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

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Abstract

Homocysteine is a marker for derangements in one-carbon metabolism. Elevated ho-mocysteine 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 Novem-ber 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.

Original languageEnglish
Article number1129
JournalNutrients
Volume14
Issue number6
DOIs
Publication statusPublished - 3 Mar 2022

Bibliographical note

Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 812660. K.D.S. was in receipt of funding from the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/K017810/1).


Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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