妊娠期糖尿病对胎儿心功能影响的随访研究
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摘要
产前胎儿监测是围产医学的重要内容。胎儿超声心动图作为一项有效的诊断技术,可用来测量胎儿心脏功能而深入、精细的对胎儿状况进行评估;通过研究正常胎儿的心功能,可掌握胎儿宫内心脏的变化趋势和成熟过程,有助于评估高危妊娠和病理状态下胎儿心功能的改变,为产科医师提供更全面的资料,从而指导产前胎儿监护。Tei指数可作为一项评价胎儿心室整体功能的良好指标,但测量方法的差异限制了其在临床的应用,探寻更准确而简便的测量方法可使其更好的应用于胎儿心功能评价。
妊娠期糖尿病(GDM)是常见的妊娠高危因素之一,在我国孕妇中的发生率为2—5%,并有逐年上升的趋势。既往对于妊娠合并糖尿病的研究发现,母体高血糖通过胎盘影响胎儿,可致其心脏解剖和功能的变化。我们推测妊娠期糖尿病中胎儿心脏可能发生同样的改变,并可能致胎儿循环中一些心血管系统的重要调节因子水平发生改变,如脑钠肽(BNP)和胰岛素样生长因子(IGF-1)。通过胎儿超声心动图检查和脐血因子水平测定,可较全面评估该病理因素下胎儿心功能的变化,以期为产科医师提供更多临床信息。
对糖尿病妊娠胎儿出生后心功能的随访研究目前并不多,而这正是广大孕妇和医师更为关注的问题。在本课题中我们选取一部分妊娠期糖尿病孕妇的婴儿,在2—3月龄时进行超声心动图随访,以了解其出生后的心脏状况,从而更全面的评价该病对胎儿的近远期影响。
本课题分为以下几部分:
第一部分
(一)正常胎儿孕期心功能变化的研究
目的:评价正常胎儿孕期心功能的变化。对象和方法:上海一家三级妇产科医院行产前检查的正常孕妇100例,20—40周,平均28.4±4.5周,按孕周分为＜24周、≥124而＜28周、≥28而＜32周和≥32周四组,应用胎儿超声心动图测量胎儿心脏解剖指标和收缩、舒张功能指标。结果:正常胎儿心脏的心腔长横径、心室壁厚度、心胸比例均随孕周的增长而增加,其中右心大于左心。大动脉血流指标、心室搏出量、心输出量均在孕期增长;其中主动脉流速大于肺动脉,但左心输出量小于右心,且差值随孕周增长更显著;左室缩短分数和射血分数在孕期无明显变化。二、三尖瓣E峰和E/A比值随孕周增长而增加;三尖瓣A峰轻度增加,下腔静脉前负荷指数在孕期轻度下降;而二尖瓣A峰和左房缩短分数在孕期无明显变化。结论:正常胎儿的心脏解剖和功能指标随孕周增长逐渐成熟,其中右心占主导。胚胎期心室已具有一定的收缩功能和顺应性,发育过程中以心室血流量的增加和主动松弛功能的增强为主,心室前、后负荷随孕周增长渐下降。
(二)心率校正的脉冲多普勒法测量Tei指数的应用探讨及其对正常胎儿整体心功能的评价
目的:探寻更实用而准确的胎儿心室Tei指数的测量方法及正常值。对象和方法:正常孕妇100例同(一)。用脉冲多普勒分别取得房室瓣口和大动脉瓣口的血流频谱,分别测量前一次A峰结束到下一次E峰开始相隔的时间“a”,射血时间“b”,同时测量各频谱当时的心率;计算平均胎心率,用平均心率对各瓣口a、b进行校正,校正公式为:校正后a、b=实测a、b×当时心率/平均心率;用校正后的a、b计算心室Tei指数,公式=(a—b)/b。结果:Tei指数在所有胎儿中均成功测得。正常胎儿左、右心室Tei指数分别为0.311±0.069和0.297+0.074,中晚孕期无明显变化,和心率无关联,左、右心室之间无明显差别。结论:采用平均心率校正的脉冲多普勒方法可避免传统方法的缺点,更简便、准确的测量胎儿心室Tei指数。整个中晚孕期,用Tei指数评价的胎儿心室整体功能趋于稳定。
第二部分
(一)妊娠期糖尿病孕妇胎儿心功能的随访研究
目的:研究在不同血糖控制水平下,妊娠期糖尿病孕妇胎儿的心脏解剖和功能在孕期的变化。对象和方法:上海市两家三级妇产科医院诊断GDM的孕妇44例接受了78次检查,按检查时血糖情况分为控制欠佳和控制较好组,设正常孕妇70例为对照组,均按孕周分为＜28周、≥28周而＜34周、≥34周三组,测量胎儿心室壁厚度、心脏收缩、舒张功能指标,用心率校正法测量心室整体功能即Tei指数。结果:GDM两组胎儿的心室壁厚度明显大于对照组,以室间隔最为显著,其中血糖控制欠佳的胎儿室壁增厚更明显。GDM胎儿的左心和右心血流指标分别在＜28周和≥28周起明显大于对照组,右心与左心输出量比值随孕周增长而轻度下降;血糖控制欠佳胎儿的右心血流指标增加更明显。GDM胎儿的左房缩短分数在34周以后明显小于对照组;三尖瓣E/A比值和下腔静脉前负荷指数分别在28周以后和＜28周起与对照组有明显差别。左、右心室Tei指数在血糖控制欠佳的胎儿中分别在≥28周和＜28周起高于对照组;在血糖控制较好的胎儿中则在34周以后方大于对照组。结论:GDM胎儿的心脏解剖和功能在中晚孕期发生改变,表现为室间隔的肥厚、心室和大动脉收缩血量的增加、心室舒张功能及整体功能的受损,Tei指数的升高较单一功能指标的变化更早,右室功能受损早于左室,血糖控制不佳孕妇的胎儿心脏改变更早、更显著。
(二)测定脐血BNP和IGF-1评价糖尿病妊娠胎儿心功能的初步探讨
目的:探讨通过脐血因子水平评价糖尿病妊娠胎儿围产期心功能的可行性及其可能的改变。对象和方法:上海市一家三级妇产科医院分娩的孕妇24例,其中GDM19例,妊娠期糖耐量受损(GIGT)孕妇5例,按孕晚期血糖情况分为控制欠佳组7例和控制较好组17例,正常妊娠孕妇25例作为对照。于分娩时留脐血,分别用ELISA试剂盒和Immulite1000测定仪测定脐血BNP和IGF-1浓度。结果:糖尿病妊娠胎儿脐血BNP浓度明显高于对照组(80.6±13.7 pg/ml),其中血糖控制欠佳组高于控制较好组(分别为142.1±44.1和102.4±31.2 pg/ml),GDM和GIGT组间无明显差别;BNP和孕期胎儿左室壁厚度呈正相关,和二尖瓣E/A比值呈负相关。脐血IGF-1水平在糖尿病妊娠不同诊断组、不同血糖控制组和对照组间均无明显差别。结论:测定脐血BNP和IGF—1均可行。糖尿病妊娠胎儿的脐血BNP明显升高,并同临床血糖控制情况及心功能变化一致,IGF—1水平未在胎儿循环中出现改变。
(三)糖尿病妊娠胎儿出生后心功能的随访研究
目的:用小儿超声心动图评价妊娠期糖尿病胎儿出生后心功能的变化和状况。对象和方法:上海市一家三级妇产科医院的GDM孕妇18例,血糖控制可,孕末期行胎儿心超检查,胎儿出生后2-3月时预约至一家三级儿科医院行小儿心超检查,心脏解剖和功能指标测量同胎儿期,对照组为同期同年龄正常妊娠分娩的健康婴儿。结果:GDM婴儿的室间隔厚度较胎儿期变薄,收缩期左室壁和室间隔厚度大于正常组婴儿;除右室搏出量和右心输出量大于正常组外,大动脉血流指标和左室收缩功能在两组婴儿中均无明显差别;GDM婴儿的左房缩短分数明显小于对照组;左右心室Tei指数较胎儿期明显降低,与正常婴儿组无差别。结论:血糖控制良好的GDM母亲的婴儿在2—3月时室壁肥厚较胎儿期有所恢复,但仍未达正常水平,左室舒张功能仍较低,主要表现在心室顺应性上,心室整体功能恢复较早并达正常水平。
总结
1、胎儿超声心动图可有效用于胎儿心功能的评价。胎儿心脏的收缩、舒张和整体功能在孕期呈现一定的成熟规律。
2、首次提出应用心率校正的脉冲多普勒方法测量胎儿心室Tei指数,它较传统方法更简便而准确。
3、妊娠期糖尿病母亲胎儿的心脏解剖和功能均发生了一定的改变,在血糖控制不佳的胎儿中更明显;某些心血管系统调节因子可能参与其中并反映在胎儿循环中;妊娠期糖尿病母亲的婴儿在生后2-3月时心脏改变已有所恢复,但尚未达正常水平。
Prenatal monitoring is an important part in Perinatology.As a useful technology, fetal echocardiography can be used to detect and evaluate fetal cardiac function deeply and precisely.By the measurement of cardiac function in normal fetuses,one can know the process of maturation in fetal heart,which conduces to evaluate the abnormal cardiac function in high-risk pregnancies.Therefore more clinical information can be supplied to obstetrician and guide prenatal monitoring.Tei index is useful in assessment of fetal global ventricular function,but the differences of the methods have limited its application in clinic.Trying a precise and easy method is important.
Gestational diabetes mellitus(GDM) is one of the most common high risk factors in pregnancies.It has an incidence of 2-5%in China,and is increasing every year. Previous studies on pregnancies complicated by diabetes suggested that high level of maternal blood glucose could influence fetuses and caused the alterations of cardiac anatomy and function.We suppose that the same changes could be observed in fetuses of GDM,and some important factors adjusting cardiovascular system may change in fetal circulation,such as brain natriuretic peptide(BNP) and insulin-like growth factors-1(IGF-1).By fetal echo examination and detection in cord blood,we can evaluate the alteration of cardiac function in GDM fetuses overall and offer more clinical information to obstetrician.
Follow-up studies on postnatal cardiac function in fetuses of diabetic mothers have been less reported,which is just more noticed by mothers and doctors.In this study,we examined some infants of GDM mothers aging 2 to 3 months using pediatric echocardiography,to evaluate the long-term influences of GDM on fetuses.
PartⅠ
1.Fetal cardiac function in uncomplicated pregnancies
Objective:To evaluate the changing process of fetal cardiac function in normal pregnancies.Methods:In a tertiary obstetrics and gynecology hospital in Shanghai 100 fetuses of normal pregnancies were studied,aging 20-40 weeks(mean 28.4±4.5 weeks).All the fetuses were divided into 4 groups(＜24,≥24 and＜28,≥28 and＜32, ≥32 weeks).Cardiac anatomy and function were measured by using fetal echo.
Results:The size of four chambers,thickness of ventricular walls and cardiothoracic ratio all increased with gestational age in normal fetuses,with the size of right ventricle(RV) larger than left ventricle(LV).Blood in great arteries,ventricular stroke volume(SV) and cardiac output(CO) also increased in pregnancies.Peak velocities of aorta(AO) were higher than pulmonary artery(PA),but CO of LV were smaller than RV,and the difference increased with gestational age.Fractional shortening(FS) and ejection fraction(EF) of LV had no changes in gestation.With increasing gestational age,E wave peak velocities and E/A ratio ofmitral and tricuspid valves(MV and TV) increased,preload index(PLI) in inferior vena cava(IVC) decreased slightly,but no changes were found in A wave peak velocities of MV and left atrial shortening fraction(LASF).Conclusions:Cardiac anatomy and function gradually and steadily became mature in normal pregnancies with RV predominant.In human embryonic cardiac development period systolic function and compliance had formed,the ventricular blood volumes and active relaxation increased respectively.Preload and afterload of both ventricles decreased with gestation.
2.Evaluating global ventricular function in normal fetuses by using heart rates adjusted Tei index
Objective:Try to approach a more practical and precise method to measure fetal ventricular Tei index.Methods:The same 100 fetuses as PartⅠ-1.Ventricular inflow and outflow patterns were obtained by pulsed Doppler.In every flow pattern,time intervals as "a" "b" and the heart rates were measured,then average heart rates were calculated to adjust each "a" "b".Tei index was calculated using the adjusted time intervals due to the formula:(a-b)/b.Results:Tei index was measured successfully in every fetus.LV and RV Tei index in normal fetuses were 0.311±0.069 and 0.297±0.074 respectively,and kept constant in middle and late pregnancy.Tei index was not related to heart rate and no significant difference was found between LV and RV Tei index.Conclusions:Heart rate adjusted pulsed Doppler is an easier and more precise method to measure fetal ventricular Tei index,which can avoid the disadvantages in previous methods.Fetal global ventricular function is constant in the whole middle and late gestation.
PartⅡ
1.The change of fetal cardiac function in pregnancy of gestational diabetes mellitus
Objective:To evaluate the alterations of cardiac anatomy and function in GDM fetuses with different maternal glucose control.Methods:In two tertiary obstetrics and gynecology hospitals of Shanghai,44 GDM mothers received 78 examinations of fetal echo and were divided into two subgroups of good and poor glucose control due to the maternal blood glucose at examination.70 normal mothers were selected as control group.All the fetuses were divided into three groups due to the gestation age (＜28,≥28 and＜34 and≥34 weeks).The parameters of cardiac anatomy and function were same as PartⅠ.Results:The thicknesses of ventricular walls in GDM group were larger than control,especially interventricular septum(IVS),and more obviously in fetuses with poor glucose control.LV and RV blood flow in GDM fetuses became significantly larger than control since＜28 and＞28 weeks respectively,more obviously in poor glucose control fetuses.The RV/LV output ratio decreased slightly with the increasing gestation.LASF in GDM fetuses was smaller than control group after 34 weeks,and differences were found in E/A ratio of TV and PLI of IVC between GDM and control groups since≥28 and＜28 weeks.In poor glucose control subgroup,fetal LV and RV Tei index were higher than control since≥28 and＜28 weeks,but in good control subgroup Tei index increased significantly after 34 weeks in both ventricles.Conclusions:Cardiac anatomy and function of GDM fetuses were changed in the middle and late pregnancy,mainly including the thickening of IVS, increasing of ventricular blood flow and impairment of cardiac diastolic and global function,among which Tei index increased earlier than other parameters.RV was influenced earlier than LV.More significant and earlier changes were observed in fetuses of poor maternal glucose control.
2.Assessment of cardiac function in fetuses of diabetic mothers by detecting BNP and IGF-1 in cord blood
Objective:To approach the possibility of evaluating perinatal cardiac function in diabetic fetuses by BNP and IGF-1 detection and their level in cord blood.Methods: 19 GDM and 5 gestational impaired glucose tolerance(GIGT) mothers delivered in a tertiary obstetrics and gynecology hospitals of Shanghai.All the 24 mothers were divided into two subgroups of good and poor glucose control due to the maternal blood glucose before birth.25 uncomplicated mothers were selected as control.Cord blood were sampled for detecting the concentrations of BNP and IGF-1.Results:The concentration of BNP in cord blood of diabetic group were significantly higher than control(80.6±13.7 pg/ml),among which the poor glucose control subgroup higher than good glucose control(142.1±44.1 and 102.4±31.2 pg/ml respectively).No difference was found between GDM and GIGT groups.The level of BNP was positively relate to prenatal thicknesses of fetal LV walls,and negatively to E/A ratio of fetal MV flow.No differences in the concentration of IGF-1 were observed among not only GDM and GIGT groups,but also good and poor glucose control subgroups and control groups.Conclusions:It's possible to detect BNP and IGF-1 in cord blood. Fetuses of diabetic pregnancies had an increased BNP in cord blood,which was in concordance with maternal glucose control and fetal cardiac function.IGF-1 had no change in fetal circulation.
3.Cardiac function follow-up in infants of mothers with gestational diabetes mellitus
Objective:To evaluate the postnatal cardiac function of GDM fetuses.Methods: In a tertiary obstetrics and gynecology hospital of Shanghai,18 mothers with GDM and good glucose control received fetal echo examination in the late pregnancy.2 to 3 months after birth,their infants received sonographic follow-up in another children's hospital.Age-matched healthy infants of normal pregnancies were as control.Results: In GDM group the thicknesses of IVS in infants were smaller than fetuses,but the thicknesses of end-systolic LV walls and IVS were till larger than control infants. Blood flow in great arteries and LV systolic function had no differences between GDM and control infants,except SV and CO of RV.LASF in GDM infants was smaller than control.In GDM group both LV and RV Tel index were significantly lower in infants than in fetuses and had no differences in GDM and control infants.
Conclusions:In infants of mothers with GDM and good glucose control,thicknesses of ventricular walls were in recovery but still abnormal.LV diastolic function remained abnormal,mainly because of the impaired compliance.Ventricular global function recovered earlier and reached a normal level.
Summary
1.Fetal echocardiography can effectively evaluate fetal cardiac function.During gestational period fetal systolic,diastolic and global cardiac function present a maturation pattern.
2.For the first time we report a new method of heart rates adjusted pulsed Doppler measuring ventricular Tel index in fetuses.It demonstrated more precise and easier consequence than traditional methods.
3.Cardiac anatomy and function have altered in fetuses of mothers with GDM,more significantly in those of glucose poor-controlled mothers.Some adjusting factors in cardiovascular system may participate in the mechanism and show the change in fetal circulation.2 to 3 months after birth,the infants of GDM mothers are in the process of recovery of cardiac anatomy and function but still not reach a complete normal level.
妊娠期糖尿病(GDM)是常见的妊娠高危因素之一,在我国孕妇中的发生率为2—5%,并有逐年上升的趋势。既往对于妊娠合并糖尿病的研究发现,母体高血糖通过胎盘影响胎儿,可致其心脏解剖和功能的变化。我们推测妊娠期糖尿病中胎儿心脏可能发生同样的改变,并可能致胎儿循环中一些心血管系统的重要调节因子水平发生改变,如脑钠肽(BNP)和胰岛素样生长因子(IGF-1)。通过胎儿超声心动图检查和脐血因子水平测定,可较全面评估该病理因素下胎儿心功能的变化,以期为产科医师提供更多临床信息。
对糖尿病妊娠胎儿出生后心功能的随访研究目前并不多,而这正是广大孕妇和医师更为关注的问题。在本课题中我们选取一部分妊娠期糖尿病孕妇的婴儿,在2—3月龄时进行超声心动图随访,以了解其出生后的心脏状况,从而更全面的评价该病对胎儿的近远期影响。
本课题分为以下几部分:
第一部分
(一)正常胎儿孕期心功能变化的研究
目的:评价正常胎儿孕期心功能的变化。对象和方法:上海一家三级妇产科医院行产前检查的正常孕妇100例,20—40周,平均28.4±4.5周,按孕周分为＜24周、≥124而＜28周、≥28而＜32周和≥32周四组,应用胎儿超声心动图测量胎儿心脏解剖指标和收缩、舒张功能指标。结果:正常胎儿心脏的心腔长横径、心室壁厚度、心胸比例均随孕周的增长而增加,其中右心大于左心。大动脉血流指标、心室搏出量、心输出量均在孕期增长;其中主动脉流速大于肺动脉,但左心输出量小于右心,且差值随孕周增长更显著;左室缩短分数和射血分数在孕期无明显变化。二、三尖瓣E峰和E/A比值随孕周增长而增加;三尖瓣A峰轻度增加,下腔静脉前负荷指数在孕期轻度下降;而二尖瓣A峰和左房缩短分数在孕期无明显变化。结论:正常胎儿的心脏解剖和功能指标随孕周增长逐渐成熟,其中右心占主导。胚胎期心室已具有一定的收缩功能和顺应性,发育过程中以心室血流量的增加和主动松弛功能的增强为主,心室前、后负荷随孕周增长渐下降。
(二)心率校正的脉冲多普勒法测量Tei指数的应用探讨及其对正常胎儿整体心功能的评价
目的:探寻更实用而准确的胎儿心室Tei指数的测量方法及正常值。对象和方法:正常孕妇100例同(一)。用脉冲多普勒分别取得房室瓣口和大动脉瓣口的血流频谱,分别测量前一次A峰结束到下一次E峰开始相隔的时间“a”,射血时间“b”,同时测量各频谱当时的心率;计算平均胎心率,用平均心率对各瓣口a、b进行校正,校正公式为:校正后a、b=实测a、b×当时心率/平均心率;用校正后的a、b计算心室Tei指数,公式=(a—b)/b。结果:Tei指数在所有胎儿中均成功测得。正常胎儿左、右心室Tei指数分别为0.311±0.069和0.297+0.074,中晚孕期无明显变化,和心率无关联,左、右心室之间无明显差别。结论:采用平均心率校正的脉冲多普勒方法可避免传统方法的缺点,更简便、准确的测量胎儿心室Tei指数。整个中晚孕期,用Tei指数评价的胎儿心室整体功能趋于稳定。
第二部分
(一)妊娠期糖尿病孕妇胎儿心功能的随访研究
目的:研究在不同血糖控制水平下,妊娠期糖尿病孕妇胎儿的心脏解剖和功能在孕期的变化。对象和方法:上海市两家三级妇产科医院诊断GDM的孕妇44例接受了78次检查,按检查时血糖情况分为控制欠佳和控制较好组,设正常孕妇70例为对照组,均按孕周分为＜28周、≥28周而＜34周、≥34周三组,测量胎儿心室壁厚度、心脏收缩、舒张功能指标,用心率校正法测量心室整体功能即Tei指数。结果:GDM两组胎儿的心室壁厚度明显大于对照组,以室间隔最为显著,其中血糖控制欠佳的胎儿室壁增厚更明显。GDM胎儿的左心和右心血流指标分别在＜28周和≥28周起明显大于对照组,右心与左心输出量比值随孕周增长而轻度下降;血糖控制欠佳胎儿的右心血流指标增加更明显。GDM胎儿的左房缩短分数在34周以后明显小于对照组;三尖瓣E/A比值和下腔静脉前负荷指数分别在28周以后和＜28周起与对照组有明显差别。左、右心室Tei指数在血糖控制欠佳的胎儿中分别在≥28周和＜28周起高于对照组;在血糖控制较好的胎儿中则在34周以后方大于对照组。结论:GDM胎儿的心脏解剖和功能在中晚孕期发生改变,表现为室间隔的肥厚、心室和大动脉收缩血量的增加、心室舒张功能及整体功能的受损,Tei指数的升高较单一功能指标的变化更早,右室功能受损早于左室,血糖控制不佳孕妇的胎儿心脏改变更早、更显著。
(二)测定脐血BNP和IGF-1评价糖尿病妊娠胎儿心功能的初步探讨
目的:探讨通过脐血因子水平评价糖尿病妊娠胎儿围产期心功能的可行性及其可能的改变。对象和方法:上海市一家三级妇产科医院分娩的孕妇24例,其中GDM19例,妊娠期糖耐量受损(GIGT)孕妇5例,按孕晚期血糖情况分为控制欠佳组7例和控制较好组17例,正常妊娠孕妇25例作为对照。于分娩时留脐血,分别用ELISA试剂盒和Immulite1000测定仪测定脐血BNP和IGF-1浓度。结果:糖尿病妊娠胎儿脐血BNP浓度明显高于对照组(80.6±13.7 pg/ml),其中血糖控制欠佳组高于控制较好组(分别为142.1±44.1和102.4±31.2 pg/ml),GDM和GIGT组间无明显差别;BNP和孕期胎儿左室壁厚度呈正相关,和二尖瓣E/A比值呈负相关。脐血IGF-1水平在糖尿病妊娠不同诊断组、不同血糖控制组和对照组间均无明显差别。结论:测定脐血BNP和IGF—1均可行。糖尿病妊娠胎儿的脐血BNP明显升高,并同临床血糖控制情况及心功能变化一致,IGF—1水平未在胎儿循环中出现改变。
(三)糖尿病妊娠胎儿出生后心功能的随访研究
目的:用小儿超声心动图评价妊娠期糖尿病胎儿出生后心功能的变化和状况。对象和方法:上海市一家三级妇产科医院的GDM孕妇18例,血糖控制可,孕末期行胎儿心超检查,胎儿出生后2-3月时预约至一家三级儿科医院行小儿心超检查,心脏解剖和功能指标测量同胎儿期,对照组为同期同年龄正常妊娠分娩的健康婴儿。结果:GDM婴儿的室间隔厚度较胎儿期变薄,收缩期左室壁和室间隔厚度大于正常组婴儿;除右室搏出量和右心输出量大于正常组外,大动脉血流指标和左室收缩功能在两组婴儿中均无明显差别;GDM婴儿的左房缩短分数明显小于对照组;左右心室Tei指数较胎儿期明显降低,与正常婴儿组无差别。结论:血糖控制良好的GDM母亲的婴儿在2—3月时室壁肥厚较胎儿期有所恢复,但仍未达正常水平,左室舒张功能仍较低,主要表现在心室顺应性上,心室整体功能恢复较早并达正常水平。
总结
1、胎儿超声心动图可有效用于胎儿心功能的评价。胎儿心脏的收缩、舒张和整体功能在孕期呈现一定的成熟规律。
2、首次提出应用心率校正的脉冲多普勒方法测量胎儿心室Tei指数,它较传统方法更简便而准确。
3、妊娠期糖尿病母亲胎儿的心脏解剖和功能均发生了一定的改变,在血糖控制不佳的胎儿中更明显;某些心血管系统调节因子可能参与其中并反映在胎儿循环中;妊娠期糖尿病母亲的婴儿在生后2-3月时心脏改变已有所恢复,但尚未达正常水平。
Prenatal monitoring is an important part in Perinatology.As a useful technology, fetal echocardiography can be used to detect and evaluate fetal cardiac function deeply and precisely.By the measurement of cardiac function in normal fetuses,one can know the process of maturation in fetal heart,which conduces to evaluate the abnormal cardiac function in high-risk pregnancies.Therefore more clinical information can be supplied to obstetrician and guide prenatal monitoring.Tei index is useful in assessment of fetal global ventricular function,but the differences of the methods have limited its application in clinic.Trying a precise and easy method is important.
Gestational diabetes mellitus(GDM) is one of the most common high risk factors in pregnancies.It has an incidence of 2-5%in China,and is increasing every year. Previous studies on pregnancies complicated by diabetes suggested that high level of maternal blood glucose could influence fetuses and caused the alterations of cardiac anatomy and function.We suppose that the same changes could be observed in fetuses of GDM,and some important factors adjusting cardiovascular system may change in fetal circulation,such as brain natriuretic peptide(BNP) and insulin-like growth factors-1(IGF-1).By fetal echo examination and detection in cord blood,we can evaluate the alteration of cardiac function in GDM fetuses overall and offer more clinical information to obstetrician.
Follow-up studies on postnatal cardiac function in fetuses of diabetic mothers have been less reported,which is just more noticed by mothers and doctors.In this study,we examined some infants of GDM mothers aging 2 to 3 months using pediatric echocardiography,to evaluate the long-term influences of GDM on fetuses.
PartⅠ
1.Fetal cardiac function in uncomplicated pregnancies
Objective:To evaluate the changing process of fetal cardiac function in normal pregnancies.Methods:In a tertiary obstetrics and gynecology hospital in Shanghai 100 fetuses of normal pregnancies were studied,aging 20-40 weeks(mean 28.4±4.5 weeks).All the fetuses were divided into 4 groups(＜24,≥24 and＜28,≥28 and＜32, ≥32 weeks).Cardiac anatomy and function were measured by using fetal echo.
Results:The size of four chambers,thickness of ventricular walls and cardiothoracic ratio all increased with gestational age in normal fetuses,with the size of right ventricle(RV) larger than left ventricle(LV).Blood in great arteries,ventricular stroke volume(SV) and cardiac output(CO) also increased in pregnancies.Peak velocities of aorta(AO) were higher than pulmonary artery(PA),but CO of LV were smaller than RV,and the difference increased with gestational age.Fractional shortening(FS) and ejection fraction(EF) of LV had no changes in gestation.With increasing gestational age,E wave peak velocities and E/A ratio ofmitral and tricuspid valves(MV and TV) increased,preload index(PLI) in inferior vena cava(IVC) decreased slightly,but no changes were found in A wave peak velocities of MV and left atrial shortening fraction(LASF).Conclusions:Cardiac anatomy and function gradually and steadily became mature in normal pregnancies with RV predominant.In human embryonic cardiac development period systolic function and compliance had formed,the ventricular blood volumes and active relaxation increased respectively.Preload and afterload of both ventricles decreased with gestation.
2.Evaluating global ventricular function in normal fetuses by using heart rates adjusted Tei index
Objective:Try to approach a more practical and precise method to measure fetal ventricular Tei index.Methods:The same 100 fetuses as PartⅠ-1.Ventricular inflow and outflow patterns were obtained by pulsed Doppler.In every flow pattern,time intervals as "a" "b" and the heart rates were measured,then average heart rates were calculated to adjust each "a" "b".Tei index was calculated using the adjusted time intervals due to the formula:(a-b)/b.Results:Tei index was measured successfully in every fetus.LV and RV Tei index in normal fetuses were 0.311±0.069 and 0.297±0.074 respectively,and kept constant in middle and late pregnancy.Tei index was not related to heart rate and no significant difference was found between LV and RV Tei index.Conclusions:Heart rate adjusted pulsed Doppler is an easier and more precise method to measure fetal ventricular Tei index,which can avoid the disadvantages in previous methods.Fetal global ventricular function is constant in the whole middle and late gestation.
PartⅡ
1.The change of fetal cardiac function in pregnancy of gestational diabetes mellitus
Objective:To evaluate the alterations of cardiac anatomy and function in GDM fetuses with different maternal glucose control.Methods:In two tertiary obstetrics and gynecology hospitals of Shanghai,44 GDM mothers received 78 examinations of fetal echo and were divided into two subgroups of good and poor glucose control due to the maternal blood glucose at examination.70 normal mothers were selected as control group.All the fetuses were divided into three groups due to the gestation age (＜28,≥28 and＜34 and≥34 weeks).The parameters of cardiac anatomy and function were same as PartⅠ.Results:The thicknesses of ventricular walls in GDM group were larger than control,especially interventricular septum(IVS),and more obviously in fetuses with poor glucose control.LV and RV blood flow in GDM fetuses became significantly larger than control since＜28 and＞28 weeks respectively,more obviously in poor glucose control fetuses.The RV/LV output ratio decreased slightly with the increasing gestation.LASF in GDM fetuses was smaller than control group after 34 weeks,and differences were found in E/A ratio of TV and PLI of IVC between GDM and control groups since≥28 and＜28 weeks.In poor glucose control subgroup,fetal LV and RV Tei index were higher than control since≥28 and＜28 weeks,but in good control subgroup Tei index increased significantly after 34 weeks in both ventricles.Conclusions:Cardiac anatomy and function of GDM fetuses were changed in the middle and late pregnancy,mainly including the thickening of IVS, increasing of ventricular blood flow and impairment of cardiac diastolic and global function,among which Tei index increased earlier than other parameters.RV was influenced earlier than LV.More significant and earlier changes were observed in fetuses of poor maternal glucose control.
2.Assessment of cardiac function in fetuses of diabetic mothers by detecting BNP and IGF-1 in cord blood
Objective:To approach the possibility of evaluating perinatal cardiac function in diabetic fetuses by BNP and IGF-1 detection and their level in cord blood.Methods: 19 GDM and 5 gestational impaired glucose tolerance(GIGT) mothers delivered in a tertiary obstetrics and gynecology hospitals of Shanghai.All the 24 mothers were divided into two subgroups of good and poor glucose control due to the maternal blood glucose before birth.25 uncomplicated mothers were selected as control.Cord blood were sampled for detecting the concentrations of BNP and IGF-1.Results:The concentration of BNP in cord blood of diabetic group were significantly higher than control(80.6±13.7 pg/ml),among which the poor glucose control subgroup higher than good glucose control(142.1±44.1 and 102.4±31.2 pg/ml respectively).No difference was found between GDM and GIGT groups.The level of BNP was positively relate to prenatal thicknesses of fetal LV walls,and negatively to E/A ratio of fetal MV flow.No differences in the concentration of IGF-1 were observed among not only GDM and GIGT groups,but also good and poor glucose control subgroups and control groups.Conclusions:It's possible to detect BNP and IGF-1 in cord blood. Fetuses of diabetic pregnancies had an increased BNP in cord blood,which was in concordance with maternal glucose control and fetal cardiac function.IGF-1 had no change in fetal circulation.
3.Cardiac function follow-up in infants of mothers with gestational diabetes mellitus
Objective:To evaluate the postnatal cardiac function of GDM fetuses.Methods: In a tertiary obstetrics and gynecology hospital of Shanghai,18 mothers with GDM and good glucose control received fetal echo examination in the late pregnancy.2 to 3 months after birth,their infants received sonographic follow-up in another children's hospital.Age-matched healthy infants of normal pregnancies were as control.Results: In GDM group the thicknesses of IVS in infants were smaller than fetuses,but the thicknesses of end-systolic LV walls and IVS were till larger than control infants. Blood flow in great arteries and LV systolic function had no differences between GDM and control infants,except SV and CO of RV.LASF in GDM infants was smaller than control.In GDM group both LV and RV Tel index were significantly lower in infants than in fetuses and had no differences in GDM and control infants.
Conclusions:In infants of mothers with GDM and good glucose control,thicknesses of ventricular walls were in recovery but still abnormal.LV diastolic function remained abnormal,mainly because of the impaired compliance.Ventricular global function recovered earlier and reached a normal level.
Summary
1.Fetal echocardiography can effectively evaluate fetal cardiac function.During gestational period fetal systolic,diastolic and global cardiac function present a maturation pattern.
2.For the first time we report a new method of heart rates adjusted pulsed Doppler measuring ventricular Tel index in fetuses.It demonstrated more precise and easier consequence than traditional methods.
3.Cardiac anatomy and function have altered in fetuses of mothers with GDM,more significantly in those of glucose poor-controlled mothers.Some adjusting factors in cardiovascular system may participate in the mechanism and show the change in fetal circulation.2 to 3 months after birth,the infants of GDM mothers are in the process of recovery of cardiac anatomy and function but still not reach a complete normal level.
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