[摘 要]目的 探討母親妊娠期糖尿?。℅DM)對(duì)新生兒心臟功能的影響,并分析其超聲心動(dòng)圖特征。方法 在2019年1月至2022年1月濰坊市益都中心醫(yī)院新生兒科病房收治的無(wú)高危分娩疾病的足月新生兒中,選取GDM孕母的足月新生兒95例為GDM組,非GDM孕母的新生兒90例為對(duì)照組。檢測(cè)并比較兩組新生兒的出生血糖、出生體重、出生身長(zhǎng)、心肌損傷標(biāo)志物[肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、超敏心肌肌鈣蛋白T(hs-cTnT)]水平,以及對(duì)新生兒心臟的測(cè)量數(shù)據(jù),包括升主動(dòng)脈徑、左心房前后徑、右心室前后徑、左室前后徑、肺動(dòng)脈徑、室間隔厚度、射血分?jǐn)?shù)和先天性心臟病的發(fā)生率,并對(duì)GDM組新生兒室間隔肥厚的影響因素進(jìn)行多元線性回歸分析。結(jié)果 GDM組新生兒的出生體重、出生身長(zhǎng)、出生血糖與對(duì)照組比較差異均有統(tǒng)計(jì)學(xué)意義(t值分別為-6.627、-8.378、15.561,P<0.01)。GDM組新生兒的CK、CK-MB、hs-cTnT與對(duì)照組比較差異均有統(tǒng)計(jì)學(xué)意義(t值分別為-5.028、-10.510、-8.804,P<0.01)。GDM組新生兒的升主動(dòng)脈徑、左心房前后徑、右心室前后徑、肺動(dòng)脈徑、左室前后徑和室間隔厚度與對(duì)照組比較差異均有統(tǒng)計(jì)學(xué)意義(t值分別為-3.729、-5.612、-2.703、-3.516、-7.647、-6.028,P<0.01),而兩組的射血分?jǐn)?shù)比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。GDM組新生兒先天性心臟病發(fā)生率與對(duì)照組比較差異有統(tǒng)計(jì)學(xué)意義(χ2=5.746,P<0.05)。相關(guān)性分析表明,室間隔厚度與新生兒出生血糖水平呈負(fù)相關(guān)(r=-0.305,P<0.01),與新生兒出生體重和血清hs-cTnT均呈正相關(guān)(r值分別為0.546、0.566,P<0.01),與孕母血清C肽水平和糖化血紅蛋白均呈正相關(guān)(r值分別為0.222、0.634,P<0.01)。多元線性回歸分析顯示,新生兒出生體重、血清hs-cTnT水平、孕母糖化血紅蛋白均是室間隔厚度的影響因素(t值分別為3.628、5.777、2.538,P<0.05)。結(jié)論 母親GDM對(duì)出生新生兒的心臟功能有不良影響;監(jiān)測(cè)血清心肌損傷標(biāo)志物及超聲心動(dòng)圖可作為診斷孕母GDM的新生兒心臟損傷的早期指標(biāo)。
[關(guān)鍵詞]妊娠期糖尿病;心臟;心肌病;肥厚性;先天性心臟??;新生兒
Doi:10.3969/j.issn.1673-5293.2024.08.006
[中圖分類(lèi)號(hào)]R174""" [文獻(xiàn)標(biāo)識(shí)碼]A
[文章編號(hào)]1673-5293(2024)08-0038-06
The impact of gestational diabetes mellitus on neonatal cardiac development and function
FENG Yan1,SUN Chunlei1,GONG Jinlei1,XING Yuping1,WANG Qingfa1,LI Zhenghao1,WANG Yangang2
(1.Department of Pediatric Internal Medicine,Yidu Central Hospital of Weifang,Shandong Qingzhou 262500,China;
2.Department of Endocrinology,The Affiliated Hospital of Qingdao University,Shandong Qingdao 266000,China)
[Abstract] Objective To investigate the impact of maternal gestational diabetes mellitus(GDM)on neonatal cardiac function and analyze its echocardiographic characteristics. Methods Among the full-term newborns without high-risk delivery diseases admitted to the neonatal ward of Yidu Central Hospital of Weifang from January 2019 to January 2022,95 full-term newborns of GDM mothers were selected as the GDM group,and 90 newborns of non-GDM mothers were selected as the control group.The birth blood glucose,birth weight,birth length,myocardial injury markers [creatine kinase (CK),creatine kinase isoenzyme (CK-MB),high-sensitive cardiac troponin T (hs-cTnT)] levels and neonatal heart measurement data,including ascending aorta diameter,left atrial anteroposterior diameter,right ventricular anteroposterior diameter,left ventricular anteroposterior diameter,pulmonary artery diameter,interventricular septal thickness,ejection fraction and the incidence of congenital heart disease,were detected and compared between the two groups of newborns.Multivariate linear regression analysis was conducted to identify factors influencing interventricular septal hypertrophy in neonates of the GDM group. Results The differences in birth weight,birth length,and birth blood glucose levels between the GDM group and the control group were statistically significant (t=-6.627,-8.378,15.561,respectively,P<0.01).There were significant differences in CK,CK-MB and hs-cTnT between the GDM group and the control gruop
(t=-5.028,-10.510,-8.804,respectively,P<0.01).Significant differences were observed in the ascending aorta diameter,left atrial anteroposterior diameter,right ventricular anteroposterior diameter,pulmonary artery diameter and interventricular septal thickness between the GDM group and the control group (t=-3.729,-5.612,-2.703,-3.516,-7.647,-6.028,respectively,P<0.01).However,there was no significant difference in ejection fraction between the two groups (P>0.05).The incidence of congenital heart disease was significantly different in the GDM group compared to the control group (χ2=5.746,P<0.05).Correlation analysis indicated that interventricular septal thickness was negatively correlated with neonatal birth blood glucose levels (r=-0.305,P<0.01),and positively correlated with birth weight,serum hs-cTnT (r=0.546,0.566,respectively,P<0.01),and positively correlated with maternal serum C-peptide levels and glycosylated hemoglobin (r=0.222,0.634,respectively,P<0.01).Multivariate linear regression analysis showed that neonatal birth weight,serum hs-cTnT level,and maternal glycosylated hemoglobin were influencing factors of interventricular septal thickness (t=3.628,5.777,2.538,respectively,P<0.05). Conclusion Maternal GDM has adverse effects on the cardiac function of neonates.Monitoring serum myocardial injury markers and performing echocardiography can serve as early indicators for diagnosing cardiac injury in neonates born to mothers with GDM.
[Key words] gestational diabetes mellitus;heart;cardiomyopathy;hypertrophic;congenital heart disease;neonates
近年來(lái),隨著經(jīng)濟(jì)水平的增長(zhǎng)及二胎政策的放開(kāi),妊娠期糖尿病(gestational diabetes mellitus,GDM)在我國(guó)的發(fā)病率有逐年上升的趨勢(shì),GDM嚴(yán)重影響孕母的健康及胎兒的宮內(nèi)發(fā)育[1],并可引起新生兒心臟損害。采用新的GDM診斷標(biāo)準(zhǔn)后[2],更多孕產(chǎn)婦納入了GDM的管理,對(duì)GDM孕母及其新生兒采取有效的干預(yù)措施,可使母親和新生兒不良后果的發(fā)生風(fēng)險(xiǎn)降低[3]。關(guān)于GDM孕母出生的新生兒不良結(jié)局與血糖水平相關(guān)性的研究較多[4-6],但對(duì)于出生后新生兒心臟變化的研究相對(duì)較少。因此,本文研究了GDM孕母的新生兒心肌損傷標(biāo)志物及心臟超聲指標(biāo)的特征,以探討GDM孕母對(duì)新生兒心臟發(fā)育和功能的影響。
1研究對(duì)象與方法
1.1研究對(duì)象
2019年1月至2022年1月在濰坊市益都中心醫(yī)院產(chǎn)科出生且由新生兒科病房收治的無(wú)高危分娩疾病的足月新生兒中,篩查出GDM孕母的95例新生兒為GDM組,同期非GDM孕母的90例新生兒為對(duì)照組。在GDM組中,男49例,女46例,胎齡為37~42周;在對(duì)照組中,男45例,女45例,胎齡為37~42周。
1.2納入與排除標(biāo)準(zhǔn)
納入標(biāo)準(zhǔn):①符合2010年國(guó)際妊娠合并糖尿病研究組織(International Association of Diabetic Pregnancy Study Group,IADPSG)推薦的GDM診斷標(biāo)準(zhǔn)[7];②胎齡37~42周;③產(chǎn)婦年齡≤45歲,均順利剖宮產(chǎn)或順產(chǎn)出生,無(wú)死胎。排除標(biāo)準(zhǔn):①新生兒出生有嚴(yán)重感染,需呼吸、循環(huán)功能支持及有嚴(yán)重窒息病史;②妊娠前即合并糖尿病患者;③合并有其他妊娠期疾病,如心、肝、腎等重大疾病者;④有流產(chǎn)或畸形,選擇早期引產(chǎn)者,有多胎妊娠或早產(chǎn)的孕婦。
本研究已經(jīng)通過(guò)濰坊市益都中心醫(yī)院醫(yī)學(xué)倫理委員會(huì)審批(倫理編號(hào):2023055)。
1.3方法
1.3.1觀察指標(biāo)
①一般指標(biāo):新生兒出生胎齡、出生體重、出生身長(zhǎng)、性別、出生足底末梢血糖。②生化指標(biāo):新生兒出生24h內(nèi)送檢化驗(yàn),采用cobasc702和cobase601羅氏生化分析儀進(jìn)行血清肌酸激酶(creatine kinase,CK)、血清肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)、血清超敏心肌肌鈣蛋白T(hypersensitive cardiac troponin T,hs-cTnT)的檢測(cè);監(jiān)測(cè)GDM組母親妊娠期的糖化血紅蛋白(散射比濁,正常值4%~6%)、C肽(電化學(xué)發(fā)光法,正常參考值0.25~0.60nmol/L)。③心臟超聲指標(biāo):采用飛利浦公司的HP5500型超聲診斷儀,分別檢查并測(cè)量所有新生兒的升主動(dòng)脈徑(ascending aorta diameter,AOD)、左心房前后徑(left atrial anteroposterior diameter,LAD-ap)、右心室前后徑(right ventricular anteroposterior diameter,RVD-ap)、肺動(dòng)脈徑(pulmonary artery diameter,PAD)、左室前后徑(left ventricular anteroposterior diameter,LVD-ap)、室間隔(interventricular septum,IVS)厚度和射血分?jǐn)?shù)(ejection fraction,EF)。
1.3.2分析指標(biāo)
①比較GDM組與對(duì)照組的一般指標(biāo)、生化指標(biāo)和心臟超聲指標(biāo)。②比較兩組先天性心臟病的發(fā)生率。③分析IVS與各因素間的關(guān)系。④對(duì)GDM組新生兒室間隔肥厚的危險(xiǎn)因素進(jìn)行統(tǒng)計(jì),并進(jìn)行多元線性回歸分析,包括孕母的C肽、糖化血紅蛋白、一般指標(biāo)、生化指標(biāo)等。
1.4統(tǒng)計(jì)學(xué)方法
應(yīng)用SPSS 21統(tǒng)計(jì)學(xué)軟件對(duì)數(shù)據(jù)進(jìn)行分析,正態(tài)分布的計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x-±s)表示,兩組間比較采用獨(dú)立樣本t檢驗(yàn);計(jì)數(shù)資料以例數(shù)(百分率)[n(%)]表示,兩組間比較采用χ2檢驗(yàn);采用Pearson相關(guān)分析兩因素之間的關(guān)系,采用多元線性回歸分析相關(guān)影響因素。以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2結(jié)果
2.1 GDM組與對(duì)照組新生兒一般資料的對(duì)比
GDM組新生兒的出生體重、出生身長(zhǎng)均明顯大于對(duì)照組,出生血糖明顯低于對(duì)照組,經(jīng)比較差異均有統(tǒng)計(jì)學(xué)意義(P<0.01),兩組的性別分布及胎齡比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),見(jiàn)表1。
2.2 GDM組與對(duì)照組新生兒心肌損傷標(biāo)志物的對(duì)比
GDM組新生兒的CK、CK-MB、hs-cTnT均明顯高于對(duì)照組,經(jīng)比較差異均有統(tǒng)計(jì)學(xué)意義(P<0.01),見(jiàn)表2。
2.3 GDM組與對(duì)照組新生兒心臟超聲指標(biāo)的對(duì)比
GDM組新生兒的AOD、LAD-ap、RVD-ap、PAD、LVD-ap、IVS厚度均明顯大于對(duì)照組,經(jīng)比較差異均有統(tǒng)計(jì)學(xué)意義(P<0.01),而兩組的EF比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),見(jiàn)表3。
2.4 GDM組與對(duì)照組新生兒先天性心臟病發(fā)生率的對(duì)比
GDM組新生兒先天性心臟病共6例,其中發(fā)現(xiàn)4例室間隔缺損,1例房間隔缺損,1例動(dòng)脈導(dǎo)管未閉,先天性心臟病發(fā)病率為6.3%(6/95),對(duì)照組新生兒中未發(fā)現(xiàn)先天性心臟病,兩組比較差異有統(tǒng)計(jì)學(xué)意義(χ2=5.746,P=0.017)。
2.5 IVS厚度與各因素間的相關(guān)分析
相關(guān)性分析結(jié)果表明,IVS厚度與出生血糖水平呈負(fù)相關(guān)(r=-0.305,P<0.01),見(jiàn)圖1A;IVS厚度與出生體重呈正相關(guān)(r=0.546,P<0.01),見(jiàn)圖1B;IVS厚度與孕母血清C肽水平呈正相關(guān)(r=0.222,P<0.05),見(jiàn)圖1C;IVS厚度與孕母糖化血紅蛋白呈正相關(guān)(r=0.634,P<0.01),見(jiàn)圖1D;IVS厚度與血清hs-cTnT呈正相關(guān)(r=0.566,P<0.01),見(jiàn)圖1E。
2.6 GDM組新生兒室間隔肥厚影響因素的多元線性回歸分析
以IVS厚度為因變量,以孕母C肽、糖化血紅蛋白,以及新生兒出生胎齡、性別、出生體重、出生身長(zhǎng)、出生血糖、血清hs-cTnT水平為自變量進(jìn)行多元線性回歸分析,結(jié)果顯示,新生兒出生體重、血清hs-cTnT水平、孕母糖化血紅蛋白均是IVS厚度的影響因素(t值分別為3.628、5.777、2.538,P<0.05),見(jiàn)表4。
3討論
近年來(lái),GDM孕產(chǎn)婦發(fā)病率逐年升高,臨床上不僅孕產(chǎn)婦發(fā)生不良妊娠結(jié)局的風(fēng)險(xiǎn)增加,同時(shí)新生兒出現(xiàn)如低血糖、早產(chǎn)兒、呼吸窘迫、巨大兒、窒息等不良結(jié)局的危險(xiǎn)也有增加,現(xiàn)在更多的學(xué)者開(kāi)始關(guān)注母親GDM出生新生兒的心臟變化情況[8-9]。妊娠期各種代謝異常均會(huì)影響新生兒宮內(nèi)心臟發(fā)育過(guò)程,心臟發(fā)育畸形、心肌肥厚、心肌損害的發(fā)生率也越來(lái)越高[10]。本研究旨在探討孕母GDM對(duì)新生兒心臟發(fā)育和功能的影響,以指導(dǎo)臨床診斷和治療。
3.1妊娠期糖尿病對(duì)新生兒心臟損傷的分析
母親GDM可致出生后新生兒低血糖。本研究顯示,GDM組新生兒出生血糖明顯低于對(duì)照組,并且GDM組新生兒的CK、CK-MB、hs-cTnT水平均明顯高于對(duì)照組。GDM孕母的體內(nèi)微血管損傷及缺血,一方面使孕母宮內(nèi)紅細(xì)胞釋氧能力降低,造成組織缺氧,另一方面血容量減少,進(jìn)一步加重了胎兒缺氧[11-12]。GDM孕婦體內(nèi)高血糖狀態(tài)可直接刺激胰島細(xì)胞,并不斷分泌胰島素,使細(xì)胞代謝增快,造成相對(duì)缺氧;另外,肺表面活性物質(zhì)產(chǎn)生依賴糖皮質(zhì)激素,胰島素可抵抗糖皮質(zhì)激素,造成肺表面活性物質(zhì)產(chǎn)生障礙,同時(shí)體內(nèi)細(xì)胞代謝增快,還可刺激胎兒髓外造血功能,紅細(xì)胞產(chǎn)生過(guò)多,使胎兒心臟負(fù)荷增加,射血減少,導(dǎo)致血液黏稠,流速減緩,加重了胎兒缺氧缺血。在動(dòng)物試驗(yàn)研究中,以高倍鏡觀察動(dòng)物新生兒心肌損傷細(xì)胞顯示,部分細(xì)胞存在形態(tài)異常、排列紊亂、纖維增生等現(xiàn)象[13-14]。新生兒心肌細(xì)胞缺氧缺血受損后,細(xì)胞內(nèi)物質(zhì)可直接分解入血,如CK、CK-MB、hs-cTnT等。總之,GDM孕母在孕早中期等有多種因素可導(dǎo)致胎兒及新生兒的心肌功能受損。目前其發(fā)病機(jī)制多限于動(dòng)物模型的研究,對(duì)于GDM孕母的新生兒發(fā)生心肌損傷是否存在如炎性因子等其他因素的參與[15],尚需檢測(cè)多種生物標(biāo)志物及大樣本的研究驗(yàn)證。
3.2妊娠期糖尿病對(duì)新生兒心臟功能影響的分析
有研究發(fā)現(xiàn),GDM孕母的胎兒心臟可表現(xiàn)為心室壁與室間隔的肥厚[16]。本研究顯示,GDM組新生兒IVS厚度明顯大于對(duì)照組,GDM組新生兒IVS厚度與新生兒出生體重、血清hs-cTnT、孕母血清C肽、孕母糖化血紅蛋白均呈顯著正相關(guān),新生兒出生體重、血清hs-cTnT水平、孕母糖化血紅蛋白均是IVS厚度的影響因素。有關(guān)室間隔肥厚發(fā)生原因尚不明確,分析原因:一方面,孕期高血糖可直接作用于胎兒胰島β細(xì)胞,產(chǎn)生胰島素,造成高胰島素血癥,刺激心臟細(xì)胞,造成心肌細(xì)胞增生,進(jìn)而心肌肥厚,同時(shí)細(xì)胞代謝增快,造成胎兒相對(duì)缺氧[17],更多血液分配到左心房,血流再分配,左心收縮功能增強(qiáng),導(dǎo)致心臟損傷。胰島素生長(zhǎng)因子-1(insulin-like growth factor 1,IGF-1)可增加心肌細(xì)胞數(shù)量,促進(jìn)心肌細(xì)胞增生,而GDM孕母的新生兒體內(nèi)的IGF-1水平明顯增高,從而導(dǎo)致新生兒出現(xiàn)心肌損傷、心臟增大。有動(dòng)物試驗(yàn)顯示,GDM胎鼠體內(nèi)心肌細(xì)胞數(shù)量增多,細(xì)胞形態(tài)異常,排列紊亂,纖維增生,出現(xiàn)心肌損傷及心肌肥厚[18]。還有研究顯示,孕期高血糖可使宮內(nèi)缺氧缺血,使胎兒心肌受損,細(xì)胞內(nèi)的肌鈣蛋白出現(xiàn)外溢[19]。另有研究顯示,心肌肥厚的發(fā)生與血糖水平無(wú)相關(guān)影響[20]。因此,妊娠期各種代謝異常如何影響胎兒的心臟發(fā)育、是否存在其他潛在因素,以及孕期各病程對(duì)其的影響程度和檢測(cè)指標(biāo)尚需進(jìn)一步探討。
GDM孕母體內(nèi)的高血糖及高胰島素血癥水平會(huì)刺激胎兒心臟細(xì)胞增生肥厚,除了影響IVS厚度,胎兒先天性心臟病的發(fā)生率亦明顯升高[21-22]。本研究顯示,GDM組新生兒先天性心臟病發(fā)病率明顯高于對(duì)照組。目前糖代謝異常導(dǎo)致心臟發(fā)育畸形的發(fā)病機(jī)制在動(dòng)物實(shí)驗(yàn)中的研究相對(duì)較多,但對(duì)于GDM孕母的新生兒先天性心臟病發(fā)生的機(jī)制及如何減少發(fā)病率有待更深入的研究進(jìn)行探討。
綜上所述,GDM孕母對(duì)胎兒及新生兒心臟發(fā)育和功能的影響已逐漸受到重視[23-24]。GDM母親的新生兒發(fā)生心臟損害與其血糖控制情況密切相關(guān),血清心肌損傷標(biāo)志物水平能較好地反映出心肌損傷的程度,有助于早期診斷新生兒心肌損傷,并且隨著超聲技術(shù)的不斷完善,血清心肌損傷標(biāo)志物檢測(cè)及心臟超聲檢查可作為GDM母親的新生兒心臟損害早期診斷的檢測(cè)指標(biāo),結(jié)合臨床,及早診斷,并給予針對(duì)性的治療。
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[專(zhuān)業(yè)責(zé)任編輯:馮 玲]
[中文編輯:王 懿;英文編輯:牛 惠]
[收稿日期]2023-05-31
[基金項(xiàng)目]濰坊市衛(wèi)生健康委科研項(xiàng)目(WFWSJK-2021-232)
[作者簡(jiǎn)介]馮 燕(1987—),女,主治醫(yī)師,碩士,主要從事兒科內(nèi)分泌的研究。
[通訊作者]王顏剛,教授/博士生導(dǎo)師。