High dose folic acid in pregnancy may shorten infant telomere length, researchers say

By Olivia Brown

- Last updated on GMT


Related tags Folic acid Neural tube defects Pregnancy Nutrition Telomere length

A new study has observed a significant association between very high intakes of folic acid (FA) during pregnancy and shorter telomere lengths in children aged four.

The ‘Nutrients’ published report notes an association for those intaking ≥5000 μg/d of FA during pregnancy, with the correlation being more prevalent when they give birth to boys.

Telomeres, required for cell division, are structures made from DNA sequences and proteins found at the ends of chromosomes. The length of telomeres has been associated with many age-related disorders and mortality rates due to their role in protecting against DNA degradation.

The Spanish researchers stressed: “To our knowledge, few studies have investigated the association between maternal FAs during pregnancy and TL in children. The present study is the first to identify a negative association between a high dosage of FAs and TL in the periconceptional period and during the whole pregnancy.”

“This study suggests that high dosages of FAs in the first pregnancy period may be associated with a shorter TL in children at age four, particularly among boys,” they added.

Folate and pregnancy

Folate is an essential micronutrient for the diet which is known​ to play a vital role in DNA replication during cell synthesis and division. It has historically been studied for its role within DNA methylation and its ability to reduce risk of neural tube defects (NTDs) during pregnancy.

Following this, WHO​ recommends intakes of 400 µg per day from conception until week 12 of pregnancy to mitigate this NTD risk. Whilst present in an array of fruit, vegetables, and nuts, it is also frequently fortified into foods and supplements as its synthetic counterpart of FA due to its significant stability.

There have been concerns with regards to the potential effects of high dosages of FAs in mothers, with studies​ highlighting that supplementation with ≥1000 μg/d may negatively affect birth outcomes and cognition in later life. Previous research​ has also suggested that high FA dosages may influence telomere length in children.

Due to a lack of information on the effect of FA during pregnancy on telomere lengths in offspring, the researchers sought to further explore this potential relationship.


The study used the data from the INMA birth cohort study, which included 666 children with an average age of 4.4 and pregnant women from four regions of Spain. Information on intakes of FAs and various vitamins and minerals were obtained by interview-administered dietary questionnaires during three periods of pregnancy. Leucocyte telomere lengths were obtained using quantitative PCR techniques.

Average daily dosages of FAs were grouped into (i) <400 μg/d, (ii) ≥400 to 999 μg/d, (iii) ≥1000 to 4999 μg/d, and (iv) ≥5000 μg/d.

It was noted that during the first period of pregnancy, children whose mothers had higher intakes of FAs (≥5000 μg/d) showed significantly shorter TLs at age four, when compared children whose were mothers were in the reference group (<400 μg/d).

This association continued after mutually adjusting the first and second periods, whilst similar trends were observed for the whole pregnancy period. Furthermore, the association was found to be more prevalent in male children.


The researchers conclude that the findings suggest that high FA intakes during pregnancy may shorten offspring telomere lengths, a finding particularly prevalent in boys.

They hypothesise the potential mechanism of action: “The unmetabolised FA might disrupt the balance of DNA methylation within telomeres, leading to structural changes and functional alterations in these crucial genomic regions.”

The report urges for further studies to investigate over-consumption of this micronutrient including further countries to improve the validity and reliability of the findings.




Source: Nutrients


“Folic Acid Supplementation during Pregnancy and Its Association with Telomere Length in Children at Four Years: Results from the INMA Birth Cohort Study”

by Fanny Petermann-Rocha, Desirée Valera-Gran, Daniel Prieto-Botella, Dries S Martens, Sandra Gonzalez-Palacios, Isolina Riaño-Galán, Mario Murcia, Amaia Irizar, Jordi Julvez, Loreto Santa-Marina, Adonina Tardón, Jordi Sunyer, Jesús Vioque, Tim Nawrot and Eva-María Navarrete-Muñoz

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