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浙江大学学报(医学版)  2022, Vol. 51 Issue (4): 462-469    DOI: 10.3724/zdxbyxb-2022-0144
原著     
健康足月妊娠孕妇孕中晚期血高密度脂蛋白胆固醇水平变化与出生小于胎龄儿的关系
王晶,周梦林,陈丹青()
浙江大学医学院附属妇产科医院产科,浙江 杭州 310006
Relationship between changes of high-density lipoprotein cholesterol levels in advanced pregnancy and the risk of neonatal small for gestational age in healthy full-term puerpera
WANG Jing,ZHOU Menglin,CHEN Danqing()
Department of Obstetrics, Affiliated Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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摘要:

目的:研究健康足月妊娠孕妇孕中晚期血高密度脂蛋白胆固醇(HDL-C)水平变化与小于胎龄儿(SGA)发生风险的关系。 方法:应用回顾性巢式病例对照研究,纳入2017年在浙江大学医学院附属妇产科医院产检分娩的健康足月妊娠孕妇为回顾性队列,将确认分娩SGA的孕妇纳入SGA组,按新生儿性别和受孕年龄个案匹配原则以1∶4比例将确认分娩适于胎龄儿的孕妇纳入对照组,采集两组孕妇的临床资料、孕中期(孕24~27周)和孕晚期(孕37周后)HDL-C水平,计算孕晚期平均每4周HDL-C的变化(ΔHDL-C)。采用配对 t检验比较两组孕妇间HDL-C和ΔHDL-C的差异,再采用条件logistic回归模型分析ΔHDL-C与SGA发病风险的关系。 结果:共纳入SGA组249名及对照组996名。两组足月后HDL-C水平均较孕24~27周时降低(即ΔHDL-C均小于0, P<0.05),SGA组ΔHDL-C显著高于对照组(P<0.05)。调整混杂因素后,与低水平ΔHDL-C孕妇比较,中水平、高水平ΔHDL-C孕妇分娩SGA的风险均升高(OR=1.74,95% CI:1.22~2.50; OR=2.48,95% CI:1.65~3.70,均 P<0.05)。结论:健康足月妊娠孕妇孕晚期HDL-C下降缓慢或不降反升与SGA的发生有关,在SGA筛查中可能具有一定的临床应用价值。

关键词: 小于胎龄儿妊娠中晚期足月妊娠高密度脂蛋白胆固醇巢式病例对照研究回顾性研究    
Abstract:

Objective: To explore the relationship between changes in blood high-density lipoprotein cholesterol (HDL-C) levels in advanced pregnancy and the risk of small for gestational age (SGA) in healthy full-term pregnant women. Methods: In this retrospective nested case-control study, pregnant women who got antenatal visits and experienced a healthy full-term delivery in Affiliated Women’s Hospital, Zhejiang University School of Medicine in 2017 were enrolled. From the cohort, 249 women delivered SGA infants with completed clinical data were set as SGA group, 996 women who delivered normal neonates were randomly selected as matched controls (1∶4). The data of baseline characteristics, the HDL-C levels in 24 th-27 th week and after 37 th week were collected, the average HDL-C changes every four weeks in the third trimester (ΔHDL-C) were calculated. Paired t test was used to compare the differences of HDL-C and ΔHDL-C between cases and controls, and a conditional logistic regression model was applied to analyze the association between ΔHDL-C and the risk of SGA. Results: HDL-C levels after the 37 th week in both groups were lower than those in mid-pregnancy (ΔHDL-C<0 andP<0.05 for both groups), while the ΔHDL-C levels in SGA group were significantly higher (P<0.05). Compared with women with low ΔHDL-C, the risk of SGA was higher for women with middle and high ΔHDL-C (OR=1.74, 95% CI:1.22–2.50; OR=2.48, 95% CI:1.65–3.70, both P<0.05).Conclusion: In healthy full-term pregnant women, the risk of SGA is associated with the HDL-C changing trend, HDL-C level decreasing slowly or even raising in the third trimester indicate that SGA may be likely to occur.

Key words: Small for gestational age    Advanced pregnancy    Full-term pregnancy    High-density lipoprotein-cholesterol    Nested case-control study    Retrospective study
收稿日期: 2022-04-10 出版日期: 2022-11-16
CLC:  R714.256  
基金资助: 浙江省自然科学基金(LQ20H040005)
通讯作者: 陈丹青     E-mail: chendq@zju.edu.cn
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王晶,周梦林,陈丹青. 健康足月妊娠孕妇孕中晚期血高密度脂蛋白胆固醇水平变化与出生小于胎龄儿的关系[J]. 浙江大学学报(医学版), 2022, 51(4): 462-469.

WANG Jing,ZHOU Menglin,CHEN Danqing. Relationship between changes of high-density lipoprotein cholesterol levels in advanced pregnancy and the risk of neonatal small for gestational age in healthy full-term puerpera. J Zhejiang Univ (Med Sci), 2022, 51(4): 462-469.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0144        https://www.zjujournals.com/med/CN/Y2022/V51/I4/462

图1  研究对象筛选过程及匹配条件 HDL-C:高密度脂蛋白胆固醇;SGA:小于胎龄儿.

组别

n

新生儿性别

孕妇年龄(岁)

孕妇流产次数

男性

女性

<25

25~<30

30~<35

≥35

0

≥1

SGA组

249

137(55.0)

112(45.0)

12(4.8)

136(54.6)

82(32.9)

19(7.6)

180(72.3)

69(27.7)

对照组

996

548(55.0)

448(45.0)

43(4.3)

514(51.6)

330(33.1)

109(10.9)

658(66.1)

338(33.9)

P

0.051

组别

n

孕妇身高(cm)

孕妇孕前BMI(kg/m 2 *

孕妇分娩史

<155

155~165

>165

<18.5

18.5~<24

≥24

初产妇

经产妇

SGA组

249

23(9.2)

209(82.7)

20(8.0)

74(29.7)

167(67.1)

8(3.2)

215(86.3)

34(13.7)

对照组

996

66(6.6)

821(82.4)

109(10.9)

232(23.3)

679(68.2)

85(8.5)

783(78.6)

213(21.4)

P

<0.01

<0.01

<0.01

组别

n

孕妇孕期增重情况 #

末次分娩孕周

孕妇学历

增重过多

增重适宜

增重不足

37~<39

39~41

本科以下

本科

本科以上

SGA组

249

34(13.7)

135(54.2)

80(32.1)

50(20.1)

199(79.9)

27(10.8)

193(77.5)

29(11.6)

对照组

996

168(28.8)

541(54.3)

287(16.9)

271(27.2)

725(72.8)

132(13.3)

760(76.3)

104(10.4)

P

<0.01

<0.05

0.535

组别

n

孕妇居住地

受孕季节

孕妇职业

城市

农村

春秋

职员

无业

其他

SGA组

249

193(77.5)

56(22.5)

90(36.1)

58(23.3)

101(40.6)

191(76.7)

14(5.6)

44(17.7)

对照组

996

896(90.0)

100(10.0)

334(33.5)

220(22.1)

442(44.4)

807(81.0)

54(5.4)

135(13.6)

P

<0.01

0.554

0.242

表1  SGA组和对照组一般情况比较
图2  基于对照组五分位数的ΔHDL-C与发生小于胎龄儿的剂量-反应关系 黑色圆点表示五分位数的各区间相对于参考区间的比值比. ΔHDL-C:孕晚期平均每4周HDL-C水平的变化. HDL-C:高密度脂蛋白胆固醇.
1 World Health Organization. International classification of diseases 11th revision[DB/OL]. (2021-05)[2021-09-19]. https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f1786398813
2 VANSLAMBROUCK K , DE KOK B , TOE L C , et al.Effect of balanced energy-protein supplementation during pregnancy and lactation on birth outcomes and infant growth in rural Burkina Faso: study protocol for a randomised controlled trial[J/OL]BMJ Open, 2021, 11( 3): e038393.
doi: 10.1136/bmjopen-2020-038393
3 SERIZAWA K , OGAWA K , ARATA N , et al.Association between low maternal low-density lipoprotein cholesterol levels in the second trimester and delivery of small for gestational age infants at term: a case-control study of the national center for child health and development birth cohort[J]J Matern-Fetal Neonatal Med, 2017, 30( 12): 1383-1387.
doi: 10.1080/14767058.2016.1214701
4 CHEN Q , CHEN H , XI F , et al.Association between maternal blood lipids levels during pregnancy and risk of small-for-gestational-age infants[J]Sci Rep, 2020, 10( 1): 19865.
doi: 10.1038/s41598-020-76845-1
5 IMDAD A , BHUTTA Z A . Effect of balanced protein energy supplementation during pregnancy on birth outcomes[J]BMC Public Health, 2011, 11( Suppl 3): S17.
doi: 10.1186/1471-2458-11-S3-S17
6 ROBERGE S , NICOLAIDES K , DEMERS S , et al.The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta- analysis[J]Am J Obstet GynEcol, 2017, 216( 2): 110-120.e6.
doi: 10.1016/j.ajog.2016.09.076
7 BETTIOL A , AVAGLIANO L , LOMBARDI N , et al.Pharmacological interventions for the prevention of fetal growth restriction: a systematic review and network meta‐ analysis[J]Clin Pharmacol Ther, 2021, 110( 1): 189-199.
doi: 10.1002/cpt.2164
8 MERICQ V , MARTINEZ-AGUAYO A , UAUY R , et al.Long-term metabolic risk among children born premature or small for gestational age[J]Nat Rev Endocrinol, 2017, 13( 1): 50-62.
doi: 10.1038/nrendo.2016.127
9 CIOBANU A , ROUVALI A , SYNGELAKI A , et al.Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35–37 weeks’ gestation[J]Am J Obstet Gynecol, 2019, 220( 5): 486.e1-486.e11.
doi: 10.1016/j.ajog.2019.01.227
10 POLJAK B , AGARWAL U , JACKSON R , et al.Diagnostic accuracy of individual antenatal tools for prediction of small-for-gestational age at birth[J]Ultrasound Obstet Gynecol, 2017, 49( 4): 493-499.
doi: 10.1002/uog.17211
11 MCCARTHY F , DOYLE A , KHASHAN A , et al.Assessment of glycogen phosphorylase isoenzyme BB as a biomarker for pre-eclampsia and small for gestational age[J]Lancet, 2015, 385( Suppl 1): S67.
doi: 10.1016/S0140-6736(15)60382-8
12 KRAMER M S , KAHN S R , DAHHOU M , et al.Maternal lipids and small for gestational age birth at term[J]J Pediatr, 2013, 163( 4): 983-988.
doi: 10.1016/j.jpeds.2013.05.014
13 KALLOL S , ALBRECHT C . Materno-fetal cholesterol transport during pregnancy[J]Biochem Soc Trans, 2020, 48( 3): 775-786.
doi: 10.1042/BST20190129
14 MCCONIHAY J A , HONKOMP A M , GRANHOLM N A , et al.Maternal high density lipoproteins affect fetal mass and extra-embryonic fetal tissue sterol metabolism in the mouse[J]J Lipid Res, 2000, 41( 3): 424-432.
doi: 10.1016/S0022-2275(20)34481-3
15 JIN W , LIN S , HOU R , et al.Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China[J]BMC Pregnancy Childbirth, 2016, 60.
doi: 10.1186/s12884-020-2834-1
16 WANG H , DANG Q , ZHU H , et al.Associations between maternal serum HDL-C concentrations during pregnancy and neonatal birth weight: a population-based cohort study[J]Lipids Health Dis, 2020, 19( 1): 93.
doi: 10.1186/s12944-020-01264-0
17 首都儿科研究所, 九市儿童体格发育调查协作组. 中国不同出生胎龄新生儿出生体重、身长和头围的生长参照标准及曲线[J]. 中华儿科杂志, 2020, 58(9): 738-746
Capital Institute of Pediatrics, Collaborative Group on Child Physical Development Research in Nine Cities. Growth standard curves of birth weight, length and head circumference of Chinese newborns of different gestation[J]. Chinese Journal of Pediatrics, 2020, 58(9): 738-746. (in Chinese)
18 Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines[M]. Washington (DC): National Academies Press, 2009: 254-256
19 中华医学会妇产科学分会产科学组. 孕前和孕期保健指南(2018)[J]. 中华妇产科杂志, 2018, 53(1): 7-13
Obstetrics and Gynecology Committee of the Chinese Medical Association. Preconception and prenatal care Guidelines (2018 edition) [J]. Chinese Journal of Obstetrics and Gynecology, 2018, 53(1): 7-13. (in Chinese)
20 Cunningham F G, Leveno K, Bloom S, et al. Williams Obstetrics[M]. 21st ed. New York: McGraw-Hill Education, 2018:164-165.
21 中华人民共和国国家卫生和计划生育委员会. WS/T 428-2013 成人体重判定[S/OL]. (2013-04-18)[2022-03-20]. http://www.nhc.gov.cn/ewebeditor/uploadfile/2013/08/20130808135715967.pdf
National Health and Family Planning Commission of the People’s Republic of China. WS/T 428-2013 criteria of weight for adults.[S/OL]. (2013-04-18)[2022-03-20]. http://www.nhc.gov.cn/ewebeditor/uploadfile/2013/08/20130808135715967.pdf. (in Chinese)
22 CANTIN C , FUENZALIDA B , LEIVA A . Maternal hypercholesterolemia during pregnancy: potential modulation of cholesterol transport through the human placenta and lipoprotein profile in maternal and neonatal circulation[J]Placenta, 2020, 26-33.
doi: 10.1016/j.placenta.2020.03.007
23 MISRA V K , TRUDEAU S , PERNI U . Maternal serum lipids during pregnancy and infant birth weight: the influence of prepregnancy BMI[J]Obesity, 2011, 19( 7): 1476-1481.
doi: 10.1038/oby.2011.43
24 FARIAS D R , POSTON L , FRANCO-SENA A B , et al.Maternal lipids and leptin concentrations are associated with large-for-gestational-age births: a prospective cohort study[J]Sci Rep, 2017, 7( 1): 804.
doi: 10.1038/s41598-017-00941-y
25 KWITEROVICH P O , COCKRILL S L , VIRGIL D G , et al.A large high-density lipoprotein enriched in apolipoprotein C- I[J]JAMA, 2005, 293( 15): 1891.
doi: 10.1001/jama.293.15.1891
26 WADSACK C , TABANO S , MAIER A , et al.Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition[J/OL]Am J Physiol-Endocrinol Metab, 2007, 292( 2): E476-E484.
doi: 10.1152/ajpendo.00547.2005
27 WANG H L , LIANG N , HUANG D X , et al.The effects of high-density lipoprotein and oxidized high-density lipoprotein on forskolin-induced syncytialization of BeWo cells[J]Placenta, 2021, 199-205.
doi: 10.1016/j.placenta.2020.10.024
28 中华医学会围产医学分会胎儿医学学组, 中华医学会妇产科学分会产科学组. 胎儿生长受限专家共识(2019版)[J]. 中华围产医学杂志, 2019, 22(6): 361-380
Fetal Medicine Group, Perinatal Medicine Committee, Chinese Medical Association; Obstetrics and Gynecology Section, Chinese Medical Association. Expert consensus on fetal growth restriction (2019 edition) [J]. Chinese Journal of Perinatal Medicine, 2019, 22(6): 361-380. (in Chinese)
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