Table 11

Impact of peri-conceptional folic acid supplementation on stillbirth and perinatal mortality


Location and Type of Study


Stillbirths/Perinatal Outcomes

Reviews & meta-analyses

Lumley et al. 2001 [84]

Hungary, Ireland, United Kingdom, Israel, Australia, Canada, the former USSR, and France.

Meta-analysis (Cochrane). 3 RCTs included (N = 7,600 women).

Assessed the effects of increased consumption of folate (intervention) or multivitamins (controls) on the prevalence of neural tube defects peri-conceptionally.

SBR: RR = 0.78 (95% CI: 0.34–1.78) [NS]

[13/3915 vs.16/3685 in intervention vs. control groups, respectively]

Pena-Rosas and Viteri 2006 [86]


Meta-analysis (Cochrane). 2 RCTs included (N = 145 participants).

Assessed the efficacy, effectiveness and safety of routine antenatal daily or intermittent iron supplementation with (intervention) or without (controls) folic acid during pregnancy on the health of mothers and newborns.

PMR: RR = 2.50 (95% CI: 0.10, 59.88) [NS]

[1/77 vs. 0/68 in intervention vs. control groups, respectively]

Rumbold et al. 2005 [87].

India, Hungary, United Kingdom, Israel, Australia, Canada, the former USSR, France, Ireland, Nigeria, Nepal.

Meta-analysis (Cochrane). 6 RCTs included.

Determined the effectiveness and safety of periconceptual/antenatal folic acid supplementation + multivitamin (intervention), as compared to no folic acid/multivitamin (controls) on the risk of spontaneous miscarriage, maternal adverse outcomes and fetal and infant adverse outcomes.

SBR: RR = 1.03 (95% CI: 0.51–2.09) [NS]

[16/3511 vs. 15/3372 in intervention vs. control groups, respectively]

Observational studies

Persad et al. 2002 [125]

Canada (Nova Scotia). Birth registry data.

Population-based retrospective study (before-after comparison). Included births and stillbirths with open NTDs that occurred from 1991–2000 in the Nova Scotia Atlee Perinatal Database.

Assessed the impact on NTDs after the Canadian government fortified grain products with folic acid.

Open NTDs: RR = 0.46 (95%

CI: 0.32–0.66, P < 0.001)

Anencephaly: RR = 0.41 (95% CI: 0.22–0.77, P = 0.004)

[0.93/1000 before vs. 0.38/1000 births after intervention]

Yakoob et al. BMC Pregnancy and Childbirth 2009 9(Suppl 1):S3   doi:10.1186/1471-2393-9-S1-S3

Open Data