Standards
Prevention of
neural tube defects
for Maternal and
Neonatal Care
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
‘ŠŸŽȱ‘ŠȱŠȱŽžœȱ’Š—˜œŽȱŠœȱŠěŽŒŽȱ‹¢ȱŠȱ—Žž›Š•ȱž‹ŽȱŽŽŒȱǻǼȱ˜›ȱ
‘ŠŸŽȱ’ŸŽ—ȱ‹’›‘ȱ˜ȱŠȱ‹Š‹¢ȱ ’‘ȱȱœ‘˜ž•ȱ›ŽŒŽ’ŸŽȱ’—˜›–Š’˜—ȱ˜—ȱ‘Žȱ
›’œ”ȱ˜ȱ›ŽŒž››Ž—ŒŽǰȱ‹ŽȱŠŸ’œŽȱ˜—ȱ‘Žȱ™›˜ŽŒ’ŸŽȱŽěŽŒȱ˜ȱ™Ž›’Œ˜—ŒŽ™’˜—Š•1
˜•ŠŽȱœž™™•Ž–Ž—Š’˜—ȱŠ—ȱ‹Žȱ˜ěŽ›Žȱ‘’‘Ȭ˜œŽȱœž™™•Ž–Ž—Š’˜—ǯ
Aim
˜ȱ™›ŽŸŽ—ȱœȱŠ—ȱ˜‘Ž›ȱŒ˜—Ž—’Š•ȱ–Š•˜›–Š’˜—œȱ’—ȱ‘ŽȱŽžœǯ
Requirements
A national policy and locally adapted guidelines on folic acid supplementation are
available and are correctly implemented.
ȱ ŽŠ•‘ȱ™›˜Ÿ’Ž›œȱŠ›ŽȱŒ˜–™ŽŽ—ȱ’—ȱ‘Žȱ˜••˜ ’—ȱŠ›ŽŠœDZȱ‘Žȱ›’œ”ȱ˜ȱ˜•’ŒȱŠŒ’ȱŽęŒ’Ž—Œ¢Dzȱ
‘Žȱ‹Ž—Žęœȱ˜ȱ˜•’ŒȱŠŒ’ȱœž™™•Ž–Ž—Š’˜—ȱ‹Ž˜›ŽȱŒ˜—ŒŽ™’˜—ȱŠ—ȱž›’—ȱŽŠ›•¢ȱ
™›Ž—Š—Œ¢DzȱŒ˜››ŽŒȱœž™™•Ž–Ž—ȱ˜œŠŽœDzȱŠ—ȱ‘Žȱ’–™˜›Š—ŒŽȱ˜ȱŠŸ’œ’—ȱ™›Ž—Š—ȱ
˜–Ž—ȱ˜ȱŠ”Žȱ˜•’ŒȱŠŒ’ȱ‹Ž˜›ŽȱŒ˜—ŒŽ™’˜—ȱŠ—ȱž›’—ȱ‘Žȱꛜȱ›’–ŽœŽ›ȱ˜ȱ™›Ž—Š—Œ¢ǯ
ȱ ˜•’ŒȱŠŒ’ȱ’œȱŠŸŠ’•Š‹•ŽȱŠ—ȱŠě˜›Š‹•Žȱ˜ȱ ˜–Ž—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 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 ˜ž—œŽ•ȱ™›Ž—Š—ȱ ˜–Ž—ȱ ‘˜ȱ‘ŠŸŽȱ™›ŽŸ’˜žœ•¢ȱ‘ŠȱŠȱ‹Š‹¢ȱ ’‘ȱȱ˜›ȱ ‘˜ȱ‘ŠŸŽȱ
diabetes or who are under anticonvulsant treatment about the increased risk of a future
‹Š‹¢ȱ‹Ž’—ȱŠěŽŒŽǰȱŠ—ȱŠŸ’œŽȱ‘Ž–ȱ˜ȱŠ”Žȱśȱ–ȱ˜•’ŒȱŠŒ’ȱŠ’•¢ȱŠ—ȱ’—Œ›ŽŠœŽȱ‘Ž’›ȱ
food intake of folate.
Record the treatment given in the maternal card.
1
Ž˜›Žȱ™›Ž—Š—Œ¢ȱŠ—ȱ’—ȱ‘Žȱꛜȱ‘›ŽŽȱ–˜—‘œȱ˜ȱ™›Ž—Š—Œ¢ǯ
2006
ȱ ŽŒ˜›ȱŒŠœŽœȱ˜ȱǰȱ’—ȱŠŒŒ˜›Š—ŒŽȱ ’‘ȱ•˜ŒŠ•ȱž’Ž•’—Žœǰȱ’—ȱ‘Žȱ•˜‹˜˜”ȱŠ—ȱ’—ȱ‘Žȱ
woman’s record.
World Health Organization
Advise women trying to conceive to take a dose of 400 μg folic acid daily, starting two
months before the planned pregnancy.
Standards
1.5
Preve nt i o n o f n e u ra l t u b e d e fe c t s
2
Audit
—™žȱ’—’ŒŠ˜›œ
Policy and local guidelines on folic acid supplementation are available in clinics.
ȱ ›Š’—’—ȱ˜—ȱ˜•’ŒȱŠŒ’ȱœž™™•Ž–Ž—Š’˜—ȱŠ—ȱœȱ’œȱ™›˜Ÿ’Žȱ˜ȱ‘ŽŠ•‘ȱœŠěȱ˜ȱŠ—Ž—ŠŠ•ȱŠ—ȱ
family planning clinics.
ȱ —˜›–Š’˜—ȱ˜—ȱ‘Žȱ‹Ž—Žęœȱ˜ȱ’—Œ›ŽŠœ’—ȱ˜•’ŒȱŠŒ’ȱ’—Š”Žȱ’œȱŠŸŠ’•Š‹•ŽȱŠ—ȱ’œ™•Š¢Žȱ’—ȱŠ—Ž—ŠŠ•ȱ
and family planning clinics.
›˜ŒŽœœȱŠ—ȱ˜ž™žȱ’—’ŒŠ˜›œ
ȱ ‘Žȱ™›˜™˜›’˜—ȱ˜ȱȱŒŠ›œȱ›Ž™˜›’—ȱ ‘Ž‘Ž›ȱ˜›ȱ—˜ȱŠȱ ˜–Š—ȱ‘ŠœȱŠ”Ž—ȱ˜•’ŒȱŠŒ’ȱ™›’˜›ȱ˜ȱ
Œ˜—ŒŽ™’˜—ȱŠ—Ȧ˜›ȱž›’—ȱ‘ŽȱꛜȱŗŘȱ ŽŽ”œȱ˜ȱ™›Ž—Š—Œ¢ǯ
ȱ ‘Žȱ™›˜™˜›’˜—ȱ˜ȱ ˜–Ž—ȱ›Ž™˜›’—ȱŠ”’—ȱ˜•’ŒȱŠŒ’ȱœž™™•Ž–Ž—œȱž›’—ȱ‘Žȱ™Ž›’Œ˜—ŒŽ™’˜—Š•ȱ
period.
žŒ˜–Žȱ’—’ŒŠ˜›œ
Incidence of neural tube defects in the newborn.
Rationale
ž›Ž—ȱ˜ȱœžěŽ›’—
œȱ›Ž™›ŽœŽ—ȱ˜—Žȱ˜ȱ‘Žȱ–˜œȱŒ˜––˜—ȱ
congenital malformations in neonates
worldwide (1)ǯȱ‘Ž¢ȱŒ˜—œ’žŽȱŠȱ
heterogeneous group of disorders that occur
ž›’—ȱ‘Žȱꛜȱ ŽŽ”œȱ˜ȱŽœŠ’˜—ǰȱ’—Ÿ˜•Ÿ’—ȱ
œ™ŽŒ’ęŒȱŽ•Ž–Ž—œȱ˜ȱ‘Žȱ—Žž›Š•ȱž‹ŽȱŠ—ȱ’œȱ
derivatives (1,2)ǯȱ‘Žȱ’—Œ’Ž—ŒŽȱ˜ȱœȱ’—ȱ
the general population varies from 1 per 1000
pregnancies in the USA to 12 per 1000 in parts
of Ireland and Wales and among Indian Sikhs
and certain ethnic groups in Egypt (1,2).
‘ŽȱŽ¡ŠŒȱŒŠžœŽȱ˜ȱœȱ’œȱ—˜ȱ”—˜ —Dzȱ
˜ŸŽ›ȱşśƖȱ˜ŒŒž›ȱ’—ȱŒ˜ž™•Žœȱ ’‘ȱŠȱ—ŽŠ’ŸŽȱ
family history (1,2)ǯȱŽŸŽ›‘Ž•Žœœǰȱ‘Žȱ›’œ”ȱ˜ȱ
›ŽŒž››Ž—ŒŽȱ’œȱŗȱ’—ȱřřȱŒ˜ž™•Žœȱ ’‘ȱ˜—ŽȱŠěŽŒŽȱ
pregnancy and 1 in 10 for those with two
ŠěŽŒŽȱ™›Ž—Š—Œ’Žœȱ(1). Sisters of women
’‘ȱŠ—ȱŠěŽŒŽȱŒ‘’•ȱ‘ŠŸŽȱŠȱŗȱ’—ȱŗŖŖȱ›’œ”ȱŠ—ȱ
œ’œŽ›œȱ˜ȱŠȱ–Š—ȱ ’‘ȱŠ—ȱŠěŽŒŽȱŒ‘’•ȱ‘ŠŸŽȱŠȱŗȱ
in 300 risk (1)ǯȱ˜•’ŒȱŠŒ’ȱŠ—ȱ£’—ŒȱŽęŒ’Ž—Œ’Žœȱ
have been proposed as possible causes. Known
factors associated with higher risk include
maternal diabetes, alcohol abuse by the
mother, aminopterin ingestion and antenatal
Ȭ’››Š’Š’˜—ȱ(1). Suspected contributing
factors are anticonvulsant therapy, maternal
‘¢™Ž›‘Ž›–’ŠǰȱŠ—Ž—ŠŠ•ȱŽ¡™˜œž›Žȱ˜ȱ›ž‹Ž••Šȱ
and hallucinogen ingestion (2).
ĜŒŠŒ¢ȱŠ—ȱŽěŽŒ’ŸŽ—Žœœ
Folic acid supplementation before conception
Š—ȱž›’—ȱ‘Žȱꛜȱ›’–ŽœŽ›ȱ˜ȱ™›Ž—Š—Œ¢ȱ
is one of the few public health interventions
ŽěŽŒ’ŸŽȱ’—ȱ›ŽžŒ’—ȱ‘Žȱ›’œ”ȱ˜ȱœȱ(2–5).
Controlled randomized clinical studies
showed that folic acid supplementation
during the perinatal period reduced the risk
of recurrence in women who had previously
‹˜›—ŽȱŠȱŒ‘’•ȱ ’‘ȱœȱ(3)ǯȱ‘ŽȱŽŸ’Ž—ŒŽȱ
indicates that periconceptional folate
supplementation reduces the incidence of
œȱ’—ȱ‘ŽȱŽ—Ž›Š•ȱ™˜™ž•Š’˜—ȱ(2,4,5)ǯȱ‘Žȱ
›ŽžŒ’˜—ȱ’œȱœ’–’•Š›ȱ˜›ȱꛜȱŠ—ȱ›ŽŒž››Ž—ȱ
cases of defects. Owing to the heterogeneous
Ž’˜•˜¢ȱ˜ȱœǰȱ‘˜ ŽŸŽ›ǰȱ‘Žȱ›’œ”ȱŒŠ——˜ȱ‹Žȱ
eliminated by this intervention.
Among other factors possibly associated with
œȱ’œȱŠȱŽ—Ž’Œȱ–žŠ’˜—ȱ’—Ÿ˜•Ÿ’—ȱ‘Žȱ
methylenetetrahydrofolate reductase gene
ǻ‘ŽȱŜŝŝȱŠ••Ž•’ŒȱŸŠ›’Š—Ǽȱ(6), but it is not
Œ•ŽŠ›ȱ’ȱ‘Žȱ˜ŒŒž››Ž—ŒŽȱ˜ȱœȱŠ–˜—ȱ‘Žȱ
˜ěœ™›’—ȱ˜ȱ ˜–Ž—ȱ ’‘ȱœžŒ‘ȱŠȱ–žŠ’˜—ȱ
is reduced by a higher intake of folate
(7). It is also unclear whether there is a
link between vitamin B12ȱŽęŒ’Ž—Œ¢ȱŠ—ȱ
œȱ(8), but any future supplementation
scheme could also include this vitamin (4,9).
Folate supplementation could be especially
’–™˜›Š—ȱ’—ȱ ˜–Ž—ȱž—Ž›˜’—ȱ˜•ŠŽȬ
depleting treatment, such as with antiepileptic
drugs (2,10)ǰȱŠ–’—˜™Ž›’—ǰȱ–Ž‘˜›Ž¡ŠŽǰȱ
œž•Š–Ž‘˜¡Š£˜•Žȱ˜›ȱ™¢›’–Ž‘Š–’—Žǰȱ‹žȱ
ž›‘Ž›ȱ›ŽœŽŠ›Œ‘ȱ’œȱ—ŽŽŽȱ˜ȱ›ŽŠŒ‘ȱŠȱꛖȱ
conclusion.
Randomized trials, supported by many
observational studies, indicate that
periconceptional use of folic acid in
multivitamin supplements reduces the overall
›’œ”ȱ˜ȱ‹’›‘ȱŽŽŒœǰȱŽŸŽ—ȱŠĞŽ›ȱŽ¡Œ•ž’—ȱ
œȱ(11)ǯȱ‘’œȱ˜ŸŽ›Š••ȱ›ŽžŒ’˜—ȱœŽŽ–œȱ˜ȱ
be due to a reduced risk of cardiovascular
Š—˜–Š•’Žœȱǻ›ŽžŒ’˜—ȱ˜ȱřŚȬśŞƖȱ’—ȱ’쎛Ž—ȱ
œž’ŽœǼǰȱ˜›˜ŠŒ’Š•ȱŽŽŒœȱǻ›ŽžŒ’˜—ȱ˜ȱ
Standards
1.5
Preve nt i o n o f n e u ra l t u b e d e fe c t s
řŖƖǼǰȱ•’–‹ȱŽęŒ’Ž—Œ’Žœȱǻ›ŽžŒ’˜—ȱ˜ȱŚŜȬŞŗƖǼǰȱ
ž›’—Š›¢ȱŽŽŒœȱǻ›ŽžŒ’˜—ȱŚŖȬŞřƖǼǰȱŠ—ȱ
onphalocele and imperforate anus.
Folate supplementation has been associated
with a small increase in multiple gestation, but
a recent systematic review does not support
‘’œȱꗍ’—ȱ(3)ǯȱ˜ȱ‘Š›–ž•ȱŽěŽŒœȱ˜ȱ˜•ŠŽȱ
supplementation have been demonstrated,
either in the short or the long term (2,12).
However, if an increase in multiple gestation is
Œ˜—ę›–Žǰȱ’ȱ–’‘ȱ‹Žȱ—ŽŒŽœœŠ›¢ȱ˜ȱ›ŽŒ˜—œ’Ž›ȱ
‘Žȱ‹Ž—Žęœȱ˜ȱ˜•ŠŽȱœž™™•Ž–Ž—Š’˜—ǯȱ‘Žȱ
ŽěŽŒ’ŸŽ—Žœœȱ˜ȱ‘Žȱ’—Ž›ŸŽ—’˜—ǰȱ‹˜‘ȱ’—ȱ
developed and in less developed countries,
depends on informing women of childbearing
age and on the ability to plan a pregnancy
(13). Possible alternatives or complements
to giving folate supplements as pills could
3
be information on changing the diet (7,14)
Š—ȱ˜˜ȱ˜›’ęŒŠ’˜—ȱ(5), although these
’—Ž›ŸŽ—’˜—œȱŠ•˜—ŽȱŠ›Žȱ•ŽœœȱŽěŽŒ’ŸŽȱ’—ȱ
increasing plasma folate levels owing to lower
bioavailability (5,7,14)ǯȱȱ˜˜ȱ˜›’ęŒŠ’˜—ȱ’œȱ
employed, it is recommended that a higher
•ŽŸŽ•ȱ˜ȱ˜•ŠŽȱǻřśŖȱΐȦŗŖŖȱȱ˜˜Ǽȱ‹ŽȱžœŽȱ(15).
—ȱ‘Žȱ˜›‘ȱ–Ž›’ŒŠ—ȱœŽĴ’—ǰȱ‘’‘Ȭ˜œŠŽȱ
˜›’ęŒŠ’˜—ȱ’œȱŒ˜—œ’Ž›Žȱ˜ȱ‘ŠŸŽȱŠȱ‘’‘ȱ
‹Ž—ŽęȬ˜ȬŒ˜œȱ›Š’˜ȱ(15). It is still unclear as to
‘Ž‘Ž›ȱœȱŒŠ—ȱ‹Žȱ™›ŽŸŽ—Žȱ‹¢ȱ’—Œ›ŽŠœ’—ȱ
‘ŽȱŒ˜—œž–™’˜—ȱ˜ȱ˜˜œȱ›’Œ‘ȱ’—ȱ˜•ŠŽœǯȱ‘Ž›Žȱ
’œȱŠ•œ˜ȱž—ŒŽ›Š’—¢ȱŠœȱ˜ȱ‘Žȱ‹Ž—ŽęœȱŠ—ȱ›’œ”œȱ
˜›ȱ‘Žȱ ‘˜•Žȱ™˜™ž•Š’˜—ȱ›˜–ȱ˜›’ęŒŠ’˜—ȱ˜ȱ
‹Šœ’Œȱ˜˜œȱ ’‘ȱ˜•ŠŽDzȱ‘’œȱ’œȱ•’—”Žȱ–Š’—•¢ȱ
to the possibility of masking pernicious
anaemia in elderly patients who receive folate
supplementation (4).
‘ŽȱŠ‹•Žȱ‹Ž•˜ ȱœž––Š›’£Žœȱ‘ŽȱŽŸ’Ž—ŒŽȱ›˜–ȱ‘Žȱ–˜œȱ›Ž•ŽŸŠ—ȱœž’Žœǯȱ‘Žȱ•ŽŸŽ•ȱ˜ȱŽŸ’Ž—ŒŽȱ’œȱ
™›ŽœŽ—Žȱžœ’—ȱ‘Žȱȱ–Ž‘˜˜•˜¢ȱ ‘’Œ‘ȱŠ™™•’ŽœȱŠȱŒ˜’—ȱ›˜–ȱŗȱǻ‘’‘ȱ•ŽŸŽ•Ǽȱ˜ȱŚȱǻ•˜ ȱ•ŽŸŽ•Ǽǯȱȱȱȱ
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 Careȱ˜—ȱ‘Ĵ™DZȦȦ ǯ ‘˜ǯ’—Ȧ–Š”’—ȏ™›Ž—Š—Œ¢ȏœŠŽ›Ȧ
publications/en. For an overview of a comprehensive list of evidence, please refer to the reference
section of the standard.
Study
(Type &
ŽŸŽ•ȱ˜ȱ
ŽŸ’Ž—ŒŽǼ
2. Lumley
et al. 2004
Most recent
substantive
amendment
April 2001
¢œŽ–Š’Œȱ
›ŽŸ’Ž ȱ
1++
ŞǯȱŠ¢ȱȱǭȱ
Blom 2003
¢œŽ–Š’Œȱ
›ŽŸ’Ž ȱȱ˜ȱ
ŒŠœŽȱŒ˜—›˜•ȱ
studies
Population &
ŽĴ’—
‹“ŽŒ’ŸŽȱǭȱ—Ž›ŸŽ—’˜—
Śȱ›’Š•œǰȱŜŚŘśȱ ˜–Ž—
Australia, Canada,
France, Hungary,
Ireland, Israel,
United Kingdom,
countries of the
former USSR
Baseline risk of
ȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱ
Ȯȱ–’—’–ž–ȱŖǯŘƖȱ
Ȯȱ–Š¡’–ž–ȱŝǯŞƖ
ŗŝȱŒŠœŽȬŒ˜—›˜•ȱ
studies were
included, mean
sample size 33 cases
and 93 controls.
˜ȱŠœœŽœœȱ‘ŽȱŽěŽŒœȱ
of periconceptional
increased consumption of
folate or multivitamins on
‘Žȱ™›ŽŸŠ•Ž—ŒŽȱ˜ȱȱ
žŒ˜–Žœȱ
linked to the
standard
Results
Comments
ȱ’—Œ’Ž—ŒŽ
Folate + vitamin
supplement vs control
– minimum
– –Š¡’–ž–
ȱ ȱŜşŚȱǻśŝśȮŗŗşŖǼȱ
ȱŗŞȱǻŗśȮřŖǼȱȱȱȱȱȱȱȱȱȱȱȱ
Śȱœž’ŽœǰȱŜŚŘŚȱ ˜–Ž—
˜ȱ›’Š•œȱŒ˜–™Š›’—ȱ
folate alone vs
vitamins alone showed
‘Šȱ›ŽžŒ’˜—ȱ’—ȱȱ
is due to folate and not
to vitamins
a
b
Miscarriage
‘Žȱ˜œŽȱ˜ȱ˜•ŠŽȱ’—ȱ‘Žȱ
›’Š•œȱ›Š—Žȱ›˜–ȱŖǯřŜȱ˜ȱ
4 mg/day
˜ȱ’—ŸŽœ’ŠŽȱ‘Ž
association between
low maternal B12 and
increased risk of fetal
2++
řȱœž’ŽœǰȱŝŜŖŖȱ ˜–Ž—
Stillbirth
řȱœž’ŽœǰȱŝŜŖŖȱ ˜–Ž—
Multiple
gestation
řȱœž’ŽœǰȱŜŘŚŗȱ ˜–Ž—
Low level vs high level
of serum vitamin B12
Odds ratio 0.9–13.3
ǻŖǯŚȮŜśǯśǼ
‘Ž›ŽȱœŽŽ–œȱ˜ȱ‹ŽȱŠȱ
moderate association
between low maternal
vitamin B12 status and
‘Žȱ›’œ”ȱ˜ȱŽŠ•ȱœDzȱ
—˜ȱꗊ•ȱŒ˜—Œ•žœ’˜—œȱ
can be drawn
a
ȱž–‹Ž›ȱ—ŽŽŽȱ˜ȱ›ŽŠȱȱȱȱȱȱȱbȱ˜—Ȭœ’—’ęŒŠ—
ŽŽ›Ž—ŒŽœ
1.
Cloherty JP, Stark A, Eichenwald E. Manual of neonatal care.ȱ’™™’—Œ˜Ĵȱ’••’Š–œȱǭȱ’•”’—œǰȱ
ŗşşŞǯ
2.
Lumley J et al. Periconception supplementation with folate and/or multivitamins to prevent
—Žž›Š•ȱž‹ŽȱŽŽŒœȱǻ˜Œ‘›Š—ŽȱŽŸ’Ž Ǽǯȱ—DZȱThe Cochrane Library, Issue 4, 2001. Chichester,
˜‘—ȱ’•Ž¢ȱǭȱ˜—œǰȱŘŖŖŗǯ
řǯȱ Ž—›Š•ȱŽŒ‘—’ŒŠ•ȱ˜Ȭ˜›’—Š’—ȱ—’ǯȱž•’ŒŽ—›’Œȱœž¢ȱ˜ȱŽĜŒŠŒ¢ȱ˜ȱ™Ž›’Œ˜—ŒŽ™’˜—Š•ȱ˜•’Œȱ
acid containing vitamin supplementation in prevention of open neural tube defects from
India. Indian Journal of Medical ResearchǰȱŘŖŖŖǰȱŗŗŘDZŘŖŜȮŘŗŗǯ
Standards
1.5
Preve nt i o n o f n e u ra l t u b e d e fe c t s
4
Śǯȱ Š•ȱȱŽȱŠ•ǯȱžŠ—’¢’—ȱ‘ŽȱŽěŽŒȱ˜ȱ˜•’ŒȱŠŒ’ǯȱLancetǰȱŘŖŖŗǰȱřśŞDZŘŖŜşȮŘŖŝřǯ
śǯȱ ’••’Š–œȱȱŽȱŠ•ǯȱ›ŽŸŠ•Ž—ŒŽȱ˜ȱœ™’—Šȱ‹’ꍩȱŠ—ȱŠ—Ž—ŒŽ™‘Š•¢ȱž›’—ȱ‘Žȱ›Š—œ’’˜—ȱ˜ȱ
–Š—Š˜›¢ȱ˜•’ŒȱŠŒ’ȱ˜›’ęŒŠ’˜—ȱ’—ȱ‘Žȱ—’ŽȱŠŽœǯȱTeratologyǰȱŘŖŖŘǰȱŜŜDZřřȮřşǯ
Ŝǯȱ ŸŠ—ȱŽ›ȱžȱǰȱœ”Žœȱǰȱ•˜–ȱ
ǯȱœȱ‘ŽȱŒ˜––˜—ȱŜŝŝ ȱ–žŠ’˜—ȱ’—ȱ‘Žȱ–Ž‘¢•Ž—ŽŽ›
Š‘¢›˜˜•ŠŽȱ›ŽžŒŠœŽȱŽ—ŽȱŠȱ›’œ”ȱŠŒ˜›ȱ˜›ȱ—Žž›Š•ȱž‹ŽȱŽŽŒœǵȱȱ–ŽŠȬŠ—Š•¢œ’œǯȱQJM: An
International Journal of MedicineǰȱŗşşŝǰȱşŖDZŗŗŗȮŗŗśǯ
ŝǯȱ œ‘ꎕȬŠĴȱȱŽȱŠ•ǯȱŽ‘¢•Ž—ŽŽ›Š‘¢›˜˜•ŠŽȱ›ŽžŒŠœŽȱŜŝŝ ȱŽ—˜¢™Žȱ–˜ž•ŠŽœȱ
‘˜–˜Œ¢œŽ’—Žȱ›Žœ™˜—œŽœȱ˜ȱŠȱ˜•ŠŽȬ›’Œ‘ȱ’Žȱ˜›ȱŠȱ•˜ Ȭ˜œŽȱ˜•’ŒȱŠŒ’ȱœž™™•Ž–Ž—DZȱŠȱ›Š—˜–’£Žȱ
controlled trial. American Journal of Clinical NutritionǰȱŘŖŖŘǰȱŝŜDZŗŞŖȮŗŞŜǯ
Şǯȱ Š¢ȱǰȱ•˜–ȱ
ǯȱ’Š–’—ȱ12ȱ’—œžĜŒ’Ž—Œ¢ȱŠ—ȱ‘Žȱ›’œ”ȱ˜ȱŽŠ•ȱ—Žž›Š•ȱž‹ŽȱŽŽŒœǯȱQJM: An
International Journal of MedicineǰȱŘŖŖřǰȱşŜDZŘŞşȮŘşśǯ
şǯȱ ›˜—œ›ž™ȱȱŽȱŠ•ǯȱ쎌œȱ˜ȱ˜•’ŒȱŠŒ’ȱŠ—ȱŒ˜–‹’—Š’˜—œȱ˜ȱ˜•’ŒȱŠŒ’ȱŠ—ȱŸ’Š–’—ȱȬŗŘȱ˜—ȱ
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 BiolǯȱŗşşŞȱž—ŽDzȱŝŞǻŘǼDZŗśŗȮŜŗǯ
ŗŘǯȱ ˜‹˜ȱǰȱ£Ž’£Ž•ȱǯȱ˜—ȬŽ›–ȱœ˜–Š’ŒȱŠ—ȱ–Ž—Š•ȱŽŸŽ•˜™–Ž—ȱ˜ȱŒ‘’•›Ž—ȱŠĞŽ›ȱ
periconceptional multivitamin supplementation. European Journal of PediatricsǰȱŗşşŞǰȱşDZŝŗşȮŝŘřǯ
ŗřǯȱ ˜››Žœȱǯȱ™’Ž–’˜•˜¢ȱ˜ȱž—’—Ž—Žȱ™›Ž—Š—Œ¢ȱŠ—ȱŒ˜—›ŠŒŽ™’ŸŽȱžœŽǯȱAmerican Journal of
Obstetrics and GynecologyǰȱŗşşŚǰȱŗŝŖDZŗŚŞśȮŗŚŞşǯ
ŗŚǯȱ Ž——ȱȱŽȱŠ•ǯȱ’ŽŠ›¢ȱŒ˜ž—œŽ•’—ȱ˜ȱ’—Œ›ŽŠœŽȱ—Šž›Š•ȱ˜•ŠŽȱ’—Š”ŽDZȱŠȱ›Š—˜–’£Žǰȱ™•ŠŒŽ‹˜Ȭ
Œ˜—›˜••Žȱ›’Š•ȱ’—ȱ›ŽŽȬ•’Ÿ’—ȱœž‹“ŽŒœȱ˜ȱŠœœŽœœȱŽěŽŒœȱ˜—ȱœŽ›ž–ȱ˜•ŠŽȱŠ—ȱ™•Šœ–Šȱ˜Š•ȱ
homocysteine. American Journal of Clinical NutritionǰȱŘŖŖŘǰȱŝŜDZŝśŞȮŝŜśǯ
ŗśǯȱ ˜–Š—˜ȱȱŽȱŠ•ǯȱ˜•’ŒȱŠŒ’ȱ˜›’ęŒŠ’˜—ȱ˜ȱ›Š’—DZȱŠ—ȱŽŒ˜—˜–’ŒȱŠ—Š•¢œ’œǯȱAmerican Journal of
Public HealthǰȱŗşşśǰȱŞśDZŜŜŝȮŜŝŜǯ
’—”œȱŠ—ȱŠ’’˜—Š•ȱœ˜ž›ŒŽœ
I.
ž’Š‹•ŽȱœŠ—Š›œǯȱŠ›ŽȱŠĞŽ›ȱ‹’›‘. London, Royal College of Obstetricians and
Gynaecologists, 1999.
II. Pregnancy, childbirth, postpartum and newborn care: a guide for essential practice. Geneva, World
ŽŠ•‘ȱ›Š—’£Š’˜—ǰȱŘŖŖřȱǻ‘Ĵ™DZȦȦ ‘š•’‹˜Œǯ ‘˜ǯ’—Ȧ™ž‹•’ŒŠ’˜—œȦŘŖŖřȦşŘŚŗśşŖŞŚǯ™ǰȱ
ŠŒŒŽœœŽȱŝȱŽŒŽ–‹Ž›ȱŘŖŖŚǼǯ
‘’œȱ˜Œž–Ž—ȱ
is not a formal
publication of
the World Health
Organization
ǻ
ǼǰȱŠ—ȱ
all rights are
reserved by the
Organization.
‘Žȱ˜Œž–Ž—ȱ
may, however, be
freely reviewed,
abstracted,
reproduced and
translated, in part
or in whole, but
not for sale nor for
žœŽȱ’—ȱŒ˜—“ž—Œ’˜—ȱ
with commercial
purposes.
‘’œȱ˜Œž–Ž—ȱ’œȱ™Š›ȱ˜ȱ‘Žȱ
Standards for Maternal and Neonatal
Š›ŽȱŽŸŽ•˜™Žȱ‹¢ȱ‘ŽȱŽ™Š›–Ž—ȱ
˜ȱŠ”’—ȱ›Ž—Š—Œ¢ȱŠŽ›ǰȱ
World Health Organization.
For further information please
Œ˜—ŠŒ:
Ž™Š›–Ž—ȱ˜ȱŠ”’—ȱ›Ž—Š—Œ¢ȱ
ŠŽ›ȱǻǼ
˜›•ȱ
ŽŠ•‘ȱ›Š—’£Š’˜—ȱǻ
Ǽ
20 Avenue Appia
ŗŘŗŗȱŽ—ŽŸŠȱŘŝ
Switzerland
Ž•DZȱƸŚŗȱŘŘȱŝşŗȱřřŝŗ
Š¡DZȱƸŚŗȱŘŘȱŝşŗȱśŞśř
Email: MPSinfo@who.int
Ž‹ȱœ’ŽDZȱ ǯ ‘˜ǯ’—Ȧ–Š”’—ȏ
™›Ž—Š—Œ¢ȏœŠŽ›Ȧ™ž‹•’ŒŠ’˜—œȦŽ—Ȧ
Š—Š›œȱ˜›ȱŠŽ›—Š•ȱŠ—ȱŽ˜—ŠŠ•ȱŠ›ŽȱŽŽ›’—ȱ˜––’ĴŽŽȱȱ
‘Š’›DZȱŠž•ȱŠ—ȱ˜˜”ǰȱ’›ŽŒ˜›ǰȱŽ™Š›–Ž—ȱ˜ȱŽ™›˜žŒ’ŸŽȱ
ŽŠ•‘ȱŠ—ȱŽœŽŠ›Œ‘Dzȱȱȱȱȱȱȱȱȱȱȱȱ
›—Ž••Šȱ’—ŒŽĴ˜ǰȱ
Ž•Šȱ˜œŠǰȱŽ••Šȱ‘Ž››ŠĴǰȱ——’Žȱ˜›Ž•Šǰȱ’ŠȱŠ‹›ŠȱŠ—ȱžŒȱŽȱŽ›—’œȱ
ǻŽ™Š›–Ž—ȱ˜ȱŠ”’—ȱ›Ž—Š—Œ¢ȱŠŽ›Ǽǯ
Œ”—˜ •Ž–Ž—œȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱ
‘’œȱœŠ—Š›ȱ ŠœȱŽŸŽ•˜™Žȱ‹¢ȱ›—Ž••Šȱ’—ŒŽĴ˜ȱ ’‘ȱŸŠ•žŠ‹•Žȱ’—™žœȱ›˜–ȱ–Ž–‹Ž›œȱ
˜ȱ‘ŽȱŠ‹˜ŸŽȱœŽŽ›’—ȱŒ˜––’ĴŽŽȱŠ—ȱ
ȱŽ’˜—Š•ȱĜŒŽœȱŠ—ȱ›ŽŸ’Ž ŽȱŠȱŠȱŽŒ‘—’ŒŠ•ȱ
˜—œž•Š’˜—ȱ’—ȱŽ—ŽŸŠǰȱŗŚȬŗŜȱŒ˜‹Ž›ȱŘŖŖŘǯȱŽ–‹Ž›œȱ˜ȱ‘ŽȱŽ—Ž›ȱ˜›ȱŽŸŠ•žŠ’˜—ȱ˜ȱ
ŽěŽŒ’ŸŽ—Žœœȱ˜ȱ‘ŽŠ•‘ȱŒŠ›ŽȬŽȱǻ’–˜—Šȱ’ȱŠ›’˜ǰȱ’Ĵ˜›’˜ȱŠœŽŸ’ǰȱ’Š—›Š—Œ˜ȱ˜›’ǰȱ
Š—’Ž•Šȱ™ŽĴ˜•’ǰȱŠ—ŽȱŠ›˜—Œ’Š—’ȱŠ—ȱ’Œ˜•ŠȱŠ›’—’ǼȱŽŸŽ•˜™Žȱ‘ŽȱŠ‹•Žȱ˜ȱŽŸ’Ž—ŒŽȱŠ—ȱ
provided additional insightful review of the evidence section. We thank Bruno de Benoist
˜›ȱ›ŽŸ’Ž ’—ȱꗊ•ȱ›ŠĞǰȱ›Š—”ȱŽŒ”œ˜—ȱ˜›ȱ‘ŽȱŽ’’—ȱŠ—ȱž”Žȱ¢Š–Ž›Š‘ȱ˜›ȱ‘Žȱ•Š¢˜žǯ
ȱŠŒ”—˜ •ŽŽœȱ‘ŽȱŽ—Ž›˜žœȱŒ˜—›’‹ž’˜—ȱ˜ȱ˜ŸŽ›ȱŞŖȱ’—’Ÿ’žŠ•œȱŠ—ȱ˜›Š—’£Š’˜—œȱ’—ȱ
‘Žȱꎕȱ˜ȱ–ŠŽ›—Š•ȱŠ—ȱ—Ž˜—ŠŠ•ȱ‘ŽŠ•‘ȱ ‘˜ȱ˜˜”ȱ’–Žȱ˜ȱ›ŽŸ’Ž ȱ‘’œȱ˜Œž–Ž—ȱŠȱ’쎛Ž—ȱ
stages of its development.
‘Žȱž—’—ȱ˜ Š›œȱ‘Žȱ™›Ž™Š›Š’˜—ȱŠ—ȱ™›˜žŒ’˜—ȱ˜ȱ‘’œȱ˜Œž–Ž—ȱ™›˜Ÿ’Žȱ‹¢ȱ‘Žȱȱ
Governments of Australia, Italy and USA is gratefully acknowledged. In addition, WHO’s
Š”’—ȱ›Ž—Š—Œ¢ȱŠŽ›ȱŽ™Š›–Ž—ȱ’œȱ›ŠŽž•ȱ˜ȱ‘Žȱ˜ŸŽ›—–Ž—œȱ˜ȱŽ—–Š›”ǰȱ›Ž•Š—ǰȱ
Ž‘Ž›•Š—œǰȱ˜› Š¢ǰȱ ŽŽ—ǰȱŠ—ȱ‘Žȱ—’Žȱ’—˜–ǰȱŠ—ȱ˜ȱ‘Žȱ˜›•ȱŠ—”ǰȱȱȱȱȱ
Š—ȱȱ˜›ȱž—œ™ŽŒ’ꮍȱ™›˜›Š––Žȱœž™™˜›ǯȱ