Folic Acid: The established role of pre-conceptual folic acid and reduced risk of neural tube defects

Transcription

1 Folic Acid: The established role of pre-conceptual folic acid and reduced risk of neural tube defects Food Matters Live Seminar Programme Cradle to Grave: Mums, Babies and Toddlers Dr Michele Sadler Consultant Nutritionist Rank Nutrition Ltd, Ashford, Kent, UK

2 What are Neural Tube Defects? Congenital malformations in foetus that occur during structural development of neural tube which forms into brain and spinal cord Development and closure of the neural tube normally completed within days after conception often before pregnancy is confirmed NTDs are caused by failure of the neural tube to close properly

3 What are Neural Tube Defects? NTDs include spina bifida (cleft spine), anencephaly (cephalic end of neural tube fails to close) and encephalocoele (opening in 1+ vertebrae) Can lead to miscarriage, neonatal death, or lifelong disability Identification of affected pregnancies will often result in the decision to terminate the pregnancy

4 Well-established evidence: folic acid supplementation reduces risk of NTD Early trials: folic acid prior to conception and during 6-12 weeks pregnancy, significantly reduced risk of recurrence of NTDs e.g. Laurence et al 1981, 4mg folic acid; Smithells et al, 1983; 360mcg folic acid Definitive evidence provided in 1991 by a UK Medical Research Council (MRC) trial for recurrence; 4mg folic acid

5 Well-established evidence: folic acid supplementation reduces risk of NTD A trial in Hungary confirmed protective effect of 800mcg folic acid/day against a first occurrence of NTDs (Czeizel et al, 1994) Kirke et al, 1992; 360mcg folic acid & ICMR 2000 added to the evidence Cochrane systematic review (De Regil, 2010): consistent protective effect of daily folic acid supplementation (Risk Ratio (RR) 0.28, 95% CI 0.00 to 1.33)

6 Protective measure is straight forward Up to 70% of NTDs could be avoided through adequate folate status in women of childbearing age prior to conception A European Commission publication (2008): NTDs are one of the few rare diseases that could in many cases be prevented protective measure very straightforward - intake of folic acid supplements at appropriate time What is the appropriate time?

7 Timing of supplementation Concluded that 400mcg/day prior to and during first 12 weeks of pregnancy reduces the risk of NTD in the foetus TIMING: taken at least 1 month prior to pregnancy and for the first trimester

8 EU authorised disease risk reduction health claim As evidence well-established, UK food supplements industry applied for an EU DRR health claim DRR claims Article 14.1(a): Claims are for a risk factor of the associated disease As well as direct evidence for effect, evidence for beneficial effect of folic acid supplementation on risk factor was required

9 EU authorised DRR health claim for folic acid Identified as sub-optimal maternal folate status Two markers serum folate red blood cell (RBC) folate Both informative for incidence of NTD serum folate marker of early changes in folate status RBC folate marker of long-term folate status

10 Evidence for risk factor Data-set of >56,000 women attending a first antenatal clinic in Dublin hospitals from 1986 to 1990 Blood samples at median 15 weeks gestation Blood samples retrieved for 84 NTD cases (rate = 1.9/1000 live births) 266 controls from births without NTD in same hospital and during same period as cases

11 Evidence for risk factor >8-fold difference in risk observed between women with RBC folate levels less than 150ng/ml (risk of NTDs 6.6/1000 births) compared with women with RBC levels of 400ng/ml or above (lowest risk of NTDs 0.8/1000 births) (P<0.001) Demonstrated that RBC folate in early pregnancy is a marker of the risk of NTDs (Daly et al, 1995)

12 Intake to maintain folic acid status Further step determine folic acid intake to maintain optimal folate status Dose-finding intervention trial investigated dose response to different intakes of folic acid (Daly et al, 1997) 121 women with RBC folate concentration between 150 and 400ng/ml randomly assigned to placebo, 100, 200 or 400μg folic acid/day for 6 months 400μg folic acid/day was most protective intake Doubled RBC folate Raised above target 400ng/ml in compliant women

13 Intake to maintain folic acid status Other studies have added to evidence base Concluded that doubling of serum folate concentration halves risk of NTDs

14 Authorised wording of EU health claim Supplemental folic acid intake increases maternal folate status. Low maternal folate status is a risk factor in the development of neural tube defects in the developing foetus. Claim is for supplements only: evidence for supplements; best way to obtain effective intake as folate is present in few foods and vulnerable to storage & cooking losses Daily for at least 1 month before and up to 3 months after conception Target group defined as women of child-bearing age

15 Global recommendations for folic acid supplementation Taking a daily 400 g folic acid supplement prior to and during the early weeks of pregnancy is a global WHO recommendation (Standards for Maternal and Neonatal Care, 2006; WHO, 2012) Many EU member States give this advice

16 UK recommendations for folic acid supplementation UK Department of Health recommends that all women who could become pregnant take a daily supplement of 400μg folic acid prior to conception and during the first 12 weeks of pregnancy (DH, 1992) Measure expected to reduce NTD-affected pregnancies by 70%. If previous NTD pregnancy or family history of NTD: 5mg folic acid/ day prescribed as a medicine In addition to RNI for pregnancy ( μg folate/day) Advice to eat more foods naturally rich in folate and foods fortified with folic acid, especially breakfast cereals

17 Differences in recommendations Comparison guidelines in 20 European countries (including outside EU) - recommendations vary (Cawley et al, 2016) Discrepancies relate to: time period to start taking folic acid - from no specific timeline, to up-to 4 weeks prior to conception Target population - from women planning a pregnancy, to all women of child-bearing age or all women who might become pregnant Variations in the higher dose recommended for women with a previous NTD-affected pregnancy

18 Uptake of supplementation Large cross-sectional UK study, n=466,860 women attending antenatal screening between 1999 and 2012 for Downs syndrome and NTDs (Bestwick et al., 2014) Proportion of women taking folic acid supplements prior to pregnancy declined from 35% in to 31% in Only 6% of women aged under 20yr took folic acid supplements before pregnancy compared with 40% aged 35-39yr Health Survey for England 2002 (Blake et al., 2003) - only 43% of mothers in most SE deprived areas were likely to increase folate intake compared with 70% of mothers in least deprived areas Estimated that only 55% of pregnancies in Britain are planned

19 Mandatory fortification Mandatory folic acid fortification policies of grain products e.g. flour, to reduce NTD prevalence E.g. USA, Canada, Chile, South Africa, Argentina, Brazil, Costa Rica UK Scientific Advisory Committee on Nutrition (SACN) recommended mandatory fortification in 2006, reiterated in 2009 March 2016: UK currently has no plans to introduce mandatory fortification Scottish Ministers considering fortification; Food Standards Scotland asked SACN for an update July 2017: SACN s previous recommendation (2006 and 2009) for mandatory folic acid fortification to improve the folate status of women most at risk of NTD-affected pregnancies remains unchanged

20 Reinforcement of need for supplementaiton Even with mandatory folic acid fortification policies supplementation still required Supplementation recommendation endorsed by SACN in 2006 and 2009 remains unchanged: Current government advice for all women who could become pregnant is to take 400mcg/d of folic acid prior to conception and until the twelfth week of pregnancy. Women with a history of a previous NTD-affected pregnancy are advised to take 5mg/d of folic acid prior to conception and until the twelfth week of pregnancy

21 Evaluations of cost effectiveness of folic acid supplementation Review of economic evaluations of supplementation strategies (Sadler, 2017) Two studies evaluated cost-effectiveness of folic acid supplementation for protection against NTD Dalziel et al (2010): cost-effectiveness of general population campaign, targeted education campaign and clinician advice for Australia and New Zealand Postma et al (2002): cost-effectiveness of periconceptional supplementation with folic acid 4 weeks prior & 8 weeks after conception All approaches reported as cost effective

22 Cost effectiveness of other strategies to increase folate status Dalziel et al (2010) compared supplementation with other strategies to increase intake of folic acid to reduce NTD: mandatory and voluntary fortification and promoting a folate-rich diet Extending voluntary fortification was also cost effective mainly because of the low cost of implementation Mandatory fortification was not cost effective for New Zealand and results were uncertain for Australia, due to wide variation in estimates of costs Promoting a folate-rich diet was found to be the least cost effective approach, due to a lower impact on reducing NTD

23 Conclusions NTDs could in many cases be prevented Protective measure straightforward - intake of folic acid supplements at appropriate time 400mcg folic acid supplement/day prior to and during early weeks of pregnancy is a global WHO recommendation Supplementation required even with mandatory fortification Low % of target group take supplements Continual need to communicate the message EU health claim positive means of communication Cost effective measure

24 Thank you for listening! The book! Chapter 5 Authorised EU health claim for supplementary folic acid The review! A review of economic evaluations for beneficial health outcomes of micronutrient and long-chain omega-3 fatty acid supplementation. International Journal of Food Sciences and Nutrition, 23 rd August 2017 Dr Michèle Sadler BSc PhD RNutr ~ Nutrition Science Consultancy~ Director, Rank Nutrition Ltd Website: msadler@btconnect.com Twitter: Michele

25 Dr Michèle Sadler BSc PhD RNutr ~ Nutrition Science Consultancy~ Director, Rank Nutrition Ltd Website: msadler@btconnect.com Twitter: Michele