High doses of folic acid in the periconceptional period and risk of low weight for gestational age at birth in a population based cohort study.

Purpose: We investigated the association between maternal use of folic acid (FA) during pregnancy and child anthropometric measures at birth.

Methods: We included 2302 mother-child pairs from a population-based birth cohort in Spain (INMA Project). FA dosages at first and third trimester of pregnancy were assessed using a specific battery questionnaire and were categorized in non-user, < 1000, 1000-4999, and ≥ 5000 µg/day. Anthropometric measures at birth (weight in grams, length and head circumference in centimetres) were obtained from medical records. Small for gestational age according to weight (SGA-w), length (SGA-l) and head circumference (SGA-hc) were defined using the 10th percentile based on Spanish standardized growth reference charts. Multiple linear and logistic regression analyses were used to explore the association between FA dosages in different stages of pregnancy and child anthropometric measures at birth.

Results: In the multiple linear regression analysis, we found a tendency for a negative association between the use of high dosages of FA (≥ 5000 µg/day) in the periconceptional period of pregnancy and weight at birth compared to mothers who were non-users of FA (β = - 73.83; 95% CI - 151.71, 4.06). In the multiple logistic regression, a greater risk of SGA-w was also evident among children whose mothers took FA dosages of 1000-4999 (OR = 2.21; 95% CI 1.17, 4.19) and of ≥ 5000 µg/day (OR = 2.32; 95% CI 1.06, 5.08) compared to mothers non-users of FA in the periconceptional period of pregnancy.

Conclusion: Our findings suggest that a high dosage of FA (≥ 1000 µg/day) may be associated with an increased risk of SGA-w at birth.