妊娠期糖尿病母亲所产新生儿脐带血皮质醇水平变化及其对子代健康的影响

doi:10.3969/j.issn.1674-8115.2021.01.008

上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (1): 49-54.doi: 10.3969/j.issn.1674-8115.2021.01.008

妊娠期糖尿病母亲所产新生儿脐带血皮质醇水平变化及其对子代健康的影响

朱雅洁(), 林慧(), 陈茜, 赵奕然, 刘欣梅, 黄荷凤()

上海交通大学医学院附属国际和平妇幼保健院妇产科，上海胚胎源性疾病重点实验室，上海 200030

出版日期:2021-01-28 发布日期:2021-02-22
通讯作者: 黄荷凤 E-mail:zhuyajiesjtu@163.com;huanghefg@hotmail.com
作者简介:朱雅洁(1995—)，女，博士生；电子信箱：zhuyajiesjtu@163.com|朱雅洁(1995—)，女，博士生；电子信箱：zhuyajiesjtu@163.com
基金资助:
国家自然科学基金青年项目(31801231);上海市青年科技英才扬帆计划项目(17YF1420700);生殖遗传教育部重点实验室（浙江大学）开放基金课题项目(ZDFY2019-RG-0002)

Change of cortisol level in umbilical cord blood of neonates delivered by gestational diabetes mellitus mothers and its influence on offspring health

Ya-jie ZHU(), Hui LIN(), Xi CHEN, Yi-ran ZHAO, Xin-mei LIU, He-feng HUANG()

Department of Gynecology and Obstetrics, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China

Online:2021-01-28 Published:2021-02-22
Contact: He-feng HUANG E-mail:zhuyajiesjtu@163.com;huanghefg@hotmail.com
Supported by:
Funding Information] National Natural Science Foundation of China(31801231);Shanghai Science and Technology Sailing Program for Talent Youth(17YF1420700);Open Fund by Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education(ZDFY2019-RG-0002)

摘要/Abstract

摘要：

目的·探讨妊娠期糖尿病（gestational diabetes mellitus，GDM）对新生儿脐带血皮质醇水平的影响，并探索围产期高皮质醇暴露对子代学龄前期健康状况的影响。方法·纳入170例产妇及其足月、单胎分娩新生儿，其中GDM组产妇66例、孕期正常糖耐量（normal glucose tolerance，NGT）组产妇104例。采集新生儿的脐带血，测量其皮质醇及促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）浓度。利用SPSS软件分析GDM对新生儿脐带血皮质醇及ACTH水平的影响。采用多元线性回归模型分析新生儿脐带血皮质醇水平的影响因素。采用Pearson χ²检验分析围产期高皮质醇对子代学龄前期健康状况的影响，并采用二元Logistic回归模型分析子代学龄前期肥胖的影响因素。结果·与NGT组相比，GDM组新生儿的脐带血皮质醇水平较高，ACTH水平较低（均P<0.05）。多元线性回归分析显示，母亲孕次、75 g葡萄糖耐量试验（oral glucose tolerance test，OGTT）服糖后1 h及2 h血糖水平是新生儿脐带血皮质醇水平的独立影响因素（均P<0.05）。随访结果显示，围产期较高水平皮质醇的子代学龄前期肥胖率较高（P=0.009）。二元Logistic回归分析证实新生儿脐带血皮质醇水平≥192.00 ng/mL是学龄前期肥胖的独立危险因素（OR=4.714，P=0.016）。结论·GDM引起新生儿脐带血皮质醇升高，围产期高皮质醇暴露导致子代学龄前期肥胖风险增加，GDM可能通过围产期高皮质醇暴露引起子代远期疾病。

关键词: 妊娠期糖尿病, 脐带血, 糖皮质激素, 产前暴露迟发效应, 肥胖

Abstract:

Objective·To investigate the effect of gestational diabetes mellitus (GDM) on the cortisol level in neonatal umbilical cord blood, and explore the effects of high perinatal cortisol exposure on neonatal health status at preschool-period.

Methods·A total of 170 mothers and their full-term neonates were selected, including 66 cases in GDM group and 104 cases in normal glucose tolerance (NGT) group. The umbilical cord blood from the newborns of the two groups was collected to measure the concentrations of cortisol and adrenocorticotropic hormone (ACTH). SPSS software was used to analyze the effect of GDM on cortisol and ACTH levels in the neonatal umbilical cord blood. Multiple linear regression model was used to analyze the influencing factors of cortisol level in the umbilical cord blood. Pearson χ² method was used to analyze the effects of perinatal high cortisol on the health status of offspring at preschool-period, and binary Logistic regression model was used to analyze the influencing factors of preschool-period obesity.

Results·Compared with the NGT group, the cortisol level of neonatal umbilical cord blood in the GDM group was higher and ACTH level was lower (both P<0.05). Multiple linear regression analysis showed that maternal gestational times, and blood glucose at 1 h and 2 h after 75 g oral glucose tolerance test (OGTT) were the independent influencing factors of neonatal umbilical cord blood cortisol level (all P<0.05). The follow-up results showed that the offspring with higher perinatal cortisol level had higher pre-school obesity rate (P=0.009). Binary Logistic regression analysis confirmed that neonatal umbilical cord blood cortisol level ≥ 192.00 ng/mL was an independent risk factor of preschool-period obesity (OR=4.714, P=0.016).

Conclusion·Maternal GDM can cause the increase of neonatal umbilical cord blood cortisol level. High perinatal cortisol exposure can increase the risk of preschool-period obesity in the offspring. GDM may cause long-term diseases in the offspring through perinatal high cortisol exposure.

Key words: gestational diabetes mellitus (GDM), umbilical cord blood, glucocorticoid, prenatal exposure delayed effect, obesity

中图分类号:

R714.256

朱雅洁, 林慧, 陈茜, 赵奕然, 刘欣梅, 黄荷凤. 妊娠期糖尿病母亲所产新生儿脐带血皮质醇水平变化及其对子代健康的影响[J]. 上海交通大学学报(医学版), 2021, 41(1): 49-54.

Ya-jie ZHU, Hui LIN, Xi CHEN, Yi-ran ZHAO, Xin-mei LIU, He-feng HUANG. Change of cortisol level in umbilical cord blood of neonates delivered by gestational diabetes mellitus mothers and its influence on offspring health[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(1): 49-54.

Characteristic	NGT group (n=104)	GDM group (n=66)	P value
Mother
Age/year	30.42±2.97	31.79±3.67	0.008
Education/n (%)			0.348
High school or lower	34 (32.69)	29 (43.94)
Bachelor	55 (52.88)	31 (46.97)
Master or above	15 (14.42)	6 (9.09)
Pre-gestational weight/kg	54.61±6.79	56.73±7.53	0.058
Pre-gestational BMI/(kg·m^-2)	20.75±2.11	21.79±2.73	0.009
Weight gain during conception/kg	15.53±5.05	13.13±5.18	0.003
Pre-delivery weight/kg	70.15±7.77	69.86±8.32	0.816
Pre-delivery BMI/(kg·m^-2)	26.66±2.42	26.87±2.82	0.600
Height/cm	162.13±5.02	161.21±5.26	0.254
Gestational time/n (%)			0.407
1	43 (41.35)	25 (37.88)
2	31 (29.81)	26 (39.39)
≥3	30 (28.85)	15 (22.73)
Parity/n (%)			0.170
1	60 (57.69)	45 (68.18)
≥2	44 (42.31)	21 (31.82)
Neonate
Gestational age/week	38.89±0.70	38.90±0.71	0.865
Birth weight/g	3 400.67±306.82	3 455.00±366.34	0.316
Birth length/cm	50.01±0.51	50.16±0.57	0.070
Gender/n (%)			0.310
Male	54 (51.92)	29 (43.94)
Female	50 (48.08)	37 (56.06)

Characteristic	NGT group (n=104)	GDM group (n=66)	P value
Mother
Age/year	30.42±2.97	31.79±3.67	0.008
Education/n (%)			0.348
High school or lower	34 (32.69)	29 (43.94)
Bachelor	55 (52.88)	31 (46.97)
Master or above	15 (14.42)	6 (9.09)
Pre-gestational weight/kg	54.61±6.79	56.73±7.53	0.058
Pre-gestational BMI/(kg·m^-2)	20.75±2.11	21.79±2.73	0.009
Weight gain during conception/kg	15.53±5.05	13.13±5.18	0.003
Pre-delivery weight/kg	70.15±7.77	69.86±8.32	0.816
Pre-delivery BMI/(kg·m^-2)	26.66±2.42	26.87±2.82	0.600
Height/cm	162.13±5.02	161.21±5.26	0.254
Gestational time/n (%)			0.407
1	43 (41.35)	25 (37.88)
2	31 (29.81)	26 (39.39)
≥3	30 (28.85)	15 (22.73)
Parity/n (%)			0.170
1	60 (57.69)	45 (68.18)
≥2	44 (42.31)	21 (31.82)
Neonate
Gestational age/week	38.89±0.70	38.90±0.71	0.865
Birth weight/g	3 400.67±306.82	3 455.00±366.34	0.316
Birth length/cm	50.01±0.51	50.16±0.57	0.070
Gender/n (%)			0.310
Male	54 (51.92)	29 (43.94)
Female	50 (48.08)	37 (56.06)

Index	NGT group (n=104)	GDM group (n=66)
Fasting blood glucose/ (mmol·L^-1)	4.11±0.36	4.59±0.69
Blood glucose at 1 h after 75 g OGTT/(mmol·L^-1)	7.79±0.86	10.86±1.82
Blood glucose at 2 h after 75 g OGTT/(mmol·L^-1)	5.95±1.10	9.52±1.52

Index	NGT group (n=104)	GDM group (n=66)
Fasting blood glucose/ (mmol·L^-1)	4.11±0.36	4.59±0.69
Blood glucose at 1 h after 75 g OGTT/(mmol·L^-1)	7.79±0.86	10.86±1.82
Blood glucose at 2 h after 75 g OGTT/(mmol·L^-1)	5.95±1.10	9.52±1.52

Factor	Neonatal umbilical cord cortisol level
Factor	r value	P value
Mother
Age	0.042	0.590
Gestational time	0.183	0.021
Parity	0.131	0.099
Pre-gestational BMI	0.040	0.602
Pre-delivery BMI	0.019	0.803
Weight gain during conception	-0.041	0.605
Fasting blood glucose	0.029	0.714
Blood glucose at 1 h after 75 g OGTT	0.168	0.034
Blood glucose at 2 h after 75 g OGTT	0.168	0.033
Neonate
Gestational age	0.065	0.418
Birth weight	0.047	0.540

妊娠期糖尿病母亲所产新生儿脐带血皮质醇水平变化及其对子代健康的影响

Change of cortisol level in umbilical cord blood of neonates delivered by gestational diabetes mellitus mothers and its influence on offspring health

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Metrics

Factor	Neonatal umbilical cord cortisol level
Factor	β	95%CI	P value
Mode 1
Gestational time	6.960	0.077?13.843	0.048
Mode 2
Gestational time	6.814	0.132?13.212	0.048
Blood glucose at 1 h after 75 g OGTT	4.679	0.889?8.469	0.016
Mode 3
Gestational time	6.831	0.021?13.641	0.049
Blood glucose at 2 h after 75 g OGTT	3.749	0.244?7.254	0.036

Characteristic	Low cortisol level group (n=66)	High cortisol level group (n=66)	P value
Obesity/n (%)	5 (7.58)	16 (24.24)	0.009
Abnormal glucose metabolism/n (%)	1 (1.52)	0 （0）	0.315
Allergen sensitization/n (%)	5 (7.58)	7 (10.61)	0.545
Autism spectrum disorder/n (%)	0 （0）	0 （0）	-

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Factor	Offspring birth weight
Factor	β	95%CI	P value
Pre-delivery BMI	27.982	7.828?48.135	0.007
Neonatal gestational age	30.173	2.913?57.434	0.030
Neonatal umbilical cord blood cortisol level^①/(ng·mL^-1)
≤131.16	Ref	Ref	-
131.17?162.85	23.947	-118.160?166.054	0.740
162.86?198.52	24.072	-119.919?168.063	0.742
≥198.53	31.345	-111.935?174.625	0.666

Factor	Offspring birth weight
Factor	β	95%CI	P value
Pre-delivery BMI	27.982	7.828?48.135	0.007
Neonatal gestational age	30.173	2.913?57.434	0.030
Neonatal umbilical cord blood cortisol level^①/(ng·mL^-1)
≤131.16	Ref	Ref	-
131.17?162.85	23.947	-118.160?166.054	0.740
162.86?198.52	24.072	-119.919?168.063	0.742
≥198.53	31.345	-111.935?174.625	0.666

Factor	Preschool-period obesity in offspring
Factor	OR	95%CI	P value
Umbilical cord blood cortisol level^①/(ng·mL^-1)
≤133.82	Ref	Ref	-
133.83?163.01	0.233	0.021?2.151	0.196
163.02?191.99	0.732	0.154?3.532	0.690
≥192.00	4.714	1.342?16.572	0.016

Factor	Preschool-period obesity in offspring
Factor	OR	95%CI	P value
Umbilical cord blood cortisol level^①/(ng·mL^-1)
≤133.82	Ref	Ref	-
133.83?163.01	0.233	0.021?2.151	0.196
163.02?191.99	0.732	0.154?3.532	0.690
≥192.00	4.714	1.342?16.572	0.016