Cord Blood Brain-derived Neurotrophic Factor Research Articles

Does brain-derived neurotrophic factor play a role in the association between maternal prenatal mental health and neurodevelopment in 2-year-old children?

ObjectiveTo evaluate the role of brain-derived neurotrophic factor (BDNF)—a crucial modulator of neural development and plasticity—in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. MethodsWe included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. ResultsThe average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (β = −0.32; 95 % CI: −0.55, −0.09), depression (β = −0.30; 95 % CI: −0.52, −0.08), and perceived stress (β = −0.41; 95 % CI: −0.71, −0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. LimitationsMaternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. ConclusionsPrenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment.

Correlation of fetal heart rate dynamics to inflammatory markers and brain-derived neurotrophic factor during pregnancy.

This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (-0.309;-0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.

Clinical Importance of Serum BDNF (Brain-Derived Neurotrophic Factor) Level for the Management of Pregnancies Complicated With Meconium-Stained Amniotic Fluid.

Objective The aim of this study was to investigate the association between poor neonatal outcomes and BDNF (brain-derived neurotrophic factor) levels. We aimed to predict the need for an emergency cesarean and prevent unnecessary interventions in cases complicated with meconium-stained amniotic fluid (MSAF). Methods This study was designed as a case-control study including three groups. Group A included pregnant women who underwent cesarean due to fetal distress. Group B included the women who delivered vaginally. Groups A and B had cases with the presence of meconium in the amniotic fluid. Group C as a control group had clear amniotic fluid. Demographic features, fetal outcomes, and maternal serum and fetal cord blood BDNF levels (Human BDNF ELISA Kit; Synonyms: ANON2, BULN2; Catalog no: E-EL-H0010 96T) were evaluated. Results No significant difference was found between patients with meconium and without meconium in terms of BDNF levels. However, the BDNF level was found to be significantly lowerif fetal distress had occurred with MSAF. Conclusions In conclusion, the study demonstrated that the level of maternal and fetal cord blood BDNF are both significantly lower when fetal distress occurs with the presence of MSAF.

Correlation between antenatal magnesium sulfate (MgSO4) total dose and delivery time interval with umbilical cord blood brain-derived neurotrophic factor (BDNF) levels as a neuroprotection strategy in preterm birth

Background: Administration of antenatal magnesium sulfate (MgSO4) to pregnant women is thought to increase the synthesis of Brain-Derived Neurotrophic Factor (BDNF), which functions as a nerve-growth factor for the process of neurogenesis and also strengthen neuronal resilience in the hypoxic condition that occurs during preterm delivery. Protocols for administering antenatal MgSO4 differ between countries and institutions. One of the concerns is whether the dose is given and the time interval to delivery has a big contribution towards a better fetal outcome. These relationships have not been studied before. This study aimed to analyze the correlation of the total dose of MgSO4 and time interval to delivery with BDNF levels in cord blood. Methods: This study enrolled 72 pregnant women who will deliver the baby prematurely, with gestational age 28-34 weeks. Subjects were divided into three protocols groups: (1) 4 g iv. only, (2) 4 g iv. initial continued with 1 g/hours until maximum 24 hours, and (3) 6 g iv. initial continued with 2 g/hours until a maximum of 24 hours. At the time of delivery, cord blood of preterm babies was collected. The antenatal MgSO4 total dose and time interval to delivery were collected, and BDNF serum levels were then measured with enzyme-linked immunosorbent assay (ELISA). The correlation between antenatal MgSO4 total dose and time interval to delivery with BDNF levels was analyzed using Spearman’s correlation test. Result: There was a weak significant correlation of antenatal MgSO4 total dose and BDNF cord blood levels (p<0.001; r=0.381). There was no significant correlation between delivery time interval and BDNF cord blood levels (p=0.44; r=0.092). Conclusion: Regarding the weak correlation of total dose and time interval to delivery with BDNF, we suggest that all protocols provide comparable outcomes if seen only from the BDNF increase perspective.

Foetal umbilical cord brain-derived neurotrophic factor (BDNF) levels in pregnancy with gestational diabetes mellitus

The aim of our study was to investigate whether gestational diabetes mellitus (GDM) affects brain-derived neurotrophic factor (BDNF) levels in foetal umbilical cord blood. A total of 96 participants were divided into a GDM group (n = 43) and a non-diabetic control group (n = 53). Cord blood samples of approximately 5 cc were taken immediately after the foetal umbilical cord was clamped during delivery in order to determine BDNF levels. While the mean age, body mass index, birth weight, rate of caesarean delivery, rate of infant macrosomia, and neonatal intensive care unit admission of women with GDM were significantly higher compared to the non-diabetic control group (p < .05), pregnancy complications were comparable between the groups (p > .05). Although no significant differences were noted between the groups with respect to cord blood BDNF levels (0.79 ± 0.37 ng/ml vs. 0.69 ± 017 ng/ml, p = .122), cord blood BDNF values were higher in female infants compared to male infants (0.85 ± 0.33 ng/ml vs. 0.66 ± 0.23 ng/ml, p = .001) and in patients using insulin compared to those not using insulin in the GDM group (0.78 ± 0.14 ng/ml vs. 0.62 ± 0.09 ng/ml, p < .001). This study found that GDM has no effect on cord blood BDNF levels. More in-depth studies with larger series are needed to validate the results of the present study. Impact statement What is already known on this subject? Gestational diabetes mellitus (GDM) negatively affects the foetal neurodevelopment due to inflammation and oxidative stress caused by hyperglycaemia. Brain-derived neurotrophic factor (BDNF) expression has been shown to modulate oxidative stress and inflammation, and there may be a relationship between varying BDNF concentrations and GDM. What do the results of this study add? Our study showed that no significant differences were noted between the groups with respect to cord blood BDNF levels, cord blood BDNF values were higher in female infants compared to male infants, and in patients using insulin compared to those not using insulin in the GDM group. What are the implications of these findings for clinical practice and/or further research? GDM negatively affects the foetal neurodevelopment due to inflammation and oxidative stress caused by hyperglycaemia. BDNF expression has also been shown to modulate oxidative stress and inflammation, and there may be a relationship between varying BDNF concentrations and GDM. The association between BDNF expression and GDM has not been clearly elucidated in the literature. More in-depth studies with larger series are needed to determine this relationship.

Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial.

Background: The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance.Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 557, 266 females) were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24–42 months of age to investigate effects on offspring neurodevelopment.Results: Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.Conclusion: Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.

Effect of Maternal Depression on Brain-derived Neurotrophic Factor Levels in Fetal Cord Blood.

ObjectiveWe aimed to assess the association between cord blood brain-derived neurotrophic factor (BDNF) concentration and maternal depression during pregnancy.MethodsA total of 48 pregnant women, admitted for elective caesarean section to Department of Obstetrics and Gynecology, The Konya Research and Training Hospital and Konya Necmettin Erbakan University Meram Medical Faculty, were included in this study. The study group included 23 women diagnosed as having depression during pregnancy and the control group included 25 pregnant women who did not experience depression during pregnancy.ResultsThe groups had similar sociodemographic characteristics. Cord blood BDNF concentration was significantly lower in babies born to mothers with major depression as compared with those in the control group. We didn’t find any correlation between the umbilical cord blood BDNF levels and BDI scores.ConclusionThe results suggest that the existence of major depression in pregnant women may negatively affect fetal circulating BDNF levels.

The Effect of Anaesthetic Techniques on Maternal and Cord Blood Brain-Derived Neurotrophic Factor Levels.

Brain-derived neurotrophic factor (BDNF), a member of neurotrophins, plays a critical role in neuronal tissue. In this study, the effects of spinal or general anaesthesia on cord and maternal peripheral blood BDNF and malondialdehyde (MDA) levels were investigated in patients undergoing elective caesarean section. Eighty patients with term pregnancy were included. General anaesthesia was induced with intravenous (IV) propofol 2 mg kg-1 in the general anaesthesia group (n=36). In the spinal anaesthesia group (n=35), hyperbaric bupivacaine 0.5%, 9 mg (1.8 mL) was injected intrathecally. Maternal blood samples were taken immediately after positioning the patient on the operating table (T1), before clamping the umbilical cord (T2) and 24 hours after the first sample was obtained (T3). Cord blood samples were drawn from the umbilical artery (T4). Maternal BDNF levels (pg mL-1) measured at T2 time point were higher in the general anaesthesia group compared to the spinal anaesthesia group (p<0.001). Cord blood BDNF levels were higher in the general anaesthesia group compared to the spinal anaesthesia group (p<0.001). In both groups, cord blood BDNF levels were significantly lower compared to the maternal blood samples collected at any time point (p<0.001, for all). There was a negative association between both maternal and cord blood BDNF levels with maternal MDA and cord blood MDA levels, respectively (r=-0.379, p<0.001; r=-0.375, p=0.001, respectively). The anaesthetic technique may have an influence on maternal peripheral and cord blood BDNF levels.

Effect of maternal iron deficiency anemia on fetal neural development.

Perinatal iron deficiency may have deleterious consequences on fetal neural development. The present study was conducted to determine the effect of maternal iron deficiency anemia (IDA) on fetal hippocampal morphogenesis and production of brain-derived neurotrophic factor (BDNF). Seventy term, singleton neonates born to mothers with IDA (hemoglobin <110g/L and serum ferritin <12 μg/L) formed the study group. Twenty gestational age-matched neonates born to healthy mothers without IDA (hemoglobin ≥110 g/L and serum ferritin >12 μg/L) served as controls. Maternal and fetal inflammatory conditions, infections and neonates with perinatal asphyxia were excluded. Cord blood BDNF concentrations were estimated by enzyme-linked immunosorbent assay. Volumetric analysis of hippocampus (right, left and combined, corrected for total intracranial volume) was done by cranial magnetic resonance imaging on days 3-5 of life. In the study group, 24 mothers had mild (hemoglobin 100.0-109.0 g/L), 24 had moderate (hemoglobin 70.0-99.0 g/L), and 22 had severe (hemoglobin <70.0 g/L) anemia. Both hippocampal volumes and serum BDNF concentrations of neonates born to iron-deficient mothers were significantly reduced compared to controls. A progressive decline in hippocampal volumes and BDNF concentrations was observed with increasing severity of maternal anemia. Pearson correlation showed significant correlations among maternal and cord blood hemoglobin, iron indices, hippocampal volumes and BDNF concentrations. Maternal IDA adversely affects hippocampal morphogenesis and fetal production of BDNF. The degree of affection is proportional to the severity of maternal anemia.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n=117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n=90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P=0.026) and cord blood BDNF (P=0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P=0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r=0.496, P<0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s=0.245, P=0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

The role of cord blood BDNF in infant cognitive impairment induced by low-level prenatal manganese exposure: LW birth cohort, China

This study aimed to examine the potential association between low-level prenatal manganese (Mn) exposure and 1-year-old children's neurodevelopment quotient (DQ) by using the Gesell Developmental Inventory (GDI) (motor, adaptive, language, and social domains) and explored the role of brain-derived neurotrophic factor (BDNF) in Mn-induced cognitive impairments. A total of 377 mothers were recruited from a prospective birth cohort in rural northern China. Cord serum concentrations of Mn and BDNF were measured and children's DQ was evaluated. The median serum Mn concentration was 3.4 μg/L. After adjusting for confounding factors, Mn level was significantly associated with gross motor scores (β = −6.0, 95% CI: −11.8 to −0.2, p < 0.05) and personal–social scores (β = −4.2, 95% CI: −8.4 to 0.1, p < 0.05). BDNF level was positively correlated with personal–social score (β = 0.7, 95% CI: 0–1.4, p < 0.05). A significant correlation was found between Mn and BDNF (r = −0.13, 95% CI: −0.23 to −0.03, p < 0.01). Furthermore, the interaction between cord serum Mn and BDNF was significant (p < 0.001). In conclusion, elevated low-level prenatal Mn exposure impaired infant's neurodevelopment, and BDNF plays an important role in cognitive impairment, especially in the personal–social ability.

Prenatal lead exposure related to cord blood brain derived neurotrophic factor (BDNF) levels and impaired neonatal neurobehavioral development

To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 μmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 μmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. Lead content in high exposure group was (0.613±0.139) μmol/L, and higher than (0.336±0.142) μmol/L in low exposure group (t=3.21, P<0.001) . NBNA summary score (36.35±1.86), active muscle tension score (6.90±0.27) and general assessment score (5.93±0.32) in high exposure group were lower than those (38.13±0.96, 7.79±0.35, 6.00±0.00) in low exposure group (t values were 8.21, 10.23, 2.32, respectively, P values were <0.001, <0.001 and 0.037) . BDNF content in high exposure group which was (3.538±1.203) ng/ml was higher than low exposure group (2.464±0.918) ng/ml (t=7.60, P<0.001). The correlation analysis found that the cord blood BDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were <0.001, respectively) . Prenatal lead exposure results poor neonatal neurobehavioral development and cord blood BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.

Influence of antenatal magnesium sulfate application on cord blood levels of brain-derived neurotrophic factor in premature infants

To investigate the influence of antenatal magnesium sulfate (MgSO4) application on cord blood brain-derived neurotrophic factor (BDNF) levels - the first-line neuroprotection for preventing cerebral palsy in prematurely born infants. A randomized controlled trial was conducted by observing 72 pregnant women who were divided into three groups: group I (preterm pregnancy with MgSO4), group II (preterm pregnancy without MgSO4), and group III (full-term pregnancy as control group). Groups I and II were selected by block permutation randomization on subjects. Inclusion criteria consisted of preterm pregnancy at 34 weeks of gestation or less who were in labor or having planned terminations and receiving antenatal corticosteroids. Exclusion criteria consisted of previous complications caused by MgSO4, previous history of antenatal MgSO4 application in the current pregnancy infant was born before 4 h administration of MgSO4 or unborn more than 72 h after maximum course of antenatal MgSO4 of 24 h, prolonged antenatal MgSO4 treatment (>24 h), refusal to participate, and emergent adverse events during the study. Group I was given intravenous MgSO4; initial dose was 4 g, which was maintained at 1 g/h up to maximum of 24 h. Meanwhile, groups II and III were not given any special treatment. BDNF was examined by ELISA by taking 5 mL cord blood sample shortly after birth. The result was statistically measured by ANOVA. The cord blood BDNF levels in premature infants with antenatal MgSO4 was significantly higher than in premature infants without antenatal MgSO4 (11,568 vs. 5027 pg/mL, P=0.000). Moreover, the result was statistically comparable to full-term infants (11,568 vs. 13,300 pg/mL, P=0.085). The application of antenatal MgSO4 in preterm delivery increased cord blood BDNF levels, which could have a potential role on fetal neuroprotection. Further investigation is needed.

Maternal generalized anxiety disorder during pregnancy and fetal brain development: A comparative study on cord blood brain-derived neurotrophic factor levels

ObjectivesThe study aimed to investigate whether maternal GAD during pregnancy affects fetal circulating brain-derived neurotrophic factor (BDNF), which plays important roles in neuronal development, by comparing cord blood BDNF levels in newborn infants of women with and without GAD. MethodsStudy sample included 19 women with GAD and 25 women without any psychiatric disorder. GAD and other psychiatric diagnoses were screened by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The blood sample for the determination of BDNF level was obtained from the umbilical cord during delivery. ResultsCord blood BDNF levels in newborn infants of healthy women were approximately two-fold compared to newborn infants of women with GAD, and the difference was statistically significant. The duration of GAD during pregnancy was the only variable correlating with cord blood BDNF levels. ConclusionsThe study results imply that prolonged maternal GAD during pregnancy may negatively influence neurodevelopment of the fetus through lower levels of circulating BDNF.

Effects of Maternal Smoking and Exposure to Methylmercury on Brain-Derived Neurotrophic Factor Concentrations in Umbilical Cord Serum

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal survival and differentiation. We examined the concentration of BDNF in cord serum from newborns exposed to methylmercury (MeHg) and polychlorinated biphenyls (PCB) in utero by maternal consumption of whale meat. The cohort consisted of 395 singleton births (206 boys and 189 girls), gestational age ranging from 38 to 42 weeks. Serum BDNF was measured by sandwich ELISA. Maternal smoking habits and other relevant factors were obtained by interviewing the mothers. The exposure to MeHg was estimated from Hg concentrations in cord blood, whereas exposure to PCB was estimated based on maternal serum concentrations. Only MeHg exposure affected the serum BDNF, which decreased in a concentration-dependent manner in girls born to nonsmoking mothers. Maternal smoking significantly increased BNDF in girls but not in boys. For further statistical analyses, we used the serum BDNF concentration as a continuous outcome variable in supervised regression models. Serum BDNF concentration increased with gestational age, increased by maternal smoking, decreased slightly with MeHg exposure, and maternal smoking enhanced the decrease in serum BDNF induced by MeHg exposure. Cord blood BDNF has been reported to increase in association with perinatal brain injuries and has been proposed as a possible predictive marker of neurodevelopmental outcomes. The negative effect that MeHg seems to exert on cord blood BDNF concentration could endanger compensatory responses to an adverse impact and therefore deserves attention.

Changes in neurotrophin levels in umbilical cord blood from infants with different gestational ages and clinical conditions.

Apoptotic neuronal loss may be responsible for altered brain development associated with prematurity and perinatal insults. Neurotrophins play crucial roles in protecting neurons from entering or progressing along an apoptotic pathway. The present study examined levels of neurotrophins in human umbilical cord blood from infants at different gestational ages and clinical conditions. We collected 60 samples of cord blood and categorized them accordingly into three gestational age groups: group A (24-28 wk), group B (29-35 wk), and group C (>/=36 wk). Neurotrophin levels were determined by using brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) ELISA. Clinical data were obtained by medical chart analysis. The BDNF levels were 884 +/- 386, 1421 +/- 616, and 2190 +/- 356 pg/mL in group A, group B, and group C, respectively. Significant differences were found between groups A and B (p = 0.038), groups A and C (p = 0.0001), and groups B and C (p = 0.001). Infants with severe intraventricular hemorrhage had significantly lower cord blood BDNF levels (925 +/- 513 pg/mL) compared with their normal counterparts (1650 +/- 674 pg/mL; p = 0.021). NT3 levels did not show significant change either across gestational ages or with the presence of intraventricular hemorrhage. Cord blood levels of BDNF may reflect the degree of neural maturity in premature infants. Interestingly, when a complete course of antenatal steroids was given, BDNF and NT3 cord blood levels were higher than when no steroid was given. Increased neurotrophins levels may also mediate improved neurodevelopmental outcome in infants who received antenatal steroids.