Contents - Previous - Next

Effects of IUGR on the development of very low birthweight children

Studies of the effects of intrauterine growth failure among very low birthweight (VLBW < 1.5 kg) preterm children have mainly pertained to childhood (Sung et al, 1993; Pena et al, 1988; Robertson et al, 1990; Calame et al, 1986). Results have been confounded by the fact that some researchers have compared the children to control children of similar birthweight, whereas others compared them to control children of similar gestational age.

Robertson et al (1990) in Canada examined school performance at 8 years of preterm, small for gestational age VLBW infants and compared it to that of VLBW children born appropriate for gestational age. The IUGR children did not differ in school performance when compared to either birthweight- or gestational-age-matched controls. All the VLBW groups had significantly inferior outcomes when compared to a normal-birthweight control group.

In Cleveland we compared the school age outcomes of a cohort of 51 VLBW children who were born IUGR (with birthweights less than-2 SD for gestational age), to 198 VLBW born appropriate for gestational age. The groups did not differ in maternal socio-demographic characteristics, with the exception that more mothers of the appropriately grown (AGA) children were married (67% vs. 48%, respectively). Mothers of the IUGR children had a significantly higher rate of pregnancy hypertension. More IUGR than AGA children were multiple births (31% vs. 9%) and IUGR children had a significantly higher gestational age (32 vs. 29 wks) and lower birthweight (1113 g vs. 1192 g) compared to the AGA population. The AGA children had significantly more neonatal problems including lower 5-minute Apgar scores and a higher incidence of respiratory distress syndrome and apnea of prematurity. The populations thus differed in maternal marital status, birthweight, gestational age, and the rates of neonatal problems. No overt intrauterine infections were diagnosed.

At 8 years of age AGA children had higher rates of cerebral palsy (25% vs. 6%), but this difference was not significant. No significant differences in intelligence, language, visual-motor abilities, fine motor abilities, and academic achievement were noted between the AGA and IUGR children.

Based on the literature reported, we conclude that intrauterine growth retardation does not appear to impose an added disadvantage at school age over and above that of very low birthweight.

Discussion and conclusion

In general, the follow-up studies report overall normal intelligence with a trend to lower scores among IUGR subjects. Despite the limitations of the literature reviewed, there is no consistent evidence of a detrimental effect of IUGR on the mental and behavioral outcomes of adolescents or adults. The rates of major handicap are low, although there tend to be higher rates of minimal cerebral dysfunction, as evidenced by learning and subtle neurological and behavioral problems in IUGR children with normal intelligence. Three of the studies noted a decrease in the rates of abnormal neurodevelopment with increasing age (Douglas and Gear, 1976; Hawdon et al, 1990; Westwood et al, 1983) which could be associated with an amelioration of subtle neurological dysfunction after the onset of puberty. Support for this hypothesis is the work of Soorani-Lunsing (1993), who reported that onset of puberty was associated with a decrease in the rates of neurologic dysfunction, including fine manipulative disability, coordination problems, choreiform dyskinesia and hypotonia. She hypothesized that general maturational changes during puberty, as well as specific hormonal changes in estrogen secretion, might play a role in improving outcome.

The review of the literature reveals that ongoing detrimental effects of socio-environmental deprivation throughout the lifespan play a much greater role in determining outcome than any potential effect of intrauterine growth failure on the developing nervous system (Douglas and Gear, 1976; Hawdon et al, 1990; Drillien, 1970; Westwood et al, 1983; Illsley and Mitchell, 1984; Neligan et al, 1976; Low et al, 1992; Martyn et al, 1996; Stein et al, 1972). Warshaw (1985) has suggested that rather than representing serious pathology, IUGR may be an adaptation in which the size of the fetus is maintained appropriate to the availability of nutrients. The most consistent biologic predictors of poor later mental development and behavior in IUGR children are hypoxic ischemic injury and subnormal brain growth (Westwood et al, 1983; Berg, 1989; Ounsted et al, 1988; Harvey et al, 1982; Parkinson et al, 1981). Brain growth, as measured by the sonographic biparietal diameter or by head circumference after birth, is usually less affected than weight or length, resulting in "asymmetric" growth failure (Cooke et al, 1977; Kramer et al, 1989). This "brain sparing" may be protective when growth is restricted in utero, and outcome may be affected when this mechanism fails. This is especially evident when brain growth (head size) fails to catch up during infancy and childhood (Hack et al, 1989, 1991; Babson and Henderson, 1974; Lipper et al, 1981).

Thus, with the exception of extreme IUGR affecting brain growth, and hypoxic ischemic injury, IUGR seems to have little or no measurable effect on mental performance and behavior in adolescence or adulthood. However, since IUGR occurs more often in deprived environmental circumstances, it can serve as a marker for the associated poor outcomes throughout life.


Agarwal KN, Agarwal DK & Upadhyay SK (1995): Impact of chronic undernutrition on higher mental functions in Indian boys aged 10-12 years. Acta Paediatr. 84, 1357-1361.

Allen MC (1984): Developmental outcome and follow up of the small for gestational age infant. Semin. Perinatol. 8, 123-156.

Babson SG & Henderson NB (1974): Fetal undergrowth: relation of head growth to later intellectual performance. Pediatrics 53, 890-894.

Berg AT (1989): Indices of fetal growth-retardation, perinatal hypoxia-related factors and childhood neurologic morbidity. Early Human Dev. 19, 271-283.

Calame A, Fawer CL, Claeys V, Arrazola L, Ducret S & Jaunin L (1986): Neurodevelopmental outcome and school performance of very-low-birthweight infants at 8 years of age. Eur. J. Pediatr. 145, 461-466.

Cooke RWI, Lucas A, Yudkin PLN & Pryse-Davies J (1977): Head circumference as an index of brain weight in the fetus and newborn. Early Human Dev. 1/2, 145-149.

Douglas JWB & Gear R (1976): Children of low-birthweight in the 1946 national cohort. Arch. Dis. Child 51, 820-827.

Drillien CM (1970): The small-for-date infant: etiology and prognosis. Pediatr. Clin. North Am. 17, 9-24.

Fitzhardinge PM & Steven EM (1972): The small-for-date infant. II. Neurological and intellectual sequelae. Pediatrics 50, 50-57.

Hack M, Breslau N, Rivers FA & Fanaroff AA (1989): The appropriate and small for gestational age very low birthweight infant: Differential effects of brain growth failure on outcome. Am. J. Dis. Child 143, 63-68.

Hack M, Breslau N, Weissman B, Aram D, Klein N & Borawski E (1991): Effects of very low birth weight and subnormal head size on cognitive abilities at school age. N. Engl. J. Med. 325, 231-237.

Hack M, Fanaroff AA & Merkatz IR (1979): The low birth weight infant. Evolution of a changing outlook. N. Engl. J. Med. 301, 1152-1165.

Hadders-Algra M & Touwen BCL (1990): Body measurements, neurological and behavioral development in six-year-old children born preterm and/or small-for-gestational-age. Early Human Dev. 22, 1-13.

Harvey D, Prince J. Burton J. Parkinson C & Campbell S (1982): Abilities of children who were small-for-gestational-age babies. Pediatrics 69, 296-300

Hawdon JM, Hey E, Kolvin I & Fundudis T (1990): Born too small - is outcome still affected? Dev. Med. Child Neurol. 32, 943-953.

Hill DE (1978): Physical growth and development after intrauterine growth retardation. J. Reprod. Med. 21, 335-342.

Illsley R & Mitchell RG (1984): Low Birth Weight: A Medical, Psychological, and Social Study. John Wiley & Sons: Chichester.

Kramer MS, McLean FH, Olivier M, Willis DM & Usher RH (1989): Body proportionality and head and length 'sparing' in growth-retarded neonates: A critical reappraisal. Pediatrics 84, 717-723.

Kramer MS, Olivier M, McLean FH, Willis DM & Usher RH (1990): Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 85, 707-713.

Lagerstrom M, Bremme K, Eneroth P & Magnusson D (1991): School performance and IQ-test scores at age 13 as related to birth weight and gestational age. Scand. J. Psychol. 32, 316-324.

Lipper E, Lee KS, Gartner LM & Grellong B (1981): Determinants of neurobehavioral outcome in low-birthweight infants. Pediatrics 67, 502-505.

Low JA, Handley-Derry MH, Burke SO, Peters RD, Pater EA, Killen HL & Derrick EJ (1992): Association of intrauterine fetal growth retardation and learning deficits at age 9 to 11 years. Am. J. Obstet. Gynecol. 167,1499-1505.

Martyn CN, Gale CR, Sayer AA & Fall C (1996): Growth in utero and cognitive function in adult life: follow up study of people born between 1920 and 1943. Br. Med. J 312, 1393-1396.

Mervis CA, Decoufle P, Murphy CC & Yeargin-Allsopp M (1995): Low birthweight and the risk for mental retardation later in childhood. Paediatr. Perinat. Epidemiol. 9, 455-468.

Neligan GA, Kolvin I, Scott DM, et al (1976): Born Too Soon or Born Too Small. A Follow-up Study to Seven Years of Age. Clinics in Developmental Medicine (no. 61). JB Lippincott: Philadelphia.

Nilsen ST, Bergsjo P & Nome S (1984): Male twins at birth and 18 years later. Br. J. Obstet. Gynaecol. 91,122-127.

Ounsted M, Moar VA & Scott A (1988): Head circumference and developmental ability at the age of seven years. Acta Paediatr. Scand. 77,374-379.

Parkinson CE, Wallis S & Harvey D (1981): School achievement and behaviour of children who were small-for-dates at birth. Dev. Med. Child Neurol. 23, 41-50.

Paz I, Gale R, Laor A, Danon YL, Stevenson DK & Seidman DS (1995): The cognitive outcome of full-term small for gestational age infants at late adolescence. Obstet. Gynecol. 85, 452-456.

Pena IC, Teberg AJ & Finello KM (1988): The premature small-for-gestational-age infant during the first year of life: Comparison by birth weight and gestational age. J. Pediatr. 113, 1066-1073.

Pryor J, Silva PA & Brooke M (1995): Growth, development and behaviour in adolescents born small -for-gestational-age. J. Pediatr. Child Health 31, 403-407.

Rantakallio P (1988): The longitudinal study of the Northern Finland birth cohort of 1966. Pediatr. Perinat. Epidemiol. 2, 59-88.

Robertson CMT, Etches PC & Kyle JM (1990): Eight-year school performance and growth of preterm, small for gestational age infants: A comparative study with subjects matched for birthweight or for gestational age. J. Pediatr. 116, 19-26.

Sameroff AJ, Seifer R, Baldwin A & Baldwin C (1993): Stability of intelligence from preschool to adolescence: the influence of social and family risk factors. Child Devel. 64, 80-97.

Smeriglio VL (1989): Developmental sequelae following intrauterine growth retardation. In: Gross TL, Sokol RJ (eds). Intrauterine Growth Retardation: A Practical Approach. Year Book Medical Publishers: Chicago.

Soorani-Lunsing RJ (1993): Neurobehavioural relationships and puberty: another transformation? Early Human Dev. 34, 59-67.

Stein Z & Susser M (1975): The Dutch famine, 1944-1945, and the reproductive process. II. interrelations of caloric rations and six indices at birth. Pediatr. Res. 9, 76-83.

Stein Z, Susser M, Saenger G & Marolla F (1972): Nutrition and mental performance: Prenatal exposure to the Dutch famine of 1944-1945 seems not related to mental performance at age 19. Science 178, 708-713.

Sung I-K, Vohr B & Oh W (1993): Growth and neurodevelopmental outcome of very low birth weight infants with intrauterine growth retardation: Comparison with control subjects matched by birth weight and gestational age. J. Pediatr. 123, 618-624.

Tenovuo A, Kero P, Piekkala P, Korvenranta H & Erkkola R (1988): Fetal and neonatal mortality of small-for-gestational age infants. Eur. J. Pediatr. 147, 613-615.

Trescher WH, Lehman RAW & Vannucci RC (1990): The influence of growth retardation on perinatal hypoxic-ischemic brain damage. Early Human Dev. 21, 165-173.

Warkany J, Monroe BB & Sutherland BS (1966): Intrauterine growth retardation. Am. J. Dis. Child 112, 502-517.

Warshaw JB (1985): Intrauterine growth retardation: Adaptation or pathology? Pediatrics 76, 998-999.

Westwood M, Kramer MS, Munz D, Lovett JM & Watters GV (1983): Growth and development of full-term nonasphyxiated small-for-gestational-age newborns: follow-up through adolescence. Pediatrics 71, 376-382.


In follow-up studies of older children it becomes more and more difficult to separate prenatal and postnatal effects. Other major problems are diminishing statistical power and potential biases due to sample attrition.

Most studies of long-term outcomes of IUGR are relatively old. Considerable improvements have been made in the last few years in obstetric and emergency newborn care in industrialized countries. This means that the factors that recent survivors have been exposed to and the risks they entail could be substantially different from those of earlier study populations.

If head sparing can be observed in some IUGR babies, it is usually relative, i.e. head size is also affected, but to a lesser extent than weight and height. The extent to which head size is reduced seems closely related to the degree of growth retardation and no attempt has yet been made to dissociate the two and their effect on mental and behavioral development.

Effects of IUGR seem closely associated with accompanying factors; it is not always clear whether these should be treated as confounding factors and controlled for or not. Factors like socioeconomic status are clearly confounding factors, because they exist before and after IUGR occurs and are unlikely to be on the causal pathway between growth retardation and cognitive outcome. Asphyxia is a transient phenomenon and a factor that is likely to be on the causal pathway between IUGR and later outcomes. Where it is, at least partly, avoidable, it is of interest to know what specific outcomes, or what proportion of them, are attributable to asphyxia. If one wishes to assess the effect of IUGR in areas where factors like asphyxia are still less amenable to treatment, it seems more appropriate not to control for them.

Environmental circumstances can both enhance and reduce developmental differences and other consequences. Mothers have been observed for instance to react in a dichotomous way to the abnormal cries of malnourished children, some devoting more time and attention to them, some less. Favorable socio-economic conditions can have a protective effect, whereas under unfavorable socioeconomic conditions, adverse effects can be amplified. The general conclusion from Hack's review of the literature is that, while IUGR can produce disadvantages in childhood that are significant, at least in statistical terms, these tend to be most consistent and marked from the preschool years through adolescence and gradually overridden by environmental influences in the long-term.
Among the commonly used indicators, a length deficit at an early age seems to be the best predictor of motor and mental development. Effects associated with ponderal index could be attributable mainly to length or height. Advocates of ponderal index argue that it provides the best reflection of the timing of the insult, and that this in turn could be of prognostic importance.

Contents - Previous - Next