Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight

Figures & data

Table 1. Characteristics of PROGRESS birth cohort participants with umbilical cord DNA methylation from umbilical cord blood samples, n = 512, Mexico City, 2007–2010

	Mean	SD	Range
Maternal age (years)	27.8	5.5	18, 44
Second trimester measured BMI (kg/m^2)	26.9	4.2	17.4, 44.7
Pre-pregnancy self-reported BMI (kg/m^2)	25.2	4.2	16.0, 44.9
Gestational age (weeks)	38.8	1.8	24.4, 43.9
Birth weight (kg)	3.067	0.489	0.625, 4.625
Fenton BWT/GA Z score	−0.46	0.95	−5.72, 3.15
	n	%
Maternal education
Less than 12 years	203	39.7
12 years	169	33.0
More than 12 years	140	27.3
Multiparous	279	54.7
Household smoke exposure	239	46.8
Male infant	282	55.2

Pearson correlation = 0.89 between pre-pregnancy BMI and measured BMI.

Missing values (n) for the following variables: birth weight (n = 1), infant sex (n = 1), parity (n = 2), household smoke defined as household member in home who smokes (n = 1).

BMI, body mass index; BWT, birth weight; GA, gestational age.

Figure 1. Aryl-hydrocarbon receptor repressor (AHRR) DNA methylation (%5-methylcytocines) at 3 CpG sites in cord blood DNA and their correlations, PROGRESS birth cohort, Mexico City, n = 512.

Figure 2. Aryl-hydrocarbon receptor repressor (AHRR) DNA methylation (%5-methylcytocine) and (A) maternal BMI; (B) infant gestational age; and (C) birth weight-for gestational age, PROGRESS birth cohort, Mexico City, n = 512.

Figure 3. Distributions of aryl-hydrocarbon receptor repressor (AHRR) CpG 1 DNA methylation (%5-methylcytocines) among categories of (A) maternal BMI; (B) full-term vs. preterm births; and (C) birth weight-for-gestational age, PROGRESS birth cohort, Mexico City, n = 512. SGA, small-for-gestational age; AGA, appropriate-for-gestational age; LGA, large-for-gestational age.

Table 2. Associations of offspring AHRR DNA methylation with maternal and infant characteristics, PROGRESS birth cohort, Mexico City, 2007–2010

	Single variable models^1			Multivariable-adjusted model^2
	β (%5mC)	95% CI	P value	β (%5mC)	95% CI	P value
Maternal characteristics
Maternal age (per year)	−0.02	(−0.09, 0.05)	0.5	−0.02	(−0.09, 0.05)	0.5
Maternal BMI (per kg/m^2)	0.13	(0.05, 0.21)	0.002	0.14	(0.06, 0.22)	0.0009^3
Maternal education <12 years (vs. 12)	0.89	(0.00, 1.78)	0.05	0.77	(−0.09, 0.05)	0.08
Maternal education >12 years (vs. 12)	−0.12	(−1.10, 0.85)	0.8	−0.20	(−1.16, 0.75)	0.7
Multiparous (vs. primiparous)	−0.14	(−0.88, 0.61)	0.7	−0.33	(−1.09, 0.43)	0.4
Household smoke exposure (vs. no)	0.42	(−0.32, 1.2)	0.3	0.36	(−0.37, 1.09)	0.3
Infant characteristics
Gestational age (per week)	−0.43	(−0.78, −0.08)	0.02	−0.86	(−1.06, −0.65)	<0.0001^3
Birth weight-for-gestational age (per SD)	−0.49	(−0.88, −0.10)	0.01	−0.97	(−1.26, −0.58)	<0.0001^3
Male (vs. female)	0.87	(0.12, 1.6)	0.02	0.48	(−0.25, 1.21)	0.2

¹ Single variable models (n = 512), generalized estimating equations with robust variance used to account for correlations across 3 AHRR CpG sites.

² Multivariable model including all variables listed (n = 507) due to missing values (n) for the following variables: birth weight (n = 1), infant sex (n = 1), parity (n = 2), household smoke defined as household member in home who smokes (n = 1).

³ P value robust to Bonferroni adjustment for multiple gene comparison (6 genes analyzed = 0.05/6 = 0.008) and adjustment to account for the 8 potential predictors (age, BMI, education, parity, smoke exposure, gestational age, birth weight-for-gestational age, and sex) (0.001/8 = 0.001).

Table 3. Multivariable associations of offspring aryl-hydrocarbon receptor repressor (AHRR) DNA methylation with categories of maternal BMI, preterm vs. term birth, and categories of fetal growth, PROGRESS birth cohort, Mexico City, n = 507

	β (AHRR DNA methylation, %5mC)	95% CI	P value
Model 1
Overweight vs. normal weight	0.91	(0.08, 1.74)	0.03
Obese vs. normal weight	2.14	(1.01, 3.23)	0.0001
Model 2
Preterm vs. full term	3.15	(1.97, 4.33)	<0.0001
Model 3
SGA vs. AGA	1.11	(0.20, 2.02)	0.02
LGA vs. AGA	−3.72	(−6.20, −1.23)	0.003

All models adjusted for maternal age, parity, household smoke exposure, infant sex using generalized estimating equations with robust variance.

Model 1 additionally adjusted for gestational age at delivery and birth weight-for-gestational age. Overweight defined as 2nd trimester body mass index (BMI) >27 and <32 kg/m². Obese defined as a 2nd trimester BMI >32 kg/m².

Model 2 additionally adjusted for maternal BMI and birth weight-for-gestational age. Preterm defined as <37 completed weeks of gestation and full term defined as >37 weeks of gestation.

Model 3 additionally adjusted for maternal BMI and gestational age at delivery. SGA, small-for-gestational age and LGA, large-for-gestational age defined as <10th and >90th percentile of birth weight-for-gestational age based on Fenton,²² respectively.