Elevated Maternal Serum Folate in the Third Trimester and Reduced Fetal Growth: A Longitudinal Study

Abstract

SummaryThis study aimed to examine the association of fetal growth and elevated third trimester maternal serum folate due to folic acid (FA) supplement intake. Dietary intake, use of FA supplements, weight, and blood biomarkers of B-vitamins (serum folate, pyridoxal, vitamin B 12 , and plasma total homocysteine) were observed in 33 healthy pregnant women at the third trimester (average gestational age 35 wk). Birth outcomes were assessed through hospital birth records. Infant anthropometry and maternal blood biomarkers were followed up at 1 mo postpartum. Fourteen women were taking FA supplements at the third trimester. Dietary intake was similar among FA users and non-users, but serum folate and pyridoxal were significantly higher in users (11.6 Ϯ 6.7 vs. 6.1 Ϯ 3.2 ng/mL, and 13.8 Ϯ 21.7 vs. 3.2 Ϯ 1.4 ng/mL, respectively). Plasma total homocystein (tHcy) was higher in non-users compared to users, but not significantly. Nine FA users and eight non-users had low serum vitamin B 12 values ( Ͻ 203 pg/mL). Nine FA users and all non-users had low serum pyridoxal values ( Ͻ 7.0 ng/mL). Infant birthweight was significantly lower in users compared to non-users (2,894 Ϯ 318 vs. 3,154 Ϯ 230 g). At 1 mo postpartum, infant weight and length were similar between FA users and non-users, but infant weight gain was larger in users. Higher serum folate values due to FA use in the third trimester was related to reduced fetal size. Excess FA under low vitamin B 6 and B 12 status may affect fetal growth. Key Words pregnancy, folate, supplement use, birthweight Periconceptional folic acid (FA) supplements are currently recommended to women planning pregnancy, to avoid fetal neural tube defects (NTDs) ( 1 ) in Japan, and many other countries ( 2 ). Before its effect on NTD prevention was found, FA supplementation was previously known for its effect in preventing anemia in pregnancy ( 3 , 4 ). However, a number of recent studies have focused on other relations of folate to pregnancy health, such as pregnancy-induced hypertension ( 5-8 ), placental abruption ( 9 ), fetal growth restriction ( 10 ), and preterm birth ( 11 ), suggesting extended FA supplementation to reduce risks for these adverse pregnancy outcomes. While FA supplementation throughout pregnancy has been considered safe, concerns are arising on the long-term health effects of synthesized folate on infant health. Excess FA may induce changes to the genetic expression of the fetus, such as observed in animal experiments ( 12 , 13 ). This may pose lifetime changes to the health status of the offspring.Folate is an essential component in various metabolic processes, such as one-carbon transfer reactions including formate oxidation, amino acid metabolism and biosynthesis of thymidylate and purines ( 14 ). In regenerating methione from homocysteine, methionine synthase catalyzes the cobalamin-dependent transfer of a methyl group from 5-methyl-tetrahydrofolate. Homocysteine is also catalyzed into cysteine through the transsulfuration pathway, which involves cystathionine ␤ -synt...

Validity and reproducibility of folate and vitamin B12 intakes estimated from a self-administered diet history questionnaire in Japanese pregnant women

“…The attitudes toward dietary intakes and supplementation might have been affected by the difference between hospitals. However, serum concentrations of folate and vitamin B 12 in the present study were similar to other studies among non-supplement users [30,31]. Therefore, we considered that our participants were representative of Japanese pregnant women in the general population in terms of folate and vitamin B 12 status.…”

Maternal dietary intake of folate, vitamin B12 and MTHFR 677C>T genotype: their impact on newborn’s anthropometric parameters

“…In contrast, Pastor Valero et al (2011), who defined small-for-gestational-age for weight (SGA-W) and for height (SGA-H) as below the 10th percentile, found that women in the highest quintile of dietary intake of folate had a significantly lower risk of an SGA-W baby; however, they did not observe any association with SGA-H. Few studies examine the relationship between dietary intake of vitamin B 12 during pregnancy and anthropometric parameters at birth, withal of them focusing solely on birth weight. Takimoto et al (2011) reported a significant increase in birth weight (b = 0.08; 95 % CI 0.01, 0.15) associated with dietary intake of vitamin B 12 during the third trimester of pregnancy, while Sukla et al (2013) observed that women with deficient plasma vitamin B 12 were two times more likely of having a low weight infant than those without this deficiency. Other authors did not find an association between vitamin B 12 and birth weight (Relton et al 2005, Bergen et al 2012.…”

Suplementos en gestación: últimas recomendaciones

“…Cuando el AF sintético está en forma de pteroilmonoglutamato (PGA), el organismo lo transforma en 5-metiltetrahidrofolato, pero parece que este proceso de biotransformación del PGA se satura con dosis de 0,4 mg. Surge así la preocupación por el uso de dosis altas, ya que se superaría la capacidad metabólica del organismo, con la consiguiente acumulación plasmática de AF sintético no metabolizado. Diversos autores observan una relación entre el uso de SAF en dosis mayores a las recomendadas y efectos adversos en recién nacido (30). Dado que no hay una evidencia clara y suficiente, es importante vigilar la ingesta y dosis adecuada de SAF durante el embarazo.…”