Plasma Total Homocysteine, Pregnancy Complications, and Adverse Pregnancy Outcomes: The Hordaland Homocysteine Study

Abstract

An elevated circulating level of total homocysteine (tHcy) is a powerful and independent risk factor for vascular disease as well as an indicator of folate deficiency. Both infants with neural tube defects and their mothers have altered homocysteine metabolism, and numerous studies have pointed to a relation between plasma tHcy and both pregnancy complications and a compromised neonatal outcome. This analysis examined associations between tHcy and reproductive outcomes in 5883 women 40 to 42 years of age who were enrolled in the Hordaland Homocysteine Study conducted in Norway during 1992–1993. The findings were compared with those of 14,492 pregnancies in the same women during the years 1967–1996. Women with the highest tHcy levels smoked more than the others, drank more coffee, were less educated, and used fewer vitamin supplements. In addition, they tended to have their children at a younger age than women with lower tHcy values. Preeclampsia correlated with the tHcy level to a highly significant degree, particularly in women who delivered prematurely. Controlling for blood pressure weakened this association, but for pregnancies lasting less than 37 weeks, the odds ratio (OR) for preeclampsia in women with plasma tHcy in the upper quartile was 4.42. The risk of placental abruption was elevated in women with a high tHcy level (OR, 3.13), and elevations also correlated with premature deliveries before 37 weeks’ gestation and before 32 weeks’ gestation. Low birth weight correlated strongly with relatively high tHcy values. After 1970 the OR for very low birth weight (<1500 gm) in the upper compared with the lower tHcy quartile was 2.07. There also was a weaker association between tHcy and growth restriction. No significant relationship was apparent between tHcy and neonatal mortality or stillbirth (except for stillbirths during 1980–1996, when the adjusted OR was 2.03). For malformations, the strongest association (OR, 3.57) was for neural tube defects when the highest and lowest tHcy quartiles were compared. Congenital clubfoot also was significantly associated with tHcy. These findings, from a large-scale study, implicate an elevated level of tHcy as an important marker of pregnancy complications and negative outcomes. Prospective studies are certainly in order. Am J Clin Nutr 2000;71:962–968