First Trimester Maternal Homocysteine and Embryonic and Fetal Growth: The Rotterdam Periconception Cohort

Abstract

Homocysteine is a marker for derangements in one-carbon metabolism. Elevated homocysteine may represent a causal link between poor maternal nutrition and impaired embryonic and fetal development. We sought to investigate associations between reference range maternal homocysteine and embryonic and fetal growth. We enrolled 1060 singleton pregnancies (555 natural and 505 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies) from November 2010 to December 2020. Embryonic and fetal body and head growth was assessed throughout pregnancy using three-dimensional ultrasound scans and virtual reality techniques. Homocysteine was negatively associated with first trimester embryonic growth in the included population (crown-rump length B −0.023 mm, 95% CI −0.038,−0.007, p = 0.004, embryonic volume B −0.011 cm3, 95% CI −0.018,−0.004, p = 0.003). After stratification for conception mode, this association remained in IVF/ICSI pregnancies with frozen embryo transfer (crown-rump length B −0.051 mm, 95% CI −0.081,−0.023, p < 0.001, embryonic volume B −0.024 cm3, 95% CI −0.039,−0.009, p = 0.001), but not in IVF/ICSI pregnancies with fresh embryo transfer and natural pregnancies. Homocysteine was not associated with longitudinal measurements of head growth in first trimester, nor with second and third trimester fetal growth. Homocysteine in the highest quartile (7.3–14.9 µmol/L) as opposed to the lowest (2.5–5.2 µmol/L) was associated with reduced birth weight in natural pregnancies only (B −51.98 g, 95% CI −88.13,−15.84, p = 0.005). In conclusion, high maternal homocysteine within the reference range is negatively associated with first trimester embryonic growth and birth weight, and the effects of homocysteine are dependent on conception mode.

Biochemical Hazards during Three Phases of Assisted Reproductive Technology: Repercussions Associated with Epigenesis and Imprinting

“…It is now time to “seriously” reconsider the definition of human IVF media, [ 74 ], and the relevance of the MEA to human embryo culture. Concern regarding elevated circulating Hcy and its negative impact in conceptus quality and fertility have recently led the “Rotterdam periconception cohort” to recommend the “ routine analysis of homocysteine levels in preconceptional and pregnant women and their partners ” [ 75 ].…”

MTHFR SNPs (Methyl Tetrahydrofolate Reductase, Single Nucleotide Polymorphisms) C677T and A1298C Prevalence and Serum Homocysteine Levels in >2100 Hypofertile Caucasian Male Patients

“…Homocysteine also has a major negative impact as a cause and a consequence of oxidative stress [ 8 , 11 ], an important issue in infertility. The Rotterdam Periconception cohort has recently recommended “ routine analysis of homocysteine levels in preconceptional and pregnant women and their partners ” [ 41 ] in order to avoid the negative impact of homocysteine imbalance on gametogenesis and early embryo development. Therefore, both isoforms must be tested, although 1298AC appears to be of lesser interest.…”

Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping

“…S-adenosylmethionine (SAM) is a potent methyl donor within these cycles and serves as the principal substrate for methylation of DNA, associated proteins, and RNA. It was previously demonstrated in sheep, cattle, rodent and human studies that disrupting these cycles during early pregnancy, by either dietary means (i.e., reducing dietary vitamin B12, folate, choline and/or methionine), or through exposure to environmental chemicals such as cigarette smoking, can lead to epigenetic dysregulation and impaired foetal development with long-term consequences for offspring cardiometabolic health (22)(23)(24)(25). It was also advocated that interindividual and ethnic variability in epigenetic gene regulation arises because of single-nucleotide polymorphisms (SNPs) within 1C genes, associated epigenetic regulators, and differentially methylated target DNA sequences (15).…”