Table 3.

Proportional hazards analysis to determine the effects of PFAS serum concentrations on time to pubertal event for girls in the puberty cohort study, 2004–2024.

	Thelarche				Pubarche				Menarche
PFAS (ng/mL)a	$n$	HR	95% CI	$p$-Value	$n$	HR	95% CI	$p$-Value	$n$	HR	95% CI	$p$-Value
PFOAa	703	0.92	0.76, 1.10	0.36	700	0.83	0.70, 0.99	0.04	698	0.04b	0.01, 0.25	$<0.01$
PFOA categorical
Serum PFOA $\le 4.9$	182	1.00	Ref	—	181	1.00	Ref	—	181	1.00	Ref	—
$4.9<\text{serum}$ PFOA $\le 6.4$	178	1.05	0.84, 1.30	0.68	178	0.98	0.79, 1.23	0.87	177	0.93	0.74, 1.17	0.56
$6.4<\text{serum}$ PFOA $\le 8.55$	174	0.82	0.65, 1.02	0.07	172	0.79	0.63, 0.99	0.04	171	0.93	0.73, 1.17	0.53
$8.55<\text{serum}$ PFOA	169	0.88	0.70, 1.12	0.29	169	0.78	0.61, 0.99	0.04	169	0.02b	0.00, 0.20	$<0.01$
PFOSa	704	0.45b	0.17, 1.23	0.12	701	0.90	0.79, 1.01	0.08	699	0.18b	0.05, 0.63	0.01
PFOS categorical
Serum PFOS $\le 9.1$	180	1.00	Ref	—	179	1.00	Ref	—	178	—	Ref	—
$9.1<\text{serum}$ PFOS $\le 13.1$	177	0.95	0.76, 1.19	0.63	176	1.02	0.82, 1.29	0.84	177	0.96	0.76, 1.22	0.76
$13.1<\text{serum}$ PFOS $\le 19.1$	172	0.88	0.70, 1.10	0.27	171	0.19b	0.05, 0.78	0.02	169	0.75	0.59, 0.96	0.02
$19.0<\text{serum}$ PFOS	175	0.79	0.63, 0.98	0.03	175	0.74	0.59, 0.92	0.01	175	0.09b	0.01, 0.76	0.03
PFNAa	704	0.23b	0.07, 0.79	0.02	701	0.89	0.76, 1.05	0.16	699	1.06	0.89, 1.27	0.50
PFHxSa	704	0.93	0.87, 1.01	0.07	701	0.98	0.91, 1.05	0.55	699	0.95	0.88, 1.03	0.23
PFDeAa	641	0.85	0.72, 1.00	0.05	638	0.90	0.76, 1.06	0.20	636	0.94	0.79, 1.11	0.47
Me-PFOSA-AcOHa	704	0.42b	0.19, 0.93	0.03	701	0.88	0.80, 0.97	0.01	699	0.97	0.87, 1.08	0.61
Sum of PFASa	641	0.89	0.77, 1.02	0.89	638	0.87	0.76, 1.00	0.06	636	0.19b	0.04, 0.84	0.03

Note: All models were adjusted for race, BMI at closest visit prior to pubertal event, and site. Models of menarche were also adjusted for mother’s age of menarche. Significance declared at $p$-value $\le 0.05$. —, Not applicable; BMI, body mass index; CI, confidence interval; HR, hazard ratio; Me-PFOSA-AcOH, $2\text{-}\left(N\text{-methyl-perfluorooctane sulfonamido}\right)$ acetic acid; PFAS, per- and polyfluoroalkyl substances; PFDeA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonate; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perflurooctanesulfonic acid; Ref, reference.

^a All exposures were modeled as continuous and log transformed except when noted as categorical.

^b For models in which the proportional hazards assumption failed, a time-dependent covariate was included in the model. HRs reported in this table are prior to incorporating the time-dependent covariate. For example, with incorporating the covariate $\text{PFOA}\times \text{age}$ of the girl, the effect of log-transformed PFOA serum concentration on age at menarche was statistically significant at 11 ($\text{HR}=$ 0.57; 95% CI: 0.43, 0.77) or 12 years of age ($\text{HR}=$ 0.73; 95% CI: 0.59, 0.89).