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A Rat Model of Mild Intrauterine Hypoperfusion with Microcoil Stenosis
Published on: January 7, 2018
Intrauterine growth restriction, brain-sparing effect, and neurotrophins
Ariadne Malamitsi-Puchner1, K E Nikolaou, K-P Puchner
1Neonatal Division, Second Department of Obstetrics and Gynecology, University of Athens, 19, Soultani Str., GR-10682 Athens, Greece. malamitsi@aias.gr
Insights
Circulating neurotrophin levels, including BDNF, NT-3, and NT-4, did not differ between infants with intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) infants. However, nerve growth factor (NGF) was lower in IUGR infants.
Area of Science:
- Perinatal Medicine
- Neuroscience
- Developmental Biology
Background:
- Intrauterine growth restriction (IUGR) impairs fetal growth due to feto-placental-maternal unit disorders, often leading to chronic hypoxia.
- Chronic hypoxia in IUGR triggers a 'brain-sparing effect,' redistributing fetal blood flow to vital organs.
- Neurotrophins, including NGF, BDNF, NT-3, and NT-4, are crucial for neuroprotection and brain development.
Purpose of the Study:
- To investigate circulating neurotrophin levels in term infants with and without IUGR.
- To determine if the brain-sparing effect influences neurotrophin levels in IUGR neonates.
- To explore the relationship between neurotrophin levels, birth weight, and gestational age centiles in IUGR.
Main Methods:
- Comparison of serum levels of NGF, BDNF, NT-3, and NT-4 between IUGR and appropriate for gestational age (AGA) infants.
- Correlation analysis between neurotrophin levels and clinical parameters like birth weight and customized centiles.
- Utilizing established immunoassay techniques for neurotrophin quantification.
Main Results:
- Circulating levels of NT-3, NT-4, and BDNF were comparable between IUGR and AGA infants.
- Nerve growth factor (NGF) levels were significantly lower in the IUGR group compared to the AGA group.
- NGF levels showed a positive correlation with customized centiles and birth weight, both reduced in IUGR infants.
Conclusions:
- The brain-sparing effect may maintain stable levels of BDNF, NT-3, and NT-4 in term IUGR infants.
- Reduced NGF levels in IUGR infants may reflect impaired neurotrophic support or altered growth trajectories.
- NGF may serve as a potential biomarker for assessing fetal growth and neurodevelopmental outcomes in IUGR.
Abstract:
Intrauterine growth restriction (IUGR) is failure of the fetus to achieve his or her intrinsic growth potential, due to anatomical/functional diseases or disorders in the feto-placental-maternal unit. Growth restriction successfully balances reduced oxygen delivery and consumption; however, chronic hypoxia is responsible for fetal blood flow redistribution to cardinal organs (brain, myocardium, and adrenal glands), the so-called brain-sparing effect. The neurotrophin family comprises four structurally related molecules: the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF), the neurotrophin-3 (NT-3), and the neurotrophin-4 (NT-4). By exerting neuroprotection, neurotrophins are critical for pre- and postnatal brain development. Based on the assumption that the brain-sparing effect might be activated in full-term IUGR infants, we hypothesized that circulating neurotrophin levels should not differ between IUGR and appropriate for gestational age (AGA) infants. Indeed, we found that in both groups, circulating NT-3, NT-4, and BDNF levels do not differ, and this finding could possibly be attributed to the activation of the brain-sparing effect. In contrast, NGF levels were higher in the AGA compared to the IUGR group. However, only NGF levels positively correlated with the customized centile and the birth weight of the infants, and both of them were lower in the IUGR group.
