Umbilical Cord and Maternal Blood Leptin Concentrations in Intrauterine Growth Retardation

Abstract

Leptin, the ob gene product, plays an important role in the regulation of body fat mass and weight. In previous studies, it was demonstrated that leptin is detectable in human fetal cord blood as early as at 18 weeks of gestation and that serum leptin concentrations are significantly reduced in small gestational age newborns. In the present study, we investigated whether umbilical and maternal serum leptin concentrations correlate with intrauterine growth retardation (IUGR). In addition, we aimed to determine the relationships between leptin concentration in the maternal and cord blood. We studied 40 newborn infants (21 female and 19 male; gestational age, 38-42 weeks) and their mothers. Of the infants studied, 10 had IUGR. Serum leptin concentrations were measured by radioimmunoassay. All newborns had detectable leptin concentrations. Leptin concentrations were significantly lower in newborns with IUGR and in their mothers (n = 10; 3.53 +/- 1.42 ng/ml, 6.75 +/- 1.47 ng/ml, respectively) than in infants experiencing normal growth and their mothers (n = 30; 5.58 +/- 2.98 ng/ml, 9.85 +/- 6.50 ng/ml, respectively) (p < 0.01 for newborns, p < 0.05 for mothers). There was no significant correlation between umbilical leptin concentration and maternal leptin concentration (r = 0.229; p = 0.155) in all study groups but, significantly, a correlation was observed in the group with IUGR (r = 0.736; p = 0.015). There were no significant correlations between both umbilical and maternal leptin concentrations and parity, delivery type and gestational age. There was a correlation between umbilical leptin concentration and birth weight of newborns (r = 0.383; p = 0.015) but no correlation with body mass index (BMI) of the newborns (r = 0.034; p = 0.834). Maternal leptin concentrations correlated with maternal weight and BMI (r=0.606; p=0.000, r=0.535; p=0.000, respectively). There was no correlation between maternal leptin concentrations and birth weight of the newborns (r=0.179; p=0.269) and with BMI of the newborns (r = 0.146; p = 0.367). There was no gender difference in leptin concentrations in the newborns (n=21; 5.50 +/- 3.37 ng/ml, for females; n = 19; 4.58 +/- 1.98 ng/ml for males) (p = 0.296). In summary, we have shown that IUGR is associated with a decreased leptin concentration in newborns and their mothers. The association between umbilical serum leptin and birth weight in this and other studies suggests a pivotal role of fetal leptin in regulating fetal growth and development.

Differential Placental Gene Expression in Term Pregnancies Affected by Fetal Growth Restriction and Macrosomia

“…The leptin receptor is abundantly expressed in the arcuate nucleus of the hypothalamus [32] and this protein plays a crucial role in the endocrine regulation of appetite, energy homeostasis and insulin secretion. Interestingly, the changes seen in leptin gene expression oppose those seen in the concentration of leptin in cord blood of macrosomic infants, suggesting that the regulatory mechanisms involved in translating gene into protein expression are complex [30,33,34,35,36,37,38,39,40,41,42,43]. Leptin together with 10 other focused genes ( ATRX , CASP4 , FGF7 , FRZB , GCH1 , GFRA2 , GNGT1 , PHIP , PPIG , and SMC 3) are involved in a network that contributes to digestive system development and function; disturbance of this network suggests a higher risk for nutritional disease and behavioural disorders in macrosomic infants.…”

Fetal Responses during Placental Malaria Modify the Risk of Low Birth Weight

“…During pregnancy, the human placenta (40) and other fetal tissues, including adipose, heart, and liver tissues (15), produce leptin. Cord blood leptin levels correlate with fetal size (20,27), and both placental and fetal leptin levels are decreased in pregnancies complicated by fetal growth retardation (18,39). However, PM appears to disrupt the relationship between cord leptin and birth weight.…”

“…In healthy neonates, cord blood levels of the hormone leptin are positively associated with birth weight (39), but the role of leptin in PM has not been examined. Leptin, which regulates appetite and metabolism, is produced by adipocytes, and leptin levels normally reflect body fat stores (21).…”

Intrauterine growth restriction and adult disease: the role of adipocytokines

“…Several studies demonstrated lower circulating leptin concentrations in IUGR neonates at birth, due to reduced fat mass (58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72) and/or decreased placental production (73)(74)(75). In some of these studies, fetal leptin levels per kilogram of fetal weight, as well as fetal leptin levels before 34 weeks of gestation, were not significantly different in IUGR, indicating that leptin secretion is mainly associated with adipose tissue accumulation (61)(62)(63)(64).…”

“…Although most studies suggest that fetal leptin levels are lower in IUGR (58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75), other investigators determined similar (80) and also higher (81) leptin concentrations. In this respect, a recent study from our group demonstrated lack of significant differences in fetal leptin concentrations between characteristic IUGR (birth weight!third customized centile) cases and appropriate-for-gestational-age (AGA) controls, possibly due to a more active production of leptin by visceral fat in the former (80).…”