DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY
INVITED REVIEW
Growth, head growth, and neurocognitive outcome in children born very preterm: methodological aspects and selected results MICHAEL B RANKE 1
1 € | INGEBORG KR AGELOH-MANN | BRIGITTE VOLLMER2
1 University Children’s Hospital, T€ubingen, Germany. 2 Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK. Correspondence to Michael B Ranke, University Children’s Hospital, Hoppe-Seyler-Strasse 1, D-72076 Tubingen, Germany. E-mail: [email protected]
PUBLICATION DATA
Accepted for publication 24th June 2014. Published online ABBREVIATIONS
AGA SGA
Appropriate for gestational age Small for gestational age
In light of the growing number of surviving children born very preterm, there is an increasing focus on their long-term outcomes in terms of growth, metabolic status, and neurocognitive development. Therefore, it is of importance to follow such children from birth onwards with the aim of identifying the causes of atypical development, developing preventative measures, and improving outcomes. Since such long-term follow-up needs to be conducted with the least possible burden, clinical investigations such as anthropometry and neurocognitive tests, if conducted rigorously, will continue to have a predominant role. The aim of this review is to discuss the complexity of longitudinal anthropometry in children born very preterm and to provide an overview of the main studies that have examined associations between growth, in particular head growth, and neurocognitive outcomes at around school age.
During the past decades we have observed dramatic changes in the medical and social environment in Western societies which have also affected human reproduction.1 The number of multiple pregnancies has increased as a result of new artificial reproductive techniques2,3 and, overall, as a consequence of advances in perinatal care, there are more preterm deliveries accompanied by increased survival of extremely preterm infants.4 However, a proportion of children who are small at birth and/or born preterm remain at risk of adverse development. They may continue to be of less than average height,5 they may develop neurological and/or cognitive impairments,6 and they are at risk of developing a metabolic syndrome in adult life.7 Because of the complexity of perinatal risk factors it remains somewhat unclear which pre- or postnatal factors are predominantly associated with such sequelae. In order to identify factors that may affect negatively the outcomes of small and/or preterm children, longitudinal studies have been conducted following various aspects of development in these children. Since brain growth and brain development are essential for optimal neurological and cognitive outcome, assessment of brain growth should be part of such follow-up studies. The aims of this review are to discuss some methodological aspects in the evaluation of growth parameters, including head growth, from intrauterine life to childhood, and to summarize the results of the main studies which have investigated growth, and cognitive and neurological outcome at school age in children who are very small at birth and/or are born preterm.
Anthropometric growth parameters For clinical and scientific purposes, growth evaluation in children can most easily be made by measuring various © 2014 Mac Keith Press
body components (anthropometry).8,9 Ideally, the description of an individual’s growth process will take into account several components and their interrelationships. While normative reference data are available for a multitude of anthropometric parameters during childhood, for newborns (both term-born and preterm) mostly only those for weight, total body length/height and head circumference have been established.10
Weight Weight gives summarized information about all body components. It is the anthropometric parameter commonly measured after birth with sufficient accuracy.8,11 Newborns should be weighed naked immediately (within 1h) after birth. In order to express weight controlled for length/ height, indices such as the body mass index (weight [kg]/ length² [m]) or the ponderal index (weight [kg]/length³ [m]) can be derived. Classification of newborns based on weight and/or gestational age Based on birthweight – irrespective of gestational age – newborns are commonly classified into groups: low birthweight infants (weight between 1500g and 2499g); very low-birthweight infants (weight between 1000g and 1499g); and extremely low-birthweight infants (weight below 1000g). Since this classification does not consider gestational age groups, groups categorized according to birthweight may be quite heterogeneous. Birthweight in relation to the norms for gestational age is traditionally used to classify newborns into three major categories: (1) appropriate for gestational age (AGA; weight within normal range); (2) small for gestational age (SGA; weight below normal range); and (3) large for gestational DOI: 10.1111/dmcn.12582 1
age (weight above normal range). While neonatologists still tend to use the 10/90 centiles (equivalent to mean1.28SD) as cut-offs, endocrinologists tend to use the 3/97 centiles (equivalent to mean2.0SD). In conjunction with the timing of birth (pre-term, full-term, post-term) further subclassifications may be formed. To base such classifications on weight alone without considering length is not fully correct. However, length is often not measured at birth.
Length Total body length, or crown–heel length, which is the supine equivalent to standing height, is also a composite of several body components (e.g. head, trunk, extremities) which are under varying environmental or genetic control. Because of the fetal positioning in utero, length measurements after birth are quite difficult to perform. In order to increase accuracy, length measurements can be postponed to 48 to 72 hours after birth. The inter- and intra-observer error of the measurement is in the range 0.3 to 0.5cm.8,11 Head size and head circumference Head growth is mainly determined by the development of the brain, which reflects the increase in neuronal cells, neuroglia cells, and supportive connective tissue. Prenatally, head size and brain structures can clinically be investigated by means of ultrasonography or fetal magnetic resonance imaging (MRI).12 In utero fronto-occipital and/ or biparietal diameters are taken as measures of head size. Head circumference, which used to be termed frontooccipital head circumference, is practically the largest head circumference measurable with a flexible, but not extensible, tape. The measuring error is about 0.3 to 0.4cm.8,11 Head circumference can also be calculated from cranial diameters; e.g. head circumference=(biparietal diameter9occipito-frontal diameter9p/2). Since deformities and soft tissue swelling do occur during the process of birth, measurements taken some time after birth (48–72h) may give a more accurate reflection of neonatal head size than measurements taken directly after birth. Brain weight is proportional to the cube of the head circumference from birth until 18 years of age.13 In newborns and children, head circumference is well correlated with brain size as measured by neuroimaging, e.g. MRI or computed tomography.14,15 Postnatally, ultrasonography of the head is also easily accessible. This technique is well suited to document larger anatomical abnormalities as a result of bleeding or
•
What this paper adds For optimal follow-up of children born very preterm, anthropometric and neurocognitive investigations need to be combined.
major ischaemic insults. However, ultrasonography is less well suited for detecting hypoxic–ischaemic lesions in the absence of larger bleeds or of minor or diffuse hypoxic insults,16 which may no less impair the long-term development of the brain. Since it is easy to measure head circumference, this is still the most frequently used surrogate measurement of overall brain growth in longitudinal cohort studies of children born preterm, but may be replaced in the future by serial neuroimaging.16,17 The difference in the dynamics of length/height and head circumference during fetal and early postnatal development is illustrated in Table I.
Evaluation of growth parameters Longitudinal investigation of a biological parameter in children requires the measuring technique to provide accurate information about the aspect in question over many years and during different developmental phases. Equally important, the evaluation of any biological (e.g. anthropometric) parameter in individuals requires the comparison with normative reference data derived from individuals of the same ethnicity, age, and sex. For clinical use, graphical growth reference charts give a useful orientation. However, in order to render possible an exact description in relation to the reference, numerical data of means and their error need to be available. If the parameter in question is normally distributed (e.g. length, height, head circumference), such a calculation is straightforward. However, if the distribution is skewed (e.g. weight), more complex measures for normalization need to be applied.20,21 These figures allow us to calculate an SD score (SDS), a term which describes the distance between the individual’s value and the mean of the reference: (SDS=[patient value minus the mean value of matched references]: SD of the mean value of matched references). The calculation of an individual’s SDS allows deviations in relation to the reference (or norm) to be described longitudinally. SDSs can also be used to deal with group data in exact numerical terms. References of growth parameters The establishment of robust normative references in children is complex since the population investigated must be
Table I: Difference in the dynamics of length/height and head circumference during typical fetal and early postnatal development Age
Length/height (cm)
% of adult height
Head circumference (cm)
% of adult size
10y 2y 1y 40wks 32wks 28wks
140 88 76 50 42 37
79 50 43 28 23 21
53 50 47 35 30 25
94 88 84 62 53 44
Swiss reference (males); Largo et al.,18 Prader et al.19
2 Developmental Medicine & Child Neurology 2014
stratified for a number of factors such as sex, ethnicity, and social aspects, and needs to cover the whole age range, with sufficient numbers investigated. If investigations need to be conducted in individuals followed from preterm birth on, or potentially even from before birth, the requirements for the establishment of references are most difficult to fulfil. Some aspects are particularly relevant for this deliberation. Prenatal anthropometric parameters cannot be measured in the same way as postnatally. For example, in order to approximate prenatal weight or head circumference, regression equations are applied incorporating sonographic measurements of certain body parts. Before 2 years of age supine length but not standing height is measured. Thus, references need to be created for different phases of life (e.g. prenatal, after birth up to the normal end of pregnancy [term=40wks (37–42wks)]; from term up to 2y of age; after 2y of age). References for children born preterm are by definition not based on ‘normal’ newborns since prematurity is not considered normality. Thus, references for anthropometric parameters based on preterm newborns do not reflect those of truly healthy newborns. Intrauterine measurements in healthy children born at term may reflect the norm, but are not directly comparable to those taken after birth. In particular, the growth development of preterm children after birth – often within neonatal intensive care units – is unlikely to reflect the normal course of an assumed healthy infant of the same age.10 The chronological age of an individual from its birth date can be calculated exactly. However, the age of gestation needs to be determined. Gestational age is the elapsed time from the reported first day of the last menstrual period until birth. Normal mean gestational age is 40 weeks (280d) with an estimated range of error of 2 weeks. Conceptual age is the time since fertilization, which is assumed to be gestational age minus 14 days, that is 38 weeks (266d). It has been shown that, when the exact day of conception is known, sonography during the first 22 weeks of pregnancy allows gestational age to be determined within a 95% confidence range of 1 week.22 Despite these problems, growth parameters of infants born preterm and measured postnatally are commonly compared with references obtained from birth cohorts. Thus, patients with an age equal to gestational age plus postnatal chronological age are compared with reference values based on gestational age. In order to accommodate differences in the age (gestational age, chronological age), complex mathematical multilevel modelling may be used for an adjustment23 for covariates in cohorts of preterm infants followed prospectively. Smoothing of data in order to accommodate disjunctures in the different transitional phases may be applied.10 Even if anthropometric references from the same population are available, the data may not be up to date or preand post-term data may have been collected during different time periods. In order to facilitate an evaluation of children’s growth in countries without ethnically homogenous references there are international activities (e.g. World
Health Organization, Centers for Disease Control) to establish ‘global’ references for several essential parameters (e.g. head circumference).24,25 However, by applying such references to specific populations, incorrect conclusions may be drawn. Thus, for longitudinal follow-up studies in children born preterm, the choice of references must be made with great care.10,26 Users should not only consider references that are most closely representative of their population but preferentially use those of the highest quality.
Neurological, developmental, and cognitive evaluation For accurate assessment of associations between growth, head growth, and neurological and cognitive development it is important to use age-appropriate, recently standardized, and valid (for the population under investigation) psychometric tools. Whether such tools are used and, if so, which tools differs between studies, and is also dependent on the age at assessment. Only a rather small proportion of studies that have examined relationships between anthropometric measures and neurological outcome in children who do not have cerebral palsy have used standardized methods; in fact, neurological status and neuromotor function are frequently neglected. In contrast, the majority of studies assessing neurodevelopment and overall cognitive abilities at pre-school and school age have used standardized psychometric tests. Associations between growth, head size, and neurological and cognitive outcome In typical development, it appears that head size and its growth dynamics in early life are more important for later cognitive function than head growth after infancy. For example, Gale et al.,27 in a large population-based study, examined associations between head growth in different periods of life and overall cognitive function, assessed with the Wechsler Scales, at age 9 years in a large unselected sample. They showed that head growth during both early infancy (in this study between birth and age 9mo) and late infancy/early childhood (9mo–9y) is related to Full-scale IQ after adjustment for sex, maternal education and social class, and duration of breastfeeding. Interestingly, Verbal IQ and Performance IQ appeared to be affected differently by head growth in the two time periods, with Verbal IQ being more affected by growth in the later period, and Performance IQ being more affected by growth in the earlier period. In contrast, head size at 18 weeks’ gestation and head circumference at birth were not associated with IQ scores at age 9 years. Furthermore, there is some evidence that head growth after infancy does not compensate for poor growth prenatally and in infancy.28 It is important to note that the study by Gale et al.28 suggests that, although prenatal head growth is important for later cognitive function, early postnatal head growth is more important, at least in children whose head size is in the normal range at time of birth. Most available studies in preterm children that look into associations between growth (both head growth and bodily Review
3
4 Developmental Medicine & Child Neurology 2014
29
Hospital-based, observational, longitudinal study Birth years 1996–2005
Cohort study, retrospective and crosssectional, hospital-based Birth years 1996–2001
Raz et al.34
Prospective observational cohort study, populationbased
Population-based, prospective, longitudinal, observational (Victoria Infant Collaborative Study) Birth years 1991–1992
Hospital-based, one tertiary centre, Birth years 1996–1999 (all received early neonatal nutritional support) Observational, crosssectional and retrospective study; Liverpool region (Liverpool Hospitals) Birth years 1991–1992
Study type/design
Claas et al.33
€nen et al.32 Leppa
Kan et al.31
Cooke et al.30
Franz et al.
Authors
birthweight
n=264 GA
INVITED REVIEW
Growth, head growth, and neurocognitive outcome in children born very preterm: methodological aspects and selected results MICHAEL B RANKE 1
1 € | INGEBORG KR AGELOH-MANN | BRIGITTE VOLLMER2
1 University Children’s Hospital, T€ubingen, Germany. 2 Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK. Correspondence to Michael B Ranke, University Children’s Hospital, Hoppe-Seyler-Strasse 1, D-72076 Tubingen, Germany. E-mail: [email protected]
PUBLICATION DATA
Accepted for publication 24th June 2014. Published online ABBREVIATIONS
AGA SGA
Appropriate for gestational age Small for gestational age
In light of the growing number of surviving children born very preterm, there is an increasing focus on their long-term outcomes in terms of growth, metabolic status, and neurocognitive development. Therefore, it is of importance to follow such children from birth onwards with the aim of identifying the causes of atypical development, developing preventative measures, and improving outcomes. Since such long-term follow-up needs to be conducted with the least possible burden, clinical investigations such as anthropometry and neurocognitive tests, if conducted rigorously, will continue to have a predominant role. The aim of this review is to discuss the complexity of longitudinal anthropometry in children born very preterm and to provide an overview of the main studies that have examined associations between growth, in particular head growth, and neurocognitive outcomes at around school age.
During the past decades we have observed dramatic changes in the medical and social environment in Western societies which have also affected human reproduction.1 The number of multiple pregnancies has increased as a result of new artificial reproductive techniques2,3 and, overall, as a consequence of advances in perinatal care, there are more preterm deliveries accompanied by increased survival of extremely preterm infants.4 However, a proportion of children who are small at birth and/or born preterm remain at risk of adverse development. They may continue to be of less than average height,5 they may develop neurological and/or cognitive impairments,6 and they are at risk of developing a metabolic syndrome in adult life.7 Because of the complexity of perinatal risk factors it remains somewhat unclear which pre- or postnatal factors are predominantly associated with such sequelae. In order to identify factors that may affect negatively the outcomes of small and/or preterm children, longitudinal studies have been conducted following various aspects of development in these children. Since brain growth and brain development are essential for optimal neurological and cognitive outcome, assessment of brain growth should be part of such follow-up studies. The aims of this review are to discuss some methodological aspects in the evaluation of growth parameters, including head growth, from intrauterine life to childhood, and to summarize the results of the main studies which have investigated growth, and cognitive and neurological outcome at school age in children who are very small at birth and/or are born preterm.
Anthropometric growth parameters For clinical and scientific purposes, growth evaluation in children can most easily be made by measuring various © 2014 Mac Keith Press
body components (anthropometry).8,9 Ideally, the description of an individual’s growth process will take into account several components and their interrelationships. While normative reference data are available for a multitude of anthropometric parameters during childhood, for newborns (both term-born and preterm) mostly only those for weight, total body length/height and head circumference have been established.10
Weight Weight gives summarized information about all body components. It is the anthropometric parameter commonly measured after birth with sufficient accuracy.8,11 Newborns should be weighed naked immediately (within 1h) after birth. In order to express weight controlled for length/ height, indices such as the body mass index (weight [kg]/ length² [m]) or the ponderal index (weight [kg]/length³ [m]) can be derived. Classification of newborns based on weight and/or gestational age Based on birthweight – irrespective of gestational age – newborns are commonly classified into groups: low birthweight infants (weight between 1500g and 2499g); very low-birthweight infants (weight between 1000g and 1499g); and extremely low-birthweight infants (weight below 1000g). Since this classification does not consider gestational age groups, groups categorized according to birthweight may be quite heterogeneous. Birthweight in relation to the norms for gestational age is traditionally used to classify newborns into three major categories: (1) appropriate for gestational age (AGA; weight within normal range); (2) small for gestational age (SGA; weight below normal range); and (3) large for gestational DOI: 10.1111/dmcn.12582 1
age (weight above normal range). While neonatologists still tend to use the 10/90 centiles (equivalent to mean1.28SD) as cut-offs, endocrinologists tend to use the 3/97 centiles (equivalent to mean2.0SD). In conjunction with the timing of birth (pre-term, full-term, post-term) further subclassifications may be formed. To base such classifications on weight alone without considering length is not fully correct. However, length is often not measured at birth.
Length Total body length, or crown–heel length, which is the supine equivalent to standing height, is also a composite of several body components (e.g. head, trunk, extremities) which are under varying environmental or genetic control. Because of the fetal positioning in utero, length measurements after birth are quite difficult to perform. In order to increase accuracy, length measurements can be postponed to 48 to 72 hours after birth. The inter- and intra-observer error of the measurement is in the range 0.3 to 0.5cm.8,11 Head size and head circumference Head growth is mainly determined by the development of the brain, which reflects the increase in neuronal cells, neuroglia cells, and supportive connective tissue. Prenatally, head size and brain structures can clinically be investigated by means of ultrasonography or fetal magnetic resonance imaging (MRI).12 In utero fronto-occipital and/ or biparietal diameters are taken as measures of head size. Head circumference, which used to be termed frontooccipital head circumference, is practically the largest head circumference measurable with a flexible, but not extensible, tape. The measuring error is about 0.3 to 0.4cm.8,11 Head circumference can also be calculated from cranial diameters; e.g. head circumference=(biparietal diameter9occipito-frontal diameter9p/2). Since deformities and soft tissue swelling do occur during the process of birth, measurements taken some time after birth (48–72h) may give a more accurate reflection of neonatal head size than measurements taken directly after birth. Brain weight is proportional to the cube of the head circumference from birth until 18 years of age.13 In newborns and children, head circumference is well correlated with brain size as measured by neuroimaging, e.g. MRI or computed tomography.14,15 Postnatally, ultrasonography of the head is also easily accessible. This technique is well suited to document larger anatomical abnormalities as a result of bleeding or
•
What this paper adds For optimal follow-up of children born very preterm, anthropometric and neurocognitive investigations need to be combined.
major ischaemic insults. However, ultrasonography is less well suited for detecting hypoxic–ischaemic lesions in the absence of larger bleeds or of minor or diffuse hypoxic insults,16 which may no less impair the long-term development of the brain. Since it is easy to measure head circumference, this is still the most frequently used surrogate measurement of overall brain growth in longitudinal cohort studies of children born preterm, but may be replaced in the future by serial neuroimaging.16,17 The difference in the dynamics of length/height and head circumference during fetal and early postnatal development is illustrated in Table I.
Evaluation of growth parameters Longitudinal investigation of a biological parameter in children requires the measuring technique to provide accurate information about the aspect in question over many years and during different developmental phases. Equally important, the evaluation of any biological (e.g. anthropometric) parameter in individuals requires the comparison with normative reference data derived from individuals of the same ethnicity, age, and sex. For clinical use, graphical growth reference charts give a useful orientation. However, in order to render possible an exact description in relation to the reference, numerical data of means and their error need to be available. If the parameter in question is normally distributed (e.g. length, height, head circumference), such a calculation is straightforward. However, if the distribution is skewed (e.g. weight), more complex measures for normalization need to be applied.20,21 These figures allow us to calculate an SD score (SDS), a term which describes the distance between the individual’s value and the mean of the reference: (SDS=[patient value minus the mean value of matched references]: SD of the mean value of matched references). The calculation of an individual’s SDS allows deviations in relation to the reference (or norm) to be described longitudinally. SDSs can also be used to deal with group data in exact numerical terms. References of growth parameters The establishment of robust normative references in children is complex since the population investigated must be
Table I: Difference in the dynamics of length/height and head circumference during typical fetal and early postnatal development Age
Length/height (cm)
% of adult height
Head circumference (cm)
% of adult size
10y 2y 1y 40wks 32wks 28wks
140 88 76 50 42 37
79 50 43 28 23 21
53 50 47 35 30 25
94 88 84 62 53 44
Swiss reference (males); Largo et al.,18 Prader et al.19
2 Developmental Medicine & Child Neurology 2014
stratified for a number of factors such as sex, ethnicity, and social aspects, and needs to cover the whole age range, with sufficient numbers investigated. If investigations need to be conducted in individuals followed from preterm birth on, or potentially even from before birth, the requirements for the establishment of references are most difficult to fulfil. Some aspects are particularly relevant for this deliberation. Prenatal anthropometric parameters cannot be measured in the same way as postnatally. For example, in order to approximate prenatal weight or head circumference, regression equations are applied incorporating sonographic measurements of certain body parts. Before 2 years of age supine length but not standing height is measured. Thus, references need to be created for different phases of life (e.g. prenatal, after birth up to the normal end of pregnancy [term=40wks (37–42wks)]; from term up to 2y of age; after 2y of age). References for children born preterm are by definition not based on ‘normal’ newborns since prematurity is not considered normality. Thus, references for anthropometric parameters based on preterm newborns do not reflect those of truly healthy newborns. Intrauterine measurements in healthy children born at term may reflect the norm, but are not directly comparable to those taken after birth. In particular, the growth development of preterm children after birth – often within neonatal intensive care units – is unlikely to reflect the normal course of an assumed healthy infant of the same age.10 The chronological age of an individual from its birth date can be calculated exactly. However, the age of gestation needs to be determined. Gestational age is the elapsed time from the reported first day of the last menstrual period until birth. Normal mean gestational age is 40 weeks (280d) with an estimated range of error of 2 weeks. Conceptual age is the time since fertilization, which is assumed to be gestational age minus 14 days, that is 38 weeks (266d). It has been shown that, when the exact day of conception is known, sonography during the first 22 weeks of pregnancy allows gestational age to be determined within a 95% confidence range of 1 week.22 Despite these problems, growth parameters of infants born preterm and measured postnatally are commonly compared with references obtained from birth cohorts. Thus, patients with an age equal to gestational age plus postnatal chronological age are compared with reference values based on gestational age. In order to accommodate differences in the age (gestational age, chronological age), complex mathematical multilevel modelling may be used for an adjustment23 for covariates in cohorts of preterm infants followed prospectively. Smoothing of data in order to accommodate disjunctures in the different transitional phases may be applied.10 Even if anthropometric references from the same population are available, the data may not be up to date or preand post-term data may have been collected during different time periods. In order to facilitate an evaluation of children’s growth in countries without ethnically homogenous references there are international activities (e.g. World
Health Organization, Centers for Disease Control) to establish ‘global’ references for several essential parameters (e.g. head circumference).24,25 However, by applying such references to specific populations, incorrect conclusions may be drawn. Thus, for longitudinal follow-up studies in children born preterm, the choice of references must be made with great care.10,26 Users should not only consider references that are most closely representative of their population but preferentially use those of the highest quality.
Neurological, developmental, and cognitive evaluation For accurate assessment of associations between growth, head growth, and neurological and cognitive development it is important to use age-appropriate, recently standardized, and valid (for the population under investigation) psychometric tools. Whether such tools are used and, if so, which tools differs between studies, and is also dependent on the age at assessment. Only a rather small proportion of studies that have examined relationships between anthropometric measures and neurological outcome in children who do not have cerebral palsy have used standardized methods; in fact, neurological status and neuromotor function are frequently neglected. In contrast, the majority of studies assessing neurodevelopment and overall cognitive abilities at pre-school and school age have used standardized psychometric tests. Associations between growth, head size, and neurological and cognitive outcome In typical development, it appears that head size and its growth dynamics in early life are more important for later cognitive function than head growth after infancy. For example, Gale et al.,27 in a large population-based study, examined associations between head growth in different periods of life and overall cognitive function, assessed with the Wechsler Scales, at age 9 years in a large unselected sample. They showed that head growth during both early infancy (in this study between birth and age 9mo) and late infancy/early childhood (9mo–9y) is related to Full-scale IQ after adjustment for sex, maternal education and social class, and duration of breastfeeding. Interestingly, Verbal IQ and Performance IQ appeared to be affected differently by head growth in the two time periods, with Verbal IQ being more affected by growth in the later period, and Performance IQ being more affected by growth in the earlier period. In contrast, head size at 18 weeks’ gestation and head circumference at birth were not associated with IQ scores at age 9 years. Furthermore, there is some evidence that head growth after infancy does not compensate for poor growth prenatally and in infancy.28 It is important to note that the study by Gale et al.28 suggests that, although prenatal head growth is important for later cognitive function, early postnatal head growth is more important, at least in children whose head size is in the normal range at time of birth. Most available studies in preterm children that look into associations between growth (both head growth and bodily Review
3
4 Developmental Medicine & Child Neurology 2014
29
Hospital-based, observational, longitudinal study Birth years 1996–2005
Cohort study, retrospective and crosssectional, hospital-based Birth years 1996–2001
Raz et al.34
Prospective observational cohort study, populationbased
Population-based, prospective, longitudinal, observational (Victoria Infant Collaborative Study) Birth years 1991–1992
Hospital-based, one tertiary centre, Birth years 1996–1999 (all received early neonatal nutritional support) Observational, crosssectional and retrospective study; Liverpool region (Liverpool Hospitals) Birth years 1991–1992
Study type/design
Claas et al.33
€nen et al.32 Leppa
Kan et al.31
Cooke et al.30
Franz et al.
Authors
birthweight
n=264 GA
