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PEDIATRICS Vol. 108 No. 1 July 2001, pp. 111-115
, and
From the * INSERM U149, Villejuif; and Objective. To investigate the
relation between school difficulties and being born small for
gestational age (SGA) at full term in adolescents and young adults.
Methods. A total of 236 full-term singletons who were born
SGA (birth weight and/or length below the third percentile) from 1971 through 1978 and 281 full-term singletons who were born appropriate for gestational age (AGA; between the 25th and 75th percentiles) from the
maternity registry of Haguenau, France. Participants were evaluated at
a mean age of 20.6 (±2.1) years. The outcomes measured were late entry
into secondary school (normal age: 11 years) and failure to take or
pass the baccalaureate examination at the end of secondary school
(normal age: 18 years).
Results. Late entry into secondary school was more
frequent for the SGA than the AGA children (odds ratio: 2.3) after
adjustment for maternal age and educational level, parental
socioeconomic status, family size, and gender. A significantly higher
proportion of term SGA adolescents failed to take or pass the
baccalaureate examination than AGA adolescents (odds ratio: 1.6). SGA
participants with a smaller head circumference entered secondary school
late more often than SGA participants with a larger head circumference, but the association was not significant after adjustment.
Conclusion. Being born SGA at term is associated with
poorer school performance at 12 and 18 years. Fetal adaptation to
conditions that retard growth during gestation may not be successful in
maintaining brain development.
Paediatric
Endocrinology and Diabetes Unit, Hôpital Robert Debré,
Paris, France.
ABSTRACT
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Results
Discussion
Conclusion
References
Intrauterine growth retardation (IUGR) is associated with
increased perinatal mortality and morbidity1 and postnatal growth failure2; it also contributes to such
late-onset disorders as cardiovascular disease, insulin resistance, and
non-insulin-dependent diabetes.2,3 The metabolic
adaptations made by a fetus that is undernourished in utero may program
these later diseases.4 IUGR may be related to identifiable
genetic or toxic factors or to reduced nutrient or oxygen delivery to the fetus, mostly related to placental dysfunction.5 Experimental data show that undernutrition at vulnerable periods during
brain development may have long-term effects on brain architecture and
differentiation that can affect learning and memory.6,7
Studies of neurobehavioral and cognitive outcomes in several groups of
young school children born small for gestational age (SGA) have yielded
conflicting results.8 Some found no difference with
participants who were appropriate for gestational age (AGA) for
cognitive9,10 or school performance indicators,11 whereas others reported minor neurologic dysfunction12 or cognitive deficits.13 There are limited studies from the recent era on follow-up of adolescents or
adults born SGA at term; these observed lower educational
achievement14 and intelligence scores15 than
among control participants. In a recent well-conducted study with a
high number of SGA participants, Strauss16 observed lower
school performance at 16 years and lower income or fewer professional
or managerial jobs at 26 years in SGA than in AGA patients.
Nonetheless, other studies of cognitive development among term SGA
children often involved small sample size and lack of comparison group
and did not always control adequately for social factors that may
influence test results. This study aimed to investigate whether term
SGA adolescents were at risk of impaired school performance during
childhood and adolescence.
Participants were identified from a population-based birth
registry in and around the city of Haguenau, France. This registry recorded information on all pregnancies, deliveries, and perinatal events from 1971 to 1985.17 Gestational age was determined from the date of the last menstrual period and by physical examination during pregnancy and was confirmed by ultrasound measurements when
available. Local standard growth curves by gestational age and gender
were derived from all live births registered (nearly 20 000 births).
The growth standards of the population of Haguenau are different from
those of the population of France in general because of persons of
northern origin who are taller: comparing with reference curves of
Leroy and Lefort18 established in the Paris region in 1971 and commonly used in France, the 50th percentile was higher by
approximately 100 g for Haguenau's infants born at Sixteen of the 903 patients were excluded because of aberrant growth
measurements at birth, and 10 were excluded because of adoption; 41 died, 32 (7%) in the SGA group and 9 (2%) in AGA group. Of the 836 survivors who could be included, therefore, 517 (62%) participated in
the study (236 SGA and 281 AGA). Participants were contacted by letter
at the address of the parents' home or a more recent address known by
the hospital. All participants (16-24 years old) underwent detailed
clinical investigations and completed a questionnaire, as previously
described.2
The questionnaire included information on schooling, from which we
selected 2 outcome measures. The first was age at starting secondary
school (normally 11). Participants who were older ( The second outcome measurement was the final examination of secondary
school, the baccalaureate. This diploma is not obtained by adolescents
who failed it and those who took a short vocational program. The normal
age for the baccalaureate is approximately 18 years. The mean (standard
deviation: SD) age of the population at the follow-up was 20.6 ± 2.1 years (range: 16-24 years). We analyzed baccalaureate success only
among participants who were at least 19 years old.
To evaluate the severity of growth retardation, birth weight, length,
and head circumference were calculated as SD scores corrected for
gestational age and gender. We evaluated intrauterine nutritional
status with the ponderal index (PI) [birth weight in g/(birth length
in cm)3] × 100, corrected for gestational age,
according to Miller and Hassanein.19
Participation was lower among the SGA (57%) than the AGA group (64%;
P = .04). SGA participants and nonparticipants did not differ for birth weight or length, head circumference, or PI. Within
the SGA group, participation was lower among those whose mothers were
unmarried or smoked during pregnancy and those whose fathers had a low
educational level or socioeconomic status. Among the AGA group, the
participation was lower among males and among children whose mothers
were born abroad.
The study protocol was reviewed and approved by the faculty ethics
committee, and all participants and parents gave signed written
consent.
Statistical Analysis
SGA and AGA participants were compared for both school
indicators, means were compared with the 2-tailed t test,
and differences in proportions were compared with
Table 1 shows the clinical
characteristics at birth of the 2 study groups. The groups did not
differ significantly for gender or gestational age. Among the SGA
group, 101 (47%) had birth weight TABLE 1
METHODS
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Methods
Results
Discussion
Conclusion
References
37 weeks.
SGA was defined as birth weight or length below the third percentile of
these curves. All full-term (37 weeks' gestation) singleton patients
who were born SGA from 1971 to 1978 (N = 452) were
selected.2 The control participants were 451 full-term
singletons who were (AGA; birth weight between the 25th and 75th
percentiles). The first AGA infant listed in the registry after each
SGA birth was selected as a control.
12 years) had
repeated at least 1 grade in primary school (from 6 to 11 years). For
this analysis of academic results, we excluded 10 adolescents who had
psychomotor handicaps or were institutionalised (all were SGA) and 10 who had severe chronic illnesses or malformations that might have
interfered with school performance. Among them, 8 born SGA patients
were excluded for malformation of inner ear and vertebral malformation
(1), dwarfism (1), congenital heart defects (3), adrenocortical
hyperfunction (1), fibrocystic disease (1), and Gilbert disease (1),
and 2 born AGA were excluded for malformation of urinary system (1) and
medullar aplasia (1). Age at entry into secondary school was known for
the 218 who were born SGA and 279 who were born AGA.
2 tests. The associations between SGA status
and school indicators were estimated as adjusted odds ratios and their
95% confidence intervals (CIs), with unconditional logistic regression
used to control for confounders. Confounders selected were maternal age at birth (<25, 25 years), maternal educational level (missing, primary or less, higher), gender, number of children in the family (<3, 3), parents' socioeconomic status (highest of mother's or father's occupation in 1994-1995: low, high, no occupation). We also
examined the outcome variables among SGA patients by symmetry of growth
retardation (asymmetric PI <third percentile; symmetric PI third
percentile) and by the severity of growth retardation for birth weight,
length, and head circumference (
or >2 SD). SAS (SAS Institute,
Cary, NC) and BMDP (BMDP Statistical Software, Inc, Los Angeles, CA)
were used for statistical analysis.
RESULTS
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Abstract
Methods
Results
Discussion
Conclusion
References
2 SD, 100 (47%) had birth length
2 SD, 32 (19%) had birth head circumference 
2 SD, and 46 (21%)
had a birth PI <third percentile.
Characteristics of SGA and AGA Participants at Birth
The main social characteristics of the AGA and SGA groups are shown in Table 2. Parents of those born SGA more frequently were not married and were of low socioeconomic status. Mothers of those born SGA more often were smokers. Among those born AGA, a late entry into secondary school was related to younger maternal age, larger family size, missing or low maternal educational level, and parental low socioeconomic status or unemployment (Table 2). We therefore adjusted the relation between school indicators and the SGA status for these parameters. As Table 3 shows, the proportion of late entrants into secondary school was higher among SGA than the AGA group, and more SGA participants failed to take or pass the baccalaureate examination.
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Among the SGA group, the severity of IUGR described by a birth weight
or length <2 SD was not related to school achievements. Late entry
into secondary school and no baccalaureate were more frequent among SGA
participants whose head circumference was <2 SD, but this difference
was not significant after adjustment for confounders (Table
4). In the SGA group, significantly fewer
participants with an asymmetric body proportion at birth (PI <third
percentile) failed to take or pass the baccalaureate compared with
patients with symmetric proportions (PI third percentile). Participants with IP <third percentile had a significantly lower birth
weight, a higher height, and a lower head circumference than
participants with IP third percentile. The difference was no longer
significant after adjustment on head circumference (odds ratio: 0.4;
95% CI: 0.15-1.08; P = .06).
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DISCUSSION |
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Results
Discussion
Conclusion
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This study shows that SGA participants have an increased risk of impaired school performance in late childhood and adolescence than AGA participants. Our findings are not due to low socioeconomic status, which has been found to be related to SGA birth20 and school performance as we have adjusted for it. Nevertheless, the contribution of parental intelligence, measured by IQ, was not investigated,21 and we could not assess the quality of the home environment.22
Studies on younger children showed conflicting results regarding psychomotor development.8 At adolescence, 2 studies were performed with few participants.14,23 Paz et al14 found, after adjustment for parental socioeconomic status, that 34 SGA males at age 17 had lower levels of academic achievement (more of them either did not complete 12 years of schooling or finished their studies at a vocational school) and that 71 SGA females had lower intelligence scores than those who were AGA. Westwood et al23 found a trend toward lower intelligence test scores for 33 adolescent singleton SGA (versus AGA) patients.
Results from the 1970 British Birth Cohort in which school performance was assessed at 16 and 26 years were published recently.16 At 16 years, those born SGA (birth weight <fifth percentile) demonstrated small but significant deficits in academic achievement, and teachers were less likely to rate those who were born SGA in the top 15th percentile of the class compared with those who were born AGA. At 26 years, the 489 adults who were born SGA did not demonstrate any differences in years of education, but they were less likely to have professional or managerial jobs and reported lower income than the 6981 AGA participants. This study had methodological strength with a high number of participants and adjustment for social confounders. Our results confirm these recent findings in a different country of an equivalent level of care, in a study that also has a sufficient number of SGA participants and is adjusted adequately.
Studies of younger children have not always detected significant differences in intelligence tests or school indicators.8 Most developmental studies of SGA young children have used IQ tests, which may lack the specificity or sensitivity to identify subtle effects on such school-related skills as spatial working memory and recognition memory. Subtle developmental disabilities might not be obvious in early childhood and can only be reliably tested for later in life. For young adults or adolescents, direct measures of economic success such as educational attainment, occupation, and income also may be useful to assess the ability to cope with problems encountered in life.16
We must emphasize that our study defined SGA by stringent criteria
(<third percentile, taking gestational age and gender into account):
the results of previous studies among children or adolescents may have
been confounded by definitions of IUGR as a birth weight below the 15th
or 10th percentile or as 2500 g. Only the smallest infants (<fifth
percentile) showed increased mortality and morbidity.1
Our follow-up rate was 62%, high for a study at 20 years from a population-based registry and higher than in the British Birth Cohort16 at 26 years (53%). The bias as a result of nonresponders in studies that deal with child development generally decreases the likelihood of finding an association, because children with poorer development or/and parents with low socioeconomic status tend to participate less in follow-up studies.24 This pattern was verified in our study. Accordingly, the association found in our study most probably is an underestimation.
A small head circumference in SGA children has been found to be associated with poorer neurodevelopmental outcome during childhood.9,25,26 Strauss16 found that both head size at 5 years and being SGA at birth were predictors of occupation and income at adult age. In our study, although we observed this association, the difference was not significant after adjustment for confounders; this might, however, be attributable to a lack of power of the study. The effect on childhood neurodevelopment of body proportionality at birth also has been debated,8,1327-29 and the findings were inconsistent. Our study found SGA patients with a normal PI at birth (symmetric SGA) to have higher rates of low school achievement as young adults than the asymmetric SGA patients but not significant after adjustment for head circumference.
Normal brain development requires adequate oxygenation, nutrition, and hormonal balance as well as avoidance of toxic substances. A sufficient number of cells, appropriate migration, and circuit formation are critical as are plasticity and compensation pathways.6,7 The endocrine system, most important for fetal growth, involves the insulin-like growth factors (IGFs), which may regulate nutrient partitioning between the maternal, placental, and fetal compartments.30 Although growth hormone-induced IGF-I production is not required for normal brain growth or cognitive development,31 a critical role for IGF-I in brain development has been suggested by the report of a child with mental retardation who carried a deletion of the IGF-I gene.32 Whether prolonged IGF-I deficiency induced by fetal undernutrition in utero33 might alone cause deleterious effects on normal brain and cognitive development requires further study. Thyroid status also has been postulated to play a critical role in the development of the central nervous system, and circulating free thyroid hormone concentrations have been shown to be lower in fetuses with IUGR.34 Additional studies also are necessary to determine whether this results in hypothyroidism at a tissue level, especially in the central nervous system. The evaluation of these factors and whether and how they affect the developing nervous system thus remain unclear. IUGR also is a known risk factor for hypoglycemia during the neonatal period, and a retrospective evaluation recently demonstrated that recurrent episodes of hypoglycemia during the neonatal period are associated with persistent neurodevelopmental deficits in preterm SGA infants at least until 5 years of age.35 Measures to prevent hypoglycemia should be applied during this critical period to minimize the risk of subsequent neurodevelopmental deficits.
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CONCLUSION |
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Results
Discussion
Conclusion
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Reduced fetal oxygen or nutrient availability may have late consequences, not only for final height and metabolic disorders but also for learning during childhood, late adolescence, and, probably, adulthood. Intervention strategies should be studied to ameliorate school results in these children. Data from other sources that enable careful controlling for confounding factors will help assess the risk of impaired development as a function of the different causes of IUGR.
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ACKNOWLEDGMENTS |
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This work was supported by Pharmacia Upjohn Laboratories.
We thank D. Collin, A. Pinet, E. Mairot, and W. C. Walter for assistance with the field work, and M. Kaminski for discussion about the analysis.
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FOOTNOTES |
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Received for publication Jul 10, 2000; accepted Nov 9, 2000.
Reprint requests to (B.L.) Inserm U149, 16 avenue Paul Vaillant Couturier, 94807 Villejuif, France.
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ABBREVIATIONS |
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IUGR, intrauterine growth retardation; SGA, small for gestational age; AGA, appropriate for gestational age; SD, standard deviation; PI, ponderal index; CI, confidence interval; IGF, insulin-like growth factor.
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REFERENCES |
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is outcome
still affected?
Dev Med Child Neurol
1990;
32:943-953 [Medline]This article has been cited by other articles:
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