Association of serum folate levels during pregnancy and prenatal depression

Figures & data

Table 1. Associations between serum folate* tertiles and depression during pregnancy.

	Depression during Pregnancy	Unadjusted	Adjusted for homocysteine only	Fully adjusted
	n (%)	RR (95% CI)	RR (95% CI)	RR (95% CI)
Full sample (n = 318)^a
Low/medium folate tertiles (n = 212)	33 (15.6)	2.06 (0.99–4.31)	2.10 (1.00–4.43)	1.97 (0.93–4.18)
High folate tertile (n = 106)	8 (7.5)	1	1	1
Normal weight (n = 163)^b
Low/medium folate tertiles (n = 106)	10 (9.2)	1.65 (0.47–5.75)	1.66 (0.47–5.88)	1.50 (0.34–6.66)
High folate tertile (n = 54)	3 (5.6)	1	1	1
Overweight/obese (n = 150)^b
Low/medium folate tertiles (n = 100)	22 (22)	2.20 (0.89–5.46)	2.22 (0.89–5.53)	2.61 (1.01–6.71)
High folate tertiles (n = 50)	5 (10)	1	1	1

RR: relative risk; CI: confidence interval.

^aadjusted for homocysteine (µmol/L), BMI (underweight [<18.5 kg/m²] or normal weight [18.5 ≤ 25 kg/m²] vs. overweight [25 ≤ 30 kg/m²] or obese [30+ kg/m²]), maternal age at start of pregnancy (<35 vs. 35+ years), marital status (married/partner vs. single/divorced/widowed), maternal education (high school or less, some college, college, or greater), race (Asian/Pacific Islander, Black, White, Other), ethnicity (Hispanic vs. non-Hispanic), parity (0 vs. 1 or more), alcohol use during pregnancy (yes vs. no), smoking during pregnancy (yes vs. no), and prenatal vitamin use (yes vs. no).

^bAdjusted for all covariates except marital status and alcohol, smoking during pregnancy, and vitamin use during pregnancy. *Serum folate was measured using the procedures outlined in the Center for Disease Control’s Total Folate Serum/Whole Blood Microbiological Assay Method No 4000.04 with the following modifications: 5-Methyl-THF Standard supplied by Sigma-Aldrich (St. Louis, MO, USA); Folic Acid Casei Medium (Catalog#: M543-100G) supplied by HiMedia (Mumbai, India); Lyphochek Immunoassay Plus Control (Catalog#: 370) supplied by Bio-Rad (Hercules, CA, USA). Although the range of serum folate in our sample was higher than folate values reported in the literature using liquid chromatography–tandem mass spectrometry or immune assay with chemiluminescence analyzer (range 16.5–382.2) our findings are similar to the published literature using the microbiological assay [13]. Folate concentrations overall and by pre-pregnancy BMI status (median [interquartile ratio]): The median and IQR for serum folate among women with overweight/obesity was 103.7 (IQR: 84.2–121.72) and among women with normal weight was 102.6 (IQR: 83.9–126.4).

Murphy MSQ, Muldoon KA, Sheyholislami H, et al. Impact of high-dose folic acid supplementation in pregnancy on biomarkers of folate status and 1-carbon metabolism: an ancillary study of the Folic Acid Clinical Trial (FACT). Am J Clin Nutr. 2021;113(5):1361–1371.

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