Prevention of Neural Tube Defects 2

Standards for Maternal and Prevention of Neonatal Care neural tube defects INTEGRATED MANAGEMENT OF PREGNANCY AND CHILDBIRTH (IMPAC)

The standard

All women, from the moment they begin trying to conceive until 12 weeks of gestation, should take a folic acid supplement. Women who ȱȱȱȱȱȱěȱ¢ȱȱȱȱȱǻǼȱȱ ȱȱȱȱȱ¢ȱ ȱȱȱȱȱȱȱ ȱȱǰȱȱȱȱȱȱěȱȱ1 ȱȱȱȱěȱȬȱǯ

Aim

ȱȱȱȱȱȱȱȱȱǯ

Requirements A national policy and locally adapted guidelines on folic acid supplementation are available and are correctly implemented. ȱ ȱȱȱȱȱȱ ȱǱȱȱȱȱȱȱę¢ǲȱ ȱęȱȱȱȱȱȱȱȱȱ¢ȱ ¢ǲȱȱȱǲȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱȱȱęȱȱȱ¢ǯ ȱ ȱȱȱȱȱěȱȱ ǯ A method to record the preventive treatment provided is in place. Health education activities are conducted to raise the awareness of women and of the community on the importance of taking folic acid supplements in the periconceptional period.

Applying the standard

Health providers in antenatal and family planning clinics must:

Advise women trying to conceive to take a dose of 400 μg folic acid daily, starting two Organization Health World months before the planned pregnancy. Advise women who have not been supplementing their diet and who suspect themselves to be pregnant to begin taking 400 μg folic acid daily and to continue until they are 12 weeks pregnant. ȱ ȱȱ ȱ ȱȱ¢ȱȱȱ¢ȱ ȱȱȱ ȱȱ diabetes or who are under anticonvulsant treatment about the increased risk of a future ¢ȱȱěǰȱȱȱȱȱȱśȱȱȱȱ¢ȱȱȱȱ food intake of folate. Record the treatment given in the maternal card.

ȱ ȱȱȱǰȱȱȱ ȱȱǰȱȱȱȱȱȱȱ 2006 woman’s record.

1 ȱ¢ȱȱȱȱęȱȱȱȱ¢ǯ Standards 1.5 Prevention of neural tube defects 2

Audit ȱ Policy and local guidelines on folic acid supplementation are available in clinics. ȱ ȱȱȱȱȱȱȱȱȱȱȱěȱȱȱȱ family planning clinics. ȱ ȱȱȱęȱȱȱȱȱȱȱȱȱ¢ȱȱȱ and family planning clinics.

ȱȱȱ ȱ ȱȱȱȱȱȱ ȱȱȱȱ ȱȱȱȱȱȱȱ ȱȦȱȱȱęȱŗŘȱ ȱȱ¢ǯ ȱ ȱȱȱ ȱȱȱȱȱȱȱȱȱ period.

ȱ Incidence of neural tube defects in the newborn.

Rationale

ȱȱě during the perinatal period reduced the risk ȱȱȱȱȱȱȱ of recurrence in women who had previously congenital malformations in neonates ȱȱȱ ȱȱ(3)ǯȱȱȱ worldwide (1)ǯȱ¢ȱȱȱ indicates that periconceptional folate heterogeneous group of disorders that occur supplementation reduces the incidence of ȱȱęȱ ȱȱǰȱȱ ȱȱȱȱȱ(2,4,5)ǯȱȱ ęȱȱȱȱȱȱȱȱ ȱȱȱȱęȱȱȱ derivatives (1,2)ǯȱȱȱȱȱȱ cases of defects. Owing to the heterogeneous the general population varies from 1 per 1000 ¢ȱȱǰȱ ǰȱȱȱȱȱ pregnancies in the USA to 12 per 1000 in parts eliminated by this intervention. of Ireland and Wales and among Indian Sikhs and certain ethnic groups in Egypt (1,2). Among other factors possibly associated with ȱȱȱȱȱȱȱ ȱ¡ȱȱȱȱȱȱ ǲȱ methylenetetrahydrofolate reductase gene ȱşśƖȱȱȱȱ ȱȱȱ ǻȱŜŝŝȱȱǼȱ(6), but it is not family history (1,2)ǯȱǰȱȱȱȱ ȱȱȱȱȱȱȱȱ ȱȱŗȱȱřřȱȱ ȱȱěȱ ěȱȱ ȱ ȱȱȱȱ pregnancy and 1 in 10 for those with two is reduced by a higher intake of folate ěȱȱ(1). Sisters of women (7). It is also unclear whether there is a ȱȱěȱȱȱȱŗȱȱŗŖŖȱȱȱ link between vitamin B12ȱę¢ȱȱ ȱȱȱȱ ȱȱěȱȱȱȱŗȱ ȱ(8), but any future supplementation in 300 risk (1)ǯȱȱȱȱ£ȱęȱ scheme could also include this vitamin (4,9). have been proposed as possible causes. Known Folate supplementation could be especially factors associated with higher risk include ȱȱ ȱȱȬ maternal diabetes, alcohol abuse by the depleting treatment, such as with antiepileptic mother, aminopterin ingestion and antenatal drugs (2,10)ǰȱǰȱ¡ǰȱ Ȭȱ(1). Suspected contributing ¡£ȱȱ¢ǰȱȱ factors are anticonvulsant therapy, maternal ȱȱȱȱȱȱȱęȱ ¢ǰȱȱ¡ȱȱȱ conclusion. and hallucinogen ingestion (2). Randomized trials, supported by many observational studies, indicate that Ĝ¢ȱȱě periconceptional use of folic acid in Folic acid supplementation before conception multivitamin supplements reduces the overall ȱȱȱęȱȱȱ¢ȱ ȱȱȱǰȱȱĞȱ¡ȱ is one of the few public health interventions ȱ(11)ǯȱȱȱȱȱȱ ěȱȱȱȱȱȱȱ(2–5). be due to a reduced risk of cardiovascular Controlled randomized clinical studies ȱǻȱȱřŚȬśŞƖȱȱěȱ showed that folic acid supplementation Ǽǰȱȱȱǻȱȱ Standards 1.5 Prevention of neural tube defects 3

řŖƖǼǰȱȱęȱǻȱȱŚŜȬŞŗƖǼǰȱ be information on changing the diet (7,14) ¢ȱȱǻȱŚŖȬŞřƖǼǰȱȱ ȱȱęȱ(5), although these onphalocele and imperforate anus. ȱȱȱȱěȱȱ increasing plasma folate levels owing to lower Folate supplementation has been associated bioavailability (5,7,14)ǯȱ ȱȱęȱȱ with a small increase in multiple gestation, but employed, it is recommended that a higher a recent systematic review does not support ȱȱȱǻřśŖȱΐȦŗŖŖȱȱǼȱȱȱ(15). ȱęȱ(3)ǯȱȱȱěȱȱȱ ȱȱȱȱĴǰȱȬȱ supplementation have been demonstrated, ęȱȱȱȱȱȱȱ either in the short or the long term (2,12). ęȬȬȱȱ(15). It is still unclear as to However, if an increase in multiple gestation is ȱȱȱȱȱ¢ȱȱ ęǰȱȱȱȱ¢ȱȱȱ ȱȱȱȱȱȱǯȱȱ ȱęȱȱȱǯȱȱ ȱȱ¢ȱȱȱȱęȱȱȱ ěȱȱȱǰȱȱȱ ȱȱ ȱȱȱęȱȱ developed and in less developed countries, ȱȱ ȱǲȱȱȱȱ¢ȱ depends on informing women of childbearing to the possibility of masking pernicious age and on the ability to plan a pregnancy anaemia in elderly patients who receive folate (13). Possible alternatives or complements supplementation (4). to giving folate supplements as pills could

ȱȱ ȱ£ȱȱȱȱȱȱȱǯȱȱȱȱȱȱ ȱȱȱ ȱ¢ȱ ȱȱȱȱȱŗȱǻȱǼȱȱŚȱǻ ȱǼǯȱȱȱȱ For details, see also the Introduction to the Standards for Maternal and Neonatal Care and the Process to develop the Standards for Maternal and Neonatal CareȱȱĴǱȦȦ ǯ ǯȦȏ¢ȏȦ publications/en. For an overview of a comprehensive list of evidence, please refer to the reference section of the standard.

Study ȱ (Type & Population & ȱǭȱ linked to the Results Comments ȱȱ Ĵ standard Ǽ 2. Lumley ŚȱǰȱŜŚŘśȱ ȱȱȱěȱ ȱ Folate + vitamin ȱȱȱ et al. 2004 of periconceptional supplement vs control folate alone vs Australia, Canada, increased consumption of a vitamins alone showed Most recent France, Hungary, – minimum ȱ ȱŜşŚȱǻśŝśȮŗŗşŖǼȱ folate or multivitamins on ȱȱȱȱ substantive Ireland, Israel, – ¡ ȱŗŞȱǻŗśȮřŖǼȱȱȱȱȱȱȱȱȱȱȱȱ ȱȱȱȱ is due to folate and not amendment United Kingdom, ŚȱǰȱŜŚŘŚȱ to vitamins April 2001 countries of the b former USSR Miscarriage řȱǰȱŝŜŖŖȱ ȱȱȱȱȱȱ ¢ȱ Baseline risk of ȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱ ȱȱȱŖǯřŜȱȱ ȱ Stillbirth 4 mg/day řȱǰȱŝŜŖŖȱ 1++ ȮȱȱŖǯŘƖȱ Ȯȱ¡ȱŝǯŞƖ Multiple gestation řȱǰȱŜŘŚŗȱ Şǯȱ¢ȱȱǭȱ ŗŝȱȬȱ ȱȱ Low level vs high level ȱȱȱȱȱ Blom 2003 studies were association between of serum vitamin B12 moderate association included, mean low maternal B12 and between low maternal ¢ȱ Odds ratio 0.9–13.3 ȱȱȱ sample size 33 cases increased risk of fetal ǻŖǯŚȮŜśǯśǼ vitamin B12 status and ȱȱȱȱǲȱ ȱȱ and 93 controls. studies ȱęȱȱ can be drawn 2++ a ȱȱȱȱȱȱȱȱȱȱȱbȱȬę

1. Cloherty JP, Stark A, Eichenwald E. Manual of neonatal care.ȱĴȱȱǭȱǰȱ ŗşşŞǯ 2. Lumley J et al. Periconception supplementation with folate and/or multivitamins to prevent ȱȱȱǻȱ Ǽǯȱ ǱȱThe Cochrane Library, Issue 4, 2001. Chichester, ȱ¢ȱǭȱǰȱŘŖŖŗǯ řǯȱ ȱȱȬȱǯȱȱ¢ȱȱĜ¢ȱȱȱȱ acid containing vitamin supplementation in prevention of open neural tube defects from India. Indian Journal of Medical ResearchǰȱŘŖŖŖǰȱŗŗŘǱŘŖŜȮŘŗŗǯ Standards 1.5 Prevention of neural tube defects 4

Śǯȱ ȱ ȱȱǯȱ¢ȱȱěȱȱȱǯȱLancetǰȱŘŖŖŗǰȱřśŞǱŘŖŜşȮŘŖŝřǯ śǯȱ ȱ ȱȱǯȱȱȱȱęȱȱ¢ȱȱȱȱȱ ¢ȱȱȱęȱȱȱȱǯȱTeratologyǰȱŘŖŖŘǰȱŜŜǱřřȮřşǯ Ŝǯȱ ȱȱȱǰȱȱ ǰȱȱ ǯȱ ȱȱȱŜŝŝ ȱȱȱȱ¢ ¢ȱȱȱȱȱȱȱȱȱǵȱȱȬ¢ǯȱQJM: An International Journal of MedicineǰȱŗşşŝǰȱşŖǱŗŗŗȮŗŗśǯ ŝǯȱ ęȬĴȱȱȱǯȱ¢¢ȱȱŜŝŝ ȱ¢ȱȱ ¢ȱȱȱȱȬȱȱȱȱ ȬȱȱȱǱȱȱ£ȱ controlled trial. American Journal of Clinical NutritionǰȱŘŖŖŘǰȱŝŜǱŗŞŖȮŗŞŜǯ

Şǯȱ ¢ȱ ǰȱȱ ǯȱȱ12ȱĜ¢ȱȱȱȱȱȱȱȱǯȱQJM: An International Journal of MedicineǰȱŘŖŖřǰȱşŜǱŘŞşȮŘşśǯ şǯȱ ȱȱȱǯȱěȱȱȱȱȱȱȱȱȱȱȱȬŗŘȱȱ plasma homocysteine concentrations in healthy, young women. American Journal of Clinical NutritionǰȱŗşşŞǰȱśǱŗŗŖŚȮŗŗŗŖǯ 10. Yerby MS. Management issues for women with epilepsy: neural tube defects and folic acid supplementation. NeurologyǰȱŘŖŖřǰȱŜŗǱŘřȮŘŜǯ 11. Czeizel AE. Periconceptional folic acid containing multivitamin supplementation. Eur J Obstet Gynecol Reprod BiolǯȱŗşşŞȱ ǲȱŝŞǻŘǼǱŗśŗȮŜŗǯ ŗŘǯȱ ȱǰȱ££ȱǯȱȬȱȱȱȱȱȱȱĞȱ periconceptional multivitamin supplementation. European Journal of PediatricsǰȱŗşşŞǰȱşǱŝŗşȮŝŘřǯ ŗřǯȱ ȱ ǯȱ¢ȱȱȱ¢ȱȱȱǯȱAmerican Journal of Obstetrics and GynecologyǰȱŗşşŚǰȱŗŝŖǱŗŚŞśȮŗŚŞşǯ ŗŚǯȱ ȱ ȱȱǯȱ¢ȱȱȱȱȱȱǱȱȱ£ǰȱȬ ȱȱȱȬȱȱȱȱěȱȱȱȱȱȱȱ homocysteine. American Journal of Clinical NutritionǰȱŘŖŖŘǰȱŝŜǱŝśŞȮŝŜśǯ ŗśǯȱ ȱȱȱǯȱȱȱęȱȱǱȱȱȱ¢ǯȱAmerican Journal of Public HealthǰȱŗşşśǰȱŞśǱŜŜŝȮŜŝŜǯ

ȱȱȱ I. ȱǯȱȱĞȱ. London, Royal College of Obstetricians and Gynaecologists, 1999. II. Pregnancy, childbirth, postpartum and newborn care: a guide for essential practice. Geneva, World ȱ£ǰȱŘŖŖřȱǻĴǱȦȦ ǯ ǯȦȦŘŖŖřȦşŘŚŗśşŖŞŚǯǰȱ ȱŝȱȱŘŖŖŚǼǯ

ȱȱ ȱȱȱȱȱȱȱĴȱȱ ȱȱȱȱȱȱ Ǳȱȱȱǰȱǰȱȱȱȱ ȱȱǲȱȱȱȱȱȱȱȱȱȱȱȱ is not a formal Standards for Maternal and Neonatal publication of ȱĴǰȱ ȱǰȱȱĴǰȱȱǰȱȱ ȱȱȱȱȱ ȱȱ¢ȱȱȱ ǻȱȱȱ¢ȱǼǯ the World Health ȱȱ¢ȱǰȱ Organization World Health Organization. ȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱ ǻ Ǽǰȱȱ ȱȱ ȱȱ¢ȱȱĴȱ ȱȱȱȱȱ all rights are For further information please ȱȱȱȱĴȱȱ ȱȱĜȱȱ ȱȱȱȱ reserved by the ȱȱ ǰȱŗŚȬŗŜȱȱŘŖŖŘǯȱȱȱȱȱȱȱȱ : Organization. ěȱȱȱȬȱǻȱȱǰȱĴȱǰȱ ȱ ǰȱ ȱȱȱ¢ȱ ȱȱ ȱĴǰȱȱȱȱȱǼȱȱȱȱȱȱȱ ȱǻǼ provided additional insightful review of the evidence section. We thank Bruno de Benoist may, however, be ȱ ȱ£ȱǻ Ǽ ȱ ȱęȱĞǰȱȱȱȱȱȱȱȱ ¢ȱȱȱ¢ǯ freely reviewed, 20 Avenue Appia abstracted, ŗŘŗŗȱ ȱŘŝ ȱ ȱȱȱȱȱȱŞŖȱȱȱ£ȱȱ reproduced and ȱęȱȱȱȱȱȱ ȱȱȱȱ ȱȱȱȱěȱ Switzerland translated, in part stages of its development. ǱȱƸŚŗȱŘŘȱŝşŗȱřřŝŗ or in whole, but ¡ǱȱƸŚŗȱŘŘȱŝşŗȱśŞśř ȱȱ ȱȱȱȱȱȱȱȱȱ¢ȱȱȱ not for sale nor for Email: [email protected] Governments of Australia, Italy and USA is gratefully acknowledged. In addition, WHO’s ȱȱȱ ȱǱȱ ǯ ǯȦȏ ȱ¢ȱȱȱȱȱȱȱ ȱȱǰȱ ǰȱ with commercial ǰȱ ¢ǰȱ ǰȱȱȱȱ ǰȱȱȱȱȱǰȱ ȱȱȱȱ ¢ȏȦȦȦ purposes. ȱȱȱęȱȱǯȱ