Infant cortisol stress–response is associated with thymic function and vaccine response

Figures & data

Table 1. Characteristics of the participants.

Characteristics	n^a	Statistics^b
Mother age, year	229	23.3 ± 4.07
Gestational age, week	227	39.3 ± 1.58
Birth weight, kg	229	2.73 ± 0.375
Birth length, cm	229	46.5 ± 2.17
Sex, boys	229	46.7%
Type of delivery, C-section	229	59.8%
WHZ score (week)
6	229	–0.028 ± 1.16
10	227	–0.215 ± 1.290
15	227	–0.310 ± 1.175
WHZ-score <–2 WHZ (week)
6	229	4.80%
10	227	7.42%
15	227	7.42%
HAZ-score (week)
6	229	–1.07 ± 1.06
10	227	–0.834 ± 0.984
15	227	–0.853 ± 1.02
HAZ-score <–2 HAZ (week)
6	229	17.5%
10	227	10.0%
15	227	11.9%
Exclusive breastfeeding (week)
at 1	229	82.5%
up to 6	229	59.4%
up to 10	227	40.1%
up to 15	227	28.2%

^aGestational age was not available from two subjects. Two subjects withdraw consent at 10 weeks thus total subjects were 227 at 10 and 15 weeks of age.

^bMean ± SD or frequency.

Figure 1. Post-vaccine salivary cortisol was significantly higher than pre-vaccine cortisol (n = 229). Comparison was calculated by independent two group t-test. Box =25th–75th percentile, whiskers =10th–90th percentile, + = mean, horizontal bar = median, *** = p < .001.

Table 2. Associations between thymic indices and 6 week vaccination-induced cortisol responsiveness (ΔCortisol) in infants determined by multivariate regression modeling.

	Male				Female
	Regression model		ΔCortisol (µg/dL)		Regression model		ΔCortisol (µg/dL)
	R^2	p	β (SE)	p	R^2	p	β (SE)	p
Thymic index (week)
1	0.243	.016	–5.50 (1.81)	.0032	0.346	<.001	1.60 (1.46)	.28
6	0.315	<.001	–10.4 (2.95)	<.001	0.216	.0085	–1.278 (2.97)	.67
10	0.286	.0028	–11.6 (3.21)	<.001	0.172	.021	–2.309 (2.92)	.43
15	0.222	.034	–12.5 (3.27)	<.001	0.204	.014	–1.99 (3.04)	.51

Regression models determined association between thymic index and cortisol response (ΔCortisol) controlling the factors: infant’s behavior during saliva collection, saliva collection time, pre-vaccine cortisol, mode of delivery, birthweight, length for age Z-score, weight for length Z-score and breastfeeding status. 1 week regression model was determined using birthweight and birth length instead of weight for length and length for age Z-scores, respectively.

Table 3. Associations between T cell concentrations and TREC concentrations (per million PBMC) and 6 weeks vaccination-induced cortisol responsiveness in infants determined by multivariate regression modeling.

	Regression model		ΔCortisol (µg/dL)
	R^2	p	β (SE)	p
Total T cells (week)
6	0.135	.0064	–1974 (904)	.030
15	0.0512	.63	–1889 (1192)	.12
CD4^+ T cells(week)
6	0.189	<.001	–1685 (619)	.0071
15	0.132	.0067	–1773 (720)	.015
Total naïve T cells(week)
6	0.143	.0034	–2225 (819)	.0072
15	0.064	.41	–2032 (1078)	.061
Naïve CD4^+ T cells(week)
6	0.209	<.001	–1671 (565)	.0035
15	0.134	.0056	–1800 (675)	.0083
Total memory T cells(week)
6	0.0652	.41	0.300 (0.484)	.54
15	0.0683	.34	0.208 (0.395)	.60
Memory CD4^+ cells(week)
6	0.0461	.74	0.193 (0.370)	.60
15	0.0599	.48	–0.988 (0.295)	.74
TREC levels(week)
6	0.0903	.26	225.3 (309)	.47
15	0.0583	.66	4.59 (295.7)	.99

Regression models determined association between immune cells and cortisol response (ΔCortisol) controlling the factors: infant’s behavior during saliva collection, saliva collection time, pre-vaccine cortisol, sex, mode of delivery, birthweight, length for age Z-score, weight for length Z-score and breastfeeding status.

Figure 2. Predicted probability of observing positive PPD skin test at 15 weeks by cortisol responsiveness quartiles in normally delivered exclusively breastfeed infants having median baseline cortisol, cortisol collection time, HAZ and WHZ scores. Bar represents 95% CI. Mean and CI were predicted from the regression model described in the Table 4.

Table 4. Associations between vaccine responses and 6-week vaccination-induced cortisol responsiveness in infants.

	Regression model		ΔCortisol (µg/dL)
	R^2	p	β (SE)	p
CD4^+ T-cell SI at 6 weeks
PPD	0.119	.23	–0.286 (0.958)	.77
SEB	0.0947	.46	–1.22 (1.18)	.30
CD4^+ T-cell SI at 15 weeks
PPD	0.0718	.48	0.428 (1.08)	.69
SEB	0.0676	.68	–0.517 (1.01)	.61
TT	0.0786	.36	40.5 (58.2)	.49
HBV	0.141	.024	34.1(55.7)	.54
ALS antibody at 15 weeks
TT IgG, mIU/mL	0.0592	.564	–1.26 (1.33)	.35
Polio IgG, mIU/mL	0.0933	.14	1.26e–06 (6.75e–07)	.065
HBV IgG, mIU/mL	0.157	.13	–0.0197 (0.0245)	.43
PPD skin test at 15 weeks
Area (cm^2)	0.0659	.37	–110.4 (55.8)	.049
Positive (n = 187), Negative =0 (n = 37)	–		–5.31 (2.51)	.034

Regression models determined association between vaccine response and cortisol response (ΔCortisol) controlling the factors: infant’s behavior during saliva collection, pre-vaccine cortisol, saliva collection time, sex, mode of delivery, birthweight, length for age Z-score, weight for length Z-score and breastfeeding status.