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 80cord 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.