Fetal Brain-Sparing, Postnatal Cerebral Oxygenation, and Neurodevelopment at 4 Years of Age Following Fetal Growth Restriction

Abstract

Objectives: To assess the role of fetal brain-sparing and postnatal cerebral oxygen saturation (r_cSO₂) as determinants of long-term neurodevelopmental outcome following fetal growth restriction (FGR). Methods: This was a prospective follow-up study of an FGR cohort of 41 children. Prenatally, the presence of fetal brain-sparing (cerebroplacental ratio < 1) was assessed by Doppler ultrasound. During the first two days after birth, r_cSO₂ was measured with near-infrared spectroscopy. At 4 years of age, intelligence (IQ points), behavior (T-scores), and executive function (T-scores) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Child Behavior Checklist, and Behavior Rating Inventory of Executive Function-Preschool Version, respectively. Using linear regression analyses, we tested the association (p < 0.05) between brain-sparing/r_cSO₂ and normed neurodevelopmental scores. Results: Twenty-six children (gestational age ranging from 28.0 to 39.9 weeks) participated in the follow-up at a median age of 4.3 (range: 3.6 to 4.4) years. Autism spectrum disorder was reported in three children (11.5%). Fetal brain-sparing was associated with better total and externalizing behavior (betas: -0.519 and -0.494, respectively). R_cSO₂ levels above the lowest quartile, particularly on postnatal day 2 (≥ 77%), were associated with better total and internalizing behavior and executive functioning (betas: -0.582, -0.489, and -0.467, respectively), but also lower performance IQ (beta: -0.530). Brain-sparing mediated some but not all of these associations. Conclusions: In this FGR cohort, fetal brain-sparing and high postnatal r_cSO₂ were-independently, but also as a reflection of the same mechanism-associated with better behavior and executive function. Postnatal cerebral hyperoxia, however, was negatively associated with brain functions responsible for performance IQ.

Keywords: behavior; cerebroplacental ratio; executive function; fetal brain-sparing; fetal doppler; intelligence; near-infrared spectroscopy; regional cerebral oxygen saturation.

Figure 1

Inclusion flowchart. CPR, cerebroplacental ratio; FGR, fetal growth restriction; NIRS, near-infrared spectroscopy.

Figure 2

Box -Whisker plots depicting differences in neurodevelopmental outcome (A: cognition, B: behavior, C: executive function) in 4-year-old children with and without fetal brain-sparing following fetal growth restriction. Boxes represent interquartile ranges, whiskers the total range of values excluding outliers, circles represent outliers and asterisks extreme outliers. Dotted lines indicate the cut-off between normal and abnormal scores. *and **demonstrate a difference below the 10 and 5% significance level, respectively. EF, executive function; EMI, Emergent Metacognition Index; FI, Flexibility Index; IQ, intelligence quotient; ISCI, Inhibitory Self-Control Index.

Figure 3

Scatterplots depicting the association between cerebral oxygen saturation on postnatal day 1 (white squares), day 2 (black dots), and neurodevelopmental outcome (A: cognition, B: behavior, and C: executive function) in children at 4 years of age following fetal growth restriction. Dotted lines indicate the cut-off between normal and abnormal scores. IQ, intelligence quotient.

Figure 4

Box-Whisker plot depicting the association between fetal brain-sparing and the cerebral oxygen saturation on postnatal days 1 and 2 in infants born following fetal growth restriction. Boxes represent interquartile ranges and whiskers the total range of values. **demonstrates a difference below the 5% significance level.