Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

Figures & data

Table 1. Characteristics of children who contributed serum antibody concentrations at the two follow-up examinations in Cohort 5.

	Age 18 months (N = 275)	Age 5 years (N = 349)
	n (%)	n (%)
Sex, girls	139 (50.6)	173 (49.6)
	Median (25; 75 percentile)	Median (25; 75 percentile)
Age (months)	18.5 (18.1; 18.9)	60.4 (59.9; 60.9)
PFOS (ng/ml)	7.1 (4.5; 10.0)	4.7 (3.5; 6.3)
PFOA (ng/ml)	2.8 (2.0; 4.5)	2.2 (1.8; 2.8)
PFHxS (ng/ml)	0.2 (0.1; 0.4)	0.3 (0.2; 0.4)
PFNA (ng/ml)	1.0 (0.6; 1.5)	1.1 (0.8; 1.6)
PFDA (ng/ml)	0.3 (0.2; 0.4)	0.3 (0.2; 0.5)
Tetanus (IU/ml)	1.5 (0.5; 3.0)	0.1 (0.1; 0.3)
Diphtheria (IU/ml)	1.6 (0.8; 3.2)	0.1 (0.1; 0.3)
Duration of exclusive breastfeeding (months)	5 (4; 6)
Duration of mixed breastfeeding (months)	4 (2; 7)

Table 2. Change (in percent) of the pre-booster serum-antibody concentrations at age 5 years associated with a doubling of the serum concentration of major PFASs at three different times of examination.

	Cohort 5			Cohort 3			Joint
	Change	95% CI	p	Change	95% CI	p	Change	95% CI	p
Tetanus
At birth
PFOS	−10.84	−28.34; 10.94	0.30	−10.09	−31.78; 18.51	0.45	−10.55	−24.63; 6.16	0.20
PFOA	−22.25	−35.25; –6.63	0.007	−10.46	−28.04; 11.41	0.32	−17.59	−28.38; –5.17	0.007
PFHxS	−11.31	−21.72; 0.49	0.060	−6.30	−15.05; 3.34	0.19	−8.24	−15.05; –0.89	0.029
PFNA	−7.11	−26.59; 17.53	0.54	11.16	−8.46; 34.98	0.29	3.36	−11.02; 20.07	0.67
PFDA	−8.40	−26.27; 13.79	0.43	−2.45	−18.39; 16.61	0.79	−4.90	−17.14; 9.15	0.47
18 months
PFOS	−7.027	−21.63; 10.30	0.40	−8.05	−55.26; 89.01	0.82	−7.08	−21.29; 9.70	0.39
PFOA	−16.31	−29.04; –1.31	0.034	−19.24	−59.75; 62.05	0.55	−16.47	−28.84; –1.96	0.028
PFHxS	−2.616	−10.08; 5.47	0.51	−5.18	−51.71; 86.19	0.88	−2.65	−10.05; 5.36	0.50
PFNA	−6.981	−21.10; 9.67	0.39	−33.79	−64.36; 23.01	0.19	−9.04	−22.43; 6.65	0.24
PFDA	−5.780	−23.56; 16.13	0.58	−14.47	−56.88; 69.66	0.65	−6.55	−23.47; 14.09	0.50
60 months
PFOS	−9.076	−28.10; 14.98	0.43	−11.86	−29.79; 10.65	0.28	−10.52	−24.00; 5.35	0.18
PFOA	−25.26	−42.63; –2.64	0.031	−13.28	−31.34; 9.54	0.23	−18.75	−31.79; –3.21	0.020
PFHxS	−4.432	−21.26; 15.99	0.65	−6.29	−17.45; 6.38	0.32	−5.74	−15.22; 4.81	0.27
PFNA	−10.31	−24.39; 6.40	0.21	−5.87	−21.67; 13.12	0.52	−8.28	−19.06; 3.940	0.18
PFDA	−1.756	−16.73; 15.91	0.83	−13.55	−26.18; 1.24	0.071	−8.11	−18.03; 3.01	0.15
Diphtheria
At birth
PFOS	−14.00	−31.59; 8.11	0.20	−38.64	−54.07; –18.04	0.001	−24.47	−36.90; –9.60	0.002
PFOA	−18.93	−33.16; –1.66	0.033	−16.24	−33.43; 5.40	0.13	−17.82	−29.11; –4.74	0.009
PFHxS	−3.33	−15.28; 10.30	0.61	−6.41	−15.62; 3.80	0.21	−5.25	−12.66; 2.79	0.19
PFNA	4.79	−18.21; 34.27	0.71	−14.82	−30.55; 4.47	0.12	−7.38	−20.89; 8.43	0.34
PFDA	−3.54	−23.19; 21.15	0.76	−21.73	−35.09; –5.63	0.010	−14.86	−26.33; –1.60	0.029
18 months
PFOS	17.55	−0.84; 39.34	0.062	−21.21	−61.54; 61.40	0.51	15.07	−2.49; 35.79	0.096
PFOA	4.19	−11.76; 23.02	0.63	30.49	−35.31; 163.21	0.46	5.44	−10.28; 23.92	0.52
PFHxS	7.85	−0.38; 16.76	0.062	−12.42	−55.25; 71.43	0.70	7.54	−0.60; 16.35	0.070
PFNA	24.43	5.72; 46.45	0.009	−35.28	−64.95; 19.48	0.16	19.18	1.72; 39.62	0.030
PFDA	25.52	2.00; 54.48	0.032	−22.87	−60.92; 52.24	0.45	20.42	−1.29; 46.90	0.067
60 months
PFOS	17.17	−8.66; 50.31	0.21	−16.02	−34.01; 6.87	0.16	−1.34	−17.05; 17.34	0.88
PFOA	18.31	−10.72; 56.78	0.24	−6.84	−27.26; 19.30	0.57	3.38	−14.16; 24.50	0.73
PFHxS	4.26	−15.12; 28.08	0.69	4.98	−8.25; 20.13	0.48	4.77	−6.40; 17.26	0.42
PFNA	−8.85	−23.95; 9.25	0.32	−17.70	−32.30; 0.03	0.050	−13.06	−23.86; –0.72	0.039
PFDA	−8.99	−23.63; 8.46	0.29	−15.96	−28.91; –0.66	0.042	−12.71	−22.66; –1.48	0.028

Figure 1. Serum concentrations of (a) PFOA and (b) PFOS at age 18 months, as calculated from neonatal concentration and the duration of breastfeeding (vertical scale) and compared to the measured concentration (horizontal scale).

Table 3. Percentage change in serum-PFAS concentrations per month during exclusive breastfeeding, partial, and none.

		Cohort 5			Cohort 3			Joint
Exposure	Nursing	Change	95% CI	p	Change	95% CI	p	Change	95% CI	p
PFOS	Exclusive	14.76	(13.13, 16.41)	<0.001	21.03	(17.02, 25.19)	<0.001	15.74	(14.24, 17.26)	<0.001
	Mixed	6.32	(5.29, 7.37)	<0.001	3.26	(0.32, 6.29)	0.030	5.99	(5.00, 6.98)	<0.001
	None	−0.07	(−0.50, 0.36)	0.75	−0.71	(−1.77, 0.35)	0.19	−0.2	(−0.60, 0.19)	0.31
PFOA	Exclusive	16.69	(14.82, 18.60)	<0.001	24.05	(19.35, 28.93)	<0.001	17.78	(16.05, 19.54)	<0.001
	Mixed	7.22	(6.04, 8.41)	<0.001	5.08	(1.58, 8.71)	0.004	7.01	(5.88, 8.14)	<0.001
	None	0.8	(0.30, 1.29)	0.002	1.31	(0.04, 2.59)	0.043	0.77	(0.31, 1.23)	0.001
PFHxS	Exclusive	23.91	(19.83, 28.12)	<0.001	−2.95	(−8.46, 2.88)	0.31	20.56	(16.68, 24.56)	<0.001
	Mixed	2.25	(−0.07, 4.61)	0.057	−11.54	(−16.72, −6.04)	<0.001	2.1	(−0.19, 4.45)	0.073
	None	−7.91	(−8.83, −6.98)	<0.001	−16.82	(−18.70, −14.90)	<0.001	−7.48	(−8.38, −6.56)	<0.001
PFNA	Exclusive	13.77	(12.05, 15.51)	<0.001	20.15	(15.82, 24.65)	<0.001	14.55	(12.96, 16.16)	<0.001
	Mixed	8.55	(7.43, 9.69)	<0.001	4.61	(1.37, 7.95)	0.005	8.17	(7.09, 9.25)	<0.001
	None	0.91	(0.45, 1.37)	<0.001	−1.29	(−2.44, −0.12)	0.030	0.66	(0.24, 1.09)	0.002
PFDA	Exclusive	11.5	(9.83, 13.19)	<0.001	14.51	(8.98, 20.32)	<0.001	11.45	(9.85, 13.08)	<0.001
	Mixed	9.64	(8.51, 10.78)	<0.001	5.03	(0.73, 9.51)	0.021	9.49	(8.38, 10.61)	<0.001
	None	4.21	(3.73, 4.69)	<0.001	0.29	(−1.24, 1.86)	0.71	4.05	(3.58, 4.51)	<0.001

Table 4. Effect of doubling in predicted serum concentration of PFOA and PFOA at different ages (in months) with adjustment for differences in dependence on breastfeeding in the two cohorts.

Vaccine/			Cohort 5			Cohort 3			Joint
Exposure	Age	Change	95% CI	p	Change	95% CI	p	Change	95% CI	p
Tetanus
PFOS	3	−20.03	(−38.88, 4.62)	0.10	−24.75	(−53.37, 21.42)	0.24	−21.16	(−37.60, −0.38)	0.046
	6	−13.13	(−30.52, 8.62)	0.22	−27.74	(−46.26, −2.86)	0.031	−18.81	(−32.06, −2.99)	0.022
	12	−6.58	(−22.62, 12.78)	0.48	−16.92	(−32.17, 1.77)	0.073	−11.50	(−22.91, 1.60)	0.083
PFOA	3	−32.63	(−46.72, −14.82)	0.001	−23.03	(−48.45, 14.94)	0.20	−30.35	(−43.20, −14.59)	0.001
	6	−24.81	(−38.43, −8.19)	0.005	−28.17	(−45.08, −6.07)	0.016	−26.06	(−37.01, −13.20)	<0.001
	12	−16.92	(−30.11, −1.25)	0.035	−17.75	(−32.01, −0.51)	0.044	−17.31	(−27.25, −6.02)	0.004
Diphtheria
PFOS	3	−0.90	(−24.02, 29.26)	0.95	−54.36	(−73.91, −20.16)	0.006	−15.30	(−33.08, 7.21)	0.17
	6	3.35	(−17.16, 28.95)	0.77	−27.40	(−47.47, 0.34)	0.052	−7.32	(−22.79, 11.25)	0.42
	12	3.65	(−13.90, 24.78)	0.71	−2.70	(−22.31, 21.85)	0.81	1.12	(−12.38, 16.69)	0.88
PFOA	3	−12.36	(−30.61, 10.69)	0.27	−31.05	(−56.20, 8.54)	0.11	−16.87	(−32.35, 2.15)	0.079
	6	−6.42	(−23.28, 14.14)	0.51	−16.46	(−37.69, 12.02)	0.23	−9.73	(−23.41, 6.39)	0.22
	12	−3.88	(−18.97, 14.02)	0.65	2.63	(−16.87, 26.69)	0.81	−1.28	(−13.54, 12.72)	0.85