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Determinants of neonatal brain-derived neurotrophic factor and association with child development

Published online by Cambridge University Press:  02 May 2017

Akhgar Ghassabian ,
Rajeshwari Sundaram ,
Nikhita Chahal ,
Alexander C. McLain ,
Erin Bell ,
David A. Lawrence  and
Edwina H. Yeung
Akhgar Ghassabian
Affiliation:
National Institutes of Health
Rajeshwari Sundaram
Affiliation:
National Institutes of Health
Nikhita Chahal
Affiliation:
National Institutes of Health
Alexander C. McLain
Affiliation:
University of South Carolina
Erin Bell
Affiliation:
Albany School of Public Health
David A. Lawrence
Affiliation:
Albany School of Public Health Wadsworth Center
Edwina H. Yeung*
Affiliation:
National Institutes of Health
*
Address correspondence and reprint requests to: Edwina Yeung, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Boulevard, 7B03, Bethesda, MD 20892; E-mail: [email protected].
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Abstract

Using a population-based birth cohort in upstate New York (2008–2010), we examined the determinants of brain-derived neurotrophic factor (BDNF) measured in newborn dried blood spots (n = 2,637). We also examined the association between neonatal BDNF and children's development. The cohort was initially designed to examine the influence of infertility treatment on child development but found no impact. Mothers rated children's development in five domains repeatedly through age 3 years. Socioeconomic and maternal lifestyle determinants of BDNF were examined using multivariable linear regression models. Generalized linear mixed models estimated odds ratios for neonatal BDNF in relation to failing a developmental domain. Smoking and drinking in pregnancy, nulliparity, non-White ethnicity/race, and prepregnancy obesity were associated with lower neonatal BDNF. Neonatal BDNF was not associated with failure for developmental domains; however, there was an interaction between BDNF and preterm birth. In preterm infants, a higher BDNF was associated with lower odds of failing any developmental domains, after adjusting for confounders and infertility treatment. This result was particularly significant for failure in communication. Our findings suggest that BDNF levels in neonates may be impacted by maternal lifestyle characteristics. More specifically, lower neonatal BDNF might be an early marker of aberrant neurodevelopment in preterm infants.

Type
Regular Articles
Information
Development and Psychopathology , Volume 29 , Issue 4 , October 2017 , pp. 1499 - 1511
Creative Commons
This is a work of the US Government and is not subject to copyright protection in the United States.
Copyright
Copyright © Cambridge University Press 2017

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Footnotes

This research was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts HHSN275201200005C and HHSN267200700019C). The authors thank all the Upstate KIDS families and staff for their important contributions.

References

Abdallah, M. W., Mortensen, E. L., Greaves-Lord, K., Larsen, N., Bonefeld-Jørgensen, E. C., Nørgaard-Pedersen, B., … Grove, J. (2013). Neonatal levels of neurotrophic factors and risk of autism spectrum disorders. Acta Psychiatrica Scandinavica, 128, 61–69.Google Scholar
Barde, Y. A. (1990). The nerve growth factor family. Progress in Growth Factor Research, 2, 237–248.Google Scholar
Boschen, K. E., Criss, K. J., Palamarchouk, V., Roth, T. L., & Klintsova, A. Y. (2015). Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats. International Journal of Developmental Neuroscience, 43, 16–24.CrossRefGoogle ScholarPubMed
Braithwaite, E. C., Kundakovic, M., Ramchandani, P. G., Murphy, S. E., & Champagne, F. A. (2015). Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics, 10, 408–417.Google Scholar
Buck Louis, G. M., Hediger, M. L., Bell, E. M., Kus, C. A., Sundaram, R., McLain, A. C., … Druschel, C. M. (2014). Methodology for establishing a population-based birth cohort focusing on couple fertility and children's development, the Upstate KIDS Study. Paediatric and Perinatal Epidemiology, 28, 191–202.CrossRefGoogle ScholarPubMed
Bus, B. A., Molendijk, M. L., Penninx, B. J., Buitelaar, J. K., Kenis, G., Prickaerts, J., … Voshaar, R. C. (2011). Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology, 36, 228–239.Google Scholar
Chouthai, N. S., Sampers, J., Desai, N., & Smith, G. M. (2003). Changes in neurotrophin levels in umbilical cord blood from infants with different gestational ages and clinical conditions. Pediatric Research, 53, 965–969.CrossRefGoogle ScholarPubMed
Connolly, A. M., Chez, M., Streif, E. M., Keeling, R. M., Golumbek, P. T., Kwon, J. M., … Deuel, R. M. (2006). Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biological Psychiatry, 59, 354–363.CrossRefGoogle ScholarPubMed
Croen, L. A., Goines, P., Braunschweig, D., Yolken, R., Yoshida, C. K., Grether, J. K., … Van de Water, J. (2008). Brain-derived neurotrophic factor and autism: Maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study. Autism Research, 1, 130–137.Google Scholar
Fitzmaurice, G., Laird, N., & Ware, J. (2004) Applied longitudinal analysis. New York: Wiley.Google Scholar
Flock, A., Weber, S. K., Ferrari, N., Fietz, C., Graf, C., Fimmers, R., … Merz, W. M. (2015). Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum. Psychoneuroendocrinology, 63, 191–197.CrossRefGoogle ScholarPubMed
Gollenberg, A. L., Lynch, C. D., Jackson, L. W., McGuinness, B. M., & Msall, M. E. (2010). Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. with the Bayley Scales of Infant Development II in a low-risk sample. Child: Care, Health and Development, 36, 485–490.CrossRefGoogle Scholar
Guevara, J. P., Gerdes, M., Localio, R., Huang, Y. V., Pinto-Martin, J., Minkovitz, C. S., … Pati, S. (2013). Effectiveness of developmental screening in an urban setting. Pediatrics, 131, 30–37.Google Scholar
Harrod, S. B., Lacy, R. T., Zhu, J., Hughes, B. A., Perna, M. K., & Brown, R. W. (2011). Gestational IV nicotine produces elevated brain-derived neurotrophic factor in the mesocorticolimbic dopamine system of adolescent rat offspring. Synapse, 65, 1382–1392.CrossRefGoogle ScholarPubMed
Heaton, M. B., Mitchell, J. J., Paiva, M., & Walker, D. W. (2000). Ethanol-induced alterations in the expression of neurotrophic factors in the developing rat central nervous system. Brain Research. Developmental Brain Research, 121, 97–107.CrossRefGoogle ScholarPubMed
Janke, K. L., Cominski, T. P., Kuzhikandathil, E. V., Servatius, R. J., & Pang, K. C. (2015). Investigating the role of hippocampal BDNF in anxiety vulnerability using classical eyeblink conditioning. Frontiers in Psychiatry, 6, 106.CrossRefGoogle ScholarPubMed
Jo, H., Schieve, L. A., Sharma, A. J., Hinkle, S. N., Li, R., & Lind, J. N. (2015). Maternal prepregnancy body mass index and child psychosocial development at 6 years of age. Pediatrics, 135, e1198–e1209.Google Scholar
Johnson, W. E., Li, C., & Rabinovic, A. (2007). Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics, 8, 118–127.CrossRefGoogle ScholarPubMed
Kanoski, S. E., & Grill, H. J. (2015). Hippocampus contributions to food intake control: Mnemonic, neuroanatomical, and endocrine mechanisms. Biological Psychiatry. Advance online publication. doi:10.1016/j.biopsych.2015.09.011 Google Scholar
Karege, F., Schwald, M., & Cisse, M. (2002). Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neuroscience Letters, 328, 261–264.Google Scholar
Landa, R. J., Stuart, E. A., Gross, A. L., & Faherty, A. (2013). Developmental trajectories in children with and without autism spectrum disorders: The first 3 years. Child Development, 84, 429–442.Google Scholar
Lee, B.-H., & Kim, Y.-K. (2010). The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investigation, 7, 231–235.Google Scholar
Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E., & Storey, J. D. (2012). The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics, 28, 882–883.Google Scholar
Lommatzsch, M., Schloetcke, K., Klotz, J., Schuhbaeck, K., Zingler, D., Zingler, C., … Virchow, J. C. (2005). Brain-derived neurotrophic factor in platelets and airflow limitation in asthma. American Journal of Respiratory and Critical Care Medicine, 171, 115–120.CrossRefGoogle ScholarPubMed
McDade, T., Williams, S., & Snodgrass, J. J. (2007). What a drop can do: Dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography, 44, 899–925.Google Scholar
Molenberghs, G., & Verbeke, G. (2006). Models for discrete longitudinal data. New York: Springer Science & Business Media.Google Scholar
Molendijk, M. L., Spinhoven, P., Polak, M., Bus, B. A., Penninx, B. W., & Elzinga, B. M. (2014). Serum BDNF concentrations as peripheral manifestations of depression: Evidence from a systematic review and meta-analyses on 179 associations (N = 9484). Molecular Psychiatry, 19, 791–800.Google Scholar
Mou, Z., Hyde, T. M., Lipska, B. K., Martinowich, K., Wei, P., Ong, C. J., … Han, J. C. (2015). Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus. Cell Reports, 13, 1073–1080.Google Scholar
Mueller, S. C., Aouidad, A., Gorodetsky, E., Goldman, D., Pine, D. S., & Ernst, M. (2013). Gray matter volume in adolescent anxiety: An impact of the brain-derived neurotrophic factor Val(66)Met polymorphism? Journal of American Academy of Child & Adolescent Psychiatry, 52, 184–195.CrossRefGoogle ScholarPubMed
Nelson, K. B., Grether, J. K., Croen, L. A., Dambrosia, J. M., Dickens, B. F., Jelliffe, L. L., … Phillips, T. M. (2001). Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Annals of Neurology, 49, 597–606.CrossRefGoogle ScholarPubMed
Nelson, P. G., Kuddo, T., Song, E. Y., Dambrosia, J. M., Kohler, S., Satyanarayana, G., … Nelson, K. B. (2006). Selected neurotrophins, neuropeptides, and cytokines: Developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome. International Journal of Developmental Neuroscience, 24, 73–80.Google Scholar
Nickl-Jockschat, T., & Michel, T. M. (2011). The role of neurotrophic factors in autism. Molecular Psychiatry, 16, 478–490.CrossRefGoogle ScholarPubMed
Prickaerts, J., Gieling, E. T., Bruder, A. K., van der Staay, F. J., & Vanmierlo, T. (2014). Long-term effects of prenatal allopurinol treatment on brain plasticity markers in low and normal birth weight piglets. International Journal of Developmental Neuroscience, 33, 29–32.Google Scholar
Primiani, C. T., Ryan, V. H., Rao, J. S., Cam, M. C., Ahn, K., Modi, H. R., & Rapoport, S. I. (2014). Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging. PLOS ONE, 9, e110972.CrossRefGoogle ScholarPubMed
Qin, X. Y., Feng, J. C., Cao, C., Wu, H. T., Loh, Y. P., & Cheng, Y. (2016). Association of peripheral blood levels of brain-derived neurotrophic factor with autism spectrum disorder in children: A systematic review and meta-analysis. JAMA Pediatrics, 170, 1079–1086.Google Scholar
Reiner, O., Karzburn, E., Kshirsagar, A., & Kaibuchi, K. (2016). Regulation of neuronal migration, an emerging topic in autism spectrum disorders (ASD). Journal of Neurochemistry, 136, 440–456.CrossRefGoogle Scholar
Ringstedt, T., Linnarsson, S., Wagner, J., Lendahl, U., Kokaia, Z., Arenas, E., … Ibanez, C. F. (1998). BDNF regulates reelin expression and Cajal-Retzius cell development in the cerebral cortex. Neuron, 21, 305–315.CrossRefGoogle ScholarPubMed
Roth, T. L., Matt, S., Chen, K., & Blaze, J. (2014). Bdnf DNA methylation modifications in the hippocampus and amygdala of male and female rats exposed to different caregiving environments outside the homecage. Developmental Psychobiology, 56, 1755–1763.Google Scholar
Rothman, K. J., Greenland, S., & Lash, T. L. (2008). Modern epidemiology. Philadelphia, PA: Lippincott, Williams & Wilkins.Google Scholar
Schisterman, E. F., Vexler, A., Whitcomb, B. W., & Liu, A. (2006). The limitations due to exposure detection limits for regression models. American Journal of Epidemiology, 163, 374–383.Google Scholar
Schonhaut, L., Armijo, I., Schonstedt, M., Alvarez, J., & Cordero, M. (2013). Validity of the ages and stages questionnaires in term and preterm infants. Pediatrics, 131, e1468–e1474.CrossRefGoogle ScholarPubMed
Skogstrand, K., Ekelund, C. K., Thorsen, P., Vogel, I., Jacobsson, B., Nørgaard-Pedersen, B., & Hougaard, D. M. (2008). Effects of blood sample handling procedures on measurable inflammatory markers in plasma, serum and dried blood spot samples. Journal of Immunological Methods, 336, 78–84.Google Scholar
Skovgaard, A. M., Olsen, E. M., Christiansen, E., Houmann, T., Landorph, S. L., & Jorgensen, T. (2008). Predictors (0–10 months) of psychopathology at age 11/2 years—A general population study in the Copenhagen Child Cohort CCC 2000. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 49, 553–562.Google Scholar
Spulber, S., Rantamaki, T., Nikkila, O., Castren, E., Weihe, P., Grandjean, P., & Ceccatelli, S. (2010). Effects of maternal smoking and exposure to methylmercury on brain-derived neurotrophic factor concentrations in umbilical cord serum. Toxicological Sciences, 117, 263–269.CrossRefGoogle ScholarPubMed
Squires, J., & Bricker, D. (2009). Ages & Stages Questionnaires [R], (ASQ-3 [TM]): A parent-completed child-monitoring system. Baltimore, MD: Brookes.Google Scholar
Squires, J., Potter, L., & Bricker, D. (1999). The ASQ user's guide for the Ages & Stages Questionnaires: A parent-completed, child-monitoring system. Baltimore, MD: Brookes.Google Scholar
Tozuka, Y., Kumon, M., Wada, E., Onodera, M., Mochizuki, H., & Wada, K. (2010). Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring. Neurochemistry International, 57, 235–247.Google Scholar
Uguz, F., Sonmez, E. O., Sahingoz, M., Gokmen, Z., Basaran, M., Gezginc, K., … Tasyurek, E. (2013). Maternal generalized anxiety disorder during pregnancy and fetal brain development: A comparative study on cord blood brain-derived neurotrophic factor levels. Journal of Psychosomatic Research, 75, 346–350.CrossRefGoogle ScholarPubMed
Van den Hove, D. L., Steinbusch, H. W., Scheepens, A., Van de Berg, W. D., Kooiman, L. A., Boosten, B. J., … Blanco, C. E. (2006). Prenatal stress and neonatal rat brain development. Neuroscience, 137, 145–155.Google Scholar
Van Lieshout, R. J. (2013). Role of maternal adiposity prior to and during pregnancy in cognitive and psychiatric problems in offspring. Nutrition Reviews, 71(Suppl. 1), S95–S101.CrossRefGoogle ScholarPubMed
Vega, S. R., Kleinert, J., Sulprizio, M., Hollmann, W., Bloch, W., & Struder, H. K. (2011). Responses of serum neurotrophic factors to exercise in pregnant and postpartum women. Psychoneuroendocrinology, 36, 220–227.Google Scholar
Wang, M., Chen, H., Yu, T., Cui, G., Jiao, A., & Liang, H. (2015). Increased serum levels of brain-derived neurotrophic factor in autism spectrum disorder. NeuroReport, 26, 638–641.CrossRefGoogle ScholarPubMed
Ward, N. L., & Hagg, T. (2000). BDNF is needed for postnatal maturation of basal forebrain and neostriatum cholinergic neurons in vivo. Experimental Neurology, 162, 297–310.Google Scholar
Weickert, C. S., Hyde, T. M., Lipska, B. K., Herman, M. M., Weinberger, D. R., & Kleinman, J. E. (2003). Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Molecular Psychiatry, 8, 592–610.Google Scholar
Wiebe, S. A., Clark, C. A., De Jong, D. M., Chevalier, N., Espy, K. A., & Wakschlag, L. (2015). Prenatal tobacco exposure and self-regulation in early childhood: Implications for developmental psychopathology. Development and Psychopathology, 27, 397–409.Google Scholar
Yeung, E., Buck Louis, G. M, Lawrence, D., Kannan, K., McLain, A. C., Caggana, M., … Bell, E. (2016). Eliciting parental support for the use of newborn blood spots for pediatric research. BMC Medical Research Methodology, 16, 14.Google Scholar
Yeung, E., Sundaram, R., Bell, E. M., Druschel, C., Kus, C., Ghassabian, A., … Buck Louis, G. M. (2016). Examining infertility treatment and early childhood development in the Upstate KIDS Study. JAMA Pediatrics, 170, 251–258.Google Scholar
Yeung, E., Sundaram, R., Ghassabian, A., Xie, Y., & Buck Louis, G. M. (in press). Parental obesity and early childhood development. Pediatrics.Google Scholar
Yirmiya, N., & Charman, T. (2010). The prodrome of autism: Early behavioral and biological signs, regression, peri- and post-natal development and genetics. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 51, 432–458.CrossRefGoogle ScholarPubMed
Yochum, C., Doherty-Lyon, S., Hoffman, C., Hossain, M. M., Zelikoff, J. T., & Richardson, J. R. (2014). Prenatal cigarette smoke exposure causes hyperactivity and aggressive behavior: Role of altered catecholamines and BDNF. Experimental Neurology, 254, 145–152.Google Scholar
Yu, X., Chen, L., Wang, C., Yang, X., Gao, Y., & Tian, Y. (2016). The role of cord blood BDNF in infant cognitive impairment induced by low-level prenatal manganese exposure: LW birth cohort, China. Chemosphere, 163, 446–451.CrossRefGoogle ScholarPubMed