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Objectives: Adequate vascular development of the placental bed is essential for normal pregnancy. We assessed serum levels of placenta growth factor, an angiogenic factor, throughout normal pregnancy and determined its association with preeclampsia., Study Design: Serum samples were collected from (1) 308 healthy pregnant women throughout normal gestation, (2) at delivery from 30 each gestational age-matched patients with normal pregnancy and preeclampsia, and (3) maternal and cord blood samples from normal deliveries with and without labor (n = 37 each). Placenta growth factor levels were determined with an antigen-capture enzyme-linked immunosorbent assay., Results: Maternal placenta growth factor levels during normal pregnancy increased from the first trimester to the late second trimester; they subsequently declined from 30 weeks' gestation to delivery. Significantly less maternal placenta growth factor (P <.0001) was found in pregnancies complicated by preeclampsia, and labor significantly lowered placenta growth factor levels in both maternal (P =.0189) and cord serum samples (P <.0001)., Conclusion: Decreased levels of placenta growth factor during preeclampsia could influence endothelial cell and trophoblast function, thereby contributing to the pathogenesis of the disease.

Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) in Taiwanese women during normal pregnancy were investigated. Three hundred and eighty-five pregnant women at various gestational ages and 30 nonpregnant females were recruited into the study. Serum concentrations of IGF-I and IGFBP-1 were determined by immunoradiometric assay (IRMA) and radioimmunoassay (RIA). Maternal serum levels of IGF-I increased as pregnancy progressed. Circulating IGF-I levels in women during the first trimester of pregnancy were higher than those in nonpregnant females. Serum levels of IGFBP-1 rose rapidly before 12 weeks of gestation and remained high until term. Serum IGFBP-1 levels in pregnant women during the first trimester were significantly higher than those in nonpregnant females. However, there was no difference in maternal serum IGFBP-1 levels between the second and the third trimester of pregnancy. It is concluded that serum IGF-I levels during pregnancy may be regulated by various classes of IGF-binding proteins other than IGFBP-1.

The aim of this study was to investigate circulating levels of insulin-like growth factor-binding protein-3 (IGFBP-3) in women with normal pregnancy. A total of 468 pregnant women at various gestational ages and 30 non-pregnant females were recruited in this study. Serum concentration of IGFBP-3 was determined by radioimmunoassay. Maternal serum levels of IGFBP-3 increased as pregnancy progressed. The concentration of IGFBP-3 in pregnancy serum was positively associated with the gestational age. The mean values of circulating IGFBP-3 in the second and third trimesters of pregnancy were higher than those in the first trimester of pregnancy and in non-pregnant females. In addition, there was a highly significant correlation between IGFBP-3 and IGF-I in pregnancy serum. We conclude that, during pregnancy, IGFBP-3 appears to be the principal binding protein for circulating IGF-I and may be involved in the regulation of fetal growth.

Two hundred Chinese primigravidae had 50 g 3-h oral glucose tolerance tests (OGTTs) twice in pregnancy; between 20 and 24 weeks and between 30 and 34 weeks of gestation. In 149 women, a single sample was taken for insulin-like growth factor-binding protein-1 (IGFBP-1) measurement 0, 1, 2 or 3 h after the glucose load at both visits; in 55 women IGFBP-1 levels were estimated in all four OGTT samples. Fetal growth was assessed by ultrasound performed at the first and second visit and, if possible, at term, and by anthropometry of the neonate. Cord serum IGFBP-1 was measured in 144 of the babies. Mothers who developed gestational diabetes were excluded. Maternal levels of IGFBP-1 were inversely related to glucose levels at 0, 1 and 2 h in the third trimester of pregnancy. IGFBP-1 measured at 1 h in an OGTT increased between the second and third trimester. There was an inverse correlation between maternal IGFBP-1 measured in the second trimester and all fetal measurements at that time, and with most neonatal measurements and birthweight. Levels of IGFBP-1 in the third trimester were inversely correlated to neonatal abdominal circumference, skinfold thickness and birthweight. Cord blood IGFBP-1 was inversely related to growth of abdominal circumference. The strongest inverse relationship was between IGFBP-1 and maternal weight. Fasting glucose in the second trimester was positively correlated to fetal subcutaneous fat and growth of abdominal circumference. In the third trimester it was related to fetal abdominal circumference, the growth of abdominal circumference, birthweight and neonatal skinfold thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-binding proteins (IGFBPs) in maternal and umbilical cord sera have been analysed by combinations of gel filtration chromatography, affinity cross-linking and electrophoresis. On gel filtration chromatography, the majority of circulating IGF-I in non-pregnant and pregnant women was present in the large molecular mass (150 kDa) binding proteins (IGFBP-3). In umbilical cord serum, by contrast, most IGF-I was present in the 40 kDa binding proteins (consisting of IGFBP-1 and IGFBP-2). Western blots demonstrated an apparent progressive attenuation of IGFBP-3 and IGFBP-2 in serum from pregnant women with an increase in IGFBP-1. After prior cross-linking with disuccinimidyl suberate, the 150 kDa fractions (IGFBP-3) from non-pregnant and pregnant serum showed a similar pattern on SDS-PAGE (several bands at different molecular masses). However, IGFBP-2 (one of the components of the 40 kDa fractions) was undetectable, even after cross-linking, in serum from pregnant women later than 8 weeks of gestational age and in a mixture of maternal serum at term delivery and serum from non-pregnant women. This suggests that serum IGFBP-2 was degraded by specific proteases present in pregnancy serum. Following acid treatment, the 150 kDa fractions from pregnancy serum were split into smaller subunits or fragments while the 40 kDa fractions remained unchanged, suggesting that the 40 kDa binding proteins, are acid-stable. The present data demonstrate that IGFBP-3 is the principal IGFBP in pregnancy serum even though there is an apparent reduction in serum IGFBP-3 activity as revealed on Western blots. The absence of IGFBP-2 in serum from pregnant women may be due to degradation by proteases. In the fetal circulation IGFBP-1 and IGFBP-2 appear to be the major binding proteins for IGF-1.

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) were measured in amniotic fluid, extraembryonic coelomic fluid and maternal serum from 23 women with apparently normal first trimester pregnancies prior to termination. The levels of IGF-1 and IGFBP-1 were significantly higher in coelomic fluid than amniotic fluid (IGF-1, P = 0.006; IGFBP-1, P = 0.0008 (paired t-test)). The levels of IGFBP-1 were lower in amniotic fluid than in maternal serum (P = 0.017), a finding in sharp contrast to the situation in the second and third trimesters of pregnancy. There was a significant relation between levels of IGF-1 and IGFBP-1 in amniotic fluid (r = 0.43; P = 0.04) and in coelomic fluid (r = 0.81; P less than 0.001) but not in maternal serum. The finding that both the absolute levels of IGFBP-1 and the ratio to IGF-1 were low in amniotic fluid implies that there is a very high level of unbound, biologically active IGF-1 in this compartment in the first trimester. Thus, the regulatory role of IGFBP-1 may change as pregnancy advances.

Insulin-like growth factor-binding protein-1 (IGFBP-1) has been purified from amniotic fluid by anion exchange, hydrophobic interaction and gel filtration chromatography. The overall recovery of the purification process was 12.2%. The purified IGFBP-1 yielded a single band on SDS-PAGE gel but showed two bands (34 kDa and 68 kDa) on Western blot under non-reducing conditions. Polyclonal antisera were raised by immunization of sheep using the purified IGFBP-1. The best antiserum bound 50% of 125I-labelled IGFBP-1 at a final dilution of 1:500,000. A radioimmunoassay for IGFBP-1 was developed. This assay had a minimum detection limit of 5 micrograms/l, and was used to determine serum levels in non-pregnant and pregnant women. There was no cross-reaction with a wide variety of materials tested. Serum IGFBP-1 levels in non-pregnant individuals (33 +/- 16 (S.D.) micrograms/l) were found to be significantly lower than those in the second (96 +/- 64 micrograms/l) and third trimesters (95 +/- 60 micrograms/l) of pregnant women. During pregnancy, circulating IGFBP-1 levels increased rapidly in the first trimester and reached a peak at 12-13 weeks of gestation (107 +/- 75 micrograms/l). The level then remained at 80 +/- 53 to 103 +/- 70 micrograms/l until term.

Retroplacental blood lymphocytes (RPL) obtained from women without complications at the term delivery were studied for proliferative response to mitogens and surface phenotype and were compared with autologous peripheral blood lymphocytes (PBL). Proliferation of RPL induced by phytohemagglutinin (PHA) was significantly lower than that of PBL in 11 of 13 cases. Also RPL proliferated poorly in response to concanavalin A (Con A) in 8 of 10 cases. On the other hand, flow cytometry analysis of T cell subsets revealed that RPL contain comparable or higher number of CD3+ cells and CD4+ cells and similar numbers of CD8+ cells as compared with PBL in most cases. These results indicate that T cell proliferative response in retroplacental space is impaired, which could be due to a functional defect of RPL.