Genetic and metabolic alterations in maternal and paternal one carbon metabolism and development of pregnancy complications of placental origin

Identifier:  TDX:3349

Handle: https://hdl.handle.net/20.500.11797/TDX3349

Authors:  Haro Barceló, Júlia

Abstract:
Placental-derived pregnancy complications including pregnancy induced hypertension (PIH) and intrauterine growth retardation (IUGR) put maternal and foetal health at risk. Suboptimal maternal folate and one carbon (1C) metabolic status and unhealthy lifestyle can lead to adverse pregnancy outcomes. The common MTHFR 677C>T and SLC19A1 80G>A polymorphisms are associated with poor folate status and elevated fasting plasma total homocysteine (tHcy). Paternal factors can contribute to impaired placentation, due to poor trophoblast invasion and remodelling of the uterine spiral arteries but are rarely considered. Data on lifestyle, clinical history and fasting blood samples were collected from 773 mother-neonate dyads and 414 mother- father- neonate triads from the Reus- Tarragona Birth Cohort. Plasma and red blood cell folate, tHcy and B12 status and MTHFR 677 C>T and SLC19A1 80G>A genotype associations with impaired placentation, PIH and IUGR were investigated. Maternal and paternal MTHFR 677C>T genotypes were not associated with IUGR and maternal genotype was not associated with impaired placentation. Elevated paternal tHcy was associated with fivefold greater probability of an IUGR-affected pregnancy and increased risk of impaired placentation [OR 95% (CI) 2.7 (1.2, 6.0)]. Compared to CC genotype, paternal MTHFR 677CT and TT genotypes were associated with impaired placentation [OR 95% (CI)]: 4.0 (1.3, 12.6) and 7.1 (1.6, 32.8) respectively. Mothers with the MTHFR 677TT compared to CC genotype were threefold more likely to develop PIH. Maternal and paternal tHcy concentrations and paternal genotype were not associated with increased risk of PIH. Maternal and paternal SLC19A1 80G>A genotypes were not associated with increased risk of any of the outcomes. In conclusion, fathers with elevated versus normal tHcy or the variant MTHFR 677T allele versus CC genotype were more likely to father pregnancies affected by impaired placentation and IUGR. Mothers with the MTHFR 677TT versus CC genotype were at increased risk of developing PIH.