European Journal of Paediatric Neurology 1998; 1: l-5

REVIEW ARTICLE

Some influences on cognition in early life: A short review of recent opinions

NEIL GORDON

Wilmslow, Cheshire, UK

Many factors can affect a child’s ability to learn, and these may operate before, during, and after birth. Some of these

are considered, and are hopefully important, but not necessarily the most obvious. The intrauterine environment may

not be so influential as the infant’s genetic endowment, but nevertheless is of considerable importance. For example,

malnutrition resulting from placental insufficiency leading to small-for-date babies can impair brain development.

Also a relationship between birth weight and cognitive function in early adult life has been demonstrated; and the

babies’ condition at birth can be a risk factor for various disabilities.

Lack of stimulation in infancy, for example if postnatal depression interferes with the mother’s interaction with her

baby, can significantly affect the infant’s learning capacity. A good paradigm is the development of language, which

starts with the way mothers ‘talk’ to their babies; and this continues into childhood. The importance of nutrition also

continues, and is one of the factors which favours breast feeding against formula foods.

The whole subject has to be viewed against the background of normal development, and the great loss of neurons

and synapses that occur in early life. If neural circuits are formed at this time, and these neurons and synapses are not

lost, the easier it will be to exploit them. This emphasizes the importance of early education, which is not always

sufficiently acknowledged.

Keywords: Cognitive development. Causes ol impairment. Early education

Introduction

It is now recognized that an increasing number of factors in early life can affect the development of a child’s intelligence; some of these will be reviewed in this article. Among them are intrauterine environment, condition at birth, nutrition and postnatal environment, especially lack of stimula- tion. Also it has to be emphasized that it will often be a combination of factors that results in an interference with development; the complex situa- tion has to be considered against a background of changes that occur during normal development.’ For example, poverty can affect cognitive develop- ment in a number of ways: malnutrition, disease, toxic agents, perinatal injury and lack of stimula- tion. It may be that the common factor in these

associations is a reduction in the brain’s capacity to engage in attentive behaviour.2 Obviously experi- ments in mice cannot be extrapolated to humans, but it is a fascinating observation of Kempermann et al.,3 that animals raised in an enriched environ- ment grow more neurons in the dentate gyrus of the hippocampus.

The intrauterine environment . .

There is evidence that the fetal brain can react to stimuli, even before birth,4 but this is unlikely to be of particular importance to future development. However, studies have shown that the intrauterine

Received 20.10.97. Revised 15.12.97. Accepted 7.1.98. Correspondence: Dr N Cordon, Huntlywood, 3 Styal Road, Wilmslow, Cheshire SK9 4AE, UK

logo-3798/98/010001+5 $18.00 0 1998 European Paediatric Neurology Society

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environment may be highly significant.5 Co-var- iance between relatives may be due not only to genes, but also to shared environments. This was studied by a model of two maternal womb environments - one for twins and another for siblings, along with a common home environment. Maternal effects accounted for 20% of co-variance between twins and 5% between siblings. It is not surprising that the intrauterine environment is so important when so much of the brain growth occurs in utero and so many factors can influence this from toxic agents to nutrition.

Malnutrition at certain stages of development can have a significant effect on the growth of the brain. If this occurs during the main spurt of brain growth, which lasts in humans from about mid- pregnancy to the end of the second year of life the formation of neurons and synapses may be permanently affected. This certainly seems to be true in developing countries, where populations may be at subsistence level.6 In developed coun- tries, the most likely prenatal cause will be an impairment of the blood supply from the placenta to the fetus7 and it has been shown that a variety of developmental disorders can often occur among small-for-date babies as they grow UP.~‘O

In a recent review of the functional abilities of school children, born extremely premature, it was found that the most common outcome was a mixture of specific learning disorders, especially those involving motor function, as well as asso- ciated behavioural disorders rather than severe multiple disabilities. I1 These results emphasize the need for long-term follow-up of these particular children throughout their school days and, as more of them survive, increased resources being reserved for their support, educational and other- wise.

Experimental work on rats has shown that malnutrition limited to the prenatal period can produce permanent alterations in brain structure as marked as those caused by postnatal malnutrition. However, the theories on how this occurs, and to what extent, have changed12 and these will be discussed when the subject of nutrition in infancy is considered.

A measure of malnutrition during pregnancy is the low weight of a baby in relation to the time of its birth, quite apart from the problems of the preterm baby. It has been shown that among preterm infants both intrauterine and extrauterine brain development can be affected.*3

Postnatal brain development of healthy prema- turely born infants was assessed to study the possible influence of premature birth and early extrauterine environment on structural, biochem-

Review article: N Gordon

ical and functional brain development. Myelination and differentiation of grey and white matter was studied by magnetic resonance imaging, changes in cerebral metabolism by magnetic resonance spec- troscopy, and the preterm infants’ behaviour was measured by suitable tests. The stage of intrauter- me and extrauterine brain development in preterm infants was compared with the stage of mainly intrauterine development in a group of full-term infants. Eighteen preterm infants with satisfactory neurological and medical status were studied at about 2 weeks of postnatal age and again at term. For comparison a group of 13 full-term born infants were assessed by magnetic resonance, and six by tests of development. When the assessments at full- term were compared with those at 2 weeks of postnatal age among the 18 preterm infants, significant maturational changes were found with magnetic imaging in the grey and white matter and in cerebral metabolism and in the measures of development. When the preterm infants at term were compared with the infants born at term, significantly less grey and white matter differentia- tion and myelination was observed as well as poorer performance in several of the neurobeha- vioural parameters. It was therefore concluded that preterm infants studied at term compared with full-term infants showed a structural and func- tional delay in brain development at 40 weeks of post-conceptional age. This outcome may depend on many factors such as genetic influences, delivery, postnatal management, nutrition and various other complications. Also, brain develop- ment will not be uniform and may not be manifest at term, so that long-term follow-up will be necessary if optimal conditions are to be provided for neuromaturation. However, this study is based on only 18 preterm infants, 13 full-term infants investigated with magnetic resonance imaging, and six full-term infants whose reactions and beha- viours were monitored with a number of performance tests, which may limit its validity.

Hutton et n1.r4 found that the effects of preterm birth and small-for gestational-age were different. The latter was associated with cognitive ability and reading comprehension, and motor ability was additionally associated with the former. This might be due to different insults acting at the same time, or the same insult acting at different stages. For preventive purposes more is known about the causes of growth retardation such as maternal smoking, hypertension and genitourinary infec- tion, than for preterm birth if the association is causal. Of the 182 children, 158 were assessed.

A study in Denmark examined the relationship between birth weight and cognitive function

Review article: Influences on cognitive functions 3

among young adults. l5 It was found that a measure of intelligence of conscripts in their early 20s increased from those with a birth weight of less than 2500g compared with those with a birth weight of 42OOg, even after an adjustment for gestational age and length at birth, maternal age and parity and other variables. However, the authors warn that further studies are needed, with careful control for confounding factors.

The condition at birth - -..-__-_- -___-~-- Perinatal factors were investigated in 53 low birth weight infants with minor neurodevelopmental dysfunction at a 2-year follow-up, and in 106 consecutive controls matched for gestational age and birth weight. The obstetrical history was significantly worse among cases than controls, suggesting that clusters of obstetrical adverse events were more frequent in the former. Analysis showed that after adjustment for the effects of gesta tional age, socioeconomic status and the education of the mother, less than three prenatal visits and a third trimester haemorrhage were the only antenatal factors significantly associated with an increased risk of minor infant neurodevelop- mental impairment. Neonatal acidosis within the first 24 hours, and male gender, were additional significant perinatal risk factorsI

Even the management of infants, especially when preterm, in the newborn intensive care unit may be significant for future development. This should enhance stimulation and reduce stress as much as possible. I7 Also neuroimaging has helped immeasurably in assessing possible brain damage in newborn infants, when evidence is shown of periventricular leukomalacia, periventricular or intraventricular haemorrhage, or of periventricular infarction.18

Postnatal development _--_-- .-- ..,-1_-._--1-.1-- 1.---1_ . . . .

Many aspects in the early life of an infant can affect learning, especially when they involve lack of stimulation. For example, a mother who suffers from postnatal depression may well fail to respond to the needs of her baby, with resulting lack of stimulation. In a survey of the literature it seems that the children of mothers suffering from post- natal depression are at risk of impaired mental and motor development and of emotional disturbances in late infancy. It has been noted that babies of mothers with symptoms of depression are more

apathetic and show electroencephalogram evi- dence of reduced frontal lobe activity in areas related to emotional expression.r9 This will tend to be greater when the depression is severe and in the context of personal and social adversity.20

The learning of language can be influenced from a very early age, as language listening affects language production. It has been shown that the ways mothers from a number of different cultures speak to their babies is similar and of considerable importance. It has unique acoustic characteristics with higher pitch, exaggerated intonations and slower cadence; sometimes referred to as ‘paren- tese’. Vowels are produced which are acoustically more extreme, resulting in an expanded vowel space, so that infant-directed speech assists in sorting language into phonetic categories by delivering information about the sound system of the infant’s native language in an exaggerated form. This effectively separates sounds into con- trasting categories and highlights the parameters by which categories are distinguished and by which speech can be imitated by the child. All this suggests that language input is not a trigger for innately stored information but that language input has universal characteristics designed to promote language leaming;21 hence the importance of mothers ‘talking’ to their babies. This interaction continues into childhood and may well account for the fact that two people of equal intelligence may have very different attainments because of their varied command of language.”

The role of nutrition among preterm babies has already been considered and it can be equally important during infan~y.~ If malnutrition does occur during the main spurt of brain growth from about mid-pregnancy to the end of the second year of life the growth of neurons and their axons may well be affected and may cause irreversible brain damage resulting in severe impairment of brain function.7 However, recent studies have confirmed that considerable recovery can occur, although permanent changes remain in the hippocampus and cerebellum. The role of adrenal steroids may be vital in the survival of neurons in the hippocampus when they are exposed to stresses.24 Also there can be longlasting and sometimes permanent alteration of neural receptor function which can lead to behavioural and cognitive disorders.r2 The investigations of Stoch and Smythe= from South Africa on undemurished children, first published in 1963, have shown that this can result in impaired intellectual develop- ment; they stress that there is a close relationship between head circumference and school perfor- mance.

4 Review article: N Gordon

One factor is the role of breast feeding. Apart from reducing the risk of infection and admission to hospital, it can be associated with better intellectual development. For example, breast milk contains docosahexaenoic acid and arachido- nit acid deposited in large amounts in the non- myelin membranes of the nervous system and essential for normal brain development; it is often absent or in short supply in formula feeds.* Rogan and Gladen enrolled 855 newborns in a prospec- tive study and developmental tests were carried out on many of them. There was a statistically significant but small increase in some of the scores among breast fed children which was detectable at school. age.

There are obviously many other factors which can affect the development of the brain in infancy: illness, trauma and conditions such as iron-defi- ciency anaemia. Infants with such anaemia are at risk of long-lasting developmental disadvantage.*’

Normal development and some disrupting fat tors

In early life the brain has an abundance of neurons and synapses, many of which are soon lost. If a neuron does not make contact with its target it dies - a case of ‘use them or lose them’, which underlies the importance of stimulation. Learning in general tends to be easier at a younger age than later in life and especially if motor skills are involved. For example, when learning ballet it seems essential to start in early childhood if perfection is to be obtained.

It can be easily accepted that neurons and synapses may rapidly decrease in old age, but it is surprising that the same thing happens at the other end of life. However, the fact that this occurs to such an extent in the first few years of life underlies the adaptability of the brain, and its amazing ability to develop specialized functions.’

There are many reasons for more neurons and synapses disappearing in childhood than nature intended. In both intrauterine and postnatal life selective vulnerability can occur, for example, the temporary germinal matrix is vulnerable to hae- morrhage in the third trimester fetus and in premature infants. The immature oligodendroglia in the developing white matter of the fetus are also vulnerable to injury, which can result in periven- tricular leukomalacia; also, during the first decade when the number of synapses are being reduced as a feature of normal development, they are more sensitive to damage, for example during hypoxia -

ischaemia glutamate receptors may be overstimu- lated.28

Just as the development of neurons, their migration and the formation of synapses continues for several years after birth, so the blood-brain barrier is not fully established until the middle of the first year of life. As a result, various toxic agents are especially hazardous during infancy. Some substances, such as psychoactive drugs and lead, may act at a later age. Perhaps this is because they act during synaptogenesis and the development of transmitter systems, or on the other hand when connections are being reduced in number.29 A hopeful note can be struck by the fact that more is now known about ways in which brain damage can be limited and the brain can be repaired,3O and Rutherford et aZ.31 have shown that after perinatal infarction the brain can grow into the infarcted area.

Conclusions

Many of the causes of impaired learning, particu- larly the prenatal and natal causes, offer great opportunities for prevention and most of these receive the attention they deserve. However, there is a special aspect of this work in the postnatal field that it seems justifiable to emphasize - and that is the importance of early education.’ In times of limited resources choices have to be made but these should not only be financial. Due attention should be given to physiological aspects, such as the way the brain develops; if the importance of early learning is accepted, this is a strong argument that more of these resources are given to early educa- tion. Efforts to ensure that children reach their full potential and that this is not jeopardized by avoidable causes, cover almost every aspect of paediatrics, and is one of its most important objectives. This is well shown in the conclusions of a case-control study on neonatal risk factors for cerebral palsy in very preterm babies.32 If the number of babies suffering from cerebral palsy and the more subtle disorders of development are to be reduced, integrated management throughout antenatal, intrapartum and neonatal periods and during early childhood, will be required because of multiple risk factors.

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Review article: Influences on cognitive functions

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