Maternal Serum Placental Growth Hormone and Insulinlike Growth Factor Binding Proteins 1 and 3 in Pregnancies Affected by Fetal Aneuploidy and Other Abnormalities: Implications for Prenatal Diagnosis of Trisomy 21

Abstract

In the present study, we determined circulating serum levels of human placental growth hormone (hPGH) and insulinlike growth factor binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) using two-site radioimmunoassays during the gestational midtrimester of pregnancies affected by chromosomal disorders with the aim of identifying potential marker substances that might have a significant discriminative and predictive value for prenatal diagnosis of fetal chromosomal aberrations and of organ malformations such as neural-tube defect. Our results show that the maternal serum levels of hPGH were significantly elevated in pregnancies affected by chromosomal anomalies or organ malformations as compared with controls. The distribution of IGFBP-1 concentrations for all experimental groups except trisomy 21 were closely similar to the normal population. IGFBP-3 decreased slightly in pregnancies affected by Down syndrome. These findings suggest that hPGH may be useful as an additional marker in prenatal screening for Down syndrome.

Human Placental Growth Hormone Is Increased in Maternal Serum in Pregnancies Affected by Down Syndrome

“…Chromosomal abnormalities in placental tissue may affect its hormonal production by unclear diverse mechanisms, leading to altered concentrations of maternal serum hCG, ␣ -fetoprotein, pregnancy-associated plasma protein-A and other placental hormones [2,3,16,17] . The present study was carried out to investigate the relationship of hPGH levels with the presence of fetuses affected by Down syndrome.…”

“…It could be hypothesized that the enhanced hPGH production may be due to an attempt of the placenta to counteract the incipient fetal growth restriction , a constant finding in the majority of Down-syndrome-affected pregnancies [24,25] . This compensatory reaction to the fetal growth retardation allows the placenta to secrete higher levels of this hormone by stimulating the placental growth hormone receptors and the IGF-I synthesis in placental tissue and maternal hepatocytes [16] . IGF-I possesses somatogenic, mitogenic and metabolic activities in both the maternal and the fetal circulation, which influence fetal growth [11,14] .…”

“…Increased transcription of IGF-I and hPGH mRNA has been shown in fetal intrauterine growth retardation term placentae, in response to growth restriction of the fetus [27] . The elevated IGF-I level has been proposed as an explanation for the reduced maternal serum IGF-I-binding protein level in trisomy 21 pregnancies [16] . This enables the organism to have more IGF in free form and, therefore, to enhance its mitogenic and metabolic activities.…”

“…Such fetuses have a reduced fetal synthetic activity and probably cannot utilize the supplied nutrients, which consequently leads to further intrauterine growth restriction and more secretion of hPGH. Furthermore, chromosomal rearrange- ments of both the fetus and the placenta may be accompanied by alterations of growth-related factors, which contribute to the pathogenesis of fetal growth restriction [16] . IGF-binding protein-3 has been reported to be a cell growth inhibitor [28] regulated partly by glucose and insulin [29] .…”

“…High serum levels of the hormone are detected in pregnancies affected by chromosomal aberrations [16,17] and organ malformations such as neural tube defects [16] . Furthermore, the maternal serum concentration of hPGH and other growth-related factors are altered in pregnancies accompanied by fetal intrauterine growth retardation [18][19][20] .…”