孕前BMI、孕期增重和孕早期维生素D与早产的关联研究

发布时间：2018-04-30 23:23

本文选题：早产 + 孕前BMI　；参考：《浙江大学》2015年博士论文

【摘要】：研究背景及目的早产(Preterm Birth,PTB)是导致新生儿死亡最主要的原因,也是导致五岁以下儿童死亡的第二大原因。在全球范围内,早产的发病率波动幅度较大(5%-18%),并呈现逐年上升的趋势。早产的高危因素及早产发生的具体生物学机制仍不完全清楚。目前认为与早产发生相关的因素主要包括孕妇的年龄、种族、职业、受教育程度、婚姻状况、孕前体重、孕期增重、体育锻炼、不良生活行为方式、营养状况、多胞胎、孕期并发症、孕期的心理压力以及早产史等。妊娠期对女性而言是一个关键时期,为了保证营养需求,孕妇往往会摄入过多的食物,但孕前肥胖及孕期增重过多与多种不良妊娠结局相关,譬如妊娠期糖尿病、先兆子病、子痫及早产等。维生素D(VitD)可通过调节免疫功能影响早产的发生。此外,肥胖和维生素D缺乏均可改变体内炎症因子的水平,而促炎因子水平升高可刺激前列腺素等宫缩蛋白水平增高,进而诱发早产。目前,关于孕前肥胖、孕期增重和维生素D对早产影响的研究结果并不一致,有研究认为孕前肥胖、孕期增重过多及维生素D缺乏会增加早产的发病风险；但也有研究并未发现这些因素与早产之间存在关联。因此,本研究以舟山市妇幼保健院为研究现场,采用前瞻性队列研究设计探讨孕前BMI和孕期增重与早产发病风险的关联；并采用巢式病例对照研究设计探讨维生素D、IL-1β和IL-10与早产发病风险的关联,为早产的防治提供科学依据。材料和方法本研究以舟山市妇幼保健院为研究现场,采用前瞻性队列研究设计,通过面对面访谈获得流行病学调查问卷资料(包括研究对象一般社会人口学特征、生活行为方式、身高及体重等基本信息),同时采集孕早、中、晚期血液样本。从2011年8月开始到2014年4月为止,共收集孕早期有效问卷1580份,孕中期有效问卷1091份。采用对数二项分布(Log-binomial)回归模型分析孕前BMI和孕期增重对早产发病风险的影响。在队列研究的基础上,按照1：2巢式病例对照研究设计,挑选孕早期有血液样本的62例早产孕妇(妊娠孕周小于37周),并根据年龄(±2岁)、相同产次和血样采集月份在对照组中选择与之匹配的124例足月产孕妇(妊娠孕周大于37周且小于42周)。采用高效液相串联质谱法检测血浆中25(OH)D、25(OH)D3和25(OH)D2水平；通过Human Inflammation Array-3芯片筛选在早产组和足月产组有显著差异的炎症因子,然后采用Elisa法对筛选出的IL-1β和IL-10进行检测。利用条件Logistic回归模型探讨25(OH)D、25(OH)D3、25(OH)D2、IL-1β、IL-10和IL-10/IL-1β与早产发病风险的关联。结果在前瞻性队列研究纳入的1580例孕妇中,早产孕妇的年龄略高于足月产孕妇(28.5vs.27.7岁,p=0.047)；而其他人口学特征和生活行为方式在两组间均衡可比。经年龄、孕期增重、受教育程度、职业、被动吸烟、饮茶和胎膜早破调整后,孕前BMI≥24kg/m2的孕妇早产的发病风险为2.55(95%CI：1.39-4.68),孕前BMI18.5kg/m2的孕妇早产的发病风险为0.73(95%CI：0.37-1.44)。根据不同分娩方式分层分析的结果显示,孕前BMI≥24kg/m2的自然分娩孕妇早产的发病风险并未显著增加(RR=1.52,95%CI:0.38-6.14),但剖宫产孕妇早产的发病风险显著增加(RR=2.53,95%CI：1.19-5.38)。孕前BMI24kg/m2的初产妇和单胎孕妇早产的发病风险均明显增加,RR值分别为2.58和3.08。被动吸烟和孕前BMI的联合作用显著增加了早产的发病风险(RR=4.38,95%CI:1.97-9.72)。虽然未发现孕早期增重和孕中期增重与早产的发病风险存在关联；但与孕早中期增重在10-15kg的孕妇相比,增重大于15kg的孕妇早产的发病风险为1.99(95%CI：1.01-3.92),增重小于10kg的孕妇早产的发病风险为1.01(95%CI:0.59-1.73)。孕早中期增重大于15kg的自然分娩孕妇早产的发病风险为3.56(95%CI：1.42-8.90)；孕早中期增重大于15kg的剖宫产孕妇早产的发病风险为1.53(95%CI：0.56-4.21)。联合作用的结果显示,年龄≥30岁且孕早中期增重15kg的孕妇早产的发病风险显著增加(RR=4.78,95%CI：1.89-12.10)；被动吸烟且孕早中期增重15kg的孕妇早产的发病风险也显著增加(RR=2.88,95%CI：1.22-6.81)。巢式病例对照研究纳入的186例孕妇孕早期VitD平均水平为17.2ng/ml;其中有67.2%的孕妇VitD缺乏,有24.2%的孕妇VitD不足,仅有8.6%的孕妇VitD适宜。VitD和VitD3呈现明显的季节差异,以冬季水平最低。与VitD20ng/ml的孕妇相比,VitD20ng/ml的孕妇早产的发病风险未显著增加(OR=1.19,95%CI:0.45-3.15)。年龄及被动吸烟与VitD缺乏的联合作用均未显著增加早产的发病风险。敏感性分析结果也未见初产、单胎妊娠或不同分娩方式影响VitD缺乏与早产发病风险的关联。VitD3和VitD2与早产的发病风险均不存在统计学关联。与IL-1β水平在0.13-0.40pg/ml的孕妇相比,IL-1β0.40pg/ml的孕妇早产的发病风险降低66%(OR=0.34,95%CI:0.13-0.87), IL-1β0.13pg/ml的孕妇早产的发病风险未见显著降低(OR=0.34,95%CI:0.12-1.00)。但未发现IL-10水平和IL-10/IL-1β比值与早产的发病风险存在统计学关联。结论与孕前体重正常的孕妇相比,孕前超重的孕妇早产的发病风险显著增加。孕早中期增重过多会显著增加早产的发病风险。年龄和被动吸烟分别与孕前BMI及孕期增重对早产发病风险呈现明显的联合作用。孕妇维生素D水平普遍偏低,并存在明显的季节差异,以冬季最低。未发现VitD、VitD3和VitD2对早产的发病风险有显著影响。与中等浓度的IL-1β相比,高水平IL-1β可降低早产的发病风险,但IL-10和IL-10/IL-1β与早产的发病风险无统计学关联。
[Abstract]:Background and purpose of research
Preterm Birth (PTB) is the leading cause of neonatal death and the second major cause of death in children under five years of age. The incidence of premature birth has fluctuated considerably (5%-18%) worldwide. The high risk factors for premature birth and the specific biological mechanism of premature birth are still not completely clear. At present, the factors associated with premature birth include the age, race, occupation, education, marital status, pre pregnancy weight, pregnancy weight gain, physical exercise, unhealthy lifestyle, nutritional status, polyplets, pregnancy complications, psychological stress during pregnancy, and the history of preterm birth.
Pregnancy is a critical period for women. In order to ensure nutritional requirements, pregnant women tend to eat too much food, but prepregnancy obesity and excessive weight gain during pregnancy are associated with a variety of bad pregnancy outcomes, such as gestational diabetes, Xian Zhaozi's disease, eclampsia, and premature delivery. Vitamin D (VitD) can affect the occurrence of preterm birth by regulating immune function. In addition, obesity and vitamin D deficiency can change the level of inflammatory factors in the body, and the increase of proinflammatory factors can stimulate the increased levels of prostaglandin and other uterine contraction proteins and induce preterm labor. Excessive weight and vitamin D deficiency may increase the risk of preterm birth; but there are also studies that have not been found to be associated with preterm labor. Therefore, a prospective cohort study was used to explore the association between pre pregnancy BMI and pregnancy weight gain and preterm birth risk in Zhoushan maternal and child health care hospital. Case control study designed to explore the association between vitamin D, IL-1 beta and IL-10 and the risk of premature delivery, so as to provide a scientific basis for prevention and treatment of premature delivery.
Materials and methods
In this study, a prospective cohort study was designed in Zhoushan maternal and child health care hospital. Through face-to-face interviews, the epidemiological survey data (including the basic information on the general demographic characteristics, lifestyle, height and weight) of the subjects were collected, and the early, middle, and late blood samples were collected from August 2011. From the beginning of April 2014, 1580 effective questionnaires were collected and 1091 effective mid-term questionnaires were collected. The effects of pre pregnancy BMI and pregnancy weight gain on the risk of preterm birth were analyzed by the logarithmic two distribution (Log-binomial) regression model.
On the basis of the cohort study, according to the 1:2 nested case control study, 62 preterm pregnant women with blood samples (gestational gestational weeks less than 37 weeks) were selected in the early pregnancy, and 124 full term pregnant women (gestational pregnancy weeks greater than 37 weeks and less than 42 weeks) were selected according to the age (+ 2 years), the same birth and blood sample months in the control group. High performance liquid phase tandem mass spectrometry was used to detect 25 (OH) D, 25 (OH) D3 and 25 (OH) D2 levels in plasma, and a Human Inflammation Array-3 chip was used to screen the inflammatory factors which were significantly different in the preterm and full term groups. Then Elisa method was used to detect IL-1 beta and IL-10. 25 (25) H) D3,25 (OH) D2, IL-1 beta, IL-10 and IL-10/IL-1 beta were associated with risk of preterm birth.
Among 1580 pregnant women who were enrolled in prospective cohort study, the age of preterm pregnant women was slightly higher than that of full term pregnant women (28.5vs.27.7 years old, p=0.047), while other demographic and lifestyle behaviors were proportional to the balance between the two groups. The age, weight gain during pregnancy, education, occupation, passive smoking, tea and premature rupture of membranes, BMI more than 24kg/ before pregnancy The risk of preterm birth of pregnant women in M2 was 2.55 (95%CI:1.39-4.68), and the risk of preterm birth of pregnant women with BMI18.5kg/m2 before pregnancy was 0.73 (95%CI:0.37-1.44). The results of stratified analysis according to different modes of childbirth showed that the risk of premature birth of pregnant women with BMI more than 24kg/m2 before pregnancy did not increase significantly (RR=1.52,95%CI:0.38-6.14), but the incidence of premature delivery was not significantly increased (RR=1.52,95%CI:0.38-6.14). The risk of preterm birth was significantly increased (RR=2.53,95%CI:1.19-5.38). The risk of preterm birth of pre pregnant BMI24kg/m2 primiparas and single pregnant women increased significantly. The combination of RR values of 2.58 and 3.08. for passive smoking and pre pregnancy BMI significantly increased the risk of premature delivery (RR=4.38,95%CI:1.97-9.72). Although no pregnancy was found, the risk of pregnancy was significantly increased. Early weight gain and midtrimester weight gain were associated with the risk of preterm birth, but the risk of preterm birth of pregnant women with weight gain more than 15kg in 10-15kg was 1.99 (95%CI:1.01-3.92), and the risk of premature birth of pregnant women with weight gain less than 10kg was 1.01 (95%CI:0.59-1.73). The weight gain of early pregnancy was greater than 15kg. The risk of preterm birth was 3.56 (95%CI:1.42-8.90), and the risk of premature birth in the cesarean section was 1.53 (95%CI:0.56-4.21). The combined effect showed that the risk of premature birth of pregnant women aged over 30 years and 15kg in the middle and middle pregnancy was significantly increased (RR=4.78,95%CI:1.89-12.10). The risk of premature delivery in women who had passive smoking and increased 15kg in the early and middle pregnancy also increased significantly (RR=2.88,95%CI:1.22-6.81).
The average VitD level of 186 pregnant women in the nested case control study was 17.2ng/ml, including 67.2% of pregnant women with VitD deficiency, 24.2% of pregnant women with VitD deficiency, and only 8.6% of pregnant women with VitD suitable for.VitD and VitD3 to present a distinct seasonal difference, with the lowest level in winter. The risk of disease was not significantly increased (OR=1.19,95%CI:0.45-3.15). The combination of age and passive smoking and VitD deficiency did not significantly increase the risk of preterm birth. No primipara, single pregnancy or different delivery methods affected the association of VitD deficiency with the risk of preterm birth, and the risk of.VitD3 and VitD2 and preterm birth were no longer associated with the risk of premature birth. There was a statistical correlation. The risk of premature birth in pregnant women with IL-1 beta 0.40pg/ml decreased by 66% (OR=0.34,95%CI:0.13-0.87) compared with IL-1 beta levels in 0.13-0.40pg/ml pregnant women, and the risk of premature delivery in pregnant women with IL-1 beta 0.13pg/ml was not significantly decreased (OR=0.34,95%CI:0.12-1.00). There was a statistically significant association between the risk of disease.
conclusion
The risk of preterm birth was significantly increased in pregnant women who were overweight before pregnancy compared with those with normal pre pregnancy weight. Excessive weight gain in the middle of early pregnancy could significantly increase the risk of preterm birth. Age and passive smoking were combined with prepregnancy BMI and weight gain during prepregnancy, respectively. The levels of vitamin D in pregnant women were generally low and coexisted. The obvious seasonal differences were lowest in winter. No VitD, VitD3 and VitD2 were found to have a significant impact on the risk of preterm birth. Compared with the medium concentration of IL-1 beta, the high level of IL-1 beta could reduce the risk of preterm birth, but there was no statistical correlation between the risk of premature birth and IL-10 and IL-10/IL-1 beta.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R714.21

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