PEDIATRICS Vol. 122 No. 2 August 2008, pp. e350-e358 (doi:10.1542/peds.2007-3851)
ARTICLE |
Birth Weight and Cognitive Ability in Childhood Among Siblings and Nonsiblings
a Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
b Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
c New York State Psychiatric Institute, New York, New York
d Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, England
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ABSTRACT |
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OBJECTIVES. The purpose of this work was to examine whether the positive association between birth weight and childhood cognitive ability is seen within siblings from the same family, as well as between nonsiblings, and to determine whether these associations vary with age.
METHODS. We compared the association of birth weight with cognitive ability measured at ages 5 to 6, 7 to 9, and 11 to 12 years among a total of 5402 children from different families with that among 2236 to 3083 sibships from the National Longitudinal Study of Youth 1979-Children.
RESULTS. In the whole cohort, there were positive associations between birth weight and cognitive ability at all ages, with the association increasing with age from a 0.81-point increase at ages 5 to 6 years to 1.30 and 1.44 points at ages 7 to 9 and 11 to 12 years, respectively, per 1 SD of gestational age- and gender-adjusted birth weight z score. With adjustment for covariates, there was marked attenuation of these associations. Mean differences were 0.28 points in children aged 5 to 6 years, 0.67 points in those aged 7 to 9 years, and 0.52 points in those aged 11 to 12 years after adjusting for child's gender, race or ethnicity, year of birth, and age at test; maternal age, height, parity, education, smoking during pregnancy, and cognitive ability; and household income. Our family-based analyses that separated within- and between-family effects found that the between-family associations were much stronger than the within-family associations. However, adjustment for potential confounders attenuated the between-family associations, and there was no evidence for a difference in association comparing the between- and within-family associations.
CONCLUSIONS. In these data, the positive association between birth weight and childhood cognitive ability at ages 5 to 12 years is explained largely by family characteristics rather than a specific intrauterine effect.
Key Words: birth weight • cognitive function • family environment • siblings
Abbreviations: SEP—socioeconomic position • NLSY79-C—National Longitudinal Survey of Youth 1979-Children • PIAT—Peabody Individual Achievement Test • CI—confidence interval
Birth weight has been positively associated with cognitive ability in childhood, across the full distribution of birth weight and cognitive ability, after adjustment for potential confounding factors.1–6 This is often interpreted as evidence for an intrauterine developmental origin to cognitive development. However, few studies have adjusted for the full range of potential confounding factors, and even those that do may be affected by residual confounding because of poor measurement. For example, socioeconomic position (SEP), maternal behavior and health, and parental intelligence and education all have important effects on both birth weight7, 8 and offspring cognitive ability9–17 and could, therefore, explain any association between the two.
Data from siblings provide opportunities to better control for family characteristics and to examine whether the characteristics shared by siblings explain the association. Family-based analysis using data from siblings18–20 allows separation of within-family effects from between-family effects and simultaneous estimation of both. If the association is largely explained by maternal and family factors, then one would expect no association or a considerably weaker association within siblings (where these factors will be very well controlled) when compared with the association between children from different families. Several such family-based studies have been conducted for birth weight and cognitive ability.21–25 In the earliest study, Record et al21 showed that differences in cognitive ability between nonsiblings aged 11 years in England were greater than those of 2521 sibling pairs and concluded that the association was largely because of confounding by SEP. A study by Lawlor et al24 also found that, although birth weight was positively associated with cognitive ability at ages 7 to 11 years in a whole-cohort analysis, there was no association within 1645 sibling pairs. By contrast, 3 studies have found positive within-sibling associations.22, 23, 25 One of these studies was small, with just 235 sibling pairs, but found within-sibling associations with cognitive ability measured at ages 5 and 14 years and in both genders. A larger study of US children with 1683 sibling pairs22 found a positive association within male siblings (although not within female siblings) at age 9 years and concluded that, at least for boys, confounding by SEP or other family characteristics did not explain the association. By far the largest family-based study to date included only men and found similar within- and between-family birth weight associations with low cognitive ability at ages 17 to 19 years in a sample of 96187 individuals from 51723 families.25
One possible reason for the inconsistency across family-based studies could be because the nature of any intrauterine developmental origin of cognitive ability varies with age. None of the previous studies had cognitive ability measured repeatedly at different ages during childhood. Therefore, we examined whether the positive association of birth weight with cognitive ability was observed within and between families among children with cognitive ability measured at ages 5 to 6, 7 to 9, and 11 to 12 years and whether either the within- or between-family association varied by age at which the cognitive ability was measured. We used data from the National Longitudinal Survey of Youth 1979-Children (NLSY79-C),26 a sample of nationally representative children in the United States who were born between 1979 and 1999. Although Deary et al17 used the same data to study the association between birth weight and cognitive ability, they focused only on the role of maternal cognitive ability without considering other family characteristics and restricted their sample to those who were term births born to white mothers and in the reference range of birth weight (>2500 g). Our study significantly extends the work of Deary et al17 by examining the association in the entire sample, using a wider range of family characteristics including mother's cognitive ability, and, importantly, considering the association in the whole sample with that observed among siblings.
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METHODS |
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Study Participants
The NLSY79-C consists of children of female participants in the NLSY79, a longitudinal study of youths aged 14 to 22 years in 1979. In 1986, the participating women were asked to provide consent for their children to be interviewed for the NLSY79-C. Children and mothers have been interviewed biennially since then. All of the existing children at any age were interviewed in 1986, and new children were added at subsequent interviews. Our study used data collected from 1986 to 2004. We excluded those who were born before 1979 when the mothers were first interviewed. We selected children who were singleton births and had cognitive ability scores measured at 5 to 6, 7 to 9, or 11 to 12 years. We chose these 3 age groups to represent an early, middle, and end period of primary schooling, respectively. Because interviews were conducted every other year, not all of the siblings were interviewed at the same age; thus, we combined 2 or 3 ages (eg, 5–6 instead of age 5 and 6 years separately) to maximize the number of participants but controlled for age in all of the analyses. There were 4372 children interviewed at ages 5 to 6years, 4502 at ages 7 to 9 years, and 3468 at ages 11 to 12 years. Of these, 52% had test scores measured at all 3 of the age groups, and 32% and 16% had 2 and only 1, respectively. The subjects were 50.8% boys and 27.6% black, 19.1% Hispanic, and 53.3% nonblack/non-Hispanic children. A total of 474 children (9%) had no sibling in the study, and they were excluded in our family-based analysis. We further excluded those whose siblings were not tested at the same ages, yielding 2831 siblings (1222 families) for ages 5 to 6years, 3083 (1312 families) for ages 7 to 9 years, and 2236 (982 families) for ages 11 to 12 years in our family-based analysis.
Measures
Birth weight and gestational age were collected from mothers at every interview. A gestational age and gender-standardized z score of birth weight was calculated for each child. Cognitive ability was measured by the Peabody Individual Achievement Test (PIAT) administered to children aged 5 to 14 years at any interview from 1986 to 2004.26 We used the PIAT total scores by summing the individual component scores of mathematics, reading comprehension, and recognition. Moderate-to-high correlations of the PIAT with the Wechsler Intelligence Scale for Children-Revised have been reported.27 Because the scores vary across calendar years, we transformed the scores to have a mean of 100 and an SD of 15 to make the scores comparable across years and also compatible with other studies of cognitive ability.
Maternal characteristics were composed of age at birth, height, and the number of previous births. Family SEP measures included household income in the birth year of a given child and maternal education (year of schooling). Household income at birth was measured at each interview and was converted to year 2000 US dollars. Maternal smoking during pregnancy of a given child (yes/no) and cognitive ability score measured in 1980 by the armed forces qualification test26 were also included as important potential confounders.
Statistical Analysis
We first examined the association between birth weight and cognitive ability in the whole cohort, taking into account the clustering of siblings within families in the estimation of SEs. Because there was no evidence of interaction with gender (all P values for interaction: >.2) and race or ethnicity (all P values for interaction: >.1), we adjusted for gender and ethnicity in our analyses. A secular trend of increasing cognitive test scores was observed, and we also adjusted for year of birth in our base model. We further adjusted for maternal characteristics, family SEP, maternal smoking during pregnancy, and maternal cognitive ability.
We then conducted analyses in a sample of families with 
2 children (family-based analysis). To simultaneously estimate the within- and between-family estimates of the association, we calculated a mean birth weight for each family for the between-family effect and a deviation from the family mean for each sibling for the individual-specific birth weight effect (the within-family association).20 The general model is: E(Yij) = β0 + βw(Xij – ) + βB, where Yij represents a child's cognitive ability for an individual j of family i. βW represents the within-family coefficient indicating the expected change in cognitive ability score for a 1-unit change in the deviation of the individual birth weight (Xij) from the family mean birth weight (), while holding the latter constant. βB is the between-family coefficient representing the expected change in cognitive ability score for a 1-unit change in the family mean birth weight, while holding the individual deviation from the family mean constant. A generalized least-squares method was used to estimate the coefficients with restricted maximum likelihood for estimating the variance parameters.20 The base model for family-based analysis also adjusted for gender, race or ethnicity, birth year, and age at the test, and covariates were adjusted subsequently.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Table 1 shows characteristics of participants in the whole-cohort analysis across 3 age groups. Mean birth weight and cognitive scores by these characteristics are presented in Appendix 1. Distributions of variables are not substantially different from the family-based analysis; thus, we present only the whole-sample characteristics.
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Table 2 shows mean differences in birth weight and PIAT scores among siblings by family size. The mean age difference among siblings was 3.4 years. Both birth weight and cognitive scores were moderately correlated within families, with correlation coefficients ranging from 0.38 to 0.62. Differences were calculated from the values of the oldest child in each family. As expected, the larger the family size, the larger the mean differences from the oldest child. These initial descriptive analyses generally show that birth weight and cognitive ability both varied among siblings within families. It should also be noted that variations across nonsiblings between families were greater than variations within siblings. For example, the intraclass correlation of birth weight was 0.37 (95% confidence interval [CI]: 0.34 to 0.41), indicating that 37% of total variations in birth weight were from within families and 63% were from between families.
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Whole-cohort Analysis
Table 3 presents the association between birth weight and cognitive ability in the whole cohort. As observed in other studies, positive associations were found across 3 age groups. We found some evidence that the magnitude of the association between birth weight and cognitive ability increased with increasing age at which the cognitive ability test was performed. There were 0.81-, 1.30-, and 1.44-point increases in cognitive ability per 1-SD increase in gestational age- and gender-adjusted birth weight in children aged 5 to 6, 7 to 9, and 11 to 12 years, respectively. Adjusting for gender, race or ethnicity, birth year, age of cognitive test, and maternal characteristics attenuated the positive association greatly in all of the ages, mainly because of race or ethnicity. Additional adjustment for family SEP further attenuated the positive association. When we examined the pattern of association with individual family SEP indicators, it was found that maternal education was mainly responsible for the attenuation in this model and that maternal education was strongly positively associated with offspring cognitive ability (Appendix 2). Additional adjustment for maternal smoking during pregnancy and maternal cognitive ability score in the final model resulted in very little attenuation from the model that included maternal education. In the final fully adjusted models, associations with childhood cognitive ability measured at ages 7 to 9 and 11 to 12 years (0.67-point and 0.52-point increase per SD birth weight, respectively) were stronger than those with childhood cognitive ability at ages 5 to 6 years, but the trend across all of the age groups was no longer evident. Although standardization for gestational age is a valid means of assessing intrauterine growth, presenting results per z score can sometimes be difficult to interpret. We, therefore, repeated our analyses with birth weight as the main exposure and adjusted for gestational age. The point estimates in the fully adjusted model were equivalent to a 1.5-point increase in PIAT total score per 1-kg increment of birth weight among children aged 7 to 9 years (95% CI: 0.6 to 2.2 points) and to 1.2 points among children aged 11 to 12 years (95% CI: 0.4 to 2.1 points).
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Family-based Analysis
Results from the family-based analyses are presented in Table 4. In the crude analyses there was a marked difference in the association, with the between-family association being much stronger than the within-family association. Consistent with the whole-cohort analyses, however, in successive multivariable models adjusting for covariates, the between-family association attenuated, whereas the within-family association remained relatively constant. The between-family estimates of the association were not statistically different from the within-family estimates once maternal characteristics were adjusted. Consequently, in the fully adjusted models there was no evidence of a difference in the associations between and within families. The magnitudes of the effect estimates were similar at all of the ages in these family-based analyses. As has been done in previous studies,24 we also conducted the same analysis in a sample of randomly selected pairs per family (for those families with >2 siblings) and found essentially identical results (data not shown). Similarly, when we repeated the analyses, including only those who had cognitive ability measures at all 3 of the ages, the findings were unchanged (results not shown).
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Secondary Analysis
We reanalyzed our data for the same-gender sibling families only. The results remained unchanged: there was a very weak within-family association of birth weight with cognition in the 3 age groups (results not shown). We further restricted our sample to term births (>37 weeks of gestational age) and excluded those with low birth weight (<2500 g) and found identical results (data not shown). Results were also robust when we used low cognitive ability (eg, bottom 10%) as our outcome rather than cognitive function across its full distribution. When we excluded children with high birth weight (>4000 g), 11% of the participants, we found stronger associations of birth weight with cognitive function across all of the age groups in the whole-cohort analysis. For example, mean differences in cognitive ability per 1 SD of birth weight were 0.50 (95% CI: –0.06 to 0.96), 1.03 (95% CI: 0.52 to 1.55), and 0.90 (95% CI: 0.35 to 1.46) at ages 5 to 6, 7 to 9, and 11 to 12 years, respectively, in fully adjusted models, whereas our main whole-cohort analyses, including the high birth weight children, showed the mean differences of 0.28 (95% CI: –0.09 to 0.64) in ages 5 to 6, 0.67 (95% CI: 0.26 to 1.08) in ages 7 to 9, and 0.52 (95% CI: 0.07 to 0.97) in ages 11 to 12 years. Overall, the family-based analyses were similar to our main analyses with these high birth weight children removed.
Our primary aim was to examine and explore the nature of birth weight across its whole distribution with cognitive ability across its whole distribution. However, we recognize that this approach might miss important associations of low birth weight (<2500 g) with cognitive ability,28, 29 and we examined this in secondary analyses. In general, the patterns of associations were similar to those found for the association of birth weight across its whole distribution. In the whole-cohort analyses, low birth weight, compared with all of the others, was associated with lower cognitive ability in univariate analyses with attenuation of the association on adjustment for covariates. As with our main analyses, the associations were somewhat stronger for cognitive ability measured at ages 7 to 9 and 11 to 12 years than they were at 5 to 6 years. For example, the mean difference in cognitive ability at ages 11 to 12 years was 3.93 points lower in those born with low birth weight (N = 228) than all of the others (95% CI: –6.00 to –1.88) in analyses adjusting for gestational age only. This attenuated to –2.41 (95% CI: –4.23 to –0.59) in the fully adjusted model. A weak association was also found within siblings (eg, the mean difference of cognitive ability at age 11 to 12 years within families in the fully adjusted model was –0.45 [95% CI: –2.85 to 1.93]). When we further restricted the analytic samples by removing those subjects who were born preterm, point estimates were all very similar to those presented above, suggesting that the associations were not driven by preterm low birth weight children.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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We examined whether the association between birth weight and cognitive ability across their full distribution in children was found both within and between families and at different ages between 5 and 12 years in a national sample of children in the United States. In the whole-cohort analysis, we found that the crude association at all of the ages was markedly attenuated on adjustment for family characteristics, in particular race or ethnicity and maternal education and cognitive ability. However, a weak association remained in children >7 years of age. When we separated this association into within and between families in our family-based analyses we found that between-family associations were much stronger than within-family associations, but with adjustment for maternal and family characteristics the between-family associations attenuated, and there was no statistical difference in the association between families compared with that within families. Overall our findings suggest that most of the positive association of birth weight with cognitive ability across their full distributions is because of between-family effects and is explained by family characteristics rather than a specific intrauterine programming effect.
Our findings are consistent with that of Deary et al.17 However, by comparing the whole-cohort analysis, a methodology that most observational studies rely on, with that based on siblings, our study shows the extent to which confounding might explain the residual association and provides a more rigorous and comprehensive approach to the research question. Our results are compatible with the findings from the Aberdeen Children of the 1950s cohort24 in that both studies suggest that most of the association between birth weight and cognitive ability is because of shared family characteristics. However, the Aberdeen Children Study found a stronger effect between than within families, presumably because they were unable to control for maternal education and cognitive ability. Thus, the family-based analysis was crucial in the Aberdeen Children Study to draw valid inferences on the nature of the association. Our study, however, had a wide range of potential confounding factors, and overall our family-based and whole-cohort analyses were consistent with each other, demonstrating that adjustment for some key differences across families explained the between-family association.
Nevertheless, there are other sibling-based studies showing within-family effects of birth weight on cognitive ability.22, 23, 25 The inconsistent results across studies may be because of differences in ages of the children, sample inclusion criteria, the use of cognitive ability score (continuous or categorical), measures of cognitive ability, and the precision of measures of birth weight and gestational age. Our secondary analyses attempted to explore possible reasons for differences between studies. First, we found no gender difference in the association, unlike 1 previous study.22 Similarly, when we examined the association of birth weight with low cognitive score (those in the lowest 10%) rather than across its distribution, as was done in 1 previous study,25 associations were also greatly attenuated with adjustment for potential confounders. Our results were not driven by low birth weight infants or those born preterm, because exclusion of these children did not alter the results. Although exclusion of large birth weight children tended to increase associations in the whole-cohort analyses, the family-based results were similar to our main analyses. Finally, our secondary analyses did not suggest that, once potential confounders were accounted for, low birth weight had a marked impact on cognitive ability. However, it should be noted that our study was not designed for this specific association, and, compared with our primary analyses using the full distribution of birth weight, we had limited statistical power, which prevents us from drawing any firm conclusion on the association between low birth weight and cognitive ability.
One of our primary aims was to examine whether family-based associations varied by age. We observed that the association was somewhat weaker for younger children at ages 5 to 6 years. This may reflect the fact that younger children are more sensitive to family environmental factors, such as maternal education, than older children.30 Alternatively, it might suggest that PIAT does not discriminate cognitive ability at younger ages. However, regardless of explanations for the age differences, our conclusions on the birth weight and cognitive ability association apply to the association at all ages. It is also worth noting that cognitive ability score increased by 
0.5 points per 1 SD of gender- and gestational age-adjusted birth weight or 1.2 to 1.5 points per 1-kg difference in birth weight at a given gestational age. A 1-kg difference in birth weight is equivalent to 5 to 6 times the difference between infants of smoking and nonsmoking mothers.31 A more achievable, realistic public health goal of birth weight increase would be 100 g, and it would be associated with at 0.10-point increase in cognitive ability scores in our whole-cohort analysis. On the other hand, 1 year of additional education in the mother is associated with a 0.27- to 0.47-point increase in cognitive ability score among children in our study (Appendix 2).
Our findings of a weak within-family association and strong between-family association shed some light on understanding the association between childhood cognitive ability and adult health.32–35 Despite these associations being found in various study populations, the mechanism underlying the association is not well understood. If cognitive test score in childhood is better represented by family and social surroundings, whether genetic or environmental, as found in our study and others,16, 36 the association between child cognitive ability and adult health could be also explained by family characteristics.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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According to these data, after full adjustment for family characteristics, there was only a weak residual association between birth weight and childhood cognitive ability at ages between 5 and 12 years. Furthermore, a complementary family-based analysis found essentially the same result, suggesting that the differences in cognitive ability in children are mostly because of family characteristics rather than intrauterine factors.
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ACKNOWLEDGMENTS |
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This research was funded by Interdisciplinary Capacity Enhancement grant HOA-80072 by the Canadian Institute of Health Research.
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FOOTNOTES |
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Accepted Mar 14, 2008.
Address correspondence to Seungmi Yang, PhD, McGill University, Department of Epidemiology, Biostatistics, and Occupational Health, 1020 Pine Ave West, Montreal, Quebec, Canada H3A 1A2. E-mail: seungmi.yang{at}mcgill.ca
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Birth weight has been positively associated with cognitive ability in childhood. Studies based on siblings that examined whether there is an intrauterine developmental origin by separating the association into the within- and between-family effects have found inconsistent results.
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| What This Study Adds Our study shows that the positive association between birth weight and cognitive ability across their full distributions is explained mainly by shared family characteristics rather than intrauterine factors among children aged 5 to 12 years in analyses of both nonsiblings and siblings from the same family.
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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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