Table 2.

Results of studies describing the association of maternal smoking and folate levels

First author (year)	Definition of smokinga	Folate metaboliteb	Measured in	Timec of measurement	Statistical analysis	Measure of association	Results	SD/SE	95% CI/IQR	P value	Adjustmentsd
Adaikalakoteswari (2015)	Any active smoking	Folate	Maternal serum	At birth	Student's t test	Difference in means	sm: 10.1 μg/L nsm: 10.7 μg/L		9.7–13.3e 10.6–13.9	ns	−
			Umbilical cord blood				sm: 16.5 μg/L nsm: 16.9 μg/L		15.8–17.7e 16.4–18.2	ns	−
Ambroszkiewicz (2007)	nm	Folate	Maternal serum	At birth	Student's t test	Difference in means	sm: 12.80 ng/ml; nsm: 13.32 ng/ml;	9.40f 3.19		ns	−
			Umbilical cord blood				Folic acid levels lower in smokers			ns	−
Baker (2009)	nm	Folate	Maternal RBC	30.3 ± 2.1 (mean ± SD)	Linear regression	Ratio of geometric means (nsm as reference)	0.82g		0.72–0.94e	0.006	−
			Maternal serum				0.80g		0.67–0.96e	0.015	−
Bergen (2012)	Any active smoking	Folate	Maternal serum	13.2 (11.4–16.2), median (90% range)	Linear regression	Regression coefficient	−0.43		−0.51 to −0.36e	<0.001	−
Bodnar (2010)	Any active smoking	Folate	Maternal serum	9.4 (7.5–12.1), median (IQR)	Pearson chi‐square	Difference in number of smokers across folate tertiles	Lowest folate tertile, sm: n = 67 (64%) Middle tertile, sm: n = 61 (58%) Upper tertile, sm: n = 47 (45%)			<0.05	−
Coker (2013)	≥3 cigarettes/day for >3 years	Folic acid	Maternal serum,	At birth	Mann–Whitney U and Wilcoxon paired tests	Difference in means	sm: 7.0 ng/ml nsm: 9.6 ng/ml	4.2h 4.5		0.041	−
			Umbilical cord blood				sm: 15.4 ng/ml nsm: 16.9 ng/ml	4.6h 4.5		0.207	−
Furness (2013)	nm	Folate	Maternal RBC	18–20	t test	Difference in means (nmol/L)	sm: 463 nsm: 687		354–571e 647–727	<0.001	−
			Maternal serum				sm: 22.6 nsm: 27.3		17.9–27.3e 25.5–29.0	0.035	−
Furness (2012)	nm	Folate	Maternal RBC	10–12	ANOVA	Difference in means	sm: 507.3 nmol/L nsm: 657.3 nmol/L			<0.001	−
					Pearson correlation	Correlation coefficient	r = −0.256			0.002	−
Gadowsky (1995)	≥1 cigarette/day	Folate	Maternal plasma	35.9 ± 0.2	Pearson correlation	Correlation coefficient	nm			ns	−
			Maternal RBC				r = −0.35			<0.009	−
Hay (2010)	Any active smoking	Folate	Umbilical cord blood	At birth	Linear regression	Partial correlation coefficient	r = −0.17			0.052	+++
Jauniaux (2007)	Cotinine levels > 25 ng/ml	Folate	Maternal serum	Median: 9.2	Least squares method and F test	Difference in medians	sm: 7.5 nmol/L nsm: 14.3 nmol/L		5.3–14.3i 11.1–20.0	<0.001	−
Knight (1994)	Any active smoking of marihuana	Folate	Maternal serum	3rd trimester	Pearson correlation	Correlation coefficient	r = −0.25			0.02	−
Larroque (1992)	≥1 cigarette/day	Folate	Maternal serum	33 (14–41)	Correlation	Correlation coefficient	r = −0.13			0.05	−
					Multiple linear regression	Beta	β = −0.02			0.39	−
			Maternal RBC		Correlation	Correlation coefficient	r = −0.12			0.06	−
					Multiple linear regression	Beta	β = −3.9			0.01	−
Matsuzaki (2008)	Any active smoking	Folate	Maternal serum	11–40	Logistic regression	Odds ratio (of normal folic acid levels)	OR = 0.632		0.276–1.45e	ns	−
McDonald (2002)	Any active smoking	Folate	Maternal serum	1st and early 2nd trimesters	Unpaired t test	Difference in means	sm: 22.7 nmol/L nsm: 29.4 nmol/L	7.6h 8.9		0.001
			Maternal RBC				sm: 766 nmol/L nsm: 900 nmol/L	246h 317		0.038
Mito (2007)	Any active smoking	Folate	Maternal serum	1st trimester	Chi‐square test	Percentage of smokers according to folate levels	<9 ng/ml: 20.6 ≥9 ng/ml: 16.7			0.327	−
Nilsen (2010)	Cotinine level ≥ 85 nmol/L	Folate	Maternal plasma	Median: 18	Spearman correlation	Correlation coefficient	r = −0.12			<0.001	++
Ozerol (2004)	≥2 cigarettes/day	Folate	Maternal serum	16–22	Mann–Whitney U test	Difference in means	sm: 4.6 nmol/L nsm: 14.1 nmol/L	0.4f 1.4		<0.001	−
Pagan (2001)	Thiocyanate blood levels in highest quartile	Folate	Maternal serum	18	Student's t test	Difference in means	sm: 47 nmol/L nsm: 54 nmol/L	31h 38		ns	−
				30			sm: 38 nmol/L nsm: 54 nmol/L	30h 39		<0.005	−
Prasodjo (2014)	Active: Cotinine > 3 ng/ml		Maternal whole blood	16	Linear regression	Beta	−94		−195 to 6e	0.07	++
	Passive: >0 and 3 ng/ml						−26		−84 to 32e	0.38	++
Relton (2005)	Any active smoking	Folate	Maternal RBC	11.5	Linear regression	Correlation coefficient	r = −1.38		−1.92 to −0.86e	<0.001	−
			Umbilical cord blood	At birth			r = 0.31		−0.62 to 1.25e	0.50	−
Sram (2005)	Any (active or passive)	Folate	Maternal plasma	At birth	nm	Difference in means	Europeans:			Nm	−
							sm: 22.0 nmol/L nsm: 26.6 nmol/L	15.9f 16.8
							Teplice Europeans:
							sm: 21.3 nmol/L nsm: 24.5 nmol/L	16.3 16.8
							Prague Europeans:
							sm: 23.4 nmol/L nsm: 28.6 nmol/L	14.8 16.3
			Umbilical cord blood				Europeans:				−
							sm: 45.2 nmol/L nsm: 49.0 nmol/L	15.7f 17.7
							Teplice Europeans:
							sm: 43.8 nmol/L nsm: 48.4 nmol/L	15.4 17.4
							Prague Europeans:
							sm: 47.9 nmol/L nsm: 49.9 nmol/L	15.7 17.5
Stark (2005)	Any (active or passive)	5‐MTHFA	Maternal plasma	24	Linear regression	Standardized beta	Maternal smoking: β = −0.12			0.23	++
							Paternal smoking: β = −0.26			0.019
					Pearson correlation	Regression coefficient	Maternal smoking: r = −0.03			ns	++
							Prepregnancy maternal smoking: r = −0.04			ns
							Paternal smoking: r = −0.21			0.043
Stark (2007)	Any active smoking	5‐MTHFA	Umbilical cord blood	24	t test	Difference in means	sm: 15.1 ng/ml nsm: 19.0 ng/ml	7.6h 7.0		0.0498; adjusted: 0.034	+
					Pearson correlation	Correlation coefficients	Number of cigarettes smoked at first prenatal visit: r = −0.31			0.019
							Number of cigarettes smoked before pregnancy: r = −0.30			0.023
					Linear regression	Standardized beta	Maternal cigarettes smoked/day: β = −0.31			0.009
Van Uitert (2014)	Any active smoking	Folate	Maternal RBC	7 (4–11)		Difference in means	sm: 1,257 nmol/L nsm: 1,627 nmol/L	239h 475		<0.01	−
						Percentage of smokers per quartile	Folate Q1: sm = 36.8%; Q2: sm = 20%; Q3: sm = 5.3%; Q4: sm = 5.3%			0.024
Van Wersch (2002)	≥20 cigarettes/day	Folate	Maternal serum	0–10	Mann–Whitney U test	Difference in medians	sm: 8.2 nmol/L nsm: 12.2 nmol/L		4.8–12.9i 8.8–48.0	ns	−
				11–20			sm: 6.4 nmol/L nsm: 11.1 nmol/L		3.0–10.1i 9.2–17.6	0.03	−
				21–30			sm: 4.1 nmol/L nsm: 12.1 nmol/L		2.0–12.2i 8.9–18.7	0.002	−
				31–40			sm: 3.7 nmol/L nsm: 9.3 nmol/L		1.6–6.9i 6.8–13.7	0.0002	−
Vandevijvere (2012)	Any active smoking	Folate	Maternal RBC	1st or 3rd trimester	Linear regression	Beta	First trimester: β = 0.974j Third trimester: β = 0.098g	0.313f 0.036f		0.002 0.006	+++
Yila (2016)	Any (active/passive)	Folate	Maternal serum	1st trimester	Logistic regression	Odds of low folate status	psm: 1.20 sm: 1.91		1.10–1.31e 1.70–2.14	<0.001	+++

Note. 5‐MTHFA: 5‐methyltetrahydrofolic acid; SE: standard error; CI: confidence interval; IQR: interquartile range; nm: not mentioned; ns: nonsignificant; sm: smoking women; nsm: nonsmoking women; psm: women exposed to passive smoking; RBC: red blood cell; ANOVA: analysis of variance.

^aSmoking refers to tobacco smoking unless mentioned otherwise.

^bNomenclature in table as in original paper.

^cWeeks of gestation.

^dAdjustment level was categorized as follows: −, unadjusted; +, 4 covariates or less; ++, 5 to 8 covariates; +++, 9 or more covariates.

^e95% CI.

^f SE.

^gLog transformed.

^h SD.

ⁱIQR.

^jRoot square transformed.