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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)

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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.

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Acknowledgments

The study was supported by the EU Integrated Projects NewGeneris, 6th Framework Programme (Contract no. FOOD-CT-2005-016320), and Chicos, 7th Framework Programme (Contract no. Health-F2-2009-241604).

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Authors and Affiliations

  1. Centre for Research in Environmental Epidemiology, Barcelona, Spain

    Eleni Papadopoulou & Manolis Kogevinas

  2. IMIM (Hospital del Mar Research Institute), Barcelona, Spain

    Eleni Papadopoulou & Manolis Kogevinas

  3. Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain

    Eleni Papadopoulou

  4. Department of Social Medicine, Faculty of Medicine, Medical School, University of Crete, PO Box 2208, 71003, Heraklion, Crete, Greece

    Nikolaos Stratakis, Theano Roumeliotaki, Katerina Sarri & Leda Chatzi

  5. National School of Public Health, Athens, Greece

    Eleni Papadopoulou & Manolis Kogevinas

  6. National Cancer Research Institute, Genoa, Italy

    Domenic F. Merlo

  7. CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain

    Manolis Kogevinas

Authors
  1. Eleni Papadopoulou
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  2. Nikolaos Stratakis
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  3. Theano Roumeliotaki
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  4. Katerina Sarri
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  7. Leda Chatzi
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Corresponding author

Correspondence to Leda Chatzi.

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Papadopoulou, E., Stratakis, N., Roumeliotaki, T. et al. 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). Eur J Nutr 52, 327–336 (2013). https://doi.org/10.1007/s00394-012-0339-z

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  • DOI: https://doi.org/10.1007/s00394-012-0339-z

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