Inverse Correlation between Insulin‑like Growth Factor‑1 and Leptin Levels in Preeclampsia
The basic pathology of preeclampsia is intense vasospasm affecting whole of the vascular system, especially renal, uterine, and cerebral vessels, which is probably due to an increase in vasopressor substances such as angiotensin II, thromboxane A2, endothelin-1, and a decrease in vasodilator substances such as nitric oxide and prostacyclin due to endothelial cell dysfunction.
The mechanisms regulating fetal growth are poorly understood. Apart from genetic predisposition, factors such as chromosomal aberrations, nutritional and environmental factors or toxic exposition during pregnancy, insulin, and insulin-like growth factors (IGFs) have been implicated as a primary determinant of fetal weight.
IGFs are released in response to growth hormone(GH) stimulation in the liver and act as hormones. Furthermore, IGFs exerts mitogenic actions through paracrine and autocrine mechanisms to stimulate cellular proliferation and differentiation. IGF-binding proteins (IGFBPs) modulate the function of IGF-1. IGFBP-1 is synthesized by the fetal liver and is highly expressed in the decidua during pregnancy. IGF-1 has been detected in preimplantation embryo and in syncytiotrophoblasts and cytotrophoblasts throughout gestation.
During placentation, IGF producing “intermediate” trophoblast of the anchoring villus invades the IGFBP-1-rich maternal decidua to gain access to the maternal blood vessels. IGF-1 and IGFBP-1 modulate placental growth and reduced levels of IGF-1 and IGFBP-1 during late first trimester has been reported.The mechanism of effect of IGF-1 on fetal growth is not clear as maternal IGF-1 cannot cross the placenta. IGF-1 levels in umbilical cord blood have been reported to positively correlate with birth weight.
Informed consent was taken from all the patients. Women with a history of chronic hypertension, any metabolic disorder before or during pregnancy, or presence of high-risk factors such as heart disease, diabetes, renal disease were excluded.
Five milliliters of blood was drawn aseptically, and serum was separated by centrifugation. Ten milliliters of umbilical cord blood was drawn, and serum was separated. Routine investigations and serum leptin and IGF-1 levels were analyzed in maternal and cord blood of women with preeclampsia and normotensive pregnant women.
SUBJECTS AND METHODS
The present study was conducted during 2011–2012 in the Department of Biochemistry in collaboration with the Department of Obstetrics and Gynaecology, Pt. B. D. Sharma, PGIMS, Rohtak. This study was approved by the Ethics Review Committee of the institute. Fifty pregnant women attending the outpatient Department of Obstetrics and Gynaecology were randomly enrolled and divided into two groups: Group I (control, n = 25) normotensive women with singleton pregnancy at the time of delivery; and Group II (study, n = 25) age- and gestation-matched women with singleton pregnancy and systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg with or without proteinuria at the time of delivery.
IGF-1 levels were lowered in maternal blood of preeclamptic as compared to normotensive mothers(P < 0.001) [Table 1]. Leptin levels were significantly increased in preeclamptic mothers as compared to normotensive mothers (P < 0.001) [Table 1 and Figure 1]. Cord blood IGF-1 levels were significantly decreased in preeclampsia mothers as compared to the normotensive mothers (P < 0.001) [Table 1], while serum leptin levels were significantly increased in preeclampsia mothers as compared to the normotensive mothers (P < 0.001) [Table 1 and Figure 1]. Maternal leptin and IGF-1 levels were about two-fold higher than fetal levels in both groups. Maternal IGF-1 had a strong inverse correlation with leptin levels in preeclamptic mothers (r = −0.528, P < 0.01). No correlation was found between normotensive mother IGF-1 and leptin levels. Cord blood IGF-1 had a negative correlation with cord blood leptin levels in both groups; however, it was statistically not significant in neither of these groups (r = −0.145,r=−0.246, P=0.49, P=0.24.). IGF-1 has a negative correlation in normotensive mothers (r = −0.024), while it has a positive correlation in preeclamptics (r = 0.407), although none of these correlations were significant. Leptin has a positive correlation with IGF in both groups and it is highly statistically significant in preeclamptic mothers (r = 0.231, r = 0.687; P = 0.27., P < 0.001 at both levels). Correlation between maternal and cord blood IGF-1, leptin is depicted.
Findings of the present study suggest that IGF-1 and leptin play a central role in controlling fetal growth.