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Limitations of available evidence
Generalizations
Neurologic and sensory outcomes
Cognition
Research needs
Recommendations
Working Group members: R Goldenberg¹, M Hack², Grantham-McGregor³ and B Schürch4
Correspondence: IDECG Secretariat, c/o Nestlé Foundation, POB 581, 1010 Lausanne, Switzerland
¹University of Alabama at
Birmingham, Birmingham, AL 35294-7333;
² Case Western Reserve University, Cleveland,
Ohio;
³ Centre for International Child Health,
Institute of Child Health, London;
4International Dietary Energy
Consultative Group (IDECG), c/o Nestlé Foundation, POB 581, 1001 Lausanne, Switzerland
Several factors hamper the interpretation of the empirical evidence relating intrauterine growth retardation (IUGR), both in infants born at term and preterm, to neurological, sensory, cognitive and behavioral function:
- The definitions of both IUGR and putative outcomes vary.
- Study samples are heterogeneous with respect to the etiology of IUGR, and one therefore cannot tell if outcomes differ as a function of the causes that led to IUGR.
- IUGR is almost always associated with other conditions having an adverse effect on outcomes. Pregnancy and neonatal complications, especially those associated with hypoxia, as well as postnatal malnutrition and childhood illness, are frequently associated with IUGR and may further aggravate the effect of IUGR. Some mediating and modifying factors, such as socioeconomic and environmental deprivation, are likely to persist and to have a continuing effect throughout the life span.
- The majority of studies have been conducted in high income countries and in the pre-intensive-care era.
- In follow-up studies of older children the control of postnatal influences and biased sample attrition become major problems.
Effects generally correlate with the
degree of early growth retardation and are aggravated by simultaneous prematurity. The
more studies control for other factors associated with IUGR, the smaller effects appear to
be, however this may reflect statistical over adjustment because they do not allow for
synergistic interactions. The most consistent and marked effects have been observed from
the preschool years through adolescence.
There are a number of neurologic and sensory outcomes that have been evaluated in relation to IUGR status including cerebral palsy, hypotonia, and decreased fine motor coordination. The evidence for an association between SGA and cerebral palsy is limited but consistent only when the largest regional prospective cohort or retrospective case-control studies are considered.
Higher rates of mild neurologic deficits, including hyperactivity, attention deficits and clumsiness, often termed minimal neurologic dysfunction, have been associated with IUGR status, although the relationship becomes attenuated when parental socio-economic status (SES) is adjusted for. These minor deficits usually persist into school age and are often associated with poor school performance, even when the child's cognitive ability is within the normal range.
IUGR infants usually have normal vision and hearing, but several studies suggest that they do not react to visual and auditory stimuli in the same way as do full term infants of normal birth weight.
In general, while these outcomes are
influenced by a number of other factors, the degree of the fetal growth deficit seems to
play a major rode. The most severely IUGR infants are most likely to manifest an adverse
neurologic outcome. Fetuses with subnormal head growth before 26 weeks of gestation, male
infants and infants from lower SES groups seem to be the most affected. Severe hypoxia may
be responsible for some of the neurologic impairments, but the overall impact of hypoxia
on the whole spectrum of adverse outcomes is not clear. It appears that favorable parental
SES and education (or adoption into favorable circumstances) can reduce the negative
impact of IUGR on various neurologic outcomes.
The reported effects of growth
retardation on children's cognition vary with the age at the time of assessment. Deficits
are less likely to be detected in infancy after that, most studies through to adolescence
have shown a small, statistically significant deficit in IQ; marked mental retardation is
not usually seen. Deficits tend to be larger in more severely growth retarded children and
are aggravated by high levels of infection, poor nutrition, low levels of stimulation and
parental education, as well as other conditions associated with poverty. Poor school
achievement has been reported from over half the studies in which it was examined. Data
from older adolescents and adults generally come from old studies with large attrition
rates, and differences have less often been demonstrated.
- Definitions of independent and dependent variables need to be reconsidered and standardized. The degree of growth retardation needs to be linked to the outcomes, and the associations between length, head circumference and weight-for-length need to be examined.
- Studies are urgently needed of neuro-developmental outcomes from low-income countries, where IUGR is a significant public health problem and where outcomes are more likely to be aggravated by poor health and nutrition, and psycho-social deprivation.
- IUGR being a common outcome of different etiologies, it is necessary to understand whether different etiologies result in different outcomes.
- IUGR is often associated with various obstetric and neonatal complications, and the extent to which these are responsible for the outcome needs to be clarified.
- There are as yet no studies of long-term outcome associated with IUGR in children who have been exposed to modern obstetric and newborn care practices. Outcome measures need to be developed and adopted that are more culturally appropriate and include measures of specific cognitive functions as well as social and emotional development.
- An attempt should be made to assess the full social and economic implications of IUGR for the individual and society. Direct measures of socio-economic success, such as educational attainment, occupation, work productivity, income and wealth, should be explored as indicators of long-term outcome.
Because SGA infants are more likely
to have perinatal complications including asphyxia and to have passed meconium in utero,
birth attendants need to be trained in methods of optimal neonatal resuscitation. In
addition, since IUGR infants are at greater risk of hypoglycemia and hypothermia, special
attention to these problems should be given in these infants. Given the demonstrated
potential for improvement in cognitive function shown by preterm babies as a result of
psycho-social intervention, it would be useful to determine to what extent interventions
can improve the development of IUGR children.