Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI

OBJECTIVE: We tested the hypothesis whether small-for-gestational-age (SGA) fetuses have different brain stem and cerebellar morphometry when compared with appropriate-for-gestational-age (AGA) fetuses and whether the differences in these structures were associated with their neonatal neurobehavior. STUDY DESIGN: Magnetic resonance imaging was performed on 51 SGA fetuses and 47 AGA fetuses at 37 weeks' gestation. Pontine width, medullar width, vermian width and height, cerebellar primary fissure's depth, and cerebellar volume were measured and corrected by biparietal diameter and cerebellar volume by total intracranial volume. Ratios were compared between cases and control subjects. The association between morphometric differences and neuro-behavioral outcome in SGAs was tested. RESULTS: Brainstem and cerebellar ratios were significantly larger in SGA fetuses: pontine width, SGA 0.143 +/- 0.01 vs AGA 0.135 +/- 0.01 (P < .01); medullar width, SGA 0.088 +/- 0.01 vs AGA 0.083 +/- 0.01 (P = .03); vermian width, SGA 0.181 +/- 0.03 vs AGA 0.162 +/- 0.02 (P < .01); vermian height, SGA 0.235 +/- 0.03 vs AGA 0.222 +/- 0.01 (P < .01); cerebellar volume, SGA 0.042 +/- 0.01 vs AGA 0.038 +/- 0.00 (P = .04); with deeper cerebellar primary fissure in SGAs, SGA 0.041 +/- 0.01 vs AGA 0.035 +/- 0.01 (P = .01). Medullar, cerebellar biometries, and volumetry were significantly associated with different Neonatal Behavioral Assessment Scale cluster scores in SGA infants. CONCLUSION: Brain stem and cerebellar morphometric measurements are significantly different in term SGA fetuses, which are associated significantly with their neurobehavioral outcome. This finding supports the existence of brain microstructural changes in SGA fetuses and lays the basis for potential image biomarkers to detect fetuses who are at risk.