【作者】 陈聪；

【导师】 曾果；

【作者基本信息】 四川大学 ， 营养与食品卫生学， 2023， 硕士

【摘要】 背景孕期是女性生命周期中的特殊阶段,为满足胎儿正常生长发育需要,孕期妇女血脂代谢活跃。孕妇血脂水平较非孕妇女发生较大变化,在孕早中期肠道对脂肪吸收能力增强,脂肪储备增加,直至孕晚期脂肪分解加剧,孕期呈现生理性血脂升高。研究提示孕期血脂水平过度升高可能造成血脂异常,增加不良妊娠结局的发生风险。出生体重是衡量胎儿宫内发育及其出生结局是否良好的一项重要指标。近年来小于胎龄儿(Small for Gestational Age,SGA)发生率在世界范围内呈显著上升趋势,严重危害子代近远期健康。研究提示孕期血脂水平影响出生体重,与SGA发生风险有关。但目前相关性研究甚少且结论不一致。此外,国内尤其西南地区缺乏孕妇人群血脂水平的系统研究,我国孕期血脂评价标准也缺乏统一。因此,本课题利用成都孕妇队列开展孕期血脂相关前瞻性研究,全面评价成都地区孕妇血脂水平及变化规律,分析孕期血脂异常的影响因素,并在此基础上探讨孕期血脂水平对子代出生体重和SGA的影响,为有效开展孕期血脂管理提供参考依据,为减少不良出生结局和制定我国孕妇人群血脂评价标准奠定基础。目的通过前瞻性研究调查评价成都地区孕妇孕期血脂水平及变化规律,分析可能影响孕期血脂异常的因素,阐述孕期血脂水平与子代出生体重和SGA的关系,为有效开展孕期监测管理、制定我国孕期血脂评价标准和预防不良出生结局提供科学依据。方法采用前瞻性队列研究,选取成都市某三甲妇幼医疗机构产前门诊建卡的孕6～14周孕妇作为研究对象,随访至分娩。通过问卷调查于纳入时收集孕妇基本信息。采用血脂标准检测方法分别在孕早、中、晚期测定甘油三酯(Triglycerides,TG)、总胆固醇(Total Cholesterol,TC)、低密度脂蛋白胆固醇(Low-Density Lipoprotein Cholesterol,LDL-C)及高密度脂蛋白胆固醇(HighDensity Lipoprotein Cholesterol,HDL-C)四项指标。参照李光辉等研究将孕期血脂水平分为血脂过低、血脂正常及血脂过高三个水平组,并根据四分位数法将孕期血脂水平由低到高分为四组(Q1～Q4),通过医院信息系统收集子代出生体重信息,获得SGA等不良出生结局。采用多重线性回归模型和多因素非条件Logistic回归模型分别探讨孕期血脂水平对子代出生体重、SGA的影响以及分析孕期血脂异常的影响因素。结果1、成都地区孕妇孕期血脂水平及影响因素孕妇孕早、中、晚期TG平均水平(mmol/L)分别为1.32±0.49、2.42±0.96、3.48±1.44,TC平均水平(mmol/L)分别为4.14±0.67、5.57±0.93、6.31±1.15,LDL-C平均水平(mmol/L)分别为2.05±0.52、3.20±0.85、3.60±1.08,HDLC平均水平(mmol/L)分别为1.67±0.35、1.65±0.32、1.52±0.30。孕早、中、晚期TG、TC、LDL-C水平呈逐渐上升趋势,孕期间差异均具有统计学意义(P<0.001);孕早、中、晚期HDL-C水平呈逐渐下降趋势,孕晚期低于孕早、中期,差异有统计学意义(P<0.001)。孕早、中、晚期TG过高率分别为12.5%、9.2%、14.8%,TC过高率分别为4.3%、2.3%、5.0%,LDL-C过高率分别为5.3%、8.8%、10.0%,HDL-C过低率分别为6.8%、13.2%、14.2%。调整相关混杂因素后,结果显示孕妇年龄和孕前BMI是孕期血脂异常的影响因素,年龄≥30岁组孕妇孕期LDL-C过高率明显高于年龄<30岁组孕妇(P<0.05)。孕前超重/肥胖组孕妇孕期TG、LDL-C过高率和HDL-C过低率均明显高于孕前体重正常组孕妇(P<0.05)。2、孕期血脂水平对子代出生体重和SGA的影响子代平均出生体重为3234.2±397.7g,SGA发生率为8.1%(87例)。调整年龄、孕前BMI等混杂因素后,孕早、中、晚期TG水平与子代出生体重呈正相关(孕早期:β=97.336,95%CI:47.552～147.121;孕中期:β=33.543,95%CI:8.777～58.309;孕晚期:β=25.198,95%CI:9.043～41.352)。孕晚期HDL-C水平与子代出生体重呈负相关(β=-96.688,95%CI:-177.651～-15.723)。未发现孕期TC、LDL-C水平对子代出生体重有明显影响(P>0.05)。孕晚期TG Q3、Q4组孕妇子代SGA发生风险均较Q1组明显降低(Q3:OR=0.429,95%CI:0.213～0.862;Q4:OR=0.429,95%CI:0.209～0.880),孕中期HDLC Q4组孕妇子代SGA发生风险较Q1组明显增加(OR=2.198,95%CI:1.164～4.153)。未发现孕期TC、LDL-C水平对SGA有明显影响(P>0.05)。结论本研究提示成都地区孕妇人群TG、TC、LDL-C水平随孕期增加呈升高趋势、HDL-C水平呈下降趋势;孕期TG、TC、LDL-C水平过高和孕期HDL-C水平过低问题值得关注,以孕晚期突出;孕妇年龄、孕前BMI可能是孕期血脂异常的影响因素,年龄≥30岁和孕前超重肥胖孕妇是血脂异常的高危人群。孕期TG水平升高可能降低子代SGA发生风险,孕期HDL-C水平升高可能增加子代SGA发生风险,尚待进一步研究确认。建议加强孕妇血脂监测和孕前体重管理,针对高危孕妇尽早实施膳食营养干预,以减少不良出生结局发生,保障母婴健康。更多还原

【Abstract】 BackgroundsPregnancy is a special stage in a woman’s life cycle.To meet the needs of fetal growth and development,pregnant lipid metabolism is active during pregnancy,and lipid profiles levels of pregnant women change significantly compared to those of non-pregnant women.Studies suggest that excessive increases in lipid profiles levels during pregnancy may cause dyslipidemia and increase the risk of adverse pregnancy outcomes.Birth weight is an important indicator of well intrauterine development and birth outcomes.The incidence of small for gestational age(SGA)has increased significantly worldwide in recent years,posing a serious risk to the short-term and long-term health of the offspring.Studies suggest that maternal lipid levels during pregnancy affect birth weight and are associated with the risk of SGA.However,there are few relevant studies and inconsistent findings.In addition,there is a lack of systematic studies on lipid levels in pregnant women in China,especially in the southwest,and a lack of uniformity in the evaluation criteria for maternal lipid profiles in China.Therefore,we conducted a prospective cohort study on maternal lipid profiles levels during pregnancy in Chengdu,to comprehensively evaluate the lipid profiles levels and changes in pregnancy in Chengdu,analyze the factors influencing dyslipidemia during pregnancy,and on this basis,investigate the effects of maternal lipid profiles levels during pregnancy on birth weight and SGA,to provide a reference basis for effective lipid profiles management during pregnancy,to reduce adverse birth outcomes and to develop a standard for the evaluation of lipid profiles levels in pregnancy in China.ObjectiveA prospective study was conducted to evaluate maternal lipid profiles levels and their changes during pregnancy in Chengdu,to analyze the possible factors influencing dyslipidemia during pregnancy,and to describe the relationship between maternal lipid profiles levels and birth weight and SGA,in order to provide a scientific basis for effective lipid profiles care during pregnancy,the development of criteria for evaluating maternal lipid profiles levels in China,and the prevention of adverse birth outcomes.MethodsA prospective cohort study was used to recruit pregnant women from 6 to 14weeks’ gestation who had their antenatal cards established in a maternal-and-fetal health care institution in Chengdu,followed up until delivery.Basic information on pregnant women was collected by questionnaire at the time of inclusion.Triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured in early,middle,and late pregnancy using standard lipid profiles testing methods,and lipid profiles levels during pregnancy were divided into low,normal,and high levels according to Li Guang Hui’s study.The groups were also divided into four groups(Q1～Q4)according to the quartile method from low to high.Birth information,including birth weight,and adverse birth outcomes such as SGA were collected through the hospital information system.Multiple linear regression models were used to analyze the effect of maternal lipid profiles on birth weight,and multi-factor unconditional logistic regression models were used to analyze the factors influencing dyslipidemia during pregnancy and the effect of maternal lipid profiles on SGA.Results1.Maternal lipid profiles levels status and influencing factors of dyslipidemia in pregnant women in ChengduThe mean levels of maternal TG among pregnant women in early,middle,and late pregnancy were 1.32±0.49,2.42±0.96,and 3.48±1.44 mmol/L.The mean levels of maternal TC among pregnant women in early,middle,and late pregnancy were 4.14±0.67,5.57±0.93,and 6.31±1.15 mmol/L.The mean levels of maternal LDL-C among pregnant women in early,middle,and late pregnancy were 2.05±0.52,3.20±0.85,3.60±1.08 mmol/L.The mean levels of maternal HDL-C of pregnant women in early,middle,and late pregnancy were 1.67±0.35,1.65±0.32,1.52±0.30 mmol/L.Maternal TG,TC,and LDL-C levels gradually increased with gestation.The differences were statistically significant(P<0.001).Maternal HDL-C levels gradually decreased with gestation.The differences were statistically significant between early and late pregnancy(P<0.001).The rates of excess maternal TG levels in early,middle and late pregnancy were 12.5%,9.2%and 14.8% respectively,the rates of excess maternal TC levels in early,middle and late pregnancy were 4.3%,2.3% and 5.0% respectively,the rates of excess maternal LDL-C levels in early,middle and late pregnancy were 5.3%,8.8% and10.0% respectively,the rates of low maternal HDL-C levels in early,middle,and late pregnancy were 12.5%,9.2% and 14.8% respectively.After adjusting for relevant confounding factors,the results of multi-factor unconditional logistic regression model showed that factors influencing dyslipidemia during pregnancy were maternal age and pre-pregnancy BMI.The rate of excess maternal LDL-C levels during pregnancy was higher in the ≥30 age group than in the <30 age group(P<0.05).Pregnant women in the overweight/obese group had higher rates of excess maternal LDL-C and TG levels and lower rates of maternal HDL-C levels during pregnancy than those in the pre-pregnancy normal weight group(P<0.05).2.Effect of maternal lipid profiles levels on birth weight and SGAThe mean birth weight was 3234.2 ± 397.7 g,with an incidence of 8.1%(87cases)of SGA.After adjusting for confounding factors such as age and prepregnancy BMI,the results of multiple linear regression model showed that maternal TG levels in early,middle,and late pregnancy were positively associated with birth weight(early pregnancy: β=97.336,95%CI:47.552～147.121;middle pregnancy: β=33.543,95%CI: 8.777～58.309;late pregnancy: β=25.198,95%CI: 9.043～41.352).Late pregnancy HDL-C levels were negatively correlated with birth weight(β=-96.688,95%CI:-177.651～-15.723).No effect of maternal TC and LDL-C levels during pregnancy on birth weight was found(P>0.05).After adjusting for confounders such as age and prepregnancy BMI,the results of multi-factor unconditional logistic regression model showed that the risk of SGA was reduced in maternal TG Q3 and Q4 groups in late pregnancy compared to maternal TG Q1 group(Q3: OR = 0.429,95% CI: 0.213 ～0.862;Q4: OR = 0.429,95%CI: 0.209～0.880).The risk of SGA increased in the middle pregnancy in maternal HDL-C Q4 group compared to the Q1 group(OR = 2.198.95%CI: 1.164～4.153).No effect of maternal TC and LDL-C levels during pregnancy was found for SGA(P>0.05).ConclusionThe study suggested that maternal levels of TG、TC、LDL-C gradually increase with gestation,and HDL-C gradually decrease.The problem of high levels of TG,TC and LDL-C and low levels of HDL-C during pregnancy is of concern,which is prominent in late pregnancy.Maternal age and pre-pregnancy BMI may be influencing factors for dyslipidemia during pregnancy,and age ≥30years and pre-pregnancy overweight and obesity are the risk group for dyslipidemia.Increased TG levels during pregnancy may reduce the risk of SGA,while increased HDL-C levels during pregnancy may increase the risk of SGA,which is yet to be confirmed by further studies.It is recommended to strengthen the monitoring of maternal lipid levels and manage pre-pregnancy weight,and to implement dietary interventions for high-risk pregnant women to reduce the risk of adverse birth outcomes and protect the health of mothers and infants.更多还原