孕晚期妇女与新生儿血浆维生素A水平的相关性分析

doi:10.19723/j.issn.1671-167X.2020.03.011

摘要/Abstract

摘要：

目的探讨孕晚期妇女静脉血与新生儿脐带血血浆维生素A(vitamin A,VitA)水平的相关性。方法 2009年5月至6月在河北省元氏县和乐亭县募集孕妇688例,采集产前静脉血和新生儿脐带血,采用高效液相色谱法检测血浆视黄醇浓度,用以反映VitA水平。根据产前静脉血血浆视黄醇浓度,孕妇VitA营养状态分为缺乏(<0.70 μmol/L)、边缘性缺乏(0.70~<1.05 μmol/L)、充足(≥1.05 μmol/L)。根据脐带血血浆视黄醇浓度,新生儿VitA营养状态分为缺乏(<0.35 μmol/L)、边缘性缺乏(0.35~<0.70 μmol/L)、充足(≥0.70 μmol/L);将脐带血血浆视黄醇浓度低于第10百分位数定义为新生儿VitA相对缺乏。新生儿与孕妇血浆视黄醇浓度比值定义为VitA胎盘转运系数。采用多元分式多项式(multivariable fractional polynomials,MFP)模型和Pearson相关探讨孕妇与新生儿血浆VitA水平的关系,采用Logistic回归模型探讨孕妇VitA营养状态对新生儿VitA缺乏的影响,采用MFP模型和Spearman相关探讨孕妇VitA水平与胎盘转运系数的关系。结果孕晚期妇女视黄醇平均浓度为(1.15±0.30)μmol/L,VitA缺乏率和边缘性缺乏率分别为4.5%和37.8%;新生儿视黄醇平均浓度为(0.78±0.13)μmol/L,无VitA缺乏,边缘性缺乏率为28.2%。调整孕妇年龄、体重指数等因素后,孕妇与新生儿VitA水平间呈线性正向剂量-反应关系(幂参数=1,P<0.05), Pearson相关系数为0.13(P<0.01)。与VitA充足组孕妇相比,缺乏组(crude OR=2.20,95%CI:1.04~4.66)和边缘性缺乏组(crude OR=1.43,95%CI:1.01~2.02)分娩VitA边缘性缺乏新生儿的风险显著升高,但多因素调整后,上述效应不再有统计学意义;VitA缺乏组孕妇分娩VitA相对缺乏新生儿的风险在调整多因素前后均显著增加(crude OR=3.02,95%CI:1.21~7.50;adjusted OR=2.76,95%CI:1.05~7.22)。孕妇VitA水平与VitA胎盘转运系数间呈非线性负向剂量-反应关系(幂参数=-0.5,P<0.05),调整后Spearman相关系数为-0.82(P<0.001)。结论孕晚期妇女与新生儿血浆VitA水平呈正向线性剂量-反应关系,提示孕妇VitA营养状态影响新生儿VitA储存水平。

关键词: 维生素A, 新生儿, 孕妇, 孕晚期

Abstract:

Objective: To study the correlation of plasma vitamin A (VitA) levels between neonates and pregnant women in third trimester.Methods: A total of 688 pregnant women were recruited in Yuanshi and Laoting counties of Hebei Province, from May to June 2009. Venous blood samples of women before delivery and cord blood samples of newborns were collected and measured for retinol (retinol concentration was used to reflect VitA level) using high performance liquid chromatography assay. According to venous blood plasma retinol concentration, maternal VitA nutritional status was divided into deficiency (<0.70 μmol/L), marginal deficiency (0.70-<1.05 μmol/L), and sufficiency (≥1.05 μmol/L). According to cord blood plasma retinol concentration, neonatal VitA nutritional status was divided into deficiency (<0.35 μmol/L), marginal deficiency (0.35-<0.70 μmol/L), and sufficiency (≥0.70 μmol/L); neonatal VitA relative deficiency was further defined as cord blood plasma retinol concentration lower than the 10th percentile. VitA placental transport ratio was defined as retinol concentration in the neonates divided by that in pregnant women. Multivariable fractional polynomials (MFP) model and Pearson correlation were used to study the dose-response relationship between maternal and neonatal plasma VitA levels, Logistic regression model to estimate the effect of maternal VitA nutritional status on neonatal VitA deficiency, and MFP model and Spearman correlation to describe the relationship between maternal VitA level and VitA placental transport ratio.Results: The average retinol concentration of the pregnant women was (1.15±0.30) μmol/L, and the prevalence of VitA deficiency and marginal deficiency were 4.5% and 37.8%, respectively. Average retinol concentration of the neonates was (0.78±0.13) μmol/L, and no neonates were VitA deficiency, 28.2% of the neonates were marginal deficiency. After multivariable adjustment, the VitA level of the neonates was positively and linearly related to maternal VitA level (p^m=1, P<0.05), with the corresponding Pearson correlation coefficient of 0.13 (P<0.01). As compared with the women with sufficient VitA, those with VitA deficiency (crude OR=2.20, 95%CI:1.04-4.66) and marginal deficiency (crude OR=1.43, 95%CI:1.01-2.02) had higher risks to deliver neonates with VitA marginal deficiency; while the risks turned to be non-significant after multivariable adjustment. The pregnant women with VitA deficiency had higher risk to deliver neonates with relative VitA deficiency before and after multivariable adjustment (crude OR=3.02, 95%CI:1.21-7.50; adjusted OR=2.76, 95%CI:1.05-7.22). The maternal VitA level was negatively and non-linearly correlated with placental transport ratio (p^m= -0.5, P<0.05), with corresponding adjusted Spearman correlation coefficient of -0.82 (P<0.001).Conclusion: There was a positive linear dose-response relationship between VitA levels of newborns and pregnant women in third trimester, indicating that neonatal VitA storing levels at birth was affected by maternal VitA nutritional status.

Key words: Vitamin A, Neonate, Pregnant woman, Third trimester

中图分类号:

R172

李秀翠,周玉博,司可艺,李宏田,张乐,张亚黎,刘菊芬,刘建蒙. 孕晚期妇女与新生儿血浆维生素A水平的相关性分析[J]. 北京大学学报（医学版）, 2020, 52(3): 464-469.

Xiu-cui LI,Yu-bo ZHOU,Ke-yi SI,Hong-tian LI,Le ZHANG,Ya-li ZHANG,Ju-fen LIU,Jian-meng LIU. Relationship of plasma vitamin A levels between neonates and pregnant women in third trimester[J]. Journal of Peking University (Health Sciences), 2020, 52(3): 464-469.

图/表 6

表1

孕妇及新生儿的基本特征和血浆VitA水平"

Characteristics	Values
Pregnant women
Retinol concentration /(μmol/L), $x ?$ ±s	1.15±0.30
Age/years, n(%)
<25	509 (74.0)
≥25	179 (26.0)
Gestational age at enrollment/weeks, $x ?$ ±s	11.5±4.7
Gestational age at delivery/weeks, $x ?$ ±s	39.5±1.7
County, n(%)
Yuanshi	383 (55.7)
Laoting	305 (44.3)
Ethnicity, n(%)
Han	683 (99.3)
Other	5 (0.7)
Occupation, n(%)
Farmer	606 (88.0)
Other	82 (12.0)
Education, n(%)
Middle school or less	553 (80.4)
High school	72 (10.5)
University or higher	63 (9.1)
Body mass index at enrollment/ (kg/m²), n(%)
<18.5	38 (5.5)
18.5-23.9	483 (70.2)
>23.9	167 (24.3)
Hemoglobin level/(g/L), n(%)
≥110	663 (96.4)
<110	25 (3.6)
Newborns
Retinol concentration/(μmol/L), $x ?$ ±s	0.78±0.13
Gender, n(%)
Male	314 (45.6)
Female	353 (51.3)
Missing	21 (3.1)
Preterm birth, n(%)
Yes (28 weeks≤ gestational age<37 weeks)	29 (4.2)
No (gestational age≥37 weeks)	659 (95.8)
Birth length/cm, $x ?$ ±s	50.28±1.02
Birth weight/g, $x ?$ ±s	3 291.5±459.7

表1

表2

孕晚期妇女和新生儿VitA水平Pearson相关分析"

Maternal VitA status	Neonatal retinol concentration/(μmol/L)	r^a	P	$r adj b$	P
VitA deficiency (n=31)	0.74±0.17	0.34	0.05	0.45	0.03
Marginal VitA deficiency(n=260)	0.77±0.13	0.11	0.06	0.11	0.10
Sufficient (n=397)	0.78±0.13	0.13	<0.01	0.13	<0.01
Total (n=688)	0.78±0.13	0.14	<0.001	0.13	<0.01

表2

图1

表3

表4

孕晚期妇女VitA水平与VitA-PTR的Spearman相关"

Items	$r s a$	P	$r sadj b$	P
Maternal VitA nutritional status
VitA deficiency	-0.08	0.65	-0.03	0.91
Marginal VitA deficiency	-0.48	<0.001	-0.48	<0.001
Sufficient	-0.62	<0.001	-0.61	<0.001
Neonatal VitA nutritional status
First definition method^c
Marginal VitA deficiency	-0.95	<0.001	-0.94	<0.001
Sufficient	-0.91	<0.001	-0.90	<0.001
Second definition method^d
Relative VitA deficiency	-0.95	<0.001	-0.94	<0.001
Sufficient	-0.88	<0.001	-0.86	<0.001
Total	-0.84	<0.001	-0.82	<0.001

表4

图2

参考文献 22

[1]	Murguia-Peniche T. Vitamin D, vitamin A, maternal-perinatal considerations: old concepts, new insights, new questions[J]. J Pediatr, 2013,162(Suppl 3):26-30.
[2]	Ahmad SM, Alam MJ, Afsana K, et al. Vitamin A supplementation during pregnancy enhances pandemic H1N1 vaccine response in mothers, but enhancement of transplacental antibody transfer may depend on when mothers are vaccinated during pregnancy[J]. J Nutr, 2018,148(12):1968-1975.
[3]	Neves PAR, Castro MC, Oliveira CVR, et al. Effect of vitamin A status during pregnancy on maternal anemia and newborn birth weight: results from a cohort study in the Western Brazilian Amazon[J]. Eur J Nutr, 2018,59(1):45-56. pmid: 30560301
[4]	Handel MN, Moon RJ, Titcombe P, et al. Maternal serum retinol and beta-carotene concentrations and neonatal bone mineralization: results from the Southampton women’s survey cohort[J]. Am J Clin Nutr, 2016,104(4):1183-1188. doi: 10.3945/ajcn.116.130146 pmid: 27629051
[5]	Hanson C, Lyden E, Anderson-Berry A, et al. Status of retinoids and carotenoids and associations with clinical outcomes in maternal-infant pairs in Nigeria[J]. Nutrients, 2018,10(9):1286.
[6]	黄娜, 刘颖. 维生素A与呼吸系统疾病关系的研究进展[J]. 国际儿科学杂志, 2019,46(7):512-515.
[7]	Ali H, Hamadani J, Mehra S, et al. Effect of maternal antenatal and newborn supplementation with vitamin A on cognitive development of school-aged children in rural Bangladesh: a follow-up of a placebo-controlled, randomized trial[J]. Am J Clin Nutr, 2017,106(1):77-87. pmid: 28490513
[8]	West KP, Sommer A. Neonatal vitamin A: time to move on?[J]. Lancet, 2015,386(9989):131-132. pmid: 26194387
[9]	刘欢, 苗静琨, 余林超, 等. 新生儿与母亲孕晚期维生素A水平的相关研究[J]. 重庆医科大学学报, 2018 ( 6):818-823.
[10]	Ramalho RA, dos Anjos LA, Flores H. Nutritional status of vitamin A in mother/newborn pairs from 2 hospital nurseries in Rio de Janeiro, Brazil[J]. Arch Latinoam Nutr, 1999,49(4):318-321.
[11]	Wassef L, Quadro L. Uptake of dietary retinoids at the maternal-fetal barrier: in vivo evidence for the role of lipoprotein lipase and alternative pathways[J]. J Biol Chem, 2011,286(37):32198-32207.
[12]	World Health Organization. Global prevalence of vitamin A deficiency in populations at risk 1995—2005: WHO global database on vitamin A deficiency[R]. Geneva: WHO, 2005.
[13]	中国疾病预防控制中心营养与健康所. 人群维生素A缺乏筛查方法: WS/T 553—2017[S/OL]. 北京: 中华人民共和国国家卫生和计划生育委员会, 2017, 8 ( 2017- 08- 01)[2020-02-20]. http://www.nhc.gov.cn/wjw/yingyang/201708/da44da0299504b9da360b4da7ebeb2a6.shtml.
[14]	Berggren SM, Fex GA, Nilsson-Ehle P. Concentrations of reti-noids in early pregnancy and in newborns and their mothers[J]. Am J Clin Nutr, 2005,81(3):633-636. pmid: 15755833
[15]	胡贻椿, 李敏, 陈竞, 等. 2010—2012年中国农村孕妇贫血及维生素A、维生素D营养状况[J]. 卫生研究, 2017,46(3):361-366, 372.
[16]	Mills JP, Terasawa E, Tanumihardjo SA. Ingestion of excessive preformed vitamin A by mothers amplifies storage of retinyl esters in early fetal livers of captive old world monkeys[J]. Comp Med, 2007,57(5):505-511.
[17]	Godel JC, Basil TK, Pabst HF, et al. Perinatal vitamin A (retinol) status of northern Canadian mothers and their infants[J]. Neonatology, 1996,69(3):133-139.
[18]	Gomes MM, Saunders C, Ramalho A, et al. Serum vitamin A in mothers and newborns in the city of Rio de Janeiro[J]. Int J Food Sci Nutr, 2009,60(4):282-292.
[19]	Agarwal K, Dabke AT, Phuljhele NL, et al. Factors affecting serum vitamin A levels in matched maternal-cord pairs[J]. Indian J Pediatr, 2008,75(5):443-446.
[20]	Hanson C, Schumacher M, Lyden E, et al. Status of vitamin A and related compounds and clinical outcomes in maternal-infant pairs in the Midwestern United States[J]. Ann Nutr Metab, 2017,71(3/4):175-182.
[21]	Ismadi SD, Olson JA. Dynamics of the fetal distribution and transfer of vitamin A between rat fetuses and their mother[J]. Int J Vitam Nutr Res, 1982,52(2):112-119. pmid: 7129792
[22]	Inorganic Toxicology and Nutrition Branch Division of Laboratory Sciences National Center for Environmental Health, The Centers for Disease Control and Prevention. Fat soluble micronutrients (vitamins A, E and carotenoids) UV-visible detection[EB/OL]. ( 2005-06-01) [2020-02-20]. https://wwwcdcgov/nchs/data/nhanes/nhanes_05_06/vitaec_d_met_aecarpdf.

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Neonatal VitA deficiency	Maternal VitA nutritional status
Neonatal VitA deficiency	VitA deficiency	Marginal VitA deficiency	Sufficient
Marginal VitA deficiency ^a
Crude OR (95%CI)	2.20 (1.04-4.66)	1.43 (1.01-2.02)	1.00
Adjusted OR (95%CI)	2.14 (0.98-4.65)	1.45 (0.99-2.12)	1.00
Relative VitA deficiency ^b
Crude OR (95%CI)	3.02 (1.21-7.50)	1.15 (0.67-1.96)	1.00
Adjusted OR (95%CI)	2.76 (1.05-7.22)	1.14 (0.64-2.04)	1.00