Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks' Gestation

      Objectives

      To determine the associations of breast milk intake after birth with neurological outcomes at term equivalent and 7 years of age in very preterm infants

      Study design

      We studied 180 infants born at <30 weeks' gestation or <1250 grams birth weight enrolled in the Victorian Infant Brain Studies cohort from 2001-2003. We calculated the number of days on which infants received >50% of enteral intake as breast milk from 0-28 days of life. Outcomes included brain volumes measured by magnetic resonance imaging at term equivalent and 7 years of age, and cognitive (IQ, reading, mathematics, attention, working memory, language, visual perception) and motor testing at 7 years of age. We adjusted for age, sex, social risk, and neonatal illness in linear regression.

      Results

      A greater number of days on which infants received >50% breast milk was associated with greater deep nuclear gray matter volume at term equivalent age (0.15 cc/d; 95% CI, 0.05-0.25); and with better performance at age 7 years of age on IQ (0.5 points/d; 95% CI, 0.2-0.8), mathematics (0.5; 95% CI, 0.1-0.9), working memory (0.5; 95% CI, 0.1-0.9), and motor function (0.1; 95% CI, 0.0-0.2) tests. No differences in regional brain volumes at 7 years of age in relation to breast milk intake were observed.

      Conclusion

      Predominant breast milk feeding in the first 28 days of life was associated with a greater deep nuclear gray matter volume at term equivalent age and better IQ, academic achievement, working memory, and motor function at 7 years of age in very preterm infants.

      Keywords

      Abbreviations:

      MRI ( Magnetic resonance imaging)
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      References

        • Kramer M.S.
        • Aboud F.
        • Mironova E.
        • Vanilovich I.
        • Platt R.W.
        • Matush L.
        • et al.
        Breastfeeding and child cognitive development: new evidence from a large randomized trial.
        Arch Gen Psychiatry. 2008; 65: 578-584
        • Belfort M.B.
        • Rifas-Shiman S.L.
        • Kleinman K.P.
        • Guthrie L.B.
        • Bellinger D.C.
        • Taveras E.M.
        • et al.
        Infant feeding and childhood cognition at ages 3 and 7 years: effects of breastfeeding duration and exclusivity.
        JAMA Pediatr. 2013; 167: 836-844
        • Smithers L.G.
        • Kramer M.S.
        • Lynch J.W.
        Effects of breastfeeding on obesity and intelligence: causal insights from different study designs.
        JAMA Pediatr. 2015; 169: 707-708
        • Demmelmair H.
        • Koletzko B.
        Importance of fatty acids in the perinatal period.
        World Rev Nutr Diet. 2015; 112: 31-47
        • Britton J.R.
        • Britton H.L.
        • Gronwaldt V.
        Breastfeeding, sensitivity, and attachment.
        Pediatrics. 2006; 118: e1436-43
        • Rahkonen P.
        • Heinonen K.
        • Pesonen A.K.
        • Lano A.
        • Autti T.
        • Puosi R.
        • et al.
        Mother-child interaction is associated with neurocognitive outcome in extremely low gestational age children.
        Scand J Psychol. 2014; 55: 311-318
        • Der G.
        • Batty G.D.
        • Deary I.J.
        Effect of breast feeding on intelligence in children: prospective study, sibling pairs analysis, and meta-analysis.
        BMJ. 2006; 333: 945
        • Kleinman R.E.
        Pediatric nutrition handbook.
        6th ed. American Academy of Pediatrics, Elk Grove Village, (IL)2009
        • Colaizy T.T.
        • Carlson S.
        • Saftlas A.F.
        • Morriss Jr, F.H.
        Growth in VLBW infants fed predominantly fortified maternal and donor human milk diets: a retrospective cohort study.
        BMC Pediatr. 2012; 12: 124
        • O'Connor D.L.
        • Jacobs J.
        • Hall R.
        • Adamkin D.
        • Auestad N.
        • Castillo M.
        • et al.
        Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula.
        J Pediatr Gastroenterol Nutr. 2003; 37: 437-446
        • Deoni S.C.
        • Dean 3rd, D.C.
        • Piryatinsky I.
        • O'Muircheartaigh J.
        • Waskiewicz N.
        • Lehman K.
        • et al.
        Breastfeeding and early white matter development: a cross-sectional study.
        Neuroimage. 2013; 82: 77-86
        • Ou X.
        • Andres A.
        • Cleves M.A.
        • Pivik R.T.
        • Snow J.H.
        • Ding Z.
        • et al.
        Sex-specific association between infant diet and white matter integrity in 8-y-old children.
        Pediatr Res. 2014; 76: 535-543
        • Kafouri S.
        • Kramer M.
        • Leonard G.
        • Perron M.
        • Pike B.
        • Richer L.
        • et al.
        Breastfeeding and brain structure in adolescence.
        Int J Epidemiol. 2013; 42: 150-159
        • Isaacs E.B.
        • Fischl B.R.
        • Quinn B.T.
        • Chong W.K.
        • Gadian D.G.
        • Lucas A.
        Impact of breast milk on intelligence quotient, brain size, and white matter development.
        Pediatr Res. 2010; 67: 357-362
        • Pogribna U.
        • Yu X.
        • Burson K.
        • Zhou Y.
        • Lasky R.E.
        • Narayana P.A.
        • et al.
        Perinatal clinical antecedents of white matter microstructural abnormalities on diffusion tensor imaging in extremely preterm infants.
        PLoS ONE. 2013; 8 (e72974)
        • Thompson D.K.
        • Lee K.J.
        • Egan G.F.
        • Warfield S.K.
        • Doyle L.W.
        • Anderson P.J.
        • et al.
        Regional white matter microstructure in very preterm infants: predictors and 7 year outcomes.
        Cortex. 2014; 52: 60-74
        • Warfield S.
        Fast k-NN classification for multichannel image data.
        Pattern Recognit Lett. 1996; 17: 713-721
        • Warfield S.K.
        • Kaus M.
        • Jolesz F.A.
        • Kilinis R.
        Adaptive, template moderated, spatially varying statistical classification.
        Med Image Anal. 2000; 4: 43-55
        • Shah D.K.
        • Anderson P.J.
        • Carlin J.B.
        • Pavlovic M.
        • Howard K.
        • Thompson D.K.
        • et al.
        Reduction in cerebellar volumes in preterm infants: relationship to white matter injury and neurodevelopment at two years of age.
        Pediatr Res. 2006; 60: 97-102
        • Thompson D.K.
        • Ahmadzai Z.M.
        • Wood S.J.
        • Inder T.E.
        • Warfield S.K.
        • Doyle L.W.
        • et al.
        Optimizing hippocampal segmentation in infants utilizing MRI post-acquisition processing.
        Neuroinformatics. 2012; 10: 173-180
        • Omizzolo C.
        • Thompson D.K.
        • Scratch S.E.
        • Stargatt R.
        • Lee K.J.
        • Cheong J.
        • et al.
        Hippocampal volume and memory and learning outcomes at 7 years in children born very preterm.
        J Int Neuropsychol Soc. 2013; 19: 1065-1075
        • Weschler D.
        Weschler Abbreviated Scale of Intelligence (WASI).
        The Psychological Corporation, 1999
        • Wilkinson G.
        • Robertson G.
        Wide range achievement test.
        4th ed. Psychological Assessment Resources, Lutz, (FL)2006
        • Manly T.
        • Anderson V.
        • Nimmo-Smith I.
        • Turner A.
        • Watson P.
        • Robertson I.H.
        The differential assessment of children's attention: the Test of Everyday Attention for Children (TEA-Ch), normative sample and ADHD performance.
        J Child Psychol Psychiatry. 2001; 42: 1065-1081
        • Pickering S.J.
        • Gathercole S.E.
        Working memory test battery for children.
        The Psychological Corporation, London, UK2001
        • Semel E.
        • Wiig E.H.
        • Secord W.
        Clinical evaluation of language fundamentals.
        4th ed. Harcourt Assessment, Marrackville, Australia2006 (Australian standardized)
        • Martin N.
        Test of visual perceptual skills.
        3rd ed. Academic Therapy Publications, Novato, (CA)2006
        • Henderson S.E.
        • Sugden D.A.
        • Barnett A.L.
        Movement assessment battery for children.
        2nd ed. The Psychological Corporation, London, UK2007
      1. The CRIB (Clinical Risk Index for Babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. The International Neonatal Network. Lancet 1993;342:193-8.

        • Roberts G.
        • Howard K.
        • Spittle A.J.
        • Brown N.C.
        • Anderson P.J.
        • Doyle L.W.
        Rates of early intervention services in very preterm children with developmental disabilities at age 2 years.
        J Paediatr Child Health. 2008; 44: 276-280
        • Fenton T.R.
        • Kim J.H.
        A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants.
        BMC Pediatr. 2013; 13: 59
        • Ehrenkranz R.A.
        • Dusick A.M.
        • Vohr B.R.
        • Wright L.L.
        • Wrage L.A.
        • Poole W.K.
        Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants.
        Pediatrics. 2006; 117: 1253-1261
        • Belfort M.B.
        • Rifas-Shiman S.L.
        • Sullivan T.
        • Collins C.T.
        • McPhee A.J.
        • Ryan P.
        • et al.
        Infant growth before and after term: effects on neurodevelopment in preterm infants.
        Pediatrics. 2011; 128: e899-906
        • Pinelli J.
        • Saigal S.
        • Atkinson S.A.
        Effect of breastmilk consumption on neurodevelopmental outcomes at 6 and 12 months of age in VLBW infants.
        Adv Neonatal Care. 2003; 3: 76-87
        • Vohr B.R.
        • Poindexter B.B.
        • Dusick A.M.
        • McKinley L.T.
        • Higgins R.D.
        • Langer J.C.
        • et al.
        Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age.
        Pediatrics. 2007; 120: e953-9
        • Luttikhuizen dos Santos E.S.
        • de Kieviet J.F.
        • Konigs M.
        • van Elburg R.M.
        • Oosterlaan J.
        Predictive value of the Bayley scales of infant development on development of very preterm/very low birth weight children: a meta-analysis.
        Early Hum Dev. 2013; 89: 487-496
        • Hack M.
        • Taylor H.G.
        • Drotar D.
        • Schluchter M.
        • Cartar L.
        • Wilson-Costello D.
        • et al.
        Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age.
        Pediatrics. 2005; 116: 333-341
        • Anderson P.J.
        • Doyle L.W.
        Executive functioning in school-aged children who were born very preterm or with extremely low birth weight in the 1990s.
        Pediatrics. 2004; 114: 50-57
        • Litt J.S.
        • Gerry Taylor H.
        • Margevicius S.
        • Schluchter M.
        • Andreias L.
        • Hack M.
        Academic achievement of adolescents born with extremely low birth weight.
        Acta Paediatr. 2012; 101: 1240-1245
        • Aarnoudse-Moens C.S.
        • Weisglas-Kuperus N.
        • van Goudoever J.B.
        • Oosterlaan J.
        Meta- analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children.
        Pediatrics. 2009; 124: 717-728
        • Anderson P.J.
        Neuropsychological outcomes of children born very preterm.
        Semin Fetal Neonatal Med. 2014; 19: 90-96
        • Roze J.C.
        • Darmaun D.
        • Boquien C.Y.
        • Flamant C.
        • Picaud J.C.
        • Savagner C.
        • et al.
        The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT.
        BMJ Open. 2012; 2: e000834
        • Smith M.M.
        • Durkin M.
        • Hinton V.J.
        • Bellinger D.
        • Kuhn L.
        Influence of breastfeeding on cognitive outcomes at age 6-8 years: follow-up of very low birth weight infants.
        Am J Epidemiol. 2003; 158: 1075-1082
        • Vohr B.R.
        • Poindexter B.B.
        • Dusick A.M.
        • McKinley L.T.
        • Wright L.L.
        • Langer J.C.
        • et al.
        Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age.
        Pediatrics. 2006; 118: e115-23
        • Furman L.
        • Taylor G.
        • Minich N.
        • Hack M.
        The effect of maternal milk on neonatal morbidity of very low-birth-weight infants.
        Arch Pediatr Adolesc Med. 2003; 157: 66-71
        • Alexander G.E.
        • DeLong M.R.
        • Strick P.L.
        Parallel organization of functionally segregated circuits linking basal ganglia and cortex.
        Annu Rev Neurosci. 1986; 9: 357-381
        • Inder T.E.
        • Warfield S.K.
        • Wang H.
        • Hüppi P.S.
        • Volpe J.J.
        Abnormal cerebral structure is present at term in premature infants.
        Pediatrics. 2005; 115: 286-294
        • Lind A.
        • Parkkola R.
        • Lehtonen L.
        • Munck P.
        • Maunu J.
        • Lapinleimu H.
        • et al.
        Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children.
        Pediatr Radiol. 2011; 41: 953-961
        • Zubiaurre-Elorza L.
        • Soria-Pastor S.
        • Junqué C.
        • Fernandez-Espejo D.
        • Segarra D.
        • Bargalló N.
        • et al.
        Thalamic changes in a preterm sample with periventricular leukomalacia: correlation with white-matter integrity and cognitive outcome at school age.
        Pediatr Res. 2012; 71: 354-360
        • Cabeza R.
        • Nyberg L.
        Neural bases of learning and memory: functional neuroimaging evidence.
        Curr Opin Neurol. 2000; 13: 415-421
        • Beauchamp M.H.
        • Thompson D.K.
        • Howard K.
        • Doyle L.W.
        • Egan G.F.
        • Inder T.E.
        • et al.
        Preterm infant hippocampal volumes correlate with later working memory deficits.
        Brain. 2008; 131: 2986-2994
        • Isaacs E.B.
        • Lucas A.
        • Chong W.K.
        • Wood S.J.
        • Johnson C.L.
        • Marshall C.
        • et al.
        Hippocampal volume and everyday memory in children of very low birth weight.
        Pediatr Res. 2000; 47: 713-720
        • American Academy of Pediatrics Section on Breastfeeding
        Breastfeeding and the use of human milk.
        Pediatrics. 2012; 129: e827-41
        • World Health Organization
        Mother's milk for low-birth-weight infants.
        (Accessed November 16, 2016)