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Soluble fms-Like Tyrosine Kinase 1 Is Increased in Preeclampsia But Not in Normotensive Pregnancies with Small-for-Gestational-Age Neonates: Relationship to Circulating Placental Growth Factor

Magee-Womens Research Institute (E.S., A.R., R.W.P., C.G., L.M.B., W.R.C., R.B.N., J.M.R., C.A.H.) and Department of Obstetrics, Gynecology & Reproductive Sciences (A.R., R.W.P., R.W.L., W.R.C., R.B.N., J.M.R., C.A.H.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Pediatrics (C.G.), Allegheny General Hospital, Pittsburgh, Pennsylvania 15212; and Departments of Epidemiology (R.B.N., J.M.R.) and Environmental and Occupational Health (C.A.H.), University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261

Address all correspondence and requests for reprints to: Carl A. Hubel, Ph.D., Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, Pennsylvania 15213. E-mail: rsicah{at}mwri.magee.edu.

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease.

Objective: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates.

Study Design: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta).

Results: sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ.

Conclusions: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

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