@article{3156652,
    title = "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)",
    author = "Papadopoulou, Eleni and Stratakis, Nikolaos and Roumeliotaki, Theano and and Sarri, Katerina and Merlo, Domenic F. and Kogevinas, Manolis and Chatzi, and Leda",
    journal = "European Journal of Nutrition",
    year = "2013",
    volume = "52",
    number = "1",
    pages = "327-336",
    publisher = "Springer Berlin Heidelberg",
    issn = "1436-6207, 1436-6215",
    doi = "10.1007/s00394-012-0339-z",
    keywords = "Folic acid; Iron; Supplements; Pregnancy; Preterm birth; Fetal growth",
    abstract = "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).
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).
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).
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."
}