body mass index (BMI) and 1st-and 2nd-trimester concentrations of sFlt-1/PlGF as a potential biologic pathway for placental insufficiency. STUDY DESIGN: We conducted secondary analyses of data and samples from a large, multi-site prospective cohort study of nulliparous pregnant women conducted in the U.S. First-and 2nd-trimester blood samples, 1st-trimester BMI, demographic, lifestyle, and pregnancy data were gathered for all participants. sFlt-1 and PlGF concentrations were measured for a subsample of 1,502 cases (delivery<37weeks, preeclampsia or eclampsia, birthweight for gestational age <5th%, or stillbirth) and 911 controls. We used one-way ANOVA and multivariable linear and logistic regression models to test the association of BMI and sFlt-1/PlGF ratio, using a previously published ratio cutoff of 38 in logistic regression. We identified potential confounders a priori and used backward elimination to determine the best-fit model. RESULTS: Plots of mean sFlt-1/PlGF ratios by BMI category and gestational week showed lower ratios in overweight and obese groups in the 1st trimester, which reversed to higher ratios among overweight and obese groups in the 2nd trimester (Fig. 1). After controlling for clinical and demographic factors, women in all high BMI groups had significantly lower mean sFlt-1/PlGF ratios than normal weight women in the 1st trimester (Table 1). In the 2nd trimester, women with BMI 35 had a 35% higher mean sFlt-1/PlGF ratio than normal weight women (p¼0.009). Logistic regression suggested increased odds of a 2nd-trimester ratio 38 among women with BMI 35, though not statistically different from 1.0 (OR 2.59, 95% CI 0.95-7.08). CONCLUSION: Early pregnancy BMI is associated with alterations in firstand second-trimester sFlt-1/PlGF ratios. Findings suggest a potential physiologic pathway between obesity and placental insufficiency.

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