TABLE 3.

Association of cytokines induced by innate stimulations with birth outcomes.

Compartment	Agonist	Receptor	Receptor localization	Cytokine ratio	Cytokine group	Coefficient (%)a	95% CI	P-valueb	BH P-valuec
Birth weight
Periphery	R848	TLR7/8	Endosomal	IL-12p70	TH1	0.599	0.019; 1.181	0.043	0.983
Placenta	R848	TLR7/8	Endosomal	IL-12p40	TH17	0.366	0.036; 0.697	0.031	0.983
Fetal hemoglobin
Periphery	MDP	NOD2	Cytosolic	IFN-γ	TH1	–32.054	−47.201; −12.561	0.004	0.294
Periphery	PAM	TLR1/2	Surface	IL-6	TH17	3.625	1.049; 6.267	0.007	0.294
Periphery	LPS	TLR4	Surface	IL-6	TH17	3.499	0.975; 6.086	0.007	0.294
Periphery	R848	TLR7/8	Endosomal	IL-6	TH17	2.594	0.307; 4.932	0.027	0.601
Periphery	R848	TLR7/8	Endosomal	IL-8	Pro-inflammatory	5.578	1.963; 9.321	0.003	0.294
Periphery	pI:C	TLR3	Endosomal	IL-8	Pro-inflammatory	8.297	2.803; 14.084	0.004	0.294
Periphery	PAM	TLR1/2	Surface	IL-8	Pro-inflammatory	5.675	1.731; 9.773	0.006	0.294
Periphery	PGN	NOD1/2	Cytosolic	IL-8	Pro-inflammatory	4.243	1.068; 7.517	0.01	0.360
Periphery	LPS	TLR4	Surface	IL-8	Pro-inflammatory	5.271	1.141; 9.569	0.013	0.410
Periphery	MDP	NOD2	Cytosolic	IL-8	Pro-inflammatory	6.625	1.011; 12.551	0.021	0.588
Periphery	PAM	TLR1/2	Surface	IP10	TH1	2.85	0.031; 5.749	0.048	0.657
Periphery	LPS	TLR4	Surface	MIP-1β	Pro-inflammatory	2.891	0.109; 5.75	0.042	0.657
Periphery	PAM	TLR1/2	Surface	MIP-1β	Pro-inflammatory	2.904	0.094; 5.794	0.043	0.657
Cord	PGN	NOD1/2	Cytosolic	IL-12p40	TH17	–5.078	−9.712; −0.207	0.042	0.657
Cord	PGN	NOD1/2	Cytosolic	IL-12p70	TH1	–13.054	−23.336; −1.393	0.03	0.601
Cord	pI:C	TLR3	Endosomal	IL-1β	Pro-inflammatory	–4.931	−9.182; −0.48	0.031	0.601
Cord	pI:C	TLR3	Endosomal	MDC	Pro-inflammatory	–10.339	−18.504; −1.356	0.026	0.601
Gestational age
Placenta	R848	TLR7/8	Endosomal	IL-12p40	TH17	0.092	0.003; 0.182	0.044	0.837
Placenta	LPS	TLR4	Surface	IP10	TH1	–0.104	−0.179; −0.028	0.008	0.837
Placenta	MDP	NOD2	Cytosolic	IP10	TH1	–0.089	−0.159; −0.02	0.013	0.837
Placenta	PAM	TLR1/2	Surface	IP10	TH1	–0.094	−0.174; −0.014	0.023	0.837
Placenta	MDP	NOD2	Cytosolic	TNF	Pro-inflammatory	0.13	0.024; 0.236	0.018	0.837
Placenta	PAM	TLR1/2	Surface	TNF	Pro-inflammatory	0.094	0.006; 0.182	0.038	0.837
Cord	MDP	NOD2	Cytosolic	IL-8	Pro-inflammatory	–0.123	−0.225; −0.02	0.021	0.837

Only results with raw p-values ≤ 0.05 are shown. ^aCoefficients show the difference in percentage in the outcome with 10% increases in cytokine ratios. It was calculated as (1.10^beta-1) × 100 and beta was obtained in multivariable regression models adjusted by age (log₁₀-transformed) and technical batch with cytokine ratios (log₁₀-transformed) as predictor variable and birth outcomes as dependent variable. Birth weight and gestational age were log₁₀-transformed. ^bRaw p-value. ^cSignificance was established at a Benjamini–Hochberg (BH) adjusted p-value ≤ 0.3. P-values were adjusted by a total of 252 tests performed for each independent variable.