Growth in utero and cognitive function in adult life: follow up study of people born between 1920 and 1943

Introduction

There is considerable evidence that malnutrition in early life can have an adverse effect on the developing brain.1 2 During various critical periods in the develop ment of the central nervous system, malnutrition has been shown to affect the morphology, physiology, and neurochemistry of the brain, and this may have important implications for future cognitive function.3 4 5 Undernutrition during proliferative growth of the brain, for example, retards the rate of cell division and causes a permanent reduction in numbers of brain cells.6 Animal studies suggest that such nutritional privation during fetal life affects later performance on tests of learning.7 In humans, low birth weight and proportionate smallness at birth, both of which may result from undernutrition in utero, have been associated with poorer performance on tests of cognitive function in early childhood.8 9 10 There have been few studies, however, on whether poor fetal growth has a lasting effect on adult cognitive performance.

In several community surveys of older people, cognitive function has been assessed by using the AH4 intelligence quotient (IQ) test and the Mill Hill vocabulary test.11 Studies have shown that cognitive skills do not all deteriorate at the same rate.12 13 The AH4 test provides a measure of fluid intelligence, which tends to decline with advancing age, while score on the Mill Hill vocabulary test gives an estimate of crystallised intelligence, which may be retained unimpaired until very late in life.14 By measuring the discrepancy between scores on the two tests an indication of the amount of decline in cognitive ability can be obtained.15 We studied the cognitive performance of older men and women who had been measured in unusual detail at birth. We investigated whether intrauterine growth was related to adult intelligence. Because we thought it possible that the rate of cognitive decline with age might be influenced by growth in utero, we also investigated whether birth measurements were associated with the discrepancy between score on the Mill Hill vocabulary test and score on the AH4 IQ test.

Subjects and methods

From 1911 onwards each child born in Hertfordshire was seen immediately after birth by a health visitor and its birth weight was recorded in centrally held registers. In Preston and Sheffield a standardised record was kept for each woman admitted to the labour wards at Sharoe Green Hospital and Jessop Hospital for Women, respectively. These records included details of the baby's birth weight, length from crown to heel, and measurements of abdominal circumference, head circumference, biparietal diameter, and occipitofrontal diameter. The NHS central register was used to trace singleton infants born to married mothers in Hertfordshire, Preston, and Sheffield. Those who were still living in the area of their birth were invited to take part in various studies into the processes by which the environment in early life influences adult disease.16 17

In this analysis we used five datasets comprising men and women who still lived in the area in which they were born. Subjects were invited to participate and were interviewed if they agreed. They were then invited to undergo psychometric testing. Table 1 gives details of the participants.

Subjects took part 1 of the AH4 IQ test, which provides a measure of logical, verbal, and numerical reasoning, and the Mill Hill vocabulary test. To obtain an estimate of the amount of decline in cognitive function, we standardised the scores on the two tests using Z scores and calculated the difference between them.15

We analysed all the datasets together, with multiple linear regression and tabulation of means to examine the relation between measurements of body size at birth, score on the AH4 intelligence test, and amount of change in cognitive function. Birth weight, length, ponderal index, and head circumference were divided into groups in the same way as in previous studies of these subjects.18 19 20 Categories of occipitofrontal diameter, biparietal diameter, head circumference to length ratio, and head circumference to abdominal circumference ratio were chosen by grouping into thirds of the distributions. We have shown the results as mean score on the AH4 test and mean amount of cognitive loss within each group of birth measurements. All values given for significance were calculated by regression with birth measurements used as continuous and not categorical variables. Mean score on the AH4 intelligence test was higher in those whose fathers were in non-manual occupations at the time of their birth and in younger subjects. Mean AH4 score also varied between the datasets. We adjusted for all these factors in regression. There were no significant differences between the sexes in either score on the AH4 test or change in cognitive function. When we analysed the sexes separately the findings were similar, and the results are shown for men and women combined.

Results

Table 2 shows mean birth measurements, age, scores on the two psychometric tests, and decline in cognitive function in all subjects combined and in each dataset separately. Mean score on the AH4 intelligence test was higher in the Preston and first Sheffield groups, in which the average age of subjects was younger. These two groups also showed less evidence of decline in cognitive function, as measured by the absolute difference between standardised scores on the Mill Hill vocabulary test and the AH4 test.

Mean score on the AH4 test was higher with increasing birth weight, but this trend was not significant (table 3). We found no relation between AH4 score and either length, head circumference, or occipitofrontal diameter at birth. Body proportions at birth, whether assessed by ponderal index, head circumference to length ratio, or head circumference to abdominal circumference ratio, were not related to AH4 score. On average, subjects who had a large biparietal diameter at birth had a higher AH4 score. After adjustment for age, social class at birth, and the individual datasets, the score on the AH4 test rose by 3.7 for each inch (2.5 cm) increase in biparietal diameter. We repeated all these analyses, excluding 82 subjects who had been born before 38 weeks of completed gestation. The relation between AH4 score and biparietal diameter persisted, but there were no associations with any other measure of body size or proportions.

We found no relation between decline in cognitive function, as estimated by the discrepancy between standardised scores on the two tests, and proportions at birth as assessed by head circumference to length ratio or head circumference to abdominal circumference ratio, nor was cognitive function related to any measure of head size (table 3). Neither birth weight nor length were associated with decline in cognitive function. We obtained similar results when we excluded subjects born before 38 completed weeks of gestation.

Discussion

In these data there were few associations between fetal growth and adult cognitive function. No relation was found between any measure of body size or proportions at birth and adult intelligence, with the exception of biparietal diameter. People with a large biparietal diameter at birth tended to gain higher scores on the AH4 IQ test. No associations were found between decline in cognitive function related to age and either size or proportions at birth.

Our results are based on 1576 subjects who took the two psychometric tests. This is 47% of those originally invited to participate. Furthermore, the participants are unrepresentative of all people born in Hertfordshire, Sheffield, or Preston because they have continued to live in the area of their birth. All comparisons, however, have been made within the study sample. Unless the relations between birth measurements and cognitive function in adult life differ in non-responders or in people who have died or moved away, no bias will have been introduced.

Measurements of head circumference correlate closely with brain size at birth.21 A small head circumference at one year has been associated with a lower score on intelligence tests in early childhood.22 We found a significant association between biparietal diameter at birth and score on the AH4 IQ test in adult life, but this is hard to interpret in the absence of any association with other measurements of head size; it may be due to chance.