The concentration of micronutrients impacts fetal development and pregnancy outcome and has been suggested to be negatively correlated with the body-mass index (BMI). We evaluated the relationship between BMI and the serum folate concentration in 802 and 660 Korean pregnant women in mid- and late pregnancy, respectively, who participated in a multicenter prospective study. There was a significant negative correlation between BMI value and the serum folate concentration at mid- and late pregnancy (P for trend 0.001 and 0.024, respectively). A general linear model confirmed this correlation at both time points after adjusting for gestational age and total folate intake. These findings are important as the serum folate concentration is a rate-limiting factor for placental folate transport to the fetus, and an inadequate folate supply may cause various malformations.
Micronutrient nutrition and metabolism in the general obese population has largely been ignored, particularly in pregnant women (Li et al., 2010). There is increasing scientific evidence for a negative correlation between body-mass index (BMI) and the concentration of micronutrients that are important for pregnancy outcome, such as folate and zinc, in both non-pregnant and pregnant populations (Kant, 2003; Tamura et al., 2004). Moreover, the development of neural-tube defects (NTDs) is not affected by periconceptional folic acid supplementation in certain obese women (Rasmussen et al., 2008). A cross-sectional study of pregnant women in the United States found that the relationship between BMI and the serum folate concentration differs with the racial/ethnic group (Lawrence et al., 2006). However, to our knowledge no studies have evaluated this relationship in the Asian populations, whose BMI is lower than that of the United States population. Therefore, we investigated the relationship between pre-pregnancy BMI and the serum folate concentration during pregnancy in Korean women who participated in the Mothers and Children's Environmental Health (MOCEH) study.
Materials and methods
This investigation was part of the MOCEH multicenter prospective cohort study, which involved 1610 women between August 2006 and October 2009. Comprehensive information about the study is available elsewhere (Kim et al., 2011). We excluded 73 women who delivered twins or who miscarried or had pregnancy complications (hypertension or diabetes), and 735 women with no data on serum folate concentrations or dietary intake at mid pregnancy. There was complete information for the 802 included women on serum folate concentrations, BMI, gestational age, age and dietary intake data (using 24-h recall) at mid pregnancy (12–28 weeks of gestation). We were able to follow-up only 660 pregnant women at late pregnancy or delivery (29–42 weeks of gestation). The pre-pregnancy BMI was calculated based on the self-reported height and weight, and gestational age (weeks) was estimated based on the date of the last menstrual period. The serum folate concentration was measured by a radioassay. Statistical analyses were performed using the SPSS statistical package (version 12.0, SPSS, Chicago, IL, USA). Generalized linear models were used to determine the relationship between log-transformed serum folate and BMI as a continuous variable. Tests for linear trend across BMI quartiles (⩽19.2, 19.3–21.0, 21.1–23.2, ⩾23.3 kg/m2) were also performed by modeling the median BMI value in each quartile as a continuous variable. The following covariates were considered potential confounders in the model: gestational age and dietary folate intake. The Institutional Review Board of the College of Medicine, Ewha Womans University, approved the project, and informed consent was obtained from each subject.
Results and discussion
Characteristics of the participants are listed in Table 1. Of 802 participants, 82 (10%) and 16 (2%) had a pre-pregnancy BMI classified as overweight (25⩽BMI<30 kg/m2) and obese (BMI⩾30 kg/m2), respectively. At mid pregnancy, unadjusted serum folate showed an overall significant decrease across quartiles (P for trend 0.001, Model 1) and remained significant after adjustment for gestational age and total folate intake (P for trend 0.003, Model 1). This suggests that the overall effect of BMI on serum folate may be independent of total folate intake. A similar trend was observed at late pregnancy (P for trend 0.024, Model 1 only, Table 2). The multiple regression analysis after adjusting for covariates showed a negative association between BMI and serum folate at mid pregnancy (P=0.005, data not shown).
Our findings suggest that folate metabolism differs according to the body weight of pregnant women, and that the pregnant women with higher body weight have chronically lower serum folate concentrations. The serum/plasma folate concentration is a rate-limiting factor for the folate supply in the placental perfusion to the fetus against the concentration gradient (Tamura and Picciano, 2006). This could explain why the risk of having an NTD-affected pregnancy is increased in women with high body weight regardless of folate intake or supplementation (Werler et al., 1996; Rasmussen et al., 2008). We propose a hypothesis that the higher incidence of other types of birth defects such as congenital heart defects reported in obese pregnant women (Mills et al., 2010) may also be related to a chronically lower supply of folate to the fetus due to an inadequate folate status or a defective folate metabolism.
Possible mechanisms underlying the inverse association between BMI and the serum folate concentration include changes in plasma volume, folate distribution among tissues and folate metabolism secondary to differences in body size or composition (Kant, 2003). Furthermore, possible differences in endocrine functioning between obese and non-obese populations could affect the serum folate concentration; however, in our population this may be complicated by hormonal changes associated with pregnancy.
This study has several limitations. We have not measured erythrocyte folate concentrations because of budgetary constraints, although red cell folate is considered to be a more reliable marker of folate status than serum folate concentrations. Furthermore, we depended on the pre-pregnancy BMI based on the self-reported weight and height, which may be less accurate than direct measurements. Despite its relatively small impact, our results suggest that assessment of serum folate in this group of pregnant Asian women may be confounded by BMI. Moreover, this association should be considered when selecting large numbers of subjects for future studies in order to avoid inappropriate sampling. For example, when selecting subjects for an investigation of the effect of prenatal zinc supplementation on fetal growth, we chose those with plasma zinc concentrations below the median of the group. However, the higher plasma zinc concentration in thinner women (Tamura et al., 2004) resulted in a cohort with a large mean BMI (Goldenberg et al., 1995).
In summary, we found a negative correlation between BMI and the serum folate concentration in mid- and late pregnancy in a Korean population. Considering that the rate of fetal malformations is high in overweight or obese women, and that the rate of obesity is rapidly increasing worldwide, urgent focus is needed on the micronutrient metabolism in overweight and obese pregnant women.
Goldenberg RL, Tamura T, Neggers Y, Copper RL, Johnston KE, DuBard MB et al. (1995). The effect of zinc supplementation on pregnancy outcome. JAMA 274, 463–468.
Kant AK (2003). Interaction of body mass index and attempt to lose weight in a national sample of US adults: association with reported food and nutrient intake, and biomarkers. Eur J Clin Nutr 57, 249–259.
Kim H, Hwang JY, Ha EH, Park H, Ha M, Lee SJ et al. (2011). Association of maternal folate nutrition and serum C-reactive protein concentrations with gestational age at delivery. Eur J Clin Nutr 65, 350–356.
Lawrence JM, Watkins ML, Chiu V, Erickson JD, Petitti DB. (2006). Do racial and ethnic differences in serum folate values exist after food fortification with folic acid? Am J Obstet Gynecol 194, 520–526.
Li Y, Wang C, Zhu K, Feng RN, Sun CH (2010). Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women. Int J Obes 34, 1070–1077.
Mills JL, Troendle J, Conley MR, Carter T, Druschel CM (2010). Maternal obesity and congenital heart defects: a population-based study. Am J Clin Nutr 91, 1543–1549.
Rasmussen SA, Chu SY, Kim SY, Schmid CH, Lau J (2008). Maternal obesity and risk of neural tube defects: a metaanalysis. Am J Obstet Gynecol 198, 611–619.
Tamura T, Goldenberg RL, Johnston KE, Chapman VR (2004). Relationship between pre-pregnancy BMI and plasma zinc concentrations in early pregnancy. Br J Nutr 91, 773–777.
Tamura T, Picciano MF (2006). Folate and human reproduction. Am J Clin Nutr 83, 993–1016.
Werler MM, Louik C, Shapiro S, Mitchell AA (1996). Prepregnant weight in relation to risk of neural tube defects. JAMA 275, 1089–1092.
This study was supported by the Mothers and Children's Environmental Health (MOCEH) Project of the Ministry of Environment, and the 2nd stage of Brain Korea 21 project, Republic of Korea. The visiting research professorship (Tsunenobu Tamura) was supported by the Korea Research Foundation and the Korean Federation of Science and Technology Societies Grant funded by the Korea Government (MOEHRD, Basic Research Promotion Fund; 091S-4-3-0222).
The authors declare no conflict of interest.
Contributors: TT and NC designed the research; HK, E-HH, HP, MH, K-YL, and Y-CH conducted the research; HK analyzed the data; HK, J-YH, K-NK, TT and NC wrote the manuscript; and NC was primarily responsible for the final content. All the authors read and approved the final manuscript.
About this article
Cite this article
Kim, H., Hwang, J., Kim, K. et al. Relationship between body-mass index and serum folate concentrations in pregnant women. Eur J Clin Nutr 66, 136–138 (2012) doi:10.1038/ejcn.2011.160
- body-mass index
Perinatal high fat diet and early life methyl donor supplementation alter one carbon metabolism and DNA methylation in the brain
Journal of Neurochemistry (2018)
The Impact of Maternal Pre-Pregnancy Body Weight and Gestational Diabetes on Markers of Folate Metabolism in the Placenta
Public Health Nutrition (2016)
Impact of Pre-Pregnancy BMI on B Vitamin and Inflammatory Status in Early Pregnancy: An Observational Cohort Study
Folic acid supplementation, preconception body mass index, and preterm delivery: findings from the preconception cohort data in a Chinese rural population
BMC Pregnancy and Childbirth (2015)