【摘要】 背景 巨大兒不僅會(huì)對(duì)孕婦及新生兒造成一定危害,也會(huì)影響子代遠(yuǎn)期代謝健康。母親體質(zhì)量狀態(tài)與妊娠結(jié)局密切相關(guān),超重肥胖者多伴有血脂異常,妊娠期血脂異常升高會(huì)影響宮內(nèi)環(huán)境和新生兒出生體質(zhì)量。目的 分析不同妊娠前BMI孕婦妊娠期血脂水平與巨大兒之間的關(guān)系。方法 本研究為單中心回顧性研究,納入2018年1月—2019年6月在首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院產(chǎn)科建檔至分娩并符合納排標(biāo)準(zhǔn)的單胎孕婦5 287例,根據(jù)妊娠前BMI將孕婦分為低體質(zhì)量、正常體質(zhì)量和超重肥胖孕婦,根據(jù)新生兒出生體質(zhì)量將低體質(zhì)量孕婦分為低體質(zhì)量孕婦非巨大兒組(A組,n=731)和低體質(zhì)量孕婦巨大兒組(B組,n=27),正常體質(zhì)量孕婦分為正常體質(zhì)量孕婦非巨大兒組(C組,n=3 539)和正常體質(zhì)量孕婦巨大兒組(D組,n=243),超重肥胖孕婦分為超重肥胖孕婦非巨大兒組(E組,n=675)和超重肥胖孕婦巨大兒組(F組,n=72)。收集孕婦相關(guān)臨床及實(shí)驗(yàn)室數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。采用二元Logistic回歸分析探究不同妊娠前BMI孕婦妊娠期血脂水平與巨大兒之間的關(guān)系。結(jié)果 B組孕婦妊娠晚期高密度脂蛋白膽固醇(HDL-C)低于A組(Plt;0.05);D組孕婦妊娠早期總膽固醇(TC)及孕晚期三酰甘油(TG)高于C組(Plt;0.05),妊娠中、晚期HDL-C低于C組(Plt;0.05)。F組妊娠早、中、晚期TG均高于E組(Plt;0.05),妊娠中、晚期HDL-C低于E組(Plt;0.05)。二元Logistic回歸分析結(jié)果示,妊娠晚期HDL-C〔OR=0.256,95%CI(0.075,0.871)〕是妊娠前低體質(zhì)量孕婦娩出巨大兒的影響因素(Plt;0.05)。孕中期和晚期HDL-C〔OR=0.661,95%CI(0.450,0.971);OR=0.406,95%CI(0.271,0.610)〕是妊娠前正常體質(zhì)量孕婦娩出巨大兒的影響因素(Plt;0.05)。妊娠早、中、晚期TG〔OR=1.546,95%CI(1.070,2.234);OR=1.399,95%CI(1.019,1.758);OR=1.289,95%CI(1.072,1.550)〕是妊娠前超重肥胖孕婦娩出巨大兒的影響因素(Plt;0.05)。結(jié)論 妊娠前低體質(zhì)量及正常體質(zhì)量孕婦妊娠期低HDL-C水平與巨大兒相關(guān),而超重肥胖孕婦妊娠期TG水平升高與巨大兒相關(guān)。產(chǎn)檢時(shí)對(duì)于胎兒偏大或預(yù)測(cè)巨大兒高風(fēng)險(xiǎn)的孕婦,需要加強(qiáng)血脂檢測(cè)及控制。
【關(guān)鍵詞】 人體質(zhì)量指數(shù);妊娠;孕婦;血脂,巨大胎兒;妊娠并發(fā)癥;影響因素分析
【中圖分類號(hào)】 R 33 【文獻(xiàn)標(biāo)識(shí)碼】 A DOI:10.12114/j.issn.1007-9572.2023.0097
【引用本文】 袁仙仙,王佳,張可欣,等. 妊娠前不同體質(zhì)指數(shù)孕婦妊娠期血脂水平與巨大兒的關(guān)系研究[J]. 中國(guó)全科醫(yī)學(xué),2023,26(24):2973-2979. DOI:10.12114/j.issn.1007-9572.2023.0097.[www.chinagp.net]
【Abstract】 Background Macrosomia is not only harmful to the pregnant women and newborns,but also to the long-term metabolic health of the offspring. Maternal body mass is closely associated with pregnancy outcomes,overweight and obese pregnant women are often associated with dyslipidemia,while elevated blood lipid levels during pregnancy can affect the intrauterine environment and neonatal birth weight has not been investigated. Objective To analyze the association between blood lipid levels and macrosomia in pregnant women with different pre-pregnancy(BMI). Methods A total of 5 287 singleton pregnant women who were registered at department of obstetrics of Beijing Obstetrics and Gynecology Hospital,Capital Medical University until delivery from January 2018 to June 2019 and met the inclusion and exclusion criteria were included in the single-center retrospective study,and divided into low-body-mass pregnant women with a non-macrosomia group (group A,n=731) and with a macrosomia group(group B,n=27),normal-body-mass pregnant women with a non-macrosomia group(group C,n=3 539) and with a macrosomia group (group D,n=243),overweight and obese pregnant women with a non-macrosomia group(group E,n=675) and with a macrosomia group(group F,n=72) according to maternal pre-pregnancy BMI and neonatal birth weight. Relevant clinical and laboratory data of pregnant women were collected for statistical analysis. Binary Logistic regression analysis was used to explore the association between blood lipid levels and macrosomia in pregnant women with different pre-pregnancy BMI. Results The level of high-density lipoprotein cholesterol(HDL-C) in the third trimester of pregnancy in group B was lower than group A(Plt;0.05). The levels of total cholesterol(TC) in the first trimester and triglyceride(TG) in the third trimester in group D were higher than group C(Plt;0.05),while the levels of HDL-C in the second and third trimesters were lower than group C(Plt;0.05). The TG levels in the first,second and third trimesters of pregnancy in group F were higher than group E(Plt;0.05),while HDL-C levels in the second and third trimesters were lower than group E(Plt;0.05). Binary Logistic regression analysis showed that HDL-C level in the third trimester〔OR=0.256,95%CI(0.075,0.871)〕 was the influencing factor of macrosomia in low body mass pre-pregnancy women(Plt;0.05). HDL-C levels in the second and third trimesters〔OR=0.661,95%CI(0.450,0.971);OR=0.406,95%CI(0.271,0.610)〕 were the influencing factors of macrosomia in normal body mass pre-pregnancy women(Plt;0.05). TG levels in the first,second and third trimesters〔OR=1.546,95%CI(1.070,2.234);OR=1.399,95%CI(1.019,1.758);OR=1.289,95%CI(1.072,1.550)〕 were the influencing factors of macrosomia in overweight and obese pre-pregnancy women(Plt;0.05). Conclusion For pre-pregnancy women with low and normal body mass,low HDL-C level during pregnancy is associated with an increased risk for macrosomia,while for overweight and obese pre-pregnancy women,high TG level during pregnancy is associated with an increased risk of macrosomia. For pregnant women with large fetuses or high risk of macrosomia during maternal examination,it is necessary to emphasize the detection and control of blood lipid levels.
【Key words】 Body mass index;Pregnancy;Pregnant women;Blood lipids;Fetal macrosomia;Pregnancy complications;Root cause analysis
巨大兒指不考慮胎齡因素,胎兒出生體質(zhì)量(birth weight,BW)絕對(duì)值gt;4 000 g或4 500 g[1]。我國(guó)對(duì)于巨大兒的定義是任何孕周胎兒BWgt;4 000 g。全球范圍內(nèi)巨大兒的發(fā)生率約為9%,但不同國(guó)家之間差異很大[2]。我國(guó)巨大兒發(fā)病率為7.3%,北方地區(qū)巨大兒的發(fā)病率(8.5%)顯著高于南方地區(qū)(5.6%)[3]。巨大兒對(duì)孕婦及新生兒均會(huì)造成一定的危害,對(duì)孕婦來(lái)說(shuō),可導(dǎo)致產(chǎn)程延長(zhǎng)或產(chǎn)程停滯,增加剖宮產(chǎn)、產(chǎn)后出血及軟產(chǎn)道裂傷的發(fā)生率等[4-6]。對(duì)新生兒來(lái)說(shuō),增加肩難產(chǎn)、死胎、低血糖、呼吸系統(tǒng)疾病的風(fēng)險(xiǎn),兒童期及以后患肥胖、糖耐量異常、代謝綜合征等疾病的風(fēng)險(xiǎn)亦顯著增加[7-9]。母親體質(zhì)量狀態(tài)與妊娠結(jié)局密切相關(guān)[10-12],研究顯示母親肥胖和妊娠期增重過多對(duì)巨大兒發(fā)生率的影響已超過糖尿?。?3-14]。超重肥胖者多伴有血脂異常,以三酰甘油(triglyceride,TG)水平升高伴高密度脂蛋白膽固醇(high density lipoprotein cholesterol,HDL-C)水平降低為特征[15],不同狀態(tài)的孕婦妊娠期血脂水平也存在明顯差異[16-17]。母體脂質(zhì)代謝的改變是妊娠期正常生理反應(yīng),循環(huán)脂質(zhì)的逐漸增加對(duì)胎兒生長(zhǎng)發(fā)育至關(guān)重要,但妊娠期血脂異常升高會(huì)影響宮內(nèi)環(huán)境和胎兒結(jié)局[18]。因此,本研究擬通過單中心回顧性研究,分析不同妊娠前BMI孕婦妊娠期血脂水平與巨大兒的關(guān)系。
1 對(duì)象與方法
1.1 研究對(duì)象 納入2018年1月—2019年6月在首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院產(chǎn)科建檔并定期產(chǎn)前檢查至分娩的單胎孕婦5 287例。納入標(biāo)準(zhǔn):年齡18~45歲,單胎妊娠,有妊娠前身高、體質(zhì)量數(shù)據(jù)及妊娠期血脂數(shù)據(jù);排除標(biāo)準(zhǔn):合并妊娠期高血糖、妊娠期高血壓疾病、甲狀腺疾?。缓喜⑻?jiǎn)文殑?dòng)脈等可能影響胎兒生長(zhǎng)發(fā)育的疾??;低BW兒( BWlt;2 500 g)。本研究經(jīng)首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院倫理委員會(huì)批準(zhǔn)(2018-ky-009-01)。
1.2 分組 先根據(jù)妊娠前BMI將孕婦分為低體質(zhì)量(BMIlt;18.5 kg/m2)、正常體質(zhì)量(18.5~lt;24.0 kg/m2)和超重肥胖孕婦(BMI≥24.0 kg/m2)[19],再根據(jù)新生兒BW〔新生兒BW 2 500~4 000 g為非巨大兒,新生兒BWgt;4 000 g為巨大兒〕分別將低體質(zhì)量孕婦分為低體質(zhì)量孕婦非巨大兒組(A組,n=731)和低體質(zhì)量孕婦巨大兒組(B組,n=27),正常體質(zhì)量孕婦分為正常體質(zhì)量孕婦非巨大兒組(C組,n=3 539)和正常體質(zhì)量孕婦巨大兒組(D組,n=243),超重肥胖孕婦分為超重肥胖孕婦非巨大兒組(E組,n=675)和超重肥胖孕婦巨大兒組(F組,n=72)。
1.3 研究方法 本研究為單中心回顧性研究,收集孕婦臨床資料、妊娠期血脂及新生兒出生資料(新生兒BW、新生兒性別),分析不同妊娠前BMI孕婦妊娠期血脂水平與巨大兒之間的關(guān)系。
1.3.1 資料收集 收集孕婦的年齡、末次月經(jīng)時(shí)間、孕產(chǎn)次、授孕方式、既往史〔包括糖尿病、高血壓、多囊卵巢綜合征(polycystic ovary syndrome,PCOS)、甲狀腺疾病等〕、妊娠期合并癥及并發(fā)癥(包括妊娠期糖尿病、妊娠期高血壓疾病、妊娠期急性脂肪肝等);體格檢查資料包括身高、妊娠前體質(zhì)量,以妊娠前體質(zhì)量(kg)/身高(m2)計(jì)算妊娠前BMI;輔助檢查資料包括妊娠早(5~14周)、中(24~28周)、晚(32~34周)三期血脂,妊娠早期及晚期空腹血糖(fasting plasma glucose,F(xiàn)BG),妊娠中期檢測(cè)口服葡萄糖耐量試驗(yàn)(oral glucose tolerance test,OGTT)結(jié)果。
1.3.2 血脂、血糖檢測(cè) 孕婦分別于妊娠早、中、晚期檢測(cè)血脂水平,禁食8 h以上次日晨起采集空腹靜脈血,應(yīng)用全自動(dòng)生化分析儀ARCHITECT ci16200(Abbott Park,IL,USA)檢測(cè)總膽固醇(total cholesterol,TC)、TG、低密度脂蛋白膽固醇(low density lipoprotein cholesterol,LDL-C)和HDL-C水平。
孕婦分別于妊娠早、晚期檢測(cè)FBG水平,禁食8 h
以上次日晨起采集空腹靜脈血,應(yīng)用全自動(dòng)生化分析儀ARCHITECT ci16200(Abbott Park,IL,USA)檢測(cè)FBG。妊娠中期行75 g OGTT檢查,分別于0 h及服糖后1 h、2 h采血,葡萄糖氧化酶法測(cè)血漿葡萄糖,血糖閾值分別為5.1、10.0、8.5 mmol/L,任何一個(gè)時(shí)間點(diǎn)血糖值≥上述標(biāo)準(zhǔn)即診斷為妊娠期糖尿?。煌瑫r(shí)計(jì)算OGTT曲線下面積。
1.4 統(tǒng)計(jì)學(xué)方法 應(yīng)用SPSS 25.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,符合正態(tài)分布的計(jì)量資料以(x-±s)表示,組間比較采用獨(dú)立樣本t檢驗(yàn);非正態(tài)分布的計(jì)量資料以M(P25,P75)表示,組間比較采用非參數(shù)檢驗(yàn);計(jì)數(shù)資料以相對(duì)數(shù)表示,組間比較采用χ2檢驗(yàn)。將單因素分析中差異有統(tǒng)計(jì)學(xué)意義的血脂指標(biāo)(TG、LDL-C、HDL-C)納入二元Logistics回歸分析,分析妊娠前不同BMI孕婦妊娠期血脂水平與巨大兒之間的關(guān)系。以Plt;0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 A組與B組基本資料及血脂水平的比較 研究共納入低體質(zhì)量孕婦758例,其中A組731例、B組27例。如表1所示,A組和B組孕婦年齡、妊娠前BMI、經(jīng)產(chǎn)婦比例、體外受精-胚胎移植(IVF-ET)比例、PCOS比例、剖宮產(chǎn)率、新生兒性別比例、妊娠早期FBG、OGTT結(jié)果(0 h血糖、0 h血糖、2 h血糖、曲線下面積)、妊娠晚期FBG及妊娠早、中期TC、TG及LDL-C,妊娠早、中期HDL-C比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(Pgt;0.05);B組孕婦妊娠期增重、分娩孕周及新生兒BW高于A組,妊娠晚期HDL-C低于A組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.05)。
2.2 C組與D組基本資料及血脂水平的比較 研究共納入正常體質(zhì)量孕婦3 782例,其中C組3 539例、D組243例。如表2所示,C組和D組孕婦經(jīng)產(chǎn)婦比例、IVF-ET比例及PCOS比例、OGTT 2 h 血糖,妊娠早期TG、HDL-C,妊娠中期TC、TG,妊娠晚期TC及妊娠早、中、晚期LDL-C比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(Pgt;0.05)。D組孕婦年齡、妊娠前BMI、妊娠期增重、分娩孕周、剖宮產(chǎn)率及新生兒BW、男性新生兒比例、妊娠早期FBG、OGTT血糖(包括0 h、1 h血糖及曲線下面積)、妊娠晚期FBG、妊娠早期TC、妊娠晚期TG水平高于C組,D組孕婦妊娠中、晚期HDL-C水平低于C組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.05)。
2.3 E組與F組基本資料及血脂水平的比較 研究共納入超重肥胖孕婦747例,其中E組675例、F組72例。如表3所示,兩組孕婦年齡、妊娠前BMI、妊娠期增重、經(jīng)產(chǎn)婦比例、PCOS比例、妊娠早期FBG、OGTT 2 h血糖及妊娠早期TC、HDL-C,妊娠中、晚期TC、LDL-C比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(Pgt;0.05)。F組孕婦IVF-ET比例、分娩孕周、剖宮產(chǎn)率及新生兒BW、男性新生兒比例、OGTT血糖(包括0 h、1 h血糖及曲線下面積)、妊娠晚期FBG及妊娠早、中、晚期TG均高于E組,孕中、晚期HDL-C低于E組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.05)。
2.4 妊娠期血脂水平與巨大兒關(guān)系的二元Logistic回歸分析 根據(jù)單因素分析結(jié)果,以巨大兒為因變量(賦值:是=1,否=0),以TG、HDL-C和LDL-C為自變量(賦值為實(shí)測(cè)值),進(jìn)行二元Logistic回歸分析,結(jié)果顯示,妊娠晚期HDL-C是妊娠前低體質(zhì)量孕婦娩出巨大兒的影響因素〔OR=0.196,95%CI(0.060,0.645),P=0.007〕,校正分娩孕周、新生兒性別、孕婦年齡、妊娠前BMI、妊娠期增重及FBG之后,相關(guān)性仍然存在〔OR=0.256,95%CI(0.075,0.871),P=0.029〕,見表4。
妊娠中期和晚期HDL-C是妊娠前正常體質(zhì)量孕婦娩出巨大兒的影響因素〔OR=0.598,95%CI(0.412,0.869);OR=0.355,95%CI(0.239,0.527)〕(Plt;0.05),校正分娩孕周、新生兒性別、孕婦年齡、妊娠前BMI、妊娠期增重及FBG之后,相關(guān)性仍然存在〔OR=0.661,95%CI(0.450,0.971);OR=0.406,95%CI(0.271,0.610);Plt;0.05〕,見表4。
妊娠早、中、晚期TG是妊娠前超重肥胖孕婦娩出巨大兒的影響因素〔OR=1.501,95%CI(1.044,2.160);OR=1.355,95%CI(1.052,1.745);OR=1.260,95%CI(1.065,1.490)〕(Plt;0.05),校正分娩孕周、新生兒性別、孕婦年齡、妊娠前BMI、妊娠期增重及FBG之后,相關(guān)性仍然存在〔OR=1.546,95%CI(1.070,2.234);OR=1.399,95%CI(1.019,1.758);OR=1.289,95%CI(1.072,1.550);Plt;0.05〕,見表4。
3 討論
不同體質(zhì)量狀態(tài)的孕婦妊娠期血脂水平存在明顯差異[16-17],超重肥胖者多伴有TG水平升高和/或HDL-C水平降低[15],母體妊娠期脂質(zhì)代謝對(duì)胎兒生長(zhǎng)發(fā)育至關(guān)重要。目前國(guó)內(nèi)外已有多項(xiàng)有關(guān)妊娠期血脂水平與巨大兒、大于胎齡兒(large for gestational age,LGA)或新生兒BW之間關(guān)系的研究,但未對(duì)孕婦體質(zhì)量進(jìn)行分層分析[18,20-23]??琢钣⒌龋?2]將北京市15家醫(yī)院2013年6月—2014年11月分娩的27 152例孕婦作為研究對(duì)象,分析妊娠期血脂水平與妊娠期糖尿病巨大兒的關(guān)系,結(jié)果發(fā)現(xiàn)巨大兒組孕婦妊娠早、中、晚期TG均高于正常體質(zhì)量組,而HDL-C低于正常體質(zhì)量組。國(guó)內(nèi)另有學(xué)者研究妊娠中期母體血脂水平對(duì)巨大兒的預(yù)測(cè)價(jià)值,結(jié)果發(fā)現(xiàn)妊娠20周時(shí)母體低HDL-C是巨大兒的獨(dú)立危險(xiǎn)因素〔OR=1.67,95%CI(1.06,2.64),P=0.026)〕[23]。妊娠期高血糖是巨大兒的重要危險(xiǎn)因素,但有研究發(fā)現(xiàn)在血糖控制良好的糖尿病孕婦中,母體妊娠期血脂水平是胎兒大小的強(qiáng)預(yù)測(cè)指標(biāo),這可能解釋了為何即使嚴(yán)格控制血糖,糖尿病孕婦巨大兒或LGA的發(fā)生率仍然很高[24-27]。在糖耐量正常的孕婦中,妊娠期血脂水平也與BW及巨大兒的風(fēng)險(xiǎn)相關(guān)[28-29],有研究顯示無(wú)糖尿病的孕婦妊娠晚期TG每升高1 mmol/L,巨大兒風(fēng)險(xiǎn)增加27%,HDL-C每升高1 mmol/L巨大兒風(fēng)險(xiǎn)降低37%,高TG同時(shí)伴有低HDL-C的孕婦巨大兒風(fēng)險(xiǎn)高于單純高TG或低HDL-C孕婦[29]。一項(xiàng)納入46項(xiàng)研究包括31 402例孕婦在內(nèi)的Meta分析結(jié)果顯示,孕婦在整個(gè)妊娠期間高TG和低HDL-C水平與BW增加、LGA風(fēng)險(xiǎn)增加以及小于胎齡兒(small for gestational age,SGA)風(fēng)險(xiǎn)降低有關(guān),在妊娠前超重或肥胖的女性中關(guān)聯(lián)性更強(qiáng)[30]。
超重肥胖者多伴有血脂異常,以TG水平升高伴HDL-C水平降低為特征[15],不同體質(zhì)量狀態(tài)的孕婦妊娠期血脂水平也存在顯著差異[16-17]。本研究根據(jù)孕婦妊娠前BMI進(jìn)行分組,在不同BMI等級(jí)中分析妊娠期血脂與巨大兒之間的關(guān)系,結(jié)果顯示娩出巨大兒與非巨大兒的不同BMI孕婦妊娠期血脂水平均有所差異,二元Logistic回歸分析結(jié)果示,低體質(zhì)量及正常體質(zhì)量孕婦妊娠期低HDL-C水平與巨大兒相關(guān),而超重肥胖孕婦妊娠期TG水平升高與巨大兒相關(guān)。有學(xué)者對(duì)超重肥胖與巨大兒的關(guān)系進(jìn)行中介分析,結(jié)果發(fā)現(xiàn)超重對(duì)巨大兒的總影響為0.006〔95%CI(0.001,0.010)〕,其中直接影響為0.005〔95%CI(0.001,0.009)〕,間接影響為0.001〔95%CI(0,0.001)〕,估計(jì)由高TG水平介導(dǎo)的比例為11.1%;此外,肥胖對(duì)巨大兒的總影響為0.026〔95%CI(0.018,0.036)〕,其中直接影響為0.025〔95%CI(0.017,0.036)〕,間接影響為0.001〔95%CI(0,0.001)〕,估計(jì)由高TG水平介導(dǎo)的比例為3.8% [31]。但也有研究發(fā)現(xiàn),在非超重肥胖孕婦中,LGA風(fēng)險(xiǎn)與妊娠早期TG水平呈正相關(guān)(OR=1.740,P=0.034),而在超重肥胖孕婦中,LGA風(fēng)險(xiǎn)與妊娠早期TG水平無(wú)相關(guān)性(OR=1.410,P=0193)[32]。另一項(xiàng)納入了143例單胎孕婦的前瞻性隊(duì)列研究,將孕婦根據(jù)妊娠前BMI分為正常體質(zhì)量組(BMI≤25.0 kg/m2)和超重肥胖組(BMIgt;25.0 kg/m2)進(jìn)行分層分析,結(jié)果顯示超重肥胖孕婦妊娠期HDL-C與BW呈負(fù)相關(guān),而在正常體質(zhì)量孕婦無(wú)相關(guān)性[33]。
脂蛋白脂酶介導(dǎo)母體TG脂解生成的非酯化脂肪酸直接通過脂肪酸轉(zhuǎn)運(yùn)蛋白或脂肪酸轉(zhuǎn)位酶CD36進(jìn)入胎盤,胰島素可激活合胞滋養(yǎng)層細(xì)胞母體側(cè)豐富的胰島素受體,通過蛋白激酶B(AKT)信號(hào)通路,誘導(dǎo)游離脂肪酸酯化成TG[34]。這些TG儲(chǔ)存在滋養(yǎng)層細(xì)胞中,經(jīng)過水解釋放出的游離脂肪酸被擴(kuò)散至胎兒血漿,進(jìn)而為胎兒提供能量[35]。超重肥胖孕婦多合并有胰島素抵抗,母體高胰島素血癥會(huì)誘導(dǎo)胎盤儲(chǔ)存大量的TG,TG經(jīng)胎盤脂蛋白酯酶水解成游離脂肪酸增加,過多的游離脂肪酸轉(zhuǎn)運(yùn)給胎兒是母親高TG血癥增加巨大兒風(fēng)險(xiǎn)的部分原因[34-35]。HDL-C在膽固醇轉(zhuǎn)運(yùn)和穩(wěn)態(tài)中發(fā)揮重要作用,動(dòng)物實(shí)驗(yàn)證實(shí)母體HDL-C參與胎兒代謝及生長(zhǎng)[36-37]。在缺乏HDL-C的小鼠模型中發(fā)現(xiàn),為了彌補(bǔ)攝取和運(yùn)輸給胎兒的膽固醇不足,胎盤甾醇合成率增加,或者胎盤代謝發(fā)生改變?cè)试S更多的膽固醇被運(yùn)輸,或者兩者都有[36-37]。這可能部分解釋了低HDL-C與巨大兒的發(fā)生相關(guān)。
綜上,不同BMI孕婦巨大兒組與非巨大兒組妊娠期血脂水平均有所差異,低體質(zhì)量及正常體質(zhì)量孕婦妊娠期HDL-C水平降低與巨大兒相關(guān),而超重肥胖孕婦妊娠期TG水平升高與巨大兒相關(guān)。因此,產(chǎn)檢時(shí)對(duì)于胎兒偏大或預(yù)測(cè)巨大兒高風(fēng)險(xiǎn)的孕婦,需要加強(qiáng)血脂檢測(cè)及控制,不僅要關(guān)注高TG還要重視低HDL-C,從而改善不良妊娠結(jié)局。但目前尚無(wú)統(tǒng)一的妊娠血脂水平的參考標(biāo)準(zhǔn),有必要開展多中心、大規(guī)模的流行病學(xué)研究,制定統(tǒng)一的妊娠期血脂異常診斷標(biāo)準(zhǔn)。
作者貢獻(xiàn):袁仙仙負(fù)責(zé)研究設(shè)計(jì)及實(shí)施、數(shù)據(jù)分析及論文撰寫;王佳、張可欣、楊蕊華負(fù)責(zé)數(shù)據(jù)整理;鄭薇負(fù)責(zé)論文修改;李光輝負(fù)責(zé)研究設(shè)計(jì)指導(dǎo)及論文修改,對(duì)論文整體負(fù)責(zé)。
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(收稿日期:2023-01-30;修回日期:2023-03-08)
(本文編輯:宋春梅)