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Folic Acid, Protein Energy and Multiple Micronutrient Supplements on Stillbirths

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More Intervention Effect Estimate Summaries

Imdad A, Yakoob MY, Bhutta ZA.  The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths.  BMC Public Health. 2011; 11 (Suppl 3): S4.


  • A woman’s nutritional status before and during pregnancy is important for a healthy pregnancy outcome. (1)  Pregnancy is a state of increased requirement of macro and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes (2, 3)
  • At least 3.2 million stillbirths occur annually (4), with 98% of these occurring in the developing world (5).
  • Poor maternal nutritional status is one of the five factors significantly associated with stillbirths. (6)

Intervention Effects

Peri-conceptional Folic Acid Fortification on Stillbirths due to Neural Tube Defects (NTDs) 

  • 41% reduction (RR: 0.59; 95% CI 0.52-0.68) in primary incidence of NTDs – 11 fortification studies (moderate quality of evidence)
  • This estimate has been recommended for inclusion in LiST as a proxy for reduction in stillbirths

Balanced Protein Energy Supplementation during Pregnancy on Stillbirths

  • 45% reduction (RR: 0.55; 95% CI 0.31-0.97) in all-cause stillbirths - 3 low-quality studies
  • Insufficient data to recommend inclusion in LiST

Multiple Micronutrient Supplementation during Pregnancy on Stillbirths

  • No significant effect on reducing stillbirths (RR: 0.98; 95% CI 0.88-1.10) or perinatal mortality (RR: 1.07; 95% CI 0.92-1.25) when compared to iron folate supplementation – 13 studies

Intervention Recommendation

  • Folic acid fortification reduces incidence of NTDs and may also have an effect on stillbirths.  The estimate of 41% reduction has been recommended as a proxy for reduction in stillbirths due to NTDs.
  • While promising, there is need of more operations research before we can recommend balanced protein energy supplementation as an intervention on large scale for reducing stillbirths.
  • There is no evidence of effect of multiple micronutrients supplementation on reducing stillbirths.

References from Imdad Paper Cited Here

  1. Maternal anthropometry and pregnancy outcomes. A WHO Collaborative Study: Introduction. Bull World Health Organ. 1995;73(Suppl):1–6.
  2. de Onis M, Villar J, Gulmezoglu M. Nutritional interventions to prevent intrauterine growth retardation: evidence from randomized controlled trials. Eur J Clin Nutr. 1998;52(Suppl 1):S83–93.
  3. Abu-Saad K, Fraser D. Maternal Nutrition and Birth Outcomes. Epidemiol Rev. 2010.
  4. Lawn JE, Yakoob MY, Haws RA, Soomro T, Darmstadt GL, Bhutta ZA. 3.2 million stillbirths: epidemiology and overview of the evidence review. BMC Pregnancy Childbirth. 2009;9(Suppl 1):S2. 
  5. Smith GC. Predicting antepartum stillbirth. Curr Opin Obstet Gynecol. 2006;18(6):625–630. 
  6. Di Mario S, Say L, Lincetto O. Risk factors for stillbirth in developing countries: a systematic review of the literature. Sex Transm Dis. 2007;34(7 Suppl):S11–21.

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