RESUMO
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.
Assuntos
Suplementos Nutricionais , Retardo do Crescimento Fetal/epidemiologia , Ácido Fólico/administração & dosagem , Ferro da Dieta/administração & dosagem , Nascimento Prematuro/epidemiologia , Adulto , Estudos de Coortes , Relação Dose-Resposta a Droga , Eritrócitos/química , Eritrócitos/citologia , Feminino , Desenvolvimento Fetal , Grécia/epidemiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Doenças do Prematuro , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Modelos Lineares , Análise Multivariada , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
OBJECTIVE: To investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age. DESIGN: The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an interviewer-administered questionnaire on folic acid supplementation at 14-18 weeks of gestation. Neurodevelopment at 18 months was assessed with the use of the Bayley Scales of Infant and Toddler Development (3rd edition). Red-blood-cell folate concentrations in cord blood were measured in a sub-sample of the study population (n 58). SETTING: Heraklion, Crete, Greece, 2007-2010. SUBJECTS: Five hundred and fifty-three mother-child pairs participating in the 'Rhea' cohort. RESULTS: Sixty-eight per cent of the study participants reported high doses of supplemental folic acid use (5 mg/d), while 24 % reported excessive doses of folic acid (>5 mg/d) in early pregnancy. Compared with non-users, daily intake of 5 mg supplemental folic acid was associated with a 5-unit increase on the scale of receptive communication and a 3·5-unit increase on the scale of expressive communication. Doses of folic acid supplementation higher than 5 mg/d were not associated with additional increase in the neurodevelopmental scales. CONCLUSIONS: This is the first prospective study showing that high doses of supplementary folic acid in early pregnancy may be associated with enhanced vocabulary development, communicational skills and verbal comprehension at 18 months of age. Additional longitudinal studies and trials are needed to confirm these results.