The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior

Figures & data

Table 1. Demographics and study variables

Variable	Women with depression (n = 66)	Women with anxiety (n = 57)	Well women (n = 398)
Growth status, n* (%)
SGA	14 (21.2)	10 (17.5)	74 (18.8)
AGA	30 (45.5)	30 (52.7)	207 (52.5)
LGA	22 (33.3)	17 (29.8)	113 (28.7)
Gestational age (weeks), n, M(SD)	66, 38.9 (0.98)	57, 38.7 (0.86)	397, 39.0 (1.06)
Maternal age (years), n, M(SD)	66, 29.2 (5.74)	57, 30.3 (5.85)	396, 29.2 (5.61)
Infant gender (n, %)
Female	34 (51.5)	31 (54.4)	206 (51.8)
Male	32 (48.5)	26 (45.6)	192 (48.2)
Maternal race (n, %)
Caucasian	48 (72.7)	49 (86.0)	284 (71.4)
African American	11 (16.7)	6 (10.6)	66 (16.6)
Other	6 (9.1)	1 (1.7)	46 (11.5)
Unknown	1 (1.5)	1 (1.7)	2 (0.5)
Maternal tobacco use during pregnancy (n, %)
No	59 (89.4)	53 (93.0)	383 (96.2)
Yes	7 (10.6)	4 (7.0)	15 (3.8)
Habituation, n, M(SD)	37, 7.32 (0.99)	34, 7.52 (1.02)	213, 7.22 (1.33)
Attention, n, M(SD)	60, 4.03 (1.35)	52, 3.99 (1.50)	357, 4.21 (1.26)
Stress abstinence, n, M(SD)	66, 0.18 (0.07)	57, 0.18 (0.07)	398, 0.18 (0.07)
Quality of movement, n, M(SD)	66, 4.04 (0.63)	57, 4.20 (0.57)	398, 4.08 (0.67)
Excitability, n, M(SD)	66, 4.41 (2.81)	57, 3.93 (2.87)	398, 4.80 (2.92)
Handling, n, M(SD)	60, 0.36 (0.21)	52, 0.37 (0.22)	377, 0.37 (0.23)
Self-regulation, n, M(SD)	65, 4.87 (0.95)	56, 5.01 (0.98)	396, 4.74 (0.92)
Arousal, n, M(SD)	66, 4.06 (0.83)	57, 4.02 (0.83)	398, 4.20 (0.81)
Hypertonicity, n, M(SD)	66, 0.48 (0.81)	57, 0.42 (0.78)	398, 0.42 (0.80)
Hypotonicity, n, M(SD)	66, 0.76 (1.15)	57, 0.65 (1.11)	398, 0.54 (0.72)
Asymmetrical reflexes, n, M(SD)	66, 1.80 (1.42)	57, 1.61 (1.33)	398, 1.73 (1.35)
Lethargy, n, M(SD)	66, 7.05 (2.84)	57, 7.16 (2.93)	398, 6.24 (2.39)
Non-optimal reflexes, n, M(SD)	66, 6.11 (2.11)	57, 6.54 (2.11)	398, 6.00 (2.13)

* Four women had missing birth weight data

Table 2. Hierarchical linear regression predicting newborn neurobehavior at birth

Predictors	β step 1	β step 2	R^2	F
Outcome: Self-regulation
Infant sex	0.07	0.05
Maternal age	−0.04	−0.06
Birth weight	0.05	0.06
Maternal anxiety	0.15	0.14
Maternal depression	<0.001	0.05
NR3C1 CpG2 methylation	0.04	0.04
			0.03	0.95
Maternal depression x NR3C1 CpG2 methylation	-	−0.16*
		∆R^2 = 0.02*	0.06	10.46
Outcome: Hypotonia
Infant sex	0.08	0.11
Maternal age	−0.10	−0.06
Birth weight	−0.36^‡	−0.37^‡
Maternal anxiety	−0.04	−0.02
Maternal depression	0.12	0.04
NR3C1 CpG2 methylation	0.03	0.03
			0.16	50.55^‡
Maternal depression x NR3C1 CpG2 methylation	—	0.25^‡
		∆R^2 = 0.06^‡	0.21	60.81^‡
Outcome: Lethargy
Infant sex	0.14	0.16*
Maternal age	−0.03	0.002
Birth weight	−0.13	−0.14
Maternal anxiety	−0.05	−0.03
Maternal depression	0.19*	0.13
NR3C1 CpG2 methylation	−0.09	−0.09
			0.06	20.04
Maternal depression x NR3C1 CpG2 methylation	–	0.19^†
		∆R^2 = 0.03^†	0.10	20.68^†
Outcome: Hypotonia
Infant sex	0.08	0.09
Maternal age	−0.06	−0.05
Birth weight	−0.27^‡	−0.27^‡
Maternal tobacco use during pregnancy	0.13*	0.13*
Maternal anxiety	−0.05	−0.08
Maternal depression	0.15^†	0.16^†
11β-HSD-2 CpG4 methylation	0.06	0.06
			0.10	50.76^‡
Maternal anxiety x 11β-HSD-2 CpG4 methylation	—	0.10*
		∆R^2 = 0.01*	0.11	30.68*

* P < 0.05, ^†P < 0.01, ^‡P < 0.001

Figure 1. Interactions between maternal depression during pregnancy and NR3C1 CpG2 on newborn self-regulation (A), hypotonia (B), and lethargy (C), and the interaction between maternal anxiety during pregnancy and 11βHSD-2 CpG4 methylation on newborn hypotonia (D). Simple slopes were tested at ± 1 SD from the mean (A, D), or 1 SD and 2 SD above the mean (B, C). * P < 0.05; ** P < 0.01; *** P < 0.001.