Table 4. Random-slope, random intercept linear mixed-effects modeling showed that malaria infection at Visit 1 (13–23 weeks) was associated with changes in inflammatory and angiogenic mediators across pregnancy.

Fixed effects included a spline of gestational age, treatment group, maternal age, gravidity, socioeconomic status, educational status, BMI, and hemoglobin at Visit 1. Malaria status at Visit 1 (13–23 weeks) was added to the model, and an interaction term for gestational age and malaria status was added to a third model; then the models were compared (χ², p value). A restricted cubic spline of gestational age was used as both main effect and in interaction terms. Extended tables including estimates for all fixed effects and parameters of model fit (AIC, BIC) are available in the supporting information (S4–S6 Tables).

Mediator	Number of subjects	Number of observations	Malaria positive at Visit 1		LR test
			Estimate	Standard error	χ2	p Value
sICAM-1	1,460	3,142	0.344	0.088	40.8	<0.001
CRP	1,394	3,007	1.010	0.123	99.0	<0.001
CHI3L1	1,460	3,142	0.300	0.081	21.9	<0.001
sTNFRII	1,460	3,142	0.954	0.069	209.2	<0.001
IL-18BP	1,460	3,140	0.383	0.053	44.7	<0.001
Angptl3	1,460	3,142	0.200	0.075	13.29	0.001
Leptin	1,460	3,135	-0.062	0.064	13.16	0.001
PlGF	1,460	3,135	-0.116	0.070	2.89	0.236
sFlt-1	1,460	3,135	0.042	0.050	1.09	0.580
sEng	1,460	3,135	0.329	0.049	38.26	<0.001

Significant p-values (p < 0.05) are bolded.

Abbreviations: AIC, Akaike information criterion; Angptl3, Angiopoietin-like 3; BIC, Bayesian information criterion; BMI, body mass index; CHI3L1, Chitinase 3-like protein-1; CRP, C-Reactive Protein; IL-18BP, Interleukin 18 Binding Protein; LR, likelihood ratio; PlGF, placental growth factor; sEng, soluble Endoglin; sFlt-1, soluble Fms-like Tyrosine Kinase-1; sICAM-1, soluble Intercellular Adhesion Molecule-1; sTNFRII, soluble Tumor Necrosis Factor receptor II