Follow-up Study: The Impact Of Gestational Diabetes Mellitus Pregnancies On Fetal Cardiac Function

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.PartⅠ1.Fetal cardiac function in uncomplicated pregnanciesObjective: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 indexObjective: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. PartⅡ1.The change of fetal cardiac function in pregnancy of gestational diabetes mellitusObjective: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 bloodObjective: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 mellitusObjective: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. Summary1.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.