European Journal of Nutrition

, Volume 52, Issue 1, pp 327–336

The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother–child cohort study in Crete, Greece (Rhea study)

  • Eleni Papadopoulou
  • Nikolaos Stratakis
  • Theano Roumeliotaki
  • Katerina Sarri
  • Domenic F. Merlo
  • Manolis Kogevinas
  • Leda Chatzi
Original Contribution

DOI: 10.1007/s00394-012-0339-z

Cite this article as:
Papadopoulou, E., Stratakis, N., Roumeliotaki, T. et al. Eur J Nutr (2013) 52: 327. doi:10.1007/s00394-012-0339-z

Abstract

Purpose

We examined whether high doses of folic acid and iron supplementation in early-to-mid pregnancy affect the risk of preterm birth, low birth weight, and small for gestational age neonates, in the mother–child cohort in Crete, Greece (Rhea study).

Methods

We included 1,279 women with singleton pregnancies with complete data on supplements use in early-to-mid pregnancy and birth outcomes. Anthropometric measurements at birth were obtained from medical records. Red blood cell folate concentrations in cord blood were measured in a subsample of the study population (n = 58).

Results

Sixty-six percent of the study participants reported high doses of supplemental folic acid use (5 mg/day), while 21 % reported excessive doses of folic acid use (>5 mg/day) in early-to-mid pregnancy. Daily intake of 5-mg supplemental folic acid was associated with a 31 % decrease in the risk of preterm birth (RR, 0.69; 95 % CI, 0.44, 0.99), 60 % decrease in the risk of delivering a low birth weight neonate (RR, 0.40; 95 % CI, 0.21, 0.76), and 66 % decrease in the risk of delivering a small for gestational age (SGA) neonate (RR, 0.34; 95 % CI, 0.16, 0.73). Daily doses of iron supplementation more than 100 mg were associated with a twofold increased risk for SGA neonates (RR, 2.14; 95 % CI, 0.99, 5.97).

Conclusion

These findings suggest that high daily doses of supplementary folic acid in early-to-mid pregnancy may be protective for preterm birth, low birth weight, and small for gestational age neonates, while high daily doses of supplementary iron may be harmful for fetal growth.

Keywords

Folic acid Iron Supplements Pregnancy Preterm birth Fetal growth 

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Eleni Papadopoulou
    • 1
    • 2
    • 3
    • 5
  • Nikolaos Stratakis
    • 4
  • Theano Roumeliotaki
    • 4
  • Katerina Sarri
    • 4
  • Domenic F. Merlo
    • 6
  • Manolis Kogevinas
    • 1
    • 2
    • 5
    • 7
  • Leda Chatzi
    • 4
  1. 1.Centre for Research in Environmental EpidemiologyBarcelonaSpain
  2. 2.IMIM (Hospital del Mar Research Institute)BarcelonaSpain
  3. 3.Department of Experimental and Health SciencesPompeu Fabra UniversityBarcelonaSpain
  4. 4.Department of Social Medicine, Faculty of Medicine, Medical SchoolUniversity of CreteHeraklionGreece
  5. 5.National School of Public HealthAthensGreece
  6. 6.National Cancer Research InstituteGenoaItaly
  7. 7.CIBER Epidemiologia y Salud Pública (CIBERESP)BarcelonaSpain

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