Breastfeeding and intelligence in adulthood: due to genetic confounding?
Authors: Bernardo L Horta, Fernando P Hartwig, Cesar G Victora
Journal: The Lancet Global Health (2018)

We previously reported1Victora CG Horta BL de Mola CL et al.Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil.Lancet Glob Health. 2015; 3: e199-e205Summary Full Text Full Text PDF PubMed Scopus (368) Google Scholar that breastfeeding was positively associated with human capital at 30 years of age. The causal nature of this association has been challenged because of the possibility of residual confounding by socioeconomic status, parental intelligence, or genetic factors, including the possibility that infants who are better developed or more mature than another child of the same age might breastfeed for longer periods. Such claims remain common, despite evidence from a randomised trial,2Kramer MS Aboud F Mironova E et al.Breastfeeding and child cognitive development: new evidence from a large randomized trial.Arch Gen Psychiatry. 2008; 65: 578-584Crossref PubMed Scopus (722) Google Scholar from cross-cohort comparisons, and from studies that adjusted for maternal intelligence quotient (IQ).3Horta BL Loret De Mola C Victora CG Breastfeeding and intelligence: a systematic review and meta-analysis.Acta Paediatr Int J Paediatr. 2015; 104: 14-19Crossref PubMed Scopus (356) Google Scholar Furthermore, in our setting,1Victora CG Horta BL de Mola CL et al.Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil.Lancet Glob Health. 2015; 3: e199-e205Summary Full Text Full Text PDF PubMed Scopus (368) Google Scholar breastfeeding at 6 months was largely independent of socioeconomic status. The availability of genome-wide genotyping data allowed us to create an allele score to predict schooling in the 1982 Pelotas Birth Cohort,4Horta BL Gigante DP Gonçalves H et al.Cohort profile update: the 1982 Pelotas (Brazil) birth cohort study.Int J Epidemiol. 2015; 44: 441Crossref PubMed Scopus (99) Google Scholar in which 3700 participants were followed up from birth to age 30 years. The score was based on 5000 independent single nucleotide polymorphisms for which the associations with attained schooling have been quantified.5Okbay A Beauchamp JP Fontana MA et al.Genome-wide association study identifies 74 loci associated with educational attainment.Nature. 2016; 533: 539-542Crossref PubMed Scopus (688) Google Scholar We investigated the genetic confounding hypothesis by assessing the association of the allele score with IQ and breastfeeding, and by testing whether adjustment for the score affected our previously reported results on the associations between breastfeeding and human capital. 2725 participants had information on IQ, breastfeeding, and the allele score, which was positively associated with maternal schooling (r=0·252, p<0·001). The score was also positively associated with the participants' IQ (r=0·306; p<0·001) and attained schooling (r=0·272; p<0·001). After controlling for confounders, the score was slightly higher among participants in intermediate categories of breastfeeding duration (table) than for those in higher or lower categories. Controlling for the schooling allele score on top of the other covariates slightly changed the estimates of the association of breastfeeding with human capital. For example, the mean difference in IQ between participants who were breastfed for at least 12 months and those breastfed for less than 1 month changed from 3·76 to 3·60 points (95% CI 1·99–5·21).TableSchooling allele score and breastfeeding durationConfounders*Adjusted for family income, maternal schooling, and genomic ancestry. for schooling allele score, pointsIQ, pointsAchieved schooling, yearsMonthly income, Brazilian reaisConfounders†Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight.Confounders†Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight. and schooling allele scoreConfounders†Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight.Confounders†Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight. and schooling allele scoreConfounders†Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight.Confounders†Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight. and schooling allele scorep value0·04‡Test for heterogeneity.<0·001§Test for linear trend.<0·001§Test for linear trend.0·003§Test for linear trend.<0·001§Test for linear trend.<0·001§Test for linear trend.0·006‡Test for heterogeneity.Breastfeeding duration, months<1(ref)(ref)(ref)(ref)(ref)(ref)(ref)1–2·90·00 (−0·05 to 0·05)0·38 (−1·03 to 1·79)0·10 (−1·34 to 1·54)0·31 (−0·13 to 0·75)0·28 (−0·17 to 0·73)222·5 (0·26–444·7)221·7 (−7·91 to 451·4)3–5·90·06 (0·01–0·11)1·77 (0·35–3·19)1·57 (0·11–3·02)0·49 (0·05–0·94)0·44 (−0·02 to 0·89)285·1 (61·0–509·2)270·5 (39·0–502·0)6–11·90·04 (−0·02 to 0·11)3·50 (1·84–5·16)3·46 (1·78–5·15)0·65 (0·12–1·17)0·62 (0·09–1·15)485·0 (222·2–747·8)491·3 (222·7–759·8)≥12−0·02 (−0·08 to 0·04)3·76 (2·20–5·33)3·60 (1·99–5·21)0·91 (0·42–1·40)0·94 (0·44–1·44)341·0 (93·8–588·3)343·6 (87·7–599·6)Data are adjusted regression coefficient (95% CI), unless otherwise specified. IQ=intelligence quotient.* Adjusted for family income, maternal schooling, and genomic ancestry.† Adjusted for family income, parental schooling, household score index, genomic ancestry, maternal smoking during pregnancy, maternal age, type of delivery, maternal prepregnancy body-mass index, gestational age, and birthweight.‡ Test for heterogeneity.§ Test for linear trend. Open table in a new tab Data are adjusted regression coefficient (95% CI), unless otherwise specified. IQ=intelligence quotient. Because intelligence is a complex trait, likely to be influenced by genetic and environmental factors,6Deary IJ Intelligence.Annu Rev Psychol. 2012; 63: 453-482Crossref PubMed Scopus (351) Google Scholar the score should capture some but not all of the genetic component of intelligence. Hence, adjustment for the score should attenuate the association between breastfeeding and intelligence. Such attenuation was not observed in our analyses; indeed, the results were virtually unchanged after adjustment. Therefore, residual genetic confounding is unlikely. To our knowledge, this study was the first to formally assess the genetic confounding hypothesis regarding the association between breastfeeding and IQ. Our findings are in line with the results of a randomised controlled trial,2Kramer MS Aboud F Mironova E et al.Breastfeeding and child cognitive development: new evidence from a large randomized trial.Arch Gen Psychiatry. 2008; 65: 578-584Crossref PubMed Scopus (722) Google Scholar which is, in principle, robust to confounders including genetic and observational studies that used specific analytical strategies to improve causal inference.3Horta BL Loret De Mola C Victora CG Breastfeeding and intelligence: a systematic review and meta-analysis.Acta Paediatr Int J Paediatr. 2015; 104: 14-19Crossref PubMed Scopus (356) Google Scholar, 7Lucas A Morley R Cole TJ Lister G Leeson-Payne C Breast milk and subsequent intelligence quotient in children born preterm.Lancet. 1992; 339: 261-264Summary PubMed Scopus (959) Google Scholar In summary, our earlier report1Victora CG Horta BL de Mola CL et al.Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil.Lancet Glob Health. 2015; 3: e199-e205Summary Full Text Full Text PDF PubMed Scopus (368) Google Scholar of positive associations between breastfeeding and human capital remain unchanged after adjustment for a robust genetic predictor of attained schooling. Considering our findings and the overall body of evidence, the genetic confounding hypothesis seems unlikely. The current analysis did not assess whether the observed association was due to an effect of human milk as a nutrient or the mother–infant interaction, and by rejecting the genetic explanation for the association between breastfeeding and IQ,3Horta BL Loret De Mola C Victora CG Breastfeeding and intelligence: a systematic review and meta-analysis.Acta Paediatr Int J Paediatr. 2015; 104: 14-19Crossref PubMed Scopus (356) Google Scholar our study results reinforce the importance of breastfeeding promotion. We have no competing interests. Data collection was funded by the Wellcome Trust. Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from BrazilBreastfeeding is associated with improved performance in intelligence tests 30 years later, and might have an important effect in real life, by increasing educational attainment and income in adulthood. Full-Text PDF Open Access