Aim. To revisit the role of first trimester homocysteine levels with the maternal and fetal outcome. Methods. This was a cohort study comprising 100 antenatal women between 8 and 12 weeks of gestation. Serum homocysteine levels were checked after overnight fasting. Results. There were significantly elevated homocysteine levels among women with prior history of hypertensive disorders of pregnancy and prior second or third trimester pregnancy losses. There was no significant difference in homocysteine levels among women with previous gestational diabetes mellitus, preterm deliveries, or fetal malformations. Homocysteine levels were significantly elevated in those who developed hypertensive disorder of pregnancy, oligohydramnios, and meconium stained amniotic fluid, had a pregnancy loss, or delivered a low birth weight baby. There was no significant difference in homocysteine levels for those who developed gestational diabetes mellitus. Conclusions. Increased first trimester serum homocysteine is associated with history of pregnancy losses, hypertensive disorders of pregnancy, and preterm birth. This is also associated with hypertensive disorders of pregnancy, pregnancy loss, oligohydramnios, meconium stained amniotic fluid, and low birth weight in the current pregnancy. This trial is registered with ClinicalTrials.gov CTRI/2013/02/003441. 1. Introduction Homocysteine is an amino acid which has sprung into prominence in the past few decades [1]. Homocysteine is intricately linked to folate metabolism and one methyl transfer. Elevated homocysteine levels have been shown to be deleterious on vascular endothelium [1, 2]. Elevated homocysteine has also served as an early marker for insulin resistance due to the effects of insulin on homocysteine metabolism and renal clearance [3]. These relationships of homocysteine to disease states in the nonpregnant adult population have been extrapolated to link it to the pregnancy specific conditions of gestational diabetes mellitus and hypertensive disorders of pregnancy. Homocysteine levels decline during pregnancy [4], and the levels are the lowest during second trimester of pregnancy and increase in the second half of the third trimester of pregnancy. Hence, samples taken within strict time frame, such as 4 weeks (between 8 to 12 weeks of gestation), would have a better success at correlating the homocysteine levels with the pregnancy outcome, by minimising the gestational age bound variation of homocysteine. In addition, most maternal complications such as hypertensive disorders of pregnancy and gestational diabetes
References
[1]
T. Forges, P. Monnier-Barbarino, J. M. Alberto, R. M. Guéant-Rodriguez, J. L. Daval, and J. L. Guéant, “Impact of folate and homocysteine metabolism on human reproductive health,” Human Reproduction Update, vol. 13, no. 3, pp. 225–238, 2007.
[2]
M. S. Kramer, S. R. Kahn, R. Rozen et al., “Vasculopathic and thrombophilic risk factors for spontaneous preterm birth,” International Journal of Epidemiology, vol. 38, no. 3, pp. 715–723, 2009.
[3]
J. B. Meigs, P. F. Jacques, J. Selhub et al., “Fasting plasma homocysteine levels in the insulin resistance syndrome,” Diabetes Care, vol. 24, no. 8, pp. 1403–1410, 2001.
[4]
L. Dodds, D. B. Fell, K. C. Dooley et al., “Effect of homocysteine concentration in early pregnancy on gestational hypertensive disorders and other pregnancy outcomes,” Clinical Chemistry, vol. 54, no. 2, pp. 326–334, 2008.
[5]
A. M. Cotter, A. M. Molloy, J. M. Scott, and S. F. Daly, “Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe preeclampsia,” American Journal of Obstetrics and Gynecology, vol. 185, no. 4, pp. 781–785, 2001.
[6]
A. M. Cotter, A. M. Molloy, J. M. Scott, and S. F. Daly, “Elevated plasma homocysteine in early pregnancy: a risk factor for the development of nonsevere preeclampsia,” American Journal of Obstetrics and Gynecology, vol. 189, no. 2, pp. 391–394, 2003.
[7]
V. A. Holmes, J. M. W. Wallace, H. D. Alexander et al., “Homocysteine is lower in the third trimester of pregnancy in women with enhanced from continued folic acid supplementation,” Clinical Chemistry, vol. 51, no. 3, pp. 629–634, 2005.
[8]
Y. Yin, T. Zhang, Y. Dai, X. Zheng, L. Pei, and X. Lu, “Pilot study of association of anembryonic pregnancy with 55 elements in the urine, and serum level of folate, homocysteine and S-adenosylhomocysteine in Shanxi Province, China,” Journal of the American College of Nutrition, vol. 28, no. 1, pp. 50–55, 2009.
[9]
M. R. Guillén, L. T. Sánchez, and J. Chen, “Dietary consumption of B vitamins, maternal MTHFR polymorphisms and risk for spontaneous abortion,” Salud Pública de México, vol. 51, no. 1, pp. 19–25, 2009.
[10]
C. S. Yajnik, S. S. Deshpande, A. A. Jackson et al., “Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study,” Diabetologia, vol. 51, no. 1, pp. 29–38, 2008.
[11]
B. B. Hogg, T. Tamura, K. E. Johnston, M. B. DuBard, and R. L. Goldenberg, “Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction,” American Journal of Obstetrics and Gynecology, vol. 183, no. 4, pp. 805–809, 2000.
[12]
Homocysteine Analysis By ADVIA Centaur Automated System, Laboratory Manual of University of California, San Francisco, Calif, USA, 2005.
[13]
M. Das, M. Ghose, N. C. Borah, and N. Choudhury, “A community based study of the relationship between homocysteine and some of the life style factors,” Indian Journal of Clinical Biochemistry, vol. 25, no. 3, pp. 295–301, 2010.
[14]
Y. S. Han, E. H. Ha, H. S. Park, Y. J. Kim, and S. S. Lee, “Relationships between pregnancy outcomes, biochemical markers and pre-pregnancy body mass index,” International Journal of Obesity, vol. 35, no. 4, pp. 570–577, 2011.
[15]
M. M. Murphy, J. M. Scott, J. M. McPartlin, and J. D. Fernandez-Ballart, “The pregnancy-related decrease in fasting plasma homocysteine is not explained by folic acid supplementation, hemodilution, or a decrease in albumin in a longitudinal study,” American Journal of Clinical Nutrition, vol. 76, no. 3, pp. 614–619, 2002.
[16]
J. M. W. Wallace, M. P. Bonham, J. J. Strain et al., “Homocysteine concentration, related B vitamins, and betaine in pregnant women recruited to the Seychelles Child Development Study,” American Journal of Clinical Nutrition, vol. 87, no. 2, pp. 391–397, 2008.
[17]
M. D. Uva, P. D. Micco, I. Strina et al., “Hyperhomocysteinemia in women with unexplained sterility or recurrent early pregnancy loss from Southern Italy: a preliminary report,” Thrombosis Journal, vol. 5, article 10, 2007.
[18]
H. Refsum, E. Nurk, A. D. Smith et al., “The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease,” The Journal of Nutrition, vol. 136, no. 6, pp. 1731S–1740S, 2006.
[19]
J. Girouard, Y. Giguère, J.-M. Moutquin, and J.-C. Forest, “Previous hypertensive disease of pregnancy is associated with alterations of markers of insulin resistance,” Hypertension, vol. 49, no. 5, pp. 1056–1062, 2007.
[20]
M. Ingec, B. Borekci, and S. Kadanali, “Elevated plasma homocysteine concentrations in severe preeclampsia and eclampsia,” Tohoku Journal of Experimental Medicine, vol. 206, no. 3, pp. 225–231, 2005.
[21]
B. Idzior-Walu?, K. Cyganek, K. Sztefko et al., “Total plasma homocysteine correlates in women with gestational diabetes,” Archives of Gynecology and Obstetrics, vol. 278, no. 4, pp. 309–313, 2008.
[22]
E. Tarim, F. Yigit, E. Kilicdag et al., “Early onset of subclinical atherosclerosis in women with gestational diabetes mellitus,” Ultrasound in Obstetrics and Gynecology, vol. 27, no. 2, pp. 177–182, 2006.
[23]
L. Wang, F. Wang, J. Guan et al., “Relation between hypomethylation of long interspersed nucleotide elements and risk of neural tube defects,” American Journal of Clinical Nutrition, vol. 91, no. 5, pp. 1359–1367, 2010.
[24]
C. V. Ananth, D. A. Elsasser, W. L. Kinzler et al., “Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption,” Molecular Genetics and Metabolism, vol. 91, no. 1, pp. 104–110, 2007.
[25]
L. E. Mignini, P. M. Latthe, J. Villar, M. D. Kilby, G. Carroli, and K. S. Khan, “Mapping the theories of preeclampsia: the role of homocysteine,” Journal of Obstetrics and Gynecology, vol. 105, no. 2, pp. 411–425, 2005.
[26]
M. M. Murphy, J. M. Scott, V. Arija, A. M. Molloy, and J. D. Fernandez-Ballart, “Maternal homocysteine before conception and throughout pregnancy predicts fetal homocysteine and birth weight,” Clinical Chemistry, vol. 50, no. 8, pp. 1406–1412, 2004.
[27]
T. Jansson, “Novel mechanism causing restricted fetal growth: does maternal homocysteine impair placental amino acid transport?” Journal of Physiology, vol. 587, no. 17, p. 4123, 2009.
[28]
A. A. Fryer, R. D. Emes, K. M. K. Ismail et al., “Quantitative, high-resolution epigenetic profling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans,” Epigenetics, vol. 6, no. 1, pp. 86–94, 2011.