Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns

Nikolaos Machairiotis; Dionysios Vrachnis; Nikolaos Antonakopoulos; Nikolaos Loukas; Alexandros Fotiou; Vasilios Pergialiotis; Sofoklis Stavros; Aimilia Mantzou; Georgios Maroudias; Christos Iavazzo; Christina Kanaka-Gantenbein; Petros Drakakis; Theodore Troupis; Konstantinos Vlasis; Nikolaos Vrachnis

doi:10.3390/jcm12124131

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns

J Clin Med. 2023 Jun 19;12(12):4131. doi: 10.3390/jcm12124131.

Authors

Nikolaos Machairiotis¹, Dionysios Vrachnis², Nikolaos Antonakopoulos^{1

3}, Nikolaos Loukas⁴, Alexandros Fotiou¹, Vasilios Pergialiotis⁵, Sofoklis Stavros¹, Aimilia Mantzou⁶, Georgios Maroudias⁴, Christos Iavazzo⁷, Christina Kanaka-Gantenbein⁶, Petros Drakakis¹, Theodore Troupis⁷, Konstantinos Vlasis⁸, Nikolaos Vrachnis¹

Affiliations

¹ Third Department of Obstetrics and Gynecology, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
² Department of Clinical Therapeutics, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 10676 Athens, Greece.
³ Department of Obstetrics and Gynecology, University Hospital of Patras, Medical School, University of Patras, 26500 Patra, Greece.
⁴ Department of Obstetrics and Gynecology, Tzaneio General Hospital, 18536 Piraeus, Greece.
⁵ First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 10676 Athens, Greece.
⁶ First Department of Pediatrics, "Aghia Sophia" Children's Hospital, Medical School, National and Kapodistrian University of Athens, 10676 Athens, Greece.
⁷ Gynecologic Oncology Department, Metaxa Memorial Cancer Hospital, 18537 Piraeus, Greece.
⁸ Department of Anatomy, Medical School, National and Kapodistrian University of Athens, 10676 Athens, Greece.

Abstract

Background: Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth.

Methods: This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at -80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits.

Results: NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant.

Conclusions: Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.

Keywords: amniotic fluid; fetal growth restriction; fetal metabolism; inflammation; large for gestational age; metabolic syndrome; nerve growth factor (NGF); neurotrophin-3 (NT-3); neurotrophins; second trimester of pregnancy; small for gestational age.

Grants and funding

The research received no external funding.