Learning outcomes

After reading this article, pharmacists should be able to:

• Describe current Irish recommendations for folic acid use before and during pregnancy;
• Identify patients requiring high-dose folic acid;
• Recommend appropriate OTC folic acid products for standard-risk patients; and
• Counsel patients on timing, duration and common concerns about supplementation.

 

Introduction

Folic acid supplementation is a well-established intervention to reduce the risk of neural tube defects (NTDs). As neural tube closure occurs within the first 28 days of pregnancy, folic acid is most effective when started before conception. In practice, many women present to the pharmacy after pregnancy is confirmed, when the critical window has already passed. This highlights the importance of opportunistic counselling in the community pharmacy, particularly in women of childbearing age who may not yet be planning pregnancy. Pharmacists are frequently asked about dosing, timing, duration, and whether higher doses are needed. This article provides a practical overview of current recommendations, high-risk groups, and key issues in everyday practice.  

Background: Folate, folic acid and NTD prevention

Folate (vitamin B9) is essential for DNA synthesis, cell division and red blood cell production, making it particularly important during periods of rapid growth, such as early pregnancy. As it cannot be synthesised by the body, adequate intake must come from diet and supplementation. Folic acid, the synthetic form, is used to treat folate-deficiency anaemia, and reduce the risk of NTDs such as spina bifida and anencephaly. Supplementation and fortification have consistently been associated with lower rates of NTDs. In Ireland, NTD rates remain among the highest in Europe and in the absence of mandatory food fortification, prevention relies heavily on supplementation. However, supplementation uptake before conception remains inconsistent, particularly in unplanned pregnancies, and lower socioeconomic groups. Continuation through early pregnancy is not always optimal. For pharmacists, this highlights the importance of early advice, as waiting until the first antenatal visit is often too late for optimal NTD prevention.  

Current international recommendations

Across major guidelines, recommendations are broadly consistent. Standard-risk women should be advised to take 400 micrograms daily before conception and during early pregnancy.

Differences between guidelines mainly relate to when to start supplementation, how high-risk groups are defined, and whether high-dose folic acid is prescribed as 4mg or 5mg (see Table 1).

 

Table 1: Summary of international folic acid recommendations 

Organisation (jurisdiction)	Standard-risk dosing	High-risk dosing	Practical points and differences between guidelines
HSE (Ireland)	400 micrograms daily from at least 14 weeks preconception to 12 weeks’ gestation.	5mg daily.	Primary reference for Irish practice.
NICE (UK)	400 micrograms daily from at least three months preconception to 12 weeks’ gestation.	5mg daily in selected high-risk groups.	2025 update: BMI ≥25mg/m2 alone is not an indication for high dose.
WHO (Global)	400 micrograms daily from trying to conceive to three months gestation	5mg daily after previous NTD-affected pregnancy.	Emphasises the periconception period.
ACOG (USA)	400 micrograms daily for average-risk women from at least one month preconception to three months gestation. Total daily folic acid intake: 600 micrograms (200 micrograms from diet).	4mg daily from at least three months preconception to three months gestation.	High risk includes epilepsy and prior NTD. Use additional folic acid alone rather than extra prenatal vitamins if high dose is required, to avoid excessive vitamin A intake (teratogenicity risk).
USPSTF (USA)	400-800 micrograms daily for anyone planning or capable of pregnancy from at least one month preconception to two to three months’ gestation.	Not specified separately.	Applies to general, not very high-risk populations.

  Abbreviations: WHO — World Health Organisation; NICE — National Institute for Health and Care Excellence; HSE — Health Service Executive; ACOG — American College of Obstetricians and Gynaecologists; USPSTF — US Preventive Services Task Force.   In practice, the key message is:

• Recommend 400 micrograms daily for standard-risk women;
• Identify those who may require high-dose folic acid; and
• Refer where prescription supply is needed.

 

High-risk groups and high-dose folic acid

High-dose folic acid (5mg daily) is recommended by the HSE for women at increased risk of an NTD-affected pregnancy. This includes those with:

• A personal or family history of NTDs;
• A previous NTD-affected pregnancy;
• Pre-existing diabetes;
• Obesity;
• Epilepsy or use of antiseizure medications (ASMs);
• Use of medications that affect folate metabolism (for example, methotrexate).

In practice, community pharmacists should identify these patients and refer them for GP review and prescription supply. A key group encountered in practice are women with epilepsy. Many ASMs are associated with an increased risk of congenital malformations, including NTDs, so high-dose folic acid is typically recommended for these women before conception and in early pregnancy. Higher-risk ASMs include valproate, and topiramate, while enzyme-inducers such as carbamazepine may also affect folate levels. In practice, dosing and duration of folic acid may be individualised by neurologists or specialists, so pharmacists should clarify the intended regimen if uncertain.   In these patients, pharmacists should:

• Confirm the patient is under appropriate medical or specialist review;
• Refer those considering pregnancy for preconception planning and high-dose folic acid;
• Reinforce adherence to both the ASM therapy and folic acid;
• Check for duplication with OTC folic acid or prenatal products; and
• Avoid concurrent use of multiple multivitamins due to the risk of excess vitamin A intake.

 

Evolving issues in practice

 

Duration beyond 12 weeks

The main benefit of folic acid relates to the preconception period and first trimester. Many women continue supplementation throughout pregnancy, but evidence for additional NTD prevention benefit beyond 12 weeks is limited. High-dose folic acid (>1mg) taken long-term may also mask vitamin-B12 deficiency. In practice, review the ongoing need for high-dose folic acid in-line with specialist recommendations and check for duplication with prenatal supplements.  

Early initiation

Folic acid is most effective when started before conception. Starting after pregnancy is confirmed may be too late to fully prevent NTDs. In practice, offer advice not only to women planning pregnancy, but also to those who could become pregnant.  

Food fortification

Unlike the United States and Canada, Ireland does not have mandatory folic acid fortification of staple foods. Voluntary fortification of some foods does exist but does not reliably ensure adequate intake, so supplementation remains the primary prevention strategy. In practice, this increases the importance of pharmacist-led advice, even in women not actively planning pregnancy.  

High-dose folic acid and cancer risk

Recent studies have explored a possible association between high-dose folic acid (≥1mg daily) and cancer risk. A large Nordic cohort study reported a slightly higher rate of childhood cancer among children of mothers with epilepsy who were prescribed high-dose folic acid before or during pregnancy. However, the overall risk was low, with cancer occurring in approximately 1.4 per cent of children exposed to high-dose folic acid, compared with 0.6 per cent of those not exposed. The study was based on prescription data and could not fully account for actual folic acid intake, or other factors like epilepsy and ASM use, which may have influenced the findings. The authors later clarified that the results do not demonstrate a causal relationship and should not change clinical practice. Other studies in women taking high-dose folic acid have reported a small increase in overall cancer risk. However, this was reduced after further analysis, with only non-Hodgkin lymphoma remaining increased. These findings are also observational and do not establish causation.   In practice, guidance remains unchanged. High dose folic acid should continue to be used where clinically indicated. Pharmacists should remain up-to-date with emerging evidence and prepared to address patient concerns, emphasising that:

• The overall risk is low;
• A causal link has not been established;
• Folic acid remains effective in preventing NTDs; and
• Guidance may evolve as new information emerges.

 

Role of the pharmacist

 

Preconception advice

Community pharmacists are often the most accessible healthcare professionals for women of childbearing age. Advice can be given opportunistically during routine consultations.

 

Identifying high-risk patients

Pharmacists should identify women who may require high-dose folic acid (for example, diabetes, obesity, relevant history, or medications affecting folate metabolism) and refer for GP review.

OTC supplement selection

For standard-risk women, recommend 400 micrograms daily. Pharmacists should check product composition carefully, as many prenatal multivitamins already contain folic acid (typically 400 micrograms). Additional standalone folic acid may result in unnecessary duplication.

Dietary advice

Foods such as green leafy vegetables, legumes, citrus fruits, and fortified cereals contribute to folate intake, but diet alone is insufficient to meet pregnancy requirements. Women should be encouraged to eat a balanced diet, but supplementation remains necessary for those who may become pregnant.

Answering patient concerns

If folic acid is started after pregnancy is recognised, it should still be continued, as some benefits may remain.  For most women, supplementation is recommended until at least 12 weeks’ gestation, covering the critical period of neural tube development, although it is often continued as part of a prenatal supplement. High-dose folic acid should be used only where clinically indicated.

 

Conclusion

Folic acid remains a key preventative intervention in pregnancy. For community pharmacists, priorities include advising early use, recommending appropriate dosing, identifying high-risk patients, and addressing concerns clearly.

In Ireland, where fortification is not mandatory, routine pharmacy interactions represent an important opportunity for harm prevention.

References available on request.

 

  Key practice points for pharmacists

• Recommend 400 micrograms of folic acid daily for standard-risk women before conception and during early pregnancy;
• Ideally start folic acid at least 14 weeks before conception and continue through at least the first 12 weeks of pregnancy;
• High-dose folic acid is reserved for women at increased risk of an NTD-affected pregnancy;
• High-dose folic acid is prescription-only and should not be recommended routinely for low-risk women;
• Diet contributes to folate intake, but supplementation remains necessary;
• Current evidence does not support changes to practice due to cancer-risk concerns; and
• Routine consultations are an important opportunity to provide preconception advice.