone growth pattern in health term infants. • Larger sample size will be necessary to make an end conclusion.

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98.3.22 新生兒科醫學會海報論文

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Aim • To evaluate whether assisted exercise could prevent the development of osteopenia of prematurity, we performed assisted exercise in the study group of very low birthweight (VLBW) premature infants.

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Methods • 16 premature infants with birthweight below 1500 g were enrolled in this study and randomly assigned into the exercise (n = 8) and control (n = 8) groups.

• Assisted exercise involved full extension and flexion range of motion of the upper and lower extremities by a trained nurse with a schedule of 5 days a week for a total of 4 weeks.

• Bone strength was determined by quantitative ultrasound measurement of tibial bone speed of sound every 2 weeks during the study period.

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Results • There was statistically significant less tibial bone speed of sound decrease in the exercise group on the sixth and eighth week of life. • During the study period, there were no statistically significant differences in blood biochemistry data, including calcium, phosphorus, magnesium, alkaline phosphatase (ALP), osteocalcin and osteoprotegerin, between the two groups.

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Assisted exercise improves bone strength in very low birthweight infants by bone quantitative ultrasound

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Journal of Paediatrics and Child Health Volume 46, Issue 11, pages 653-659, 25 AUG 2010 DOI: 10.1111/j.1440-1754.2010.01822.x http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1754.2010.01822.x/full#f1

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98.11.14 兒科醫學會口頭報告

The “normal range” at birth Bone status measured by quantitative ultrasound in newborn infants in southern Taiwan 以定量超音波測量南台灣初生嬰兒之骨質狀態 陳秀玲 廖淑玫 曾馨誼 呂志忠 楊生湳 楊瑞成 Hsiu-Lin Chen, Shu-Mei Liao, Hsing-I Tseng, Chu-Chong Lu, San-Nan Yang, Rei-Cheng Yang 高雄醫學大學附設中和紀念醫學小兒部 Department of Pediatrics, Kaohsiung Medical University Hospital

98.11.14 兒科醫學會口頭報告

The “normal range” at birth Our objectives were • To perform bone SOS to assess the status of the tibia in preterm and full-term newborns • To evaluate factors associated with bone status at birth.

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98.11.14 兒科醫學會口頭報告

Results– total 513 infants

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Neonatal characteristics of study group Gr. A (≧ 37 wks) n=271

Gr. B (32-36 wks) n=158

Gr. C (< 32 wks) n=84

Male, n (%)

150 (55.4)

86 (54.4)

43 (51.2)

Twins, n (%)

9 (3.3)

38 (24.1)

18 (21.4)

GA, weeks, mean ± SD

38.3 ± 1

34.1 ± 1.4

29.0 ± 2

BBW, grams, mean ± SD

3079.5 ± 425.2

2128.8 ± 492.2

1308.7 ± 337.3

BH, cm, mean ± SD

49.8 ± 2.5

44.9 ± 3.6

38.6 ± 4.0

HC, cm, mean ± SD

33.3 ± 1.5

30.6 ± 1.9

27.0 ± 2.2

BMI, mean ± SD

12.4 ± 1.4

10.5 ± 1.7

8.6 ± 1.3

SGA, n (%)

28 (10.3)

28 (17.7)

9 (10.7)

AGA, n (%)

228 (84.1)

126 (79.8)

75 (89.3)

LGA, n (%)

15 (5.6)

4 (2.5)

0 (0)

2964.8 ± 104.1

2951.6 ± 99.9

2867.2 ± 123.7

SOS at birth, m/s, mean ± SD

Tibial bone SOS at birth is higher on male gender 3300 3200

SOS at birth (m/s)

3100 3000 2900 2800 2700 2600 F 女孩

M 男孩 sex

SOS at birth F M

Mean 2929.34 2957.70

Std Dev 108.915 112.443

p = 0.004

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Relationship between tibial speed of sound (SOS) and gestational age (GA) 3300 3200

birth (m/s)

SOS at

3100 3000 2900 2800

出生時 的SOS

2700 2600 22

29

24

26

28

30

32 34 GA(w)

36

38

SOS at birth (m/s) = 2576.6 + 10.4*GA(w)

40

42

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Relation between tibial speed of sound (SOS) and gestational age (GA) cubic curve fitting 3300 3200

birth (m/s)

SOS at

3100 3000 2900 2800 2700 2600 22

24

26

28

30

32 34 GA(w)

36

38

40

42

SOS at birth (m/s) = 2798.3+ 4.4*GA(w) - 0.2*(GA(w)-35.5)^2 + 0.1*(GA(w)-35.5)^3 30

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Relationship between tibial speed of sound (SOS) and birth body weight (BBW) 3300 3200

birth (m/s)

SOS at

3100 3000 2900 2800 2700 2600 500

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1000 1500 2000 2500 3000 3500 4000 4500 BBW (gm)

SOS at birth (m/s) = 2888.9 + 0.02*BBW (gm)

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Comparison of tibial bone SOS among SGA, AGA, and LGA infants of total study infants 3400

3200

3000

SOS at birth

2800

2600

2400 N=

429

65

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AGA AGA

SGA

LGA

SGA

LGA

ANOVA

status_GA

1st day SOS

32

Sum of Squares Between Groups 126204.398 Within Groups 6255036.588 Total 6381240.986

df 2 510 512

Mean Square 63102.199 12264.778

F 5.145

Sig. .006

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Correlations SOS at birth

maternal age

GA(w)

BBW (gm)

BH(cm)

HC(cm)

BMI

Pearson Correlation

-.010

.342*

.161*

.211*

.221*

.116*

Sig. (2-tailed)

.824

.000

.000

.000

.000

.009

No significant difference was noted on gender, seasons of birth, delivery method, maternal age, parity, multiple gestation, or maternal disease (including gestational diabetics, preeclampsia) 33

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Multiple regression analysis Unstandardized Coefficients B (Constant) 2108.875

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Std. Error

Standardized Coefficients

t

Sig.

Beta

147.907

95% Confidence Interval for B Lower Bound

Upper Bound

14.258

.000

1818.289

2399.460

GA(w)

25.019

2.811

.826

8.901

.000

19.496

30.541

BBW (gm)

-.103

.035

-.741

-2.958

.003

-.172

-.035

BH(cm)

1.449

4.004

.067

.362

.718

-6.418

9.316

HC(cm)

3.566

3.638

.093

.980

.328

-3.582

10.713

BMI

2.367

8.310

.044

.285

.776

-13.960

18.694

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The “normal range” at birth

出生時 的SOS

Conclusions-1

• Bone status measured by quantitative 出生週 數 ultrasound (SOS) in newborn infants are 男孩 correlated with gestational age and birth anthropometrics including birth body weight, birth body height and head circumference.

• Tibial bone SOS at birth is higher on male gender.

• Bone status at birth were not related to maternal factors, and seasons of birth.

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The “normal range” at birth Conclusions-2 • The most important factors influencing bone status were male gender, gestational age and birth body weight after multiple regression analysis.

• SGA infants may have higher SOS than AGA infants at birth

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37 1071026

Chen HL, et al. Early Hum Dev. 2012 Aug;88(8), 617-622

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Chen HL, et al. Early Hum Dev. 2012 Aug;88(8), 617-622

102.11.9 兒科醫學會口頭報告

Longitudinal Changes in Tibial Bone Speed of Sound (SOS) of AGA Preterm and Full-term Infants during the First Year of Life 早產及足月嬰兒之脛骨骨聲速度於 出生後一年內之變化 陳秀玲1,2 楊瑞成1 1高雄醫學大學附設中和紀念醫學小兒部, 2高雄醫學大學呼吸治療學系 Hsiu-Lin Chen1,2, Rei-Cheng Yang 1 1Department of Pediatrics, Kaohsiung Medical University Hospital 2Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University

Postnatal growth during the first year Objective â&#x20AC;˘ The aims of our study are to evaluate how tibial SOS changes over time in term and preterm infants during the first year of life and to determine what factors influence tibial SOS change during infancy.

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A longitudinal mixed-effect model â&#x20AC;˘ To test for associations between bone SOS and possible influencing factors, an analytic approach that permits full use of available data while controlling for internal correlations and other covariates in two groups of infants. â&#x20AC;˘ This model treats each bone SOS data from each enrolled infants as a separated observation and adjusts for within-infant correlations and correlations with their prior bone SOS data.

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Postnatal growth during the first year Results-1 â&#x20AC;˘ The study consisted of 134 preterm and 35 full-term infants. (n=169) â&#x20AC;˘ A total of 856 measurements for tibial bone SOS by QUS were obtained between birth and 1 year.

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3300 3200

The growth curve of tibial bone speed of sound for preterm and full-term infants during first year of life

3100

S O S

3000 2900

( m / s

2800

Term_boy_Mean

)

Term_girl_Mean

2700

Preterm_boy_Mean Preterm_girl_Mean

2600 2500 Birth 1071026

1-2m

2-4m

4-6m

6-8m Age

8-10m

10-12m 12-15m 43

出生至 一歲的 SOS變 化

Results-2

• Although significant gender difference on tibial bone SOS values at birth were observed, there are no significant gender differences in the pattern of change in tibial bone SOS during infancy. 男孩

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Postnatal growth during the first year Conclusion-1 • This study revealed significant differences in the pattern of change in tibial bone SOS values between preterm and full-term infants during the first year of life. 出生至 一歲的 SOS變 化

足月 vs. 早產 45

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Postnatal growth during the first year Conclusion-2 • Chronological age and SOS value at birth were important factors affecting tibial bone SOS growth in both preterm and full-term newborn infants during infancy.

出生至 一歲的 SOS變 化

年齡

出生時 的SOS 46

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Postnatal Changes in Tibial Bone Speed of Sound of Preterm and Term Infants during Infancy • Preterm (n = 155) and term (n = 65) infants were enrolled in this study.

• There was a total of 1352 tibial bone SOS and anthropometric measurements taken from enrolled infants between birth and 12-15 months old.

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出生至 一歲的 SOS變 化

年齡

出生時 的SOS 47

3300.0 p < 0.0001*

p = 0.078

3200.0 p = 0.002* 3100.0 p = 0.042

Bone SOS (m/s)

3000.0

p = 0.0005* p = 0.001*

2900.0

p =0.0007*

p = 0.338

2800.0 Mean SOS Term in PNA

2700.0

Mean SOS Preterm in PNA Mean SOS Preterm in CA 2600.0

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1-2m

2-4m

4-6m

6-8m

Age class in months

8-10m

10-12m

12-15m 48

Change in bone status during infancy Femoral midshaft from birth to 6 months of age

~Best Practice & Research Clinical Endocrinology & MetabolismVol. 22, No. 1, pp. 107â&#x20AC;&#x201C;118, 2008 ~ Journal of Bone and Mineral Research.Volume 16, Issue 4, pages 597â&#x20AC;&#x201C;604, 2001

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Future work • Focus on VLBW group of postnatal growth during the first year – – – –

Peak ALP during hospitalization Morbidity (IVH, CLD, NEC, prolonged use of TPN) Nutritional status after discharge Caring pattern (sun exposure….)

To be continued……

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