Significance of Cord-Blood Leptin in Newborns of Diabetic Mothers

Human fetal adipocyte produces leptin. At birth, cord-blood leptin concentration closely correlates with the amount of newborn fat mass. It is suggested that the sexual dimorphism observed in adults already exists in utero. The higher leptin levels in newborns of diabetic mothers (1) compared with the offspring of nondiabetic mothers could reflect increased adipose tissue. It has also been postulated that hypoxic conditions during pre-eclamspsia affect cord-blood leptin (2) and that fetal insulin stimulates fetal adipocyte leptin production (3).

We assessed cord-blood levels of leptin and insulin in 56 neonates born to diabetic mothers (preexisting diabetes n = 15, gestational diabetes mellitus [GDM] n = 41) and in 25 born to control subjects and investigated whether leptin levels are related to ponderal index (PI), sex, pre-eclampsia, or fetal insulinemia. Leptin assays were performed using radioimmunoassay (Diagnostic Systems, Webster, TX). Inter- and intra-assay variations were 5.3 and 3.7%, respectively. The detection limit was 0.10 ng/ml. The PI, used for nutritional assessment of the neonate, was calculated as body weight (g)/[crown-heel length (cm)]³ × 100.

Leptin was found to correlate with PI (r = 0.31, P = 0.02). It was significantly higher in newborns of mothers with preexisting diabetes than in newborns of mothers with GDM or control subjects (median 15 ng/ml, range 9–20.2 vs. median 8.3, range 5–11.3 vs. median 9, range 5.3–16, P = 0.04). After adjustment for PI, there was a difference in sex (P = 0.002) in newborns of diabetic mothers with higher leptin values in females (median 11.2 ng/ml, range 8.1–20.2) than males (median 7.7, range 4–12). No difference was observed between the absence and presence of maternal pre-eclampsia. Reflecting maternal-hyperglycemia influence on fetal growth, offspring of mothers with preexisting diabetes had higher PI and insulin levels than those of mothers with GDM or control subjects (2.89 ± 0.25 vs. 2.69 ± 0.26 vs. 2.68 ± 0.18, P = 0.01, median 17.3 μIU/ml, range 7.1–25 vs. median 4.8, range 2.5–8.5 vs. median 2.5, range 2.5–6.2, P = 0.001). Insulin levels correlate strongly to leptin levels independently of PI, but only in the GDM group (P = 0.014).

Cord-blood leptin reflects the fetal growth in newborns of diabetic mothers. It appears as a valuable marker of fat mass at birth and allows to quantify even the mild “maternal diabetes effect” on the progeny. Nevertheless, sexual dimorphism already exists in utero and sex could affect leptin level independently of fat mass. The maternal diabetes effect on fetal leptin is likely to arise from fetal insulin overproduction, which subsequently contributes to fat deposition.