Fetal Leptin Influences Birth Weight in Twins with Discordant Growth

Abstract

The objective of this study was to determine the plasma leptin concentrations in twin pregnancies in relation to chorionicity and discordant fetal growth. We studied 53 twin pregnancies of which 26 had growth discordance of Ն20% and 27 were concordant for growth (discordance of Յ10%). Paired maternal and fetal blood samples were obtained at birth. Plasma leptin concentrations were measured by RIA. In discordant monochorionic pregnancies, fetal plasma leptin concentrations in the intrauterine growth-restricted twins were lower than the co-twins with normal growth (mean difference, 3 ng/mL; 95% CI, 2.2 to 3.3 ng/mL; p Ͻ 0.001), whereas no such differences were present between concordant monochorionic twin pairs (mean difference, 0.1 ng/mL; 95% CI, Ϫ0.2 to 0.5 ng/mL; NS). Similarly, fetal plasma leptin concentrations in appropriate-for-gestational-age twins were higher than in the intrauterine growth-restricted twins of the discordant dichorionic pregnancies (mean difference, 2.4 ng/mL; 95% CI, 1.8 to 3.1 ng/mL; p Ͻ 0.001). No such differences were present between the concordant dichorionic twin pairs (mean difference, 0.2 ng/mL; 95% CI, Ϫ0.1 to 0.5 ng/mL; NS). Maternal plasma leptin concentrations were comparable among all four groups and were higher than the fetal levels. Fetal plasma leptin concentrations of the intrauterine growth-restricted twins of discordant monochorionic and dichorionic pregnancies were comparable. There was a positive association between cord plasma leptin concentrations and the birth weight of twin pairs (y ϭ 0.002x Ϫ 0.32; r ϭ 0.63; p Ͻ 0.001; n ϭ 106). A significant positive association was also found between percent differences in birth weight and fetal delta plasma leptin concentrations of the discordant monochorionic and dichorionic twin pairs (y ϭ 0.057x ϩ 0.93; r ϭ 0.60; p Ͻ 0.001, n ϭ 26). In conclusion, irrespective of chorionicity, plasma leptin concentrations in intrauterine growth-restricted twins were 2-fold lower than their co-twins with normal growth. These differences may be attributed to placental factors. Leptin is a 16-kD protein encoded by the ob gene and produced by adipocytes (1). It regulates body weight through a negative feedback signal between the adipose tissue and the hypothalamic centers of satiety, thereby causing a decrease in food intake and increases in body temperature and energy expenditure (2). In obese or normal weight children, as in adults, plasma leptin concentrations closely correlate with body weight and percentage body fat (3, 4). Raised plasma leptin concentrations are observed during pregnancy and in fetal life (5,6). Several recent studies have demonstrated a positive correlation between plasma leptin concentrations in cord blood and body weight at birth (7,8). The mechanisms by which maternal and fetal or neonatal weight and fat mass are regulated during pregnancy and in fetal life are poorly understood.Leptin is synthesized by adipocytes and the human placenta (8, 9). The adipose tissue in the newborn is capable of synthesizing and secreting...

Maternal and Umbilical Cord Serum Leptin Concentrations in Small-for-Gestational-Age and in Appropriate-for-Gestational-Age Neonates: A Maternal, Fetal, or Placental Contribution?

“…We found that in uncomplicated concordant-weight multifetal pregnancies, as in singleton pregnancies, the umbilical cord leptin levels correlated well only with the birth weight. Recent data collected from a population of discordant sets of twin pregnancies [34] support the theory of the placental factors, rather than maternal, influencing the leptin secretion. Uniquely, we found by studying the umbilical vein leptin levels in triplets this correlation to be unaffected by chorionicity or by the number of fetuses in the set.…”

Effect of Iron Deficiency on Placental Cytokine Expression and Fetal Growth in the Pregnant Rat1

“…The presence of a placenta-specific upstream enhancer on the gene suggests that it is regulated differently from that of adipose origin [52,53]. Studies in humans have shown a correlation between cord blood and placental leptin, but not between maternal leptin and birth weight [30,54] (reviewed in [32]). This suggests that placental leptin may promote fetal growth.…”

Role of leptin in female reproduction

“…In fact, insulin is an inducer of leptin production in human placenta as shown in vivo [84], enhancing the activity of leptin promoter region [85]. This may be relevant in gestational diabetes [6,86,112,127], a state of greater insulin resistance and hyperinsulinemia than normal pregnancies. In this line, numerous studies have reported that circulating leptin levels, as well as placental leptin and LEPR expression are significantly higher in pregnant women with GDM compared to healthy control women with uncomplicated pregnancy [128,129], providing, at least, a molecular mechanism for the placenta overgrowth previously observed in GDM [99,100].…”