Association of maternal serum levels of soluble endoglin with small-for-gestational-age and preterm births

Abstract

SMALL-FOR-GESTATIONAL-AGE AND PRETERM BIRTHS JILLIAN TSAI, KAI YU, CONG QIAN, CHUN LAM, ANANTH KARUMANCHI, RICHARD LEVINE, Vanderbilt University School of Medicine, Nashville, Tennessee, Department of Health and Human Services, National Institute of Child Health and Human Development, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, Maryland, Allied TechnologyGroup, Rockville,Maryland, Center for Vascular Biology, Division of Nephrology, Department ofMedicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts OBJECTIVE: An imbalance of circulating angiogenic factors may contribute to the pathogenesis of small-for-gestational-age (SGA) births and spontaneous preterm delivery. We hypothesized that maternal levels of circulating soluble endoglin (sEng), an anti-angiogenic factor which binds TGF, are associated with SGA and preterm births. STUDY DESIGN: Random sample of 2200 women from the Calcium for Preeclampsia Prevention trial in healthy nulliparas. SGA was !10th percentile birthweight for GA, parity, infant sex, and race. After excluding women with gestational hypertension or preeclampsia and those without spontaneous onset of labor, 1206 subjects remained of whom 89 delivered SGAand 111 preterm infants. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the 2d, 3d, or 4th quartilesofsEngto the1stquartile (lowest)were computedusing logistic regression, controlling formaternal bodymass index, age, gestational age at sample collection, smoking, race (for preterm births only), and PlGF and sFlt1 levels. RESULTS: In samples obtained at 21-32 (P=0.04) and 33-42 (P=0.09) weeks women who delivered SGA infants had higher sEng levels than women with infants of appropriate size. Similarly, compared to subjects with full-term deliveries, those with preterm deliveries had higher sEng levels at 21-32 (P=0.01) and 33-42 (P=0.01) weeks. In multivariate analyses sEng was positively associated with SGA at 33-42 weeks: ORs (95% CIs) by sEng quartiles: 1.00, 1.29 (0.59-2.84), 2.52 (1.16-5.47), and 2.49 (1.05-5.89). sEng also showed marginal significant associations with preterm delivery at 21-32 weeks: ORs (95% CIs) by sEng quartiles: 1.00, 0.80 (0.42-1.52), 1.63 (0.88-3.03), and 1.11 (0.98-1.25). CONCLUSION: Higher levels of sEng at 33-42 weeks were associated with SGA and at 21-32 weeks were marginally associated with preterm delivery. These associations may indicate a role for sEng in the pathogenesis of intrauterine growth restriction and spontaneous preterm delivery through blockade of TGF signaling, reducing vasodilation and placental perfusion.