Associations between neural injury markers of intrauterine growth-restricted infants and neurodevelopment at 2 years of age

Abstract

Objectives: The aim of this study was to evaluate the relationships between brain injury biomarkers in intrauterine growth-restricted (IUGR) infants (S100B and neuron-specific enolase (NSE)) and neurodevelopment at 2 years of age.

Methods: This prospective case-control study was a cooperative effort among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler variables were measured for each infant. Maternal venous blood and fetal umbilical arterial blood samples were collected at the time of delivery and neural injury markers S100B and NSE concentrations were measured. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III).

Results: Fifty six pregnancies were included. Thirty-one infants were classified as IUGR and 25 as non-IUGR. Neurodevelopmental evaluation at 2 years of age indicated that there were no between-group differences for any of the tests. For all patients in both groups, we found statistically significant inverse relationships between the concentrations of NSE in the cord blood and the results of the cognitive test (r = −271, p = .042), fine motor subtest (r = −280, p = .036), and social-emotional test (r = −349, p = .015). We also found statistically significant differences between the concentrations of S100B in the cord blood and the results of the cognitive test (r = −306, p = .022) and expressive communication subtest (r = −304, p = .023). For the IUGR group, we found a significant inverse relationship between the concentrations of S100B in the maternal serum and the results of adaptive behavior test (p < .05). In the non-IUGR group, we found statistically significant inverse relationships between the concentration of NSE in the cord blood and the results of the fine motor subtest (r = −446, p = .025) and social-emotional test (r = −489, p = .021). The difference between the concentration of S100B in the cord blood and the language composite score was also statistically significant (p = .038).

Conclusions: At 2 years of age, the concentrations of NSE and S100B were higher in the non-IUGR and IUGR groups with the worst scores for some areas of neurodevelopmental evaluation. The value of these biomarkers for prognostic neurodevelopmental use requires further investigation for both non-IUGR and IUGR infants.

Keywords:

• Intrauterine growth restriction
• neural injury markers
• neurodevelopment
• neuron-specific enolase
• S100B

Acknowledgments

We thank the Gynecology and Obstetrics Service at the Sant Joan de Déu University Hospital in Barcelona and the RETICS.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the PI11/02613 project, integrated in the National R + D+ I and funded by the ISCIII – General Assessment Branch and Formento of Health Research – and the Fondo Europeo de Desarrollo Regional (FEDER)

This work was also funded by the PN I + D+I 2008 − 2011 (Spain), the ISCIII – Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund [ERDF, ref. RD12/0026], and the Fund for Health Research of the Spanish Social Security Service, for financial support of this project [Exp PI11/02613].

E.M., E.L., L.C., O.S., A.M.-A., M.D.G.R. were supported by Maternal and Child Health and Development Network II (SAMID II), funded by Instituto de Salud Carlos III (ISCIII), Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF), Spain.