Association between indicators of systemic inflammation biomarkers during puberty with breast density and onset of menarche

Michels, Karin B.; Keller, Kristen; Pereira, Ana; Kim, Claire E.; Santos, José L.; Shepherd, John; Corvalan, Camila; Binder, Alexandra M.

doi:10.1186/s13058-020-01338-y

Table 5 Association of quartiles of inflammatory markers measured at Tanner 2 and Tanner 4 with relative time to menarche

From: Association between indicators of systemic inflammation biomarkers during puberty with breast density and onset of menarche

Inflammatory marker	Breast Tanner stage				Relative time to menarche compared to Q1; time ratio (95% CI)^F
Inflammatory marker	Breast Tanner stage	N	Events^G	LRT p value^D	Q2	Q3	Q4	p for Trend^E
Age-adjusted model^A
CRP	Tanner 2	348	302	0.167	0.99 (0.97–1.01)	1.00 (0.99–1.02)	0.98 (0.97–1.00)	0.299
CRP	Tanner 4	298	291	< 0.0001	0.98 (0.97–1.00)*	1.01 (1.00–1.02)	1.02 (1.01–1.04)**	< 0.001
IL-6	Tanner 2	381	335	0.532	1.00 (0.98–1.02)	1.00 (0.98–1.02)	0.99 (0.97–1.01)	0.157
IL-6	Tanner 4	298	291	0.463	1.01 (0.99–1.02)	1.01 (1.00–1.03)	1.01 (1.00–1.03)	0.157
TNFR2	Tanner 2	381	335	0.103	1.01 (0.99–1.03)	1.00 (0.98–1.02)	0.98 (0.96–1.00)	0.047
TNFR2	Tanner 4	298	291	0.217	1.01 (1.00–1.03)	1.01 (0.99–1.02)	1.00 (0.98–1.02)	0.666
Age and body fatness-adjusted model^B
CRP	Tanner 2	347	301	0.280	0.99 (0.97–1.01)	1.00 (0.99–1.02)	0.99 (0.97–1.01)	0.451
CRP	Tanner 4	298	291	< 0.001	0.98 (0.97–1.00)*	1.01 (0.99–1.02)	1.02 (1.00–1.03)*	0.001
IL-6	Tanner 2	380	334	0.602	1.00 (0.98–1.02)	1.00 (0.98–1.02)	0.99 (0.97–1.01)	0.197
IL-6	Tanner 4	298	291	0.758	1.01 (0.99–1.02)	1.01 (0.99–1.02)	1.01 (0.99–1.02)	0.484
TNFR2	Tanner 2	380	334	0.121	1.01 (0.99–1.03)	1.00 (0.98–1.02)	0.98 (0.96–1.00)	0.058
TNFR2	Tanner 4	298	291	0.136	1.01 (1.00–1.03)	1.00 (0.99–1.02)	1.00 (0.98–1.01)	0.365
Multivariable-adjusted model^C
CRP	Tanner 2	336	291	0.260	0.99 (0.97–1.01)	1.01 (0.99–1.02)	0.99 (0.97–1.01)	0.839
CRP	Tanner 4	291	284	< 0.0001	0.98 (0.97–1.00)*	1.01 (1.00–1.02)	1.02 (1.00–1.03)*	< 0.001
IL-6	Tanner 2	369	324	0.048	1.00 (0.98–1.02)	1.00 (0.98–1.02)	0.97 (0.95–0.99)**	0.010
IL-6	Tanner 4	291	284	0.897	1.01 (0.99–1.02)	1.00 (0.99–1.02)	1.00 (0.99–1.02)	0.782
TNFR2	Tanner 2	369	324	0.062	1.01 (0.99–1.03)	0.99 (0.97–1.00)	0.98 (0.97–1.00)	0.044
TNFR2	Tanner 4	291	284	0.128	1.02 (1.00–1.03)*	1.01 (0.99–1.02)	1.00 (0.99–1.02)	0.911

^AAccelerated failure time model for time to menarche from birth adjusting for age at inflammatory biomarker measurement
^BModel adjusting for age at inflammatory biomarker measurement and fat percentage at biomarker measurement
^CModel adjusting for age at inflammatory biomarker measurement, fat percentage at biomarker measurement, ethnicity, birth weight, height age- and sex-specific Z-score, and maternal education
^DLikelihood ratio test (LRT) p value for whether the addition of inflammatory biomarker quartiles improved model fit relative to the model without indicators for inflammatory biomarker quartiles
^EWald test p value for log-transformed median within each quartile included as a continuous covariate in models adjusting for age at inflammatory biomarker measurement, fat percentage at biomarker measurement, ethnicity, birth weight, height age- and sex-specific Z-score, and maternal education
^FInflammatory marker quartiles at Tanner 2: CRP (mg/L) [0.1–0.3], [0.4–0.7], [0.8–2.2], [2.3–15.7]; IL-6 (pg/mL) [0.3–0.8], [0.9–1.3], [1.4–2.2], [2.3–30.4]; TNFR2 (pg/mL) [944.4–1894.1], [1897.2–2169.0], [2171.9–2533.7], [2545.9–4902.5]. Inflammatory marker quartiles at Tanner 4: CRP (mg/L) [0.1–0.2], [0.2–0.5], [0.5–1.9], [2.0–18.9]; IL-6 (pg/mL) [0.3–0.8], [0.9–1.3], [1.4–2.1], [2.2–24.0]; THFR2 (pg/mL) [1106.7–1960.4], [1971.3–2271.1], [2275.8–2638.1], [2639.9–4753.3]
^GNumber of girls reaching menarche during follow-up period
* p < 0.05
**p < 0.01
***p < 0.001

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