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Placental Expression of Soluble fms-Like Tyrosine Kinase 1 is Increased in Singletons and Twin Pregnancies with Intrauterine Growth Restriction

Department of Obstetrics and Gynecology (O.N., J.K., A.B., I.C.) and Samuel Lunenfeld Research Institute (O.N., J.X., A.M., J.K., A.B., I.C.), Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5; Hospital for Sick Children (M.P.), Toronto, Ontario, Canada M5G 1X8; Department of Obstetrics and Gynecology (O.N.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5; Department of Physiology (M.P., A.B., I.C.), University of Toronto (O.N., J.K., M.P., A.B., I.C.), Toronto, Ontario, Canada M5S 1A8; Department of Obstetrics, Gynecology, and Women’s Health (S.Z.), New Jersey Medical School, Newark, New Jersey 07101; and Department of Obstetrics and Gynecology (T.T., E.P.), University of Turin, 10124 Turin, Italy

Address all correspondence and requests for reprints to: Isabella Caniggia, M.D., Ph.D., Mount Sinai Hospital, Samuel Lunenfeld Research Institute, 600 University Avenue, Room 871C, Toronto, Ontario, Canada M5G 1X5. E-mail: caniggia{at}mshri.on.ca.

Objective: Intrauterine growth restriction (IUGR) is characterized by decreased placental perfusion. Low oxygen has been shown to increase soluble fms-like tyrosine kinase 1 (sFlt-1) expression in the human placenta. The objective of this study was to examine sFlt-1 expression in different types of IUGR pregnancies, including early-onset severe cases characterized by abnormal umbilical and uterine artery Doppler and discordant IUGR twins in which the normal cotwin represents the optimal control because both placentas share the same uterine environment.

Patients: Placentas from four subgroups were collected: early severe IUGR with umbilical artery absent end diastolic flow (n = 19), small for gestational age with normal uterine and umbilical artery Doppler (n = 11), severely growth-restricted dichorionic and monochorionic twins with abnormal umbilical artery Doppler (n = 9), preeclamptic twins (n = 3), and age-matched normal singletons (n = 19) and twin controls (n = 8).

Results: Expression of sFlt-1 mRNA and protein was significantly increased in IUGR placentas compared with small for gestational age and normal control placentas. sFlt-1 expression levels were also significantly greater in the small IUGR twin placentas from discordant twin pregnancies compared with the normal cotwin. In preeclamptic twins, sFlt-1 expression was increased in only one of the two placentas.

Conclusions: Our results demonstrate that sFlt-1 expression is increased in severe IUGR placentas with abnormal umbilical artery Doppler of singletons and also in discordant IUGR twins. Reduced placental perfusion may contribute to the increased expression of sFlt-1 in IUGR pregnancies. Our data are compatible with differential sFlt-1 expression in placentas from discordant twins.