Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study

Figures & data

Table 1. Descriptives of the study participants and excluded individuals.

	Whole sample		Group difference	Males		Group difference	Females		Group difference	Sex difference
Variable	Participants (N = 122)	Excluded (N = 67)	p	Participants (N = 68)	Excluded (N = 35)	p	Participants (N = 54)	Excluded (N = 32)	P	p
M ± SD (range)
Newborn's age (d)	305.3 ± 7.4 (291 − 325)	308.2 ± 7.6 (294 − 331)	0.010*	305.4 ± 7.0 (294 − 320)	307.5 ± 7.3 (298 − 331)	0.148	305.1 ± 7.8 (291 − 325)	308.9 ± 7.9 (294 − 326)	0.033*	0.858
Gestational age (d)	279 ± 7.9 (254 − 295)	279.6 ± 9.0 (258 − 296)	0.631	278.8 ± 7.5 (263 − 295)	279.4 ± 9.3 (258 − 293)	0.858	279.3 ± 8.3 (254 − 295)	280.2 ± 8.7 (265 − 296)	0.636	0.738
Birth weight (g)	3481.1 ± 431.7 (2530 − 4700)	3612.3 ± 429.9 (2860 − 4640)	0.049*	3567.7 ± 454.7 (2720 − 4700)	3590.9 ± 335.8 (2915 − 4190)	0.790	3372 ± 377.3 (2530 − 4340)	3637.3 ± 523.8 (2860 − 4640)	0.009*	0.012*
PRAQ-R2 (gwk 24)	24.1 ± 7.8 (10 − 46)	22.3 ± 6.9 (12 − 39)	0.105	25.6 ± 7.7 (11 − 46)	21.8 ± 5. (14 − 39)	0.007*	22.2 ± 7.6 (10 − 40)	22.8 ± 8 (12 − 38)	0.808	0.008*
EPDS & SCL sum (gwk 24)	−3.6E − 2 ± 1.8 (—1.9 − 5.8)	−0.02 ± 1.9 (−1.8 − 4.4)	0.961	−3.7E − 3 ± 1.7 (−1.9 − 5.6)	−0.2 ± 1.8 (−1.8 − 4.4)	0.595	−7.3E − 2 ± 2.0 (−1.9 − 5.8)	0.2 ± 2 (−1.8 − 4.4)	0.588	0.460
Maternal age (y)	29.8 ± 4.4 (19 − 41)	31.3 ± 3.9 (22 − 38)	0.099	30.1 ± 4.5 (19 − 41)	31.3 ± 3.8 (22 − 38)	0.414	29.3 ± 4.3 (21 − 41)	31.1 ± 4 (23 − 38)	0.113	0.292
Maternal pre-pregnancy BMI (kg/m^2)	24.2 ± 3.9 (17.5 − 38.4)	24.9 ± (18 − 40.8)	0.238	24.5 ± 4.2 (18 − 38.4)	24.4 ± 3.2 (19.5 − 30.8)	0.918	23.7 ± 3.6 (17.5 − 35)	25.5 ± 5.6 (18 − 40.8)	0.085	0.281
Frequencies; total/yes (%)
Prenatal alcohol and/or  nicotine consumption	119/35 (29.4)	65/17 (25.4)	0.639	66/23 (34.8)	34/8 (22.9)	0.246	53/12 (22.6)	31/9 (28.1)	0.604	0.105
Prenatal CNS affecting medication	118/8 (6.8)	65/6 (9)	0.551	66/6 (9.1)	34/3 (8.6)	0.965	52/2 (3.8)	31/3 (9.4)	0.357	0.228
Maternal education (low/middle/high)	33/38/51 (27/31.1/41.8)	15/19/30 (23.4/28.4/44.8)	0.780	17/20/31 (25/29.4/45.6)	8/11/14 (22.9/31.4/40)	0.726	16/18/20 (29.6/33.3/37)	7/8/16 (21.9/25/50)	0.489	0.633
Gestational diabetes	120/15 (12.3)	65/14 (20.9)	0.106	67/8 (11.9)	35/6 (17.1)	0.469	53/7 (13.2)	30/8 (25)	0.126	0.524
High blood pressure or  moderate pre-eclampsy	122/5 (4.1)	67/0 (0)	0.093	68/1 (1.8)	35/0 (0)	0.471	54/4 (7.4)	32/0 (0)	0.115	0.169
Birth complications	120/16 (13.3)	65/7 (10.3)	0.614	67/8 (11.9)	34/5 (14.3)	0.736	53/8 (15)	30/2 (6.3)	0.257	0.405

p Values (of t-tests, chi-squared tests, Mann Whitney U Tests) for group differences between the study participants and the excluded individuals are listed. Sex differences between the study participants are listed in the far right column. *p < .05; PRAQ-R2 = Preganacy Related Anxiety Questionnaire Revised 2; SCL = Symptom Checklist 90; EPDS = Edinburgh Postnatal Depression Scale; CNS = central nervous system. Maternal education was classified into three categories: 1) “low” representing educational attainment at maximum being high school graduation or vocational school, 2) “middle” representing polytechnic level education, and 3) “high” representing university level education.

Table 2. Mean raw and relative brain volumes.

	Whole sample (N = 122)	Males (N = 68)	Females (N = 54)	p
M ± SD (range)
TBV	621882.7 ± 46913.4 (517422 − 739571)	636643.8 ± 45576.4 (547872 − 739571)	603294.5 ± 42037.3 (517422 − 692269)	<.001**
Left Amygdala	267.5 ± 37.4 (170.4 − 188)	274.2 ± 41.2 (188 − 358.4)	259.1 ± 41.2 (203.9 − 356.1)	.027*
Right Amygdala	266.7 ± 39.2 (181.9 − 364.2)	278.7 ± 39.2 (181.9 − 364.2)	251.5 ± 33.7 (185.9 − 349.2)	<.001**
Left Hippocampus	767.2 ± 115.1 (514.6 − 1082.6)	793.5 ± 119.4 (514.6 − 1082.6)	734 ± 100.9 (549.4 − 989.9)	.004**
Right Hippocampus	770 ± 108.2 (467.7 − 1020.9)	788.4 ± 106.9 (560.7 − 1020.9)	746.7 ± 106.3 (467.6 − 974.9)	.034*
Left Amygdala / TBV	4.3E − 4 ± 5.0E − 5 (3.1E − 4 − 5.6E − 4)	4.3E − 4 ± 5.2E − 5 (3.1E − 4 − 5.4E − 4)	4.3E − 4 ± 4.7E − 5 (3.3E − 4 − 5.6E − 4)	.980
Right Amygdala / TBV	4.3E − 4 ± 5.2E − 5 (3.1E − 4 − 5.6E − 4)	4.4E − 4 ± 5.1E − 5 (3.1E − 4 − 5.3E − 4)	4.2E − 4 ± 5.2E − 5 (3.2E − 4 − 5.6E − 4)	.032*
Left Hippocampus / TBV	1.2E − 3 ± 1.5E − 4 (8.3E − 4 − 1.6E − 3)	1.2E − 3 ± 1.5E − 4 (8.4E − 4 − 1.6E − 3)	1.2E − 3 ± 1.5E − 4 (9.5E − 4 − 1.6E − 3)	.319
Right Hippocampus / TBV	1.2E − 3 ± 1.4E − 4 (8.0E − 4 − 1.6E − 3)	1.2E − 3 ± 1.3E − 4 (9.0E − 4 − 1.5E − 3)	1.2E − 3 ± 1.6E − 4 (8.0E − 4 − 1.6E − 3)	.960

In the right column p values of sex differences are listed. TBV = total brain volume. *p < .05, **p < .01.

Figure 1. Example of the segmentation of amygdala and hippocampus in a study subject. The amygdala and hippocampus are shown in coronal, axial, and sagittal planes with orange and blue colors respectively.

Nine black and white infant brain MR images in three rows. Each row has a coronal, axial, and sagittal view of the brain. In the first row, the plain MR images are shown. In the second row of images, the amygdala has been colored orange. In the third row of images, the hippocampus has been colored light blue.

Table 3. Correlations between the study variables and their p values.

			1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16
1	Newborn age (d)	R
		p
2	Gestational age (d)	R	−0.551
		p	<.001**
3	Birth weight (g)	R	−0.213	0.455
		p	.018*	<.001**
4	Birth complications	R	−0.161	0.062	−0.023
		p	.079	.498	.802
5	PRAQ-R2 (GW 24)	R	0.087	−0.037	0.01	0.045
		p	.34	.683	.915	.629
6	EPDS & SCL (GW 24)	R	0.071	0.019	−0.056	0.063	0.537
		p	.437	.837	.541	.494	<.001**
7	Maternal pre-pregnancy BMI (kg/m^2)	R	−0.071	−0.043	0.169	0.069	0.026	0.038
		p	.439	.64	.062	.451	.777	.681
8	Prenatal alcohol and/or  nicotine consumption	R	0.064	0.084	−0.074	0.029	0.007	−0.038	−0.15
		p	.492	.364	.427	.759	.944	.683	.104
9	Maternal education	R	0.086	−0.006	−0.151	0.071	0.133	0.071	−0.09	−0.122
		p	.348	.944	.097	.443	.144	.439	.322	.185
10	High blood pressure or pre  eclampsy during pregnancy	R	0.009	−0.121	−0.167	−0.082	0.135	0.249	0.066	−0.12	−0.037
		p	.919	.184	.066	.375	.137	.006**	.471	.192	.683
11	Gestational diabetes	R	0.124	−0.14	−0.069	0	0.059	0.016	0.349	0.104	−0.078	0.173
		p	.177	.126	.456	1	.52	.861	<.001**	.264	.398	.058
12	Maternal age (y)	R	0.056	−0.073	−0.117	−0.056	−0.084	−0.198	0.202	0.124	0.342	0.021	0.245
		p	.543	.423	.201	.546	.36	.029*	.026*	.179	<.001**	.82	.007**
13	Prenatal CNS affecting medication	R	0.034	−0.014	−0.011	0.098	0.139	0.269	0.014	−0.024	0.163	−0.051	0.004	0.028
		p	.718	.879	.902	.296	.132	.003**	.881	.795	.079	.587	.969	.767
14	Left Amygdala / TBV	R	−0.154	0.089	0.03	−0.072	−0.009	−0.141	−0.025	−0.013	0.073	0.107	−0.026	−0.027	−0.195
		p	.09	.331	.746	.432	.924	.12	.783	.892	.423	.242	.776	.768	.034*
15	Right Amygdala / TBV	R	−0.072	−0.004	0.057	0.144	0.021	−0.011	−0.014	−0.033	0.12	−0.103	−0.046	−0.038	0.019	0.186
		p	.431	.964	.533	.116	.816	.9	.877	.718	.187	.259	.621	.674	.839	.04*
16	Left Hippocampus / TBV	R	−0.097	0.118	0.031	−0.257	0.058	0.046	−0.111	0.059	−0.015	0.107	−0.086	0.004	−0.213	0.6	0.023
		p	.286	.194	.734	.005**	.526	.614	.224	.523	.872	.241	.353	.967	.02*	<.001**	.804
17	Right Hippocampus / TBV	R	0.003	0.083	0.034	0.032	−0.072	0.037	−0.091	−0.053	0.09	0.054	−0.053	−0.078	−0.042	0.125	0.641	0.12
		p	.972	.365	.708	.727	.433	.682	.317	.566	.322	.555	.562	.39	.649	.171	<.001**	.186

**p < .01, *p < .05. PRAQ-R2 = Pregnancy Related Anxiety Questionnaire Revised 2; SCL = Symptom Checklist 90; EPDS = Edinburgh Postnatal Depression Scale; BMI = Body Mass Index; CNS = central nervous system; TBV = total brain volume.

Table 4. Associations between Pregnancy-related anxiety Questionnaire scores at GW24 and newborn amygdalar and hippocampal volumes.

Volumes		PRAQ-R2 GW 24
ALL	Effect type	Adj R^2	β	p	Adj p^1	Partial η^2	Cl
Left AG / TBV	Main effect	−0.042	−4.7E-8	1.000	1.000	0.0E0	−1.3E-6 − 1.2E − 6
	Sex interaction	0.001	2.9E − 6	.017*^a	0.136	0.050	5.5E − 7 − 5.4E − 6
Right AG / TBV	Main effect	0.008	2.2E − 7	.724	0.943	0.001	−1.0E − 6 − 1.4E − 6
	Sex interaction	0.025	2.2E − 6	.084	0.336	0.026	−3.0E − 7 − 4.7E − 6
Left HC / TBV	Main effect	0.008	−4.0E − 7	.825	0.943	4.3E − 4	−4.0E − 6 − 3.2E − 6
	Sex interaction	0.012	−4.5E − 6	.225	0.548	0.013	−1.2E − 5 − 2.8E − 6
Right HC / TBV	Main effect	0.000	−1.9E − 6	.274	0.548	0.010	−5.2E − 6 − 1.4E − 6
	Sex interaction	−0.007	−1.7E − 6	.616	0.943	0.002	−8.5E − 6 − 5.1E − 6
MALES
Left AG / TBV	Main effect	−0.037	−1.3E − 6	.143	0.408	0.035	−3.0E − 6 − 4.5E − 7
Right AG / TBV	Main effect	−0.038	−7.5E − 7	.381	0.435	0.013	−2.5E − 6 − 9.5E − 7
Left HC / TBV	Main effect	0.011	2.5E − 6	.314	0.419	0.017	−2.5E − 6 − 7.6E − 6
Right HC / TBV	Main effect	−0.084	−5.8E − 7	.789	0.789	0.001	−4.9E − 6 − 3.7E − 6
FEMALES
Left AG / TBV	Main effect	0.057	1.8E − 6	.039*^b	0.312	0.087	9.3E − 8 − 3.5E − 6
Right AG / TBV	Main effect	−0.033	1.4E − 6	.153	0.408	0.043	−5.5E − 7 − 3.4E − 6
Left HC / TBV	Main effect	0.074	−3.0E − 6	.266	0.419	0.026	−8.4E − 6 − 2.3E − 6
Right HC / TBV	Main effect	0.091	−3.4E − 6	.220	0.419	0.032	−9.0E − 6 − 2.1E − 6

*Significant results (p < .05) (uncorrected for multiple comparisons). Results are adjusted for infant total age, infant birthweight, maternal education, and maternal BMI. Results for all are also adjusted for infant sex. AG = amygdala; HC = hippocampus, TBV = total brain volume, GW = gestational week, PRAQ-R2 = Pregnancy-related Questionnaire Revised 2; a) p < .05 controlling for second trimester EPDS & SCL sum score (p = .010), maternal prenatal CNS affecting medication (p = .008) and substance use (p = .003), birth complications (p = .029), gestational diabetes (p = .012) and hypertension/pre-eclampsia (p = .036); b) p < .05 controlling for second trimester EPDS & SCL sum score (p = .036) as well as maternal prenatal CNS affecting medication (p = .019) and substance use (p = .008), but p > .05 controlling for birth complications (p = .055), gestational diabetes (p = .137) and hypertension/pre-eclampsia (p = .148).¹⁾ p Values adjusted for multiple comparisons using Benjamini-Hochberg method. The corrections were performed separately for the eight tests including all the children (main effects and sex interactions) and for the eight sex-wise effects.

Figure 2. Scatter plots of the associations between Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2) at GW24 and newborn amygdalar volumes in males and females. The significant association between PRAQ-R2 and female left amygdalar volume (p = .039) is on the left.

Two scatter plot graphs side-by-side. The left-side graph plots the associations between the left amygdalar volume and the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The right-side graph plots the associations between the right amygdalar volume and the PRAQ-R2. Blue dots and lines mark the male subjects on both graphs. In both cases the line slopes downwards, with this being more pronounced in the left-side graph. Yellow dots and lines mark the female subjects. Both lines slope upwards on graphs.