Prepregnancy physiology and subsequent preterm preeclampsia

BACKGROUND: Preeclampsia is a common pregnancy complication with debated etiology. OBJECTIVE: To evaluate the contribution of prepregnancy physiology, biochemistry, and anthropometrics to the subsequent development of preterm preeclampsia. STUDY DESIGN: One hundred twenty-four participants were recruited through open recruitment and targeted mailings. Participants included 81 nulliparous women and 43 with a history of preterm preeclampsia. We characterized cardiovascular function, metabolic profile, and body composition in 100 nonpregnant women who went on to subsequent pregnancy. Measures included plasma volume, baseline cardiovascular function and cardiovascular response to volume challenge, body composition, and circulating biochemical measures. Pregnancy outcome was obtained through chart review. Prepregnancy metrics for women who developed preterm preeclampsia were compared with measurements for those who did not, with adjustment for a history of prior preterm preeclampsia. Logistic regression modeling was used to identify the strongest prepregnancy factors associated with preterm preeclampsia. RESULTS: Pregnancy outcomes included 11 women with preterm preeclampsia, 7 women with term preeclampsia, 20 women with other hypertension affecting their pregnancy, and 62 with uncomplicated pregnancies. We observed no difference in maternal age, study cycle day, lean body mass, uterine hemodynamics, or flow-mediated dilation across groups. Women with preterm preeclampsia had greater android fat content 3215 +/- 1143 vs 1918 +/- 1510 g (P=.002), faster supine pulse, 77 +/- 7 vs 67 +/- 10 beats per minute (P=.001), higher supine diastolic blood pressure 82 +/- 6 vs 68 +/- 6 mmHg (P<.001), increased cardiac output 5.6 +/- 1.1 vs 4.6 +/- 1 L/min (P=.002), faster aorticpopliteal pulse wave velocity 4.5 +/- 0.7 vs 3.8 +/- 0.5 m/sec (P<.001), and exaggerated cardiac output response to volume challenge 20 +/- 9 vs 9 +/- 12 L/min (P=.002) compared to those with other pregnancy outcomes. Women who developed preterm preeclampsia also had reduced renal vascular resistance index 0.86 +/- 0.08 vs 0.97 +/- 0.12 (P=.005) compared with other pregnancy outcomes when assessed prior to pregnancy. Women with subsequent preterm preeclampsia had higher serum c-reactive protein 10.7 +/- 12.5 vs 4.1 +/- 5.8 mg/mL (P=.003) and greater insulin resistance, as assessed by Homeostatic Model Assessment for Insulin Resistance calculation 2.2 +/- 1.1 vs 1.2 +/- 0.9 (P<.001). CONCLUSION: Prepregnancy physiology is linked to subsequent preterm preeclampsia. The same factors associated with metabolic syndrome are more prominent in patients who develop preterm preeclampsia than those who do not, including increased vessel stiffness, low vascular compliance, high cardiac output, reduced renal vascular resistance index, insulin resistance, and increased android fat, all consistent with subclinical features of the metabolic syndrome.