健康孕妇孕晚期全血游离肉碱与母婴心脏结构和功能的关系

Free carnitine levels in peripheral blood of healthy pregnant women in third trimester and their relationship with maternal and fetal cardiac function and structure

目的研究健康孕妇孕晚期全血游离肉碱及氨基酸水平及其与母胎、新生儿心脏结构及功能的关系。方法前瞻性选择2017年6月至2018年2月在北京市2家区级妇幼保健院(城区1家和远郊区1家)进行常规产前检查并分娩的单胎妊娠孕妇,于孕(18±1)周时行唐氏综合征筛查,孕(35±1)周时采用液相色谱-串联质谱技术检测孕妇全血及尿氨基酸、游离肉碱水平,同时行母亲及胎儿心脏超声检查,分娩后行新生儿心脏超声评估心脏结构、心功能。同时收集孕妇文化程度、初婚年龄、妊娠年龄、孕次、孕早期口服叶酸史等产前因素。采用t检验、方差分析、χ^(2)检验、Kolmogorov-Smirnov检验、Pearson相关检验、Kappa检验进行统计学分析。结果最终493对资料完整的孕妇及其新生儿纳入统计分析。孕妇孕晚期血游离肉碱水平为5.09~59.17μmol/L(参考值10.00~50.00μmol/L),平均(13.03±3.87)μmol/L;心脏超声未见结构异常,左室舒张末期内径为(45.70±3.08)mm,左室收缩末期内径为(29.17±3.12)mm,左室射血分数均≥55%;孕晚期胎儿心脏超声未检出心脏畸形。493例新生儿出生体重为(3340±313)g,<2500 g共5例(1.0%),其母亲血游离肉碱水平为(13.25±2.17)μmol/L(10.46~19.21μmol/L);出生体重>4000 g新生儿共15例(3.0%),其母亲血游离肉碱水平为(12.64±2.50)μmol/L(8.78~17.73μmol/L),2组差异无统计学意义(t=0.42,P>0.05)。493例新生儿左室舒张末期内径平均为(17.21±1.27)mm,左室收缩末期内径平均为(11.03±1.30)mm。其中64例(13.0%)新生儿左室射血分数<60%,其母血游离肉碱水平为(12.93±2.78)μmol/L(7.34~22.13μmol/L);59例(12.0%)新生儿左室射血分数>75%,其母血游离肉碱水平为(13.09±3.24)μmol/L(8.66~27.49μmol/L),2组差异无统计学意义(t=-0.29,P>0.05)。以血游离肉碱水平四分位数分4组,不同血游离肉碱水平组间孕妇、新生儿左室舒张末期内径及左室射血分数差异均无统计学意义(P值均>0.05)。结论健康孕妇孕晚期血游离肉碱水平处于正常低限。孕妇心脏功能及胎儿心脏结构虽未受明显影响,但孕晚期母体血游离肉碱低水平是否会影响儿童心肌功能储备及孕晚期是否需要加强肉碱摄入,值得扩大样本量继续观察。

Objective To investigate the levels of periphreal blood free carnitine and amino acids in healthy pregnant women in the third trimester and their association with maternal,fetal,and neonatal cardiac function and structure.Methods This prospective descriptive study included healthy singleton pregnancies who underwent routine obstetric examination and delivered in two district maternal and child health hospitals(one in the urban and one in the suburb an area)in Beijing from June 2017 to February 2018.All recruiters had serology Down's syndrome screening test at(18±1)gestational weeks.Besides measurement of amino acids and free carnitine levels in whole blood and urine samples by liquid chromatography-tandem mass spectrometry,all cases underwent maternal and fetal echocardiography at(35±1)weeks of gestation.And neonatal echocardiography was performed after delivery to assess the heart function and structure.Antenatal factors were also collected,including maternal education background,age at first marriage and conception,gravidity,and folic acid supplement in early pregnancy.Statistical analysis was performed using t-test,ANOVA,Chi-square test,Pearson correlation coefficient,and Kappa test.Results A total of 493 mother-neonate dyads were enrolled in this study.Blood free carnitine levels in the healthy pregnant women in the third trimester ranged from 5.09 to 59.17μmol/L(reference value:10.00-50.00μmol/L)with an average value of(13.03±3.87)μmol/L.None was found with structural abnormalities by cardiac ultrasound,showing an average left ventricular end diastolic diameter(LVEDD)and end systolic diameter(LVESD)of(45.70±3.08)mm and(29.17±3.12)mm,respectively,and left ventricular ejection fraction(LVEF)of all cases were over 55%.No cardiac malformation was detected by the third-trimester fetal echocardiography.The average birth weight of the 493 newborns was(3340±313)g.Those whose birth weight<2500 g and>4000 g were accounted for 1.0%(5 cases)and 3.0%(15 cases)with the average maternal blood free carnitine level of(13.25±2.17)μmol/L(10.46-19.21μmol/L)and(12.64±2.50)μmol/L(8.78-17.73μmol/L)(t=0.42,P>0.05).The average LVEDD and LVESD of the 493 newborns were(17.21±1.27)mm and(11.03±1.30)mm,respectively.For the 64 newborns(13.0%)whose LVEF<60%,the maternal blood free carnitine level was(12.93±2.78)μmol/L(7.34-22.13μmol/L),showing no statistical difference(t=-0.29,P>0.05)with those 59 neonates(12.0%)whose LVEF over 75%and maternal carnitine level of(13.09±3.24)μmol/L(8.66-27.49μmol/L).All cases were divided into four groups based on the quartiles of maternal blood free carnitine level and no significant difference in maternal or neonatal LVEDD or LVEF was observed among these groups(all P>0.05).Conclusions Blood free carnitine concentration in healthy pregnant women in the third trimester is at the lower limit of normal range,and no significant effect on maternal cardiac function and fetal cardiac structure is seen.However,the effect of low maternal carnitine level in the third trimester on children's myocardial function and whether carnitine should be supplemented in the third trimester are worthy of further investigation with larger sample size.