Maternal folate, one-carbon metabolism and pregnancy outcomes

Tanja Jankovic-Karasoulos; Denise L Furness; Shalem Y Leemaqz; Gustaaf A Dekker; Luke E Grzeskowiak; Jessica A Grieger; Prabha H Andraweera; Dylan McCullough; Dale McAninch; Lesley M McCowan; Tina Bianco-Miotto; Claire T Roberts

doi:10.1111/mcn.13064

Maternal folate, one-carbon metabolism and pregnancy outcomes

Matern Child Nutr. 2021 Jan;17(1):e13064. doi: 10.1111/mcn.13064. Epub 2020 Jul 28.

Authors

Tanja Jankovic-Karasoulos^{1

2

3}, Denise L Furness^{1

2}, Shalem Y Leemaqz^{1

2

3}, Gustaaf A Dekker^{1

2

4}, Luke E Grzeskowiak^{1

2}, Jessica A Grieger^{1

2}, Prabha H Andraweera^{1

2}, Dylan McCullough^{1

2

3}, Dale McAninch^{1

2}, Lesley M McCowan⁵, Tina Bianco-Miotto^{1

6}, Claire T Roberts^{1

2

3}

Affiliations

¹ Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
² Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
³ College of Medical and Public Health, Flinders University, Bedford Park, South Australia, Australia.
⁴ Department of Obstetrics and Gynaecology, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.
⁵ Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
⁶ School of Agriculture Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, South Australia, Australia.

Abstract

Single nucleotide polymorphisms and pre- and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 μg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 μg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L^-1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.

Keywords: SNP; folate; folic acid; maternal diet; neonatal outcomes; one-carbon metabolism; pregnancy outcomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbon / metabolism*
Female
Folic Acid*
Homocysteine
Humans
Infant, Newborn
Maternal Nutritional Physiological Phenomena*
Pregnancy
Pregnancy Outcome*
Premature Birth
Uterine Artery

Substances

Homocysteine
Carbon
Folic Acid