Differential expression of cord blood neurotrophins in gestational diabetes: the impact of fetal growth abnormalities.

OBJECTIVE

Gestational diabetes mellitus (GDM) may induce fetal macrosomia or growth restriction and is associated with later offspring neurodevelopmental disorders. We aimed to determine whether neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-4 (NT-4) are differentially expressed in cord blood samples at birth in large-for-gestational-age (LGA), intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) offspring of diabetic mothers, as compared to AGA controls from non-diabetic mothers.

METHODS

BDNF, NGF and NT-4 concentrations were prospectively determined in 80 cord blood samples from LGA (n = 15), IUGR (n = 12) and AGA (n = 33) diabetic, as well as from AGA normal (controls, n = 20) singleton full-term pregnancies.

RESULTS

Fetal BDNF concentrations considerably decreased in GDM, as compared with normal pregnancies [(b = -2.836, 95%CI -5.067 to (-0.604), p = 0.013)] and were higher in females (b = 2.298, 95%CI 0.357-4.238, p = 0.021). Cord blood NGF concentrations were lower in IUGR than AGA infants (p = 0.038).

CONCLUSIONS

BDNF is down-regulated in the fetus exposed to GDM, independently of the fetal growth pattern, probably representing a candidate mechanism underlying the association between maternal diabetes and later psychopathology. IUGR fetuses born to diabetic mothers present with NGF deficiency, which may contribute to their long-term neurodevelopmental sequelae. Gender-dependent differences in fetal BDNF may partly explain the higher prevalence of adverse neurodevelopmental outcomes following brain insults in male infants.