314. PREECLAMPSIA AND SMALL FOR GESTATIONAL AGE BABIES ARE ASSOCIATED WITH DEFECTS IN THE FOLATE-HOMOCYSTEINE METABOLIC PATHWAY

Abstract

The folate-homocysteine metabolic pathway plays a critical role in determining the availability of folate and methionine which are essential for placental and fetal development. Defects in this pathway can increase circulating homocysteine concentration and impair DNA synthesis. The purpose of this study was to investigate genetic polymorphisms involved in folate-homocysteine metabolism in association with preeclampsia (PE) and small for gestational age (SGA) babies. The Adelaide SCOPE (Screening for Pregnancy Outcomes) was a prospective study including 1169 nulliparous pregnant couples. Adelaide samples and patient information were collected by SCOPE research midwives. Genotyping was performed by Sequenom MassARRAY. Non-Caucasian couples were excluded from analyses. Pregnancy outcomes were strictly classified: PE (n = 71), SGA (n = 94) PE+SGA (n = 20), controls (n = 450). Chi Square and univariate with post-hoc analyses were performed. Women who developed PE and SGA had a mean BMI of 30.1 and 27.8 respectively, compared to women with healthy pregnancies 25.7 (P <0.001 and P = 0.002). Maternal and fetal MTHFD1 were associated with reduced customised birthweight centiles (P = 0.034 and P = 0.028 respectively). Paternal MTR 2756 genotype was associated with reduced customised birthweight centiles (P = 0.016) and with PE+SGA compared to healthy pregnancies P = 0.006. Neonatal MTR 2756 showed a similar trend with the G allele increased in PE+SGA P = 0.070. In addition, the paternal MTHFR 677 TT genotype was associated with PE+SG (P = 0.026). Variant polymorphisms within folate-homocysteine metabolism genes can slow enzyme activity increasing plasma homocysteine leading to maternal and placental vascular damage associated with both PE and SGA. This study builds on previous work in our laboratory that focused on maternal genotype and circulating factors shown to be associated with PE and SGA including serum folate, vitamin B12 and plasma homocysteine.