Maternal folate levels during pregnancy and offspring brain development in late childhood

Zou, Runyu; Marroun, Hanan El; Cecil, Charlotte A.M.; Jaddoe, Vincent W. V.; Hillegers, Manon H. J.; Tiemeier, Henning; White, Tonya

doi:10.1016/j.clnu.2020.11.025

Cited by 30 publications

(20 citation statements)

References 63 publications

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“…There is no clear evidence of any side-effects caused by excessive RBC folate during pregnancy; however, knowing that folate has critical roles in shaping the offspring epigenome, as evident in the well-known experiment on Agouti mouse coat colour [72], we must be conscious that exceeding recommended values may have underlying biological consequences still unknown. In agreement with such, folate deficiency (<7 nmol/L) was associated with a smaller brain volume during pregnancy [34][35][36]. With the exception of low-quality studies, there was no evidence of associations between maternal blood folate and neonatal head size at birth.…”

Section: Folatesupporting

confidence: 51%

“…The study by Takimoto et al (ErasmusAGE score 4) described that neonatal HC was negatively correlated with maternal vitamin B 6 during late pregnancy [31]. Ten studies examined the relationship between serum/plasma folate or red blood cell (RBC) folate concentrations and brain size, including one RCT [32], eight prospective cohort studies [33][34][35][36][37][38][39][40], and one cross-sectional study [41] (Table 1). Serum/plasma folate is indicative of recent folate intake, whereas RBC folate concentrations are useful to measure long-term folate status, as folate accumulates in RBCs during erythropoiesis and remains unvaried across the lifespan of the RBC (approximately 120 days) [42].…”

Section: Vitamin Bmentioning

confidence: 99%

“…Bergen et al reported no significant association between maternal folate and foetal HC in the second and third trimesters [40]. Zou et al found that brain volumes of foetuses from mothers with folate deficiency during early pregnancy were smaller in the third trimester when compared to brain volumes of foetuses from mothers without folate deficiency [35]. Nilsen et al reported no significant associations with neonatal HC [37].…”

Section: Vitamin Bmentioning

confidence: 99%

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Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

Rubini

Baijens

Horánszky

et al. 2021

Genes

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The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (> 17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (< 7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

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Section: Folatesupporting

confidence: 51%

Section: Vitamin Bmentioning

confidence: 99%

Section: Vitamin Bmentioning

confidence: 99%

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Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

Rubini

Baijens

Horánszky

et al. 2021

Genes

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show abstract

“…Low folate status is significantly associated with cognitive decline [ 87 ] and neural tube defects (NTDs) during gestation [ 88 ]. Low folate bioavailability is also associated with increased risk of spontaneous abortion and stillbirth [ 89 ].…”

Section: One Carbon Metabolism In Pregnancymentioning

confidence: 99%

Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies

Owen

Baker

Scott

et al. 2021

IJMS

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Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.

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“…Other observational studies found no direct association between low folate levels and pregnancy complications (16)(17)(18). To date, the role of folate intake to prevent NTD is veri ed (19,20). Most relevant studies adopted self-statement of multivitamin supplementation, which may be imprecise, so serum folate concentration during pregnancy would be more ideal.…”

Section: Introductionmentioning

confidence: 99%

Folate Deficiency in Early Pregnancy Increases the Risk of Low Birth Weight: Survey of Neonates in Eastern China

Chen

Ying

2021

Preprint

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Objective: Low birth weight (LBW) is a major cause of fetal mortality and morbidity. This study aims to assess the relationship between maternal serum folate levels and LBW in early pregnancy in eastern China. Methods: We conducted a retrospective study including 124 newborns with LBW (born≥1500g to <2500 g) and 393 normal birth weight neonates (NBW). The maternal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotyping was performed by the gene chip hybrid method. The concentrations of serum homocysteine (hcy), folate, vitamin B12 and vitamin D were measured before 18 weeks of pregnancy. Multivariable logistic regression model was used to identify the predictors of LBW. Results: After controlling the covariates, maternal underweight before pregnancy (AOR = 5.15: 95% CI 2.40, 11.05), folate deficiency in early pregnancy (AOR = 2.06: 95% CI 1.03, 4.09), preeclampsia during pregnancy (AOR = 6.02: 95% CI 2.83, 12.81), and premature delivery (AOR =23.81: 95% CI 12.90, 43.95) were risk factors for LBW. However, multipara (AOR = 0.53:95% CI 0.31, 0.91) was a protective factor for LBW. Conclusions: This study revealed different factors associated with LBW in eastern China. Sufficient folate before 18 weeks of pregnancy is a protective factor for LBW. Serum folate > 32.5 nmol/L can reduce the risk of LBW. Therefore, maternal screening of folate statue in the first trimester of pregnancy could be helpful.

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Maternal folate levels during pregnancy and offspring brain development in late childhood

Cited by 30 publications

References 63 publications

Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies

Folate Deficiency in Early Pregnancy Increases the Risk of Low Birth Weight: Survey of Neonates in Eastern China

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