Growth factors and vasoactive substances in intrauterine growth restriction and preeclampsia

Fetal growth restriction (FGR) is, next to prematurity, the second leading cause of perinatal morbidity and mortality. To reduce perinatal morbidity and mortality it is important to identify such fetuses in utero in order to monitor their development, and to determine the most optimal time for delivery. The etiology of intrauterine growth restriction (IUGR) is multifactorial. Factors that contribute are fetal malformations, chromosome aberrations or early intrauterine fetal infections, all with poor prognosis for the fetus. In an isolated "placental insufficiency", the prognosis for the fetus is good if delivery time is optimized. Abberations of placentation are a common feature of pathological pregnancies such as IUGR and preeclampsia. The etiology of preeclampsia is still unknown, but endothelial dysfunction is believed to be a central pathogenetic feature.

The purpose of this thesis was to evaluate the possible involvement of serum-borne growth factors and vasoactive substances in fetal growth restriction and preeclampsia. The substances that have been evaluated in fetal serum are: 1) Endothelin-1; one of the most potent vasoconstrictor known. 2) Erythropoietin; a hematopoietic growth factor, the synthesis of which is induced by tissue hypoxia. 3) IGF-I and one of its binding proteins IMP- 1; IGF-I is a growth factor belonging to the same peptide family as insulin, its production is stimulated by nutrition and it is an essential factor in regulating fetal growth. 4) TGFbeta- I; which plays important roles in many areas including embryonic growth and development, inflammation and angiogenesis. In matemal serum, fibronectin was analyzed as a marker of endothelial injury in pregnancies complicated with IUGR and/or preeclampsia.

The results showed that particularly IGF-I is a strong indicator of IUGR, and that also TGF-beta 1 is correlated to fetal growth. EPO and ET-1 appeared to be more associated to presence of hypoxia. Fibronectin may be used as a marker for preeclampsia and may indicate development of preeclampsia already in week 16. Fibronectin values may also give information on the severity of preeclampsia. The findings are relevant to the understanding of the pathophysiology of these diseases.

List of scientific papers

I. Ostlund E, Bang P, Hagenas L, Fried G (1997). "Insulin-like growth factor I in fetal serum obtained by cordocentesis is correlated with intrauterine growth retardation. " Hum Reprod 12(4): 840-4
https://pubmed.ncbi.nlm.nih.gov/9159453

II. Ostlund E, Tally M, Fried G (2001). "TGbeta-1 in fetal serum correlates to IGF-1 and fetal growth." Obstetrics and Gynecology (Submitted)

III. Ostlund E, Lindholm H, Hemsen A, Fried G (2000). "Fetal erythropoietin and endothelin-1: relation to hypoxia and intrauterine growth retardation. " Acta Obstet Gynecol Scand 79(4): 276-82
https://pubmed.ncbi.nlm.nih.gov/10746842

IV. Liu YA, Ostlund E, Fried G (1995). "Endothelin-induced contractions in human placental blood vessels are enhanced in intrauterine growth retardation, and modulated by agents that regulate levels of intracellular calcium. " Acta Physiol Scand 155(4): 405-14
https://pubmed.ncbi.nlm.nih.gov/8719260

V. Ostlund E, Hansson LO, Bremme K (2001). "Fibronectin is a marker for organ involvment and may reflect the severity of preeclampsia." Hypertension in Pregnancy 20: 79-87