Association between Brain-Derived Neurotrophic Factor (BDNF) Levels in 2^ndTrimester Amniotic Fluid and Fetal Development

Abstract

The development of the fetal nervous system mirrors general fetal development, comprising a combination of genetic resources and effects of the intrauterine environment. Our aim was to assess the 2nd trimester amniotic fluid levels of brain-derived neurotrophic factor (BDNF) and to investigate its association with fetal growth. In accordance with our study design, samples of amniotic fluid were collected from women who had undergone amniocentesis early in the 2nd trimester. All pregnancies were followed up until delivery and fetal growth patterns and birth weights were recorded, following which pregnancies were divided into three groups based on fetal weight: (1) AGA (appropriate for gestational age), (2) SGA (small for gestational age), and (3) LGA (large for gestational age). We focused on these three groups representing a reflection of the intrauterine growth spectrum. Our results revealed the presence of notably higher BDNF levels in the amniotic fluid of impaired growth fetuses by comparison with those of normal growth. Both SGA and macrosomic fetuses are characterized by notably higher amniotic fluid levels of BDNF (mean values of 36,300 pg/ml and 35,700 pg/ml, respectively) compared to normal-growth fetuses (mean value of 32,700 pg/ml). Though apparently small, this difference is, nevertheless, statistically significant (p value < 0.05) in SGA fetuses in the extremes of the distribution, i.e., below the 3rd centile. In conclusion, there is clear evidence that severe impairment of fetal growth induces the increased production of fetal brain growth factor as an adaptive mechanism in reaction to a hostile intrauterine environment, thereby accelerating fetal brain development and maturation.

Increased Fibroblast Growth Factor 21 (FGF21) Concentration in Early Second Trimester Amniotic Fluid and Its Association with Fetal Growth

“…This most interesting finding seems to point to an adaptive mechanism enhancing FGF21 availability in cases of reduced growth velocity. Similar mechanisms have been tentatively proposed regarding other growth factors in previous studies [ 41 ]. Another explanation for increased FGF21 in both growth centile extremes could be protection against oxidative stress and induction of tissue repair procedures.…”

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses

“…They found higher levels of BDNF on amniotic fluid from small for gestational age (SGA) fetuses assessed early in the second trimester. They did not study Doppler nor fetal growth status at the time of amniocentesis as it was performed for other reasons, finding BDNF levels on large for gestational age and SGA fetuses [44].…”

High maternal BMI and low maternal blood BDNF may determine the limit of detection of amniotic fluid BDNF throughout gestation: Analysis of mother-fetus trios and literature review

“…Additionally, we used uncultured AF samples. In 2018, another two studies [ 25 , 26 ] described BDNF concentrations in AF samples obtained at 14–22 weeks of gestation and correlated these with fetal or maternal clinical variables after birth. Antonakopoulos et al [ 25 ] described a need for 20-fold dilution prior to the assay as BDNF levels in AF were thousandfold higher than described in our and other studies “ Table 2 ”.…”