Neuropsychological functioning and quantitative cerebral MRI in young adults born Small-for-Gestational-Age at term

Abstract

Fetal growth restriction (FGR) is said to occur in 3-10% of fetuses. The term small-for-gestational-age (SGA) is used as a proxy for FGR in epidemiological studies, and is defined as a birth weight cut-off, adjusted for gestational age, gender and parity, where birth weight below the 10th percentile is one of the most commonly applied definitions. SGA birth has been related to increased perinatal morbidity and mortality, but consequences on brain development are still unclear, and existing studies show somewhat conflicting results. The SGA definition is problematic as it involves both constitutionally small and healthy subjects, together with subjects born small after being exposed to fetal growth restriction (FGR). Different definitions of SGA/FGR and also different measures of cognitive abilities have probably contributed to the diversity of clinical findings on follow-up in this population. Furthermore, only few long term follow-up studies exist. The aim of this thesis was to compare term born SGA with non-SGA young adults on cognitive abilities assessed by a full WAIS-III, neuropsychological functioning by a comprehensive test battery, and brain morphometry (structural cerebral MRI). We also wanted to see if perinatal data could predict later cognitive functioning and/or brain measures, and also whether brain measures were related to cognitive abilities.

The thesis is based upon data from a prospective long term follow-up study that was aimed to look at causes and consequences of being born SGA at term. The study was initially organized by the National Institute of Child Health and Human Development (NIH) and originally included theUniversities of Trondheim and Bergen in Norway, the Universities of Uppsala in Sweden, and Alabama in the United States. Subjects were born either SGA or non-SGA at term in 1986 to 1988. At the 19-20-year follow-up, only those born and living in the Trondheim area were included. A total of 59 SGA subjects and 81 controls met for assessment at 19-20 years of age, whereas we had successful MRI-data on 47 SGAs and 61 controls. We also performed a subgroup analysis looking at the effect of fetal growth on IQ, where we had repeated ultrasound measurements during fetal life of 29 SGAs and 74 controls. A total of six SGA subjects were defined as having FGR based on intrauterine growth pattern.

Our results showed that SGA young adults had more cognitive problems than the non-SGA group, and special education in school was 6-fold more common in the SGA group than in the control group. One third of the SGA subjects had IQ scores defined as low (score subgroup analysis revealed that the lower scores on the WAIS-III could be confined to SGA subjects born with FGR. About one in five of the SGA group showed deficits (score <-1.5SD) on one or more of the neuropsychological domains, whereas this was the case in only one in thirteen controls. The SGA group demonstrated reductions in brain volumes and regional reductions in cortical surface area compared with controls. We found no associations between perinatal data and cognitive functioning, and neither any relationship between IQ and brain measures.

Our study suggests that being born SGA at term may have long lasting consequences on cognitive and neuropsychological functioning, and persisting structural deviations in brain volumes and cortical surface area compared with being born with normal birth weight for gestational age. Furthermore, our subgroup analysis indicates that the lower IQ scores could be restricted to those born SGA after FGR. This thesis stresses the importance of long term follow-up of infants born SGA at term, and also the importance of screening for risk-factors and further follow-up of pregnant women to prevent fetal growth restriction and low birth weight.