The Effect Of Maternal Hyperhomocysteinemia On Fetal Growth And Development

OBJECTIVE: We designed a large prospective study to observe the change of maternalhomocysteine concentrations during normal pregnancy, and to explore the relationship betweenmaternal hyperhomocysteinemia and fetal growing development.METHODS: The study included1434singleton pregnancy women. We successfullyinvestigated1434women and their fetus, out of contact with87women. The loss ratio is5.7%.The serum homocysteine was detected during the first, second and/or third trimesters ofpregnancy by enzymatic cycling assay. All the women were examined at regular intervals. Werecorded the mothers’ age, pregnancy complications, any diseases, the checking result duringpregnancy, the fetal outcome and so on.RESULTS: There are1434women and fetus.942of them turn out to be normal. Thirty-fivefetuses were affected by congenital malformation. Eighty-nine mothers had a neonate with fetalgrowth restriction, while sixty-two women had premature delivery. Twelve fetuses died duringthe third trimesters. Twenty eight women had experienced spontaneous abortion.The mean±SD of maternal serum homocysteine was7.25±2.90[95%Confidenceinterval:(1.57,12.93)]micromol/l during normal pregnancy (n=942, age28.4±4.0y, gestationalweeks32±9.9w).Serum Hcy concentrations insignificantly decreased from6.87(2.78) in the firsttrimester to6.43(2.90) micromol/l in the second trimester, but significantly increased in the thirdtrimester[7.54(2.86) micromol/l] about1.11(0.65,1.56)micromol/l compared to the secondtrimester(P=0.000).Maternal serum Hcy concentration above the75thpercentile at the first trimester (Hcy>7.53micromol/l) were six times [risk ratio6.77,95%CI,(1.41,32.52); P <0.05], at the secondtrimester (Hcy>7.21micromol/l) were five times [4.9(1.51,15.83); P <0.05] and at the thirdtrimester (Hcy>8.32micromol/l) were four times [3.98(1.44,11.12);P <0.05] more likely to havea congenital monstrosity infants. Mothers with homocysteine concentrations over7.53micromol/l at the first trimester were four times [4.52(1.42,14.35); P <0.05], withhomocysteine concentrations over7.21micromol/l at the second trimester were three times[2.85(1.37,5.93);P<0.05] and with homocysteine concentrations over8.32micromol/l at the third trimester were double [2.56(1.51,5.35);P <0.05] more possibly to have a neonate with fetalgrowth restriction.The risk for prematurity increased two fold [2.44(1.24,4.79);P <0.05] whenserum Hcy concentration was higher than7.21micromol/L at the second trimester, and threetimes [3.63(1.12,6.32);P<0.05] when higher than8.32micromol/l at the third trimester.Accordingto this study, we didn’t find that the risk for spontaneous abortion and fetal death would increasewhile the maternal Hcy concentration was above the75thpercentile during pregnancy.The risk ratio of maternal hyperhomocysteinemia was14.37(3.14,63.12) for congenitalheart defects (CHDs),7.84(1.56，37.83) for Neural Tube Defects(NTD), and9.9(1.15,91.19) forcheilopalatognathus (CLP). We haven’t found that mother elevated homocysteine would increasethe risk for limb defects and genitourinary malformations. As one of fetal anormal screening test,the accuracy rate of maternal serum homocysteine detected by enzymatic cycling method is73percent, the sensitivity is66percent, the specificity is73percent, the positive predict value is6percent, the negative is99percent, the positive likelihood ratio is2.4, the negative is0.47, andthe Youden index is39percent.CONCLUSIONS: The serum homocysteine decrease in early pregnancy, it will be at itslowest concentration at the second trimester, and gradually increase at the third trimester.Maternal hyperhomocysteinemia can affect the fetal growth and development, it’s a risk factorfor congenital malformation, FGR and premature delivery. We haven’t found that maternalhyperhomocysteinemia will increase the risk for spontaneous abortion and fetal death.It may bedefinded as hyperhomocysteinemia when the maternal Hcy concentration is above the75thpercentile (>7.53micromol/l at the first trimester,>7.21micromol/l at the second trimester,>8.32micromol/l at the third trimester).