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Journal of Clinical Otorhinolaryngology Head and Neck Surgery logoLink to Journal of Clinical Otorhinolaryngology Head and Neck Surgery
. 2024 Mar 3;38(3):230–234. [Article in Chinese] doi: 10.13201/j.issn.2096-7993.2024.03.010

出生体重与儿童阻塞性睡眠呼吸暂停关系的研究

The relationship between birth weight and obstructive sleep apnea in children

Zhe DENG 1, Guixiang WANG 2, Yuwei HOU 1, Yujie LIU 1, Yanxia XU 1, Ying XU 1, Dongjie SENG 1, Fugen HAN 1, Jing ZHAO 2,*
PMCID: PMC11233210  PMID: 38433693

Abstract

Objective

To study the relationship between children's birth weight and obstructive sleep apnea(OSA).

Methods

The sleep data and birth information of children who underwent polysomnography in the Department of Otorhinolaryngology-Head and Neck Surgery of Henan Children's Hospital from October 2020 to July 2022 were retrospectively analyzed. The data of OSA detection rate, OSA severity, sleep structure and respiratory parameters in different birth weight groups were analyzed.

Results

A total of 2 778 children met the inclusion criteria, including 1 833 males and 945 females. According to birth weight, the selected children were divided into three groups: 122 small for gestational age(SGA) group, 2 313 appropriate for gestational age(AGA), and 343 large for gestational age(LGA) group. There was no significant difference in age between different groups(P=0.061). In each group, boys are significantly more numerous than girls(P=0.001). The difference in current body mass index(BMI) between groups was statistically significant: the current BMI was higher in the LGA group(17.51±4.01, P < 0.001). The severity of OSA was different in different birth weight groups(P=0.037). There was a strong positive correlation between the severity of OSA and birth weight(r=0.992). Children in the SGA group had shorter rapid eye movement(REM) sleep period(19.00[15.18, 23.33], P=0.012), higher obstructive apnea-hypopnea index(OAHI) values(1.75[0.60, 5.13], P=0.019), and had lower central apnea hypopnea index(CAHI) values(0.10[0.00, 0.50], P=0.020). There were no significant differences in sleep structure and respiratory parameters between the LGA group and the AGA group. Multiple regression analysis of the factors affecting the OAHI index showed that the OAHI index of boys was higher than that of girls(95%CI 1.311-2.096, P < 0.001), and age was negatively correlated with the OAHI index(r=-0.105, 95%CI 0.856-0.946, P < 0.001), current BMI and OAHI index were positively correlated(r=0.037, 95%CI 1.010-1.065, P=0.007). LGA was positively correlated with OAHI index(r=0.346, 95%CI 1.039-1.921, P=0.027), and the correlation between LGA and OAHI(r=0.346) was higher than that between SGA and OAHI(r=0.340).

Conclusion

There was no significant difference in the incidence of OSA in children with different birth weight groups, but the OSA severity of LGA group was higher. Gender, age, BMI index and large for gestational age were the influencing factors for the occurrence of OSA in children, which should be paid more attention to in clinical practice.

Keywords: birth weight, child, sleep apnea, polysomnography

阻塞性睡眠呼吸暂停(obstructive sleep apnea，OSA)是影响儿童睡眠呼吸的主要疾病，OSA患儿除了睡眠中常出现张口呼吸、打鼾、憋气、出汗和遗尿等症状，由于在睡眠中处于慢性缺氧状态，反复觉醒，也会导致正常的睡眠结构被打乱，导致白天嗜睡、注意力不集中、多动、记忆力和学习成绩下降等，严重影响儿童的身心健康[1]。引起儿童OSA的主要病因有扁桃体腺样体肥大、颅面畸形、肌张力低下、肥胖等。国外有相关研究报道，儿童OSA的其他危险因素还包括早产和低出生体重[2-4]、母亲种族[4]、低社会经济地位[5]、母亲孕期吸烟[5]、母亲孕期肥胖和糖尿病[6]以及轻度子痫前期等[7]。本研究着重分析了在耳鼻咽喉头颈外科门诊行多导睡眠监测(polysomnography，PSG)儿童的出生体重及PSG监测数据，旨在分析研究新生儿出生体重与儿童OSA的关系。

1. 资料与方法

1.1. 研究对象

2020年10月至2022年7月因睡眠张口呼吸、打鼾为主诉就诊于我科，并在睡眠中心行多导睡眠监测的儿童共2 880例。排除颅面异常、合并有综合征、精神运动迟缓或遗传神经肌肉障碍，以及腺样体扁桃体切除术后、呼吸机治疗后、睡眠效率 < 60%的儿童78例，共2 778例儿童纳入研究对象。

1.2. 研究方法

1.2.1. 资料采集

监护人根据患儿情况填写儿童OSA疾病特异性生活质量(OSA-18)量表。提取量表中患儿性别、年龄、当前身高及体重、出生体重、是否早产、母亲生孩子时年龄等信息。出生体重参照“中国不同胎龄新生儿出生体重百分位数参考值”，出生体重在同胎龄平均体重的第10百分位以下为小于胎龄儿(small for gestational age，SGA)，出生体重在同胎龄平均体重的第10~90百分位为适于胎龄儿(appropriate for gestational age，AGA)，出生体重在同胎龄平均体重的第90百分位以上为大于胎龄儿(large for gestational age，LGA)[8]。

1.2.2. PSG监测

所有患儿均在睡眠实验室行整晚PSG检查，采用澳大利亚Compumedic公司生产的Grael型号睡眠监测仪。患儿在自然状态下入睡，入睡前避免饮用咖啡、茶等兴奋性饮料，检查当日禁止服用具有中枢性兴奋或抑制的药物，有效监测时间超过7 h。睡眠监测导联包括脑电(6导，分别为额区、中央区和枕区导联各2导)、眼电、下颌肌电、鼾声、鼻气流(使用热敏、压力传感器)、胸部运动、腹部运动(使用RIP胸腹传感器)、血氧饱和度、音视频等。睡眠技师依据美国睡眠医学会睡眠监测指南2.4版本的标准[9]，对PSG进行人工分析及校对。提取报告中患儿睡眠结构和呼吸参数等数据。

1.2.3. 诊断标准

OSA诊断采用《中国儿童阻塞性睡眠呼吸暂停诊断与治疗指南(2020)》作为标准[10]。轻度：1次/h < OAHI≤5次/h，中度：5次/h < OAHI≤10次/h，重度：OAHI>10次/h。

1.3. 统计学处理

应用SPSS 22.0软件进行统计学分析。对计量资料进行正态性检验，符合正态分布的计量资料以X±S表示，3组间比较采用单因素方差分析，不符合正态分布的计量资料以M(P25，P75)表示，3组间比较采用Kruskal-Wallis H检验，采用Bonferroni法进行两两比较；等级资料采用Spearman相关性分析；计数资料以频数、%表示，组间比较采用χ2检验，采用有序logistic回归分析OSA严重程度的危险因素，P < 0.05为差异有统计学意义。

2. 结果

2.1. 临床资料

3组中男性患儿均多于女性(P=0.001)，各组之间的平均年龄无差异(P=0.061)，但现平均体重指数(body mass index，BMI)差异有统计学意义，LGA组儿童的现平均BMI较高(17.51±4.01，P < 0.001)，OSA检出率各组之间差异无统计意义(P=0.277)，见表 1。

表 1.

不同出生体重组儿童的基本特征和OSA检出率

项目 SGA AGA LGA
例数 122 2 313 343
性别/例(%)
  男 77(4.2) 1499(81.8) 257(14.0)
  女 45(4.8) 814(86.1) 86(9.1)
平均年龄/岁 5.03±2.37 5.13±2.39 5.45±2.65
平均BMI/(kg/m2) 16.21±3.15 16.45±3.30 17.51±4.01
OSA检出率/% 63.11 55.90 56.85
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2.2. OSA严重程度

不同出生体重组儿童的OSA严重程度不同(P=0.037)，见表 2。对严重程度和出生体重进行Spearman相关性分析(r=0.992)，说明OSA严重程度和出生体重之间呈强正相关性。

表 2.

不同出生体重组儿童的OSA严重程度 例(%)

项目 SGA AGA LGA
正常(OAHI≤1) 45(3.7) 1 022(84.1) 148(12.2)
轻度(1 < OAHI≤5) 45(4.4) 856(84.2) 116(11.4)
中度(5 < OAHI≤10) 14(6.7) 174(82.9) 22(10.5)
重度(OAHI>10) 18(5.4) 259(77.5) 57(17.1)
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2.3. 睡眠结构和呼吸参数

SGA组和AGA组比较，SGA组儿童快速动眼睡眠(rapid eye movement sleep，REM)期较少[19.00(15.18，23.33)，P=0.012]，阻塞性呼吸暂停低通气指数(obstructive apnea hypopnea index，OAHI)较高[1.75(0.60，5.13)，P=0.019]，中枢性呼吸暂停低通气指数(central apnea hypopnea index，CAHI)较低[0.10(0.00，0.50)，P=0.020]。LGA组和AGA组比较，睡眠结构和呼吸参数方面差异无统计意义，见表 3。

表 3.

不同出生体重组儿童的睡眠结构和呼吸参数 M(P25，P75)

参数 SGA AGA LGA H P
睡眠效率 81.90(73.63，89.25) 84.40(76.80，90.10) 83.30(74.90，90.20) 3.549 0.170
REM潜伏期 108.50(68.88，161.75) 111.50(72.50，151.38) 112.0(67.00，159.50) 0.080 0.961
N1/% 2.80(1.50，4.85) 2.70(1.40，4.40) 2.70(1.50，4.80) 2.117 0.347
N2/% 47.70(41.40，53.20) 46.60(41.40，51.88) 46.50(41.40，51.40) 1.207 0.547
N3/% 29.70(24.78，35.75) 28.50(24.30，33.40) 28.90(24.10，33.20) 1.992 0.369
REM/% 19.00(15.18，23.33) 20.70(17.20，24.60) 20.50(17.20，24.70) 8.785 0.012
平均血氧 97.00(96.00，98.00) 97.00(97.00，98.00) 97.00(96.00，98.00) 3.977 0.137
平均氧减 4.00(3.00，5.00) 4.00(3.00，5.00) 4.00(3.00，5.00) 4.100 0.129
最低氧饱和 89.00(83.75，92.00) 90.00(86.00，92.00) 89.00(86.00，92.00) 2.634 0.268
AHI 2.00(0.88，6.00) 1.70(0.80，4.10) 1.90(0.80，5.20) 4.691 0.096
OAI 0.30(0.08，0.90) 0.30(0.00，0.80) 0.30(0.00，1.10) 0.724 0.696
OAHI 1.75(0.60，5.13) 1.30(0.50，3.50) 1.30(0.50，4.10) 7.930 0.019
CAHI 0.10(0.00，0.50) 0.20(0.00，0.60) 0.20(0.00，0.50) 7.844 0.020
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2.4. 多元回归分析

将影响OAHI指数的因素进行多元回归分析发现，男童OAHI指数较女童高，年龄与OAHI指数呈负相关，BMI与OAHI指数呈正相关。LGA与OAHI指数呈正相关，且LGA与OAHI的相关性高于SGA与OAHI的相关性，见表 4。

表 4.

影响OAHI指数的因素的多元回归分析

因素 系数 调整OR 95%CI P
性别
  男 0.505 1.658 1.311~2.096 < 0.001
  女 1.000
年龄 -0.105 0.900 0.856~0.946 < 0.001
BMI 0.037 1.037 1.010~1.065 0.007
出生体重
  SGA 0.340 1.405 0.797~2.477 0.240
  AGA 1.000
  LGA 0.346 1.413 1.039~1.921 0.027
早产
  是 -0.029 0.972 0.531~1.777 0.926
  否 1.000
母亲生孩子时年龄 -0.002 0.998 0.975~1.022 0.862
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3. 讨论

本研究中，不同出生体重组中男童均多于女童，且对影响OAHI指数的因素进行多元回归分析发现，男童OAHI指数较女童高。文献表明，不同性别的儿童OSA发病及严重程度有所不同，Kang等[11]对1 842例儿童进行研究发现，在不同的年龄组中，男童的AHI值均高于女童。Inoshita等[12]研究发现不同性别的青少年患者OSA严重程度存在差异。但Horne等[13]发现儿童OSA严重程度无性别差异。OSA患病率和严重程度的性别差异在青春期前儿童中尚不清楚，但在青少年中已有明确报道。可能是由于激素变化开始于青春期，意味着肥胖和激素变化导致了不同性别儿童OSA严重程度的差异[13-15]。未来研究将进一步分析不同年龄阶段男女童OAHI指数是否有区别。

高出生体重是儿童期多种疾病的危险因素，比如代谢综合征、肥胖[16]、龋齿[17]、运动功能异常[18]、情绪行为异常[19]等。本研究中，LGA组儿童的现平均BMI值较高，多元回归分析发现，LGA儿童OSA严重程度是AGA儿童的1.413倍，相关性分析显示，OSA严重程度和出生体重之间呈强正相关性。原因可能是，出生时高体重导致儿童期肥胖的发生，而肥胖又是OSA发病的重要危险因素。有研究发现，高出生体重是0~6岁儿童出现肥胖或超重的主要危险因素[20]，另有研究称，较正常出生体重儿，巨大儿是儿童超重的独立危险因素[21]。大量研究发现肥胖儿童更易发生OSA[22-24]。肥胖与OSA的发生可相互促进：OSA患儿存在气道梗阻，出现反复低氧血症，睡眠结构片段化，导致交感神经系统兴奋促进胰岛素抵抗，从而发生糖代谢及内分泌紊乱；患儿夜间频繁觉醒使得白天精力不足，易出现疲劳嗜睡，运动量减少，促使肥胖发生。肥胖患儿过多的脂肪堆积在上气道周围引起狭窄，增加了上气道阻力，另外肥胖患者胸壁脂肪组织堆积会降低胸廓的顺应性，导致肺容量降低，间接导致咽壁顺应性增加，易于塌陷，不利于上气道开放。本研究中现BMI与OAHI指数呈正相关，与既往研究相符。另外肥胖还会导致儿童炎性因子产生、肠道菌群失调、高血压以及精神心理障碍等[25]。

低出生体重儿易发生新生儿肺炎[26]，听力障碍[27]，生长发育和神经行为发育落后[28]等。低出生体重早产儿大脑质量仅为足月儿大脑质量的65%，脑白质、灰质、胼胝体和小脑体积较小，脑沟回较少[29]。有研究报道称，低出生体重儿童存在更多的睡眠问题及运动功能落后等现象[30]。本研究发现，SGA儿童的睡眠结构中REM期占比较低，OAHI值较高，CAHI值较低。这表明低出生体重儿童睡眠结构紊乱，出现呼吸暂停或低通气的情况较多。OSA患病率方面，SGA儿童与AGA和LGA儿童之间差异无统计意义，但在影响OAHI指数方面，SGA与AGA比较，虽然差异无统计意义，但其风险性仍然较高。Chen等[31]研究发现，早产或低出生体重与儿童期OSA的临床诊断风险较高有关。一项回顾性纵向研究发现出生时体重过低的年轻人发生睡眠呼吸障碍症状的风险更大[32]。Rosen等[3]的一项基于人群的队列研究表明，早产的儿童在童年时期发生睡眠呼吸障碍的可能性增加了3~5倍。本研究中虽然早产并非影响OAHI指数的危险因素，但其与OAHI指数仍然成负相关。早产与儿童OSA关联的潜在机制可能是早产对上气道大小和呼吸控制发育有长期不利影响，增加了儿童期OSA的风险[32-34]。

本研究存在一些局限性，首先，纳入的研究对象均为有临床症状而到耳鼻喉科就诊的儿童，并未和人群中正常儿童进行比较，因此可能存在选择偏倚。未来研究将加入和正常儿童的比较，包括认知、学习能力等，探讨出生体重和儿童期疾病的发生及神经认知功能的关系。其次，本研究中的出生体重均为患儿监护人根据回忆填写生活质量调查表，可能存在回忆偏倚，但在进行数据处理时，已将偏差较大的数据剔除。未来将联合新生儿科对不同出生体重的儿童进行纵向研究，以期获得更全面的研究成果。第三，本研究未对儿童进行年龄分层，出生体重与哪个年龄段的儿童OSA发病关系最为密切，有待进一步研究。

不同出生体重儿童的OSA发生率无明显差异，但大于胎龄儿的OSA严重程度更高。性别、年龄、BMI指数、大于胎龄儿均为儿童OSA发生的主要影响因素，临床应高度关注。

Funding Statement

2022年度河南省医学科技攻关计划联合共建项目(No：LHGJ20220717)

Footnotes

利益冲突  所有作者均声明不存在利益冲突

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