Effects of being born small for gestational age on long-term intellectual performance

doi:10.1016/j.beem.2008.01.014

Best Practice & Research Clinical Endocrinology & Metabolism

Volume 22, Issue 3, June 2008, Pages 477-488

https://doi.org/10.1016/j.beem.2008.01.014 Get rights and content

Size at birth has been associated repeatedly with increased risk of cardiovascular morbidity and mortality later in life. However, there is accumulating evidence to suggest an association between being born small for gestational age (SGA) and increased risk of lower intelligence, poor academic performance, low social competence and behavioural problems, compared with individuals born appropriate for gestational age. Crude neurological handicaps, such as cerebral palsy, are extremely rare in children born SGA at term. Such handicaps are more common in very premature children. However, there does appear to be an increase in the risk for non-severe neurological dysfunction in individuals born SGA. Intellectual performance is evaluated in young children in several different ways, including standardized tests such as Weschler's Intelligence Scale – Revised, and teachers and parents' reports. In adulthood, indirect variables such as education and occupation are used in addition to standardized tests. It may be possible to modify the effects of SGA on intellectual development by breast feeding the baby for more than 6 months. Nutrient-enriched formula does not have any advantages when it comes to intellectual development, and induces a risk of rapid weight gain and eventually overweight. Growth hormone treatment may also have some effect on intelligence quotient.

Section snippets

Preschool age

Although most studies have been performed on school-age children, subnormal performance in intellectual capacity has been reported at early ages among SGA-born children compared with AGA-born children. In 2000, Sommerfelt et al presented a cohort study of 338 term infants born in Norway or Sweden with birth weights below the 15th percentile. The children were examined at 5 years of age. SGA-born children had a lower mean intelligence quotient (IQ) compared with AGA-born children, even after

Discussion

Individuals born SGA form a heterogeneous group, including those born small due to pathological reasons and those born small due to genetic, non-pathological reasons. Most studies concerning SGA and intellectual functions exclude infants born with major handicaps, such as cerebral palsy and major malformations. In the future, it would be interesting to be able to separate those infants born small but healthy in the analyses.

The mixture between pathological and non-pathological small babies will

Conclusion

Being born SGA is associated with mild to moderate school problems in childhood and adolescence, and with lower psychological and intellectual performance in young adulthood compared with AGA controls. Catch-up growth in height reduces the risks associated with being born SGA. SGA-born children seem to gain the greatest advantages from breast feeding.

Practice points

•
infants born SGA should be breast fed for at least 24 weeks
•
children born SGA without spontaneous catch-up growth may benefit from

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Fetal Growth Restriction Leads to an Enlarged Cup-to-Disc Ratio in Adults Born at Full Term
2024, American Journal of Ophthalmology
This study explores associations between fetal growth restriction or excessive fetal growth, along with perinatal factors on the optic nerve head morphology in adulthood.
Retrospective cohort study.
This retrospective cohort study involved a prospective ophthalmological examination of individuals born at full term (with a gestational age of ≥37 weeks) from 1969 to 2002. Each participant underwent nonmydriatic fundus camera photography to capture images of the optic discs, followed by manual measurements. The vertical cup-to-disc ratio (VCDR) and optic disc area were examined and analyzed in relation to the baby's birth weight relative to the gestational age. These categories included those with former moderate (birth weight percentile between the 3rd and <10th), severe SGA (below the third percentile), normal (AGA, 10th-90th percentile), and moderately (birth weight >90th-97th percentile) and severely (birth weight >97th percentile) large for gestational age (LGA) adults within the age range of 18 to 52 years.
Overall, 535 eyes of 280 individuals (age 29.7 ± 9.2 years, 144 females) born at full term were included. Multivariable analysis showed a significant association between a larger VCDR and the severe SGA group (B = 0.05, 95% CI 0.01-0.10; P = .02). In the univariable model, placental insufficiency was associated with VCDR (B = 0.10, 95% CI 0.01-0.19; P = .03). Other perinatal factors did not demonstrate an association with VCDR. Furthermore, there was an indication of an association suggesting a smaller optic disc area in individuals born moderately SGA at full term (B = −0.17, 95% CI −0.33 to −0.001; P = .05).
This study provides evidence that individuals born at-term with severe SGA have an increased VCDR, suggesting that fetal growth restriction has a lasting impact on optic disc morphology independent of prematurity throughout adulthood.
Prenatal exposure to multiple metals and birth outcomes: An observational study within the National Children's Study cohort
2021, Environment International
Citation Excerpt :
Specifically, low birthweight, an indicator of poor fetal growth, has been associated with cardiovascular disease (Barker et al., 1989; Rich-Edwards et al., 1997; Frankel et al., 1996; Lawlor et al., 2005; Eriksson et al., 2001; Zanetti et al., 2018), high blood pressure (Law and Shiell, 1996; Barker et al., 1993; Huxley et al., 2000), impaired glucose tolerance (Hales et al., 1991), and diabetes mellitus (Barker et al., 1993; Lithell et al., 1996) in adult life. Additionally, intrauterine growth restriction and infants born small for gestational age are more susceptible to several adverse health outcomes such as cardiovascular disease and neurodevelopmental dysfunction (Clayton et al., 2007; Sharma et al., 2016; Lundgren and Tuvemo, 2008). Significant risk factors for growth restriction in infants include maternal malnutrition (Wu et al., 2004), older maternal age (Muhammad et al., 2010; Odibo et al., 2006), socioeconomic factors (e.g., lower levels of educational attainment and unmarried marital status) (Phung et al., 2003; Gage et al., 2013), maternal smoking (Phung et al., 2003; Delpisheh et al., 2008; Reeves and Bernstein, 2008), maternal alcohol use (Bandoli et al., 2019; Foltran et al., 2011), short interpregnancy interval (Liauw et al., 2019; Conde-Agudelo et al., 2006), inadequate gestational weight gain (Hasan et al., 2019; Strauss and Dietz, 1999), and placental or umbilical cord abnormalities (Muhammad et al., 2010; Schmid et al., 2013; Krishna and Bhalerao, 2011).
Prenatal exposure to metals may play an important role in fetal growth. However, the epidemiologic evidence for certain metals is sparse, and most of the existing research has focused on evaluating single metals in highly exposed target populations.
We evaluated associations of cadmium, lead, manganese, selenium, and total mercury exposures during pregnancy with fetal growth using data from mother-infant pairs participating in the National Children's Study.
Prenatal metal exposures were measured using maternal blood collected from 6 to 32 weeks of gestation. Birth outcomes, including gestational age, birthweight, birth length, head circumference, and ponderal index, were ascertained through physical measurement at birth or abstraction from medical records. Regression coefficients and their 95% confidence intervals were estimated from multivariable linear regression models in the overall study population as well as among male and female infants. We further evaluated pairwise metal–metal interactions.
Sex-specific associations were observed for lead, with inverse associations for birthweight, birth length, head circumference, and gestational age observed only among female infants. Sex-specific associations were also observed for selenium, with a positive association for birthweight observed among male infants; selenium was also positively associated with ponderal index and inversely associated with birth length among female infants. Overall, total mercury was inversely associated with birthweight and ponderal index, and the association with birthweight was stronger among female infants. No significant associations were observed with cadmium and manganese. In the metal–metal interaction analyses, we found evidence of a synergistic interaction between lead and total mercury and antagonistic interaction between selenium and total mercury with selected birth outcomes.
Our findings suggest that prenatal exposure to metals may be related to birth outcomes, and infant sex may modify these associations.
Increased docosahexaenoic acid and n-3 polyunsaturated fatty acids in milk from mothers of small for gestational age preterm infants
2018, Prostaglandins Leukotrienes and Essential Fatty Acids
The study aimed to test whether or not milk fatty acid composition in mothers of small for gestational age (SGA) infants is similar to that in mothers of adequate for gestational age (AGA) infants. Thirty three mothers of SGA preterm infants and 66 mothers of AGA preterm infants were included. Milk and plasma fatty acids were analyzed using capillary gas chromatography. Milk DHA (0.68 ± 0.37 vs. 0.44 ± 0.24; p < 0.01) was higher and n-6:n-3 PUFA ratio (12.0 ± 4.64 vs. 16.0 ± 6.32; p < 0.05) was lower in mothers of SGA infants. Plasma ARA and DHA were increased in mothers of SGA infants and decreased in their infants. Milk ARA or DHA was positively related to the correspondent fatty acid in plasma (r = 0.374, p = 0.010 for ARA and r = 0.690, p < 0.001 for DHA). Breast milk in mothers of preterm infants born SGA is enriched in DHA and n-3 PUFA. Breastfeeding SGA preterm infant with own mother's milk is recommended.
Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts
2018, Environment International
There is evidence that endocrine disrupting chemicals (EDCs) have developmental effects at environmental concentrations. We investigated whether some EDCs are associated with the adverse birth outcome Small for Gestational Age (SGA).
We used PCB 153, p,p'-DDE, HCB, PFOS and PFOA measured in maternal, cord blood or breast milk samples of 5446 mother-child pairs (subset of 693 for the perfluorinated compounds) from seven European birth cohorts (1997–2012). SGA infants were those with birth weight below the 10th percentile for the norms defined by gestational age, country and infant's sex. We modelled the association between measured or estimated cord serum EDC concentrations and SGA using multiple logistic regression analyses. We explored effect modification by child's sex and maternal smoking during pregnancy.
Among the 5446 newborns, 570 (10.5%) were SGA. An interquartile range (IQR) increase in PCB 153 was associated with a modestly increased risk of SGA (odds ratio (OR) of 1.05 [95% CI: 1.04–1.07]) that was stronger in girls (OR of 1.09 [95% CI: 1.04–1.14]) than in boys (OR of 1.03 [95% CI: 1.03–1.04]) (p-interaction = 0.025). For HCB, we found a modestly increased odds of SGA in girls (OR of 1.04 [95% CI: 1.01–1.07] per IQR increase), and an inverse association in boys (OR of 0.90 [95% CI: 0.85–0.95]) (p-interaction = 0.0003). Assessment of the HCB-sex-smoking interaction suggested that the increased odds of SGA associated with HCB exposure was only in girls of smoking mothers (OR of 1.18 [95% CI: 1.11–1.25]) (p-interaction = 0.055). Higher concentrations of PFOA were associated with greater risk of SGA (OR of 1.64 [95% CI: 0.97–2.76]). Elevated PFOS levels were associated with increased odds of SGA in newborns of mothers who smoked during pregnancy (OR of 1.63 [95% CI: 1.02–2.59]), while an inverse association was found in those of non-smoking mothers (OR of 0.66 [95% CI: 0.61–0.72]) (p-interaction = 0.0004). No significant associations were found for p,p'-DDE.
Prenatal environmental exposure to organochlorine and perfluorinated compounds with endocrine disrupting properties may contribute to the prevalence of SGA. We found indication of effect modification by child's sex and smoking during pregnancy. The direction of the associations differed by chemical and these effect modifiers, suggesting diverse mechanisms of action and biological pathways.
Maternal multiple micronutrient supplementation and other biomedical and socioenvironmental influences on children's cognition at age 9–12 years in Indonesia: follow-up of the SUMMIT randomised trial
2017, The Lancet Global Health
Brain and cognitive development during the first 1000 days from conception are affected by multiple biomedical and socioenvironmental determinants including nutrition, health, nurturing, and stimulation. An improved understanding of the long-term influence of these factors is needed to prioritise public health investments to optimise human development.
We did a follow-up study of the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind, cluster-randomised trial of maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA) in Indonesia. Of 27 356 live infants from birth to 3 months of age in 2001–04, we re-enrolled 19 274 (70%) children at age 9–12 years, and randomly selected 2879 from the 18 230 who were attending school at a known location. Of these, 574 children were oversampled from mothers who were anaemic or malnourished at SUMMIT enrolment. We assessed the effects of MMN and associations of biomedical (ie, maternal and child anthropometry and haemoglobin and preterm birth) and socioenvironmental determinants (ie, parental education, socioeconomic status, home environment, and maternal depression) on general intellectual ability, declarative memory, procedural memory, executive function, academic achievement, fine motor dexterity, and socioemotional health. The SUMMIT trial was registered, number ISRCTN34151616.
Children of mothers given MMN had a mean score of 0·11 SD (95% CI 0·01–0·20, p=0·0319) higher in procedural memory than those given IFA, equivalent to the increase in scores with half a year of schooling. Children of anaemic mothers in the MMN group scored 0·18 SD (0·06–0·31, p=0·0047) higher in general intellectual ability, similar to the increase with 1 year of schooling. Overall, 18 of 21 tests showed a positive coefficient of MMN versus IFA (p=0·0431) with effect sizes from 0·00–0·18 SD. In multiple regression models, socioenvironmental determinants had coefficients of 0·00–0·43 SD and 22 of 35 tests were significant at the 95% CI level, whereas biomedical coefficients were 0·00–0·10 SD and eight of 56 tests were significant, indicating larger and more consistent impact of socioenvironmental factors (p<0·0001).
Maternal MMN had long-term benefits for child cognitive development at 9–12 years of age, thereby supporting its role in early childhood development, and policy change toward MMN. The stronger association of socioenvironmental determinants with improved cognition suggests present reproductive, maternal, neonatal, and child health programmes focused on biomedical determinants might not sufficiently enhance child cognition, and that programmes addressing socioenvironmental determinants are essential to achieve thriving populations.
Grand Challenges Canada Saving Brains Program.
Behavioral outcomes of school-aged full-term small-for-gestational-age infants: A nationwide Japanese population-based study
2017, Brain and Development
Citation Excerpt :
Furthermore, SGA infants are at increased risk of short stature, obesity, hypertension, and insulin resistance in later life [3]. Recently, much attention has been focused on the neurological prognoses of SGA infants [4]. A recent meta-analysis showed that neurological development in full-term SGA infants was poorer than that in full-term appropriate for gestational age (AGA) infants [5].
Small for gestational age (SGA) birth is linked with neurological deficits among children at pre-school age, but the evidence is still limited on whether such deficits are still observable at school age. We investigated the association between SGA birth and behavioral development at school age among full-term infants.
We analyzed data from a large, Japanese, nationwide, population-based longitudinal survey that started in 2001. We restricted the study participants to children born at 37–41 weeks of gestation with information on birth weight and behavioral outcomes at 8 years of age (n = 33,795). Behavioral outcomes including three attentional problems and four aggressive behaviors queried at 8 years of age by survey questions were used as outcome indicators. We then used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between SGA birth and each outcome, adjusting for potential infant- and parent-related confounding factors.
Among full-term children, SGA children were more likely to interrupt people (OR 1.10, 95% CI 1.01, 1.20), unable to wait his/her turn (OR 1.17, 95% CI 1.00, 1.38), and destroy toys and/or books (OR 1.15, 95% CI 1.00, 1.31).
This is the largest study ever conducted on this issue. SGA birth is negatively associated with some attentional problems and aggressive behavior at school age among full-term children. Appropriate long-term developmental follow-up and support may be needed for full-term SGA infants.

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6Effects of being born small for gestational age on long-term intellectual performance

Section snippets

Preschool age

Discussion

Conclusion

Practice points

American Journal of Obstetrics and Gynecology

The Journal of Pediatrics

Early Human Development

Early Human Development

Early Human Development

Seminars in Perinatology

American Journal of Clinical Nutrition

Cognitive development of term small for gestational age children at five years of age

Archives of Disease in Childhood

A longitudinal study of the intelligence and behavior of preterm and small for gestational age children

Journal of Developmental and Behavioral Pediatrics

School difficulties in 20-year-olds who were born small for gestational age at term in a regional cohort study

Pediatrics

Academic achievement of small-for-gestational-age children at age 10 years

Archives of Pediatrics & Adolescent Medicine

Learning, cognitive, and attentional problems in adolescents born small for gestational age

Pediatrics

Intelligence and psychosocial functioning during long-term growth hormone therapy in children born small for gestational age

The Journal of Clinical Endocrinology and Metabolism

Outcome of low birthweight in China: a 16-year longitudinal study

Acta Paediatrica

Pune low birth weight study – cognitive abilities and educational performance at twelve years

Indian Journal of Pediatrics

Delayed growth and reduced intelligence in 9–17 year old intrauterine growth retarded children compared with their monozygous co-twins

Acta Paediatrica Scandinavica

Adult functional outcome of those born small for gestational age: twenty-six-year follow-up of the 1970 British Birth Cohort

The Journal of the American Medical Association

Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study

BMJ (Clinical Research Ed.)

Intellectual and psychological performance in males born small for gestational age with and without catch-up growth

Pediatric Research

Birth characteristics and risk of low intellectual performance in early adulthood: are the associations confounded by socioeconomic factors in adolescence or familial effects?

Pediatrics

Neuropsychological follow-up into young adulthood of term infants born small for gestational age

Medical Science Monitor

Early growth and development in low-birthweight infants following treatment in an intensive care nursery

Pediatrics

Growth and development of full-term nonasphyxiated small-for-gestational-age newborns: follow-up through adolescence

Pediatrics

6
Effects of being born small for gestational age on long-term intellectual performance