Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-26T15:54:08.043Z Has data issue: false hasContentIssue false
  • English
  • Français

Prenatal choline, cannabis, and infection, and their association with offspring development of attention and social problems through 4 years of age

Published online by Cambridge University Press:  25 January 2021

Sharon K. Hunter Open the ORCID record for Sharon K. Hunter [Opens in a new window] ,
M. Camille Hoffman ,
Angelo D'Alessandro ,
Anna Wyrwa ,
Kathleen Noonan ,
Steven H. Zeisel ,
Amanda J. Law  and
Robert Freedman
Sharon K. Hunter*
Affiliation:
Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045, USA
M. Camille Hoffman
Affiliation:
Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045, USA Department of Obstetrics and Gynecology, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
Angelo D'Alessandro
Affiliation:
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA
Anna Wyrwa
Affiliation:
Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045, USA
Kathleen Noonan
Affiliation:
Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045, USA
Steven H. Zeisel
Affiliation:
Departments of Nutrition and Pediatrics, University of North Carolina, Chapel Hill, NC 27599, USA
Amanda J. Law
Affiliation:
Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045, USA Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Robert Freedman
Affiliation:
Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045, USA
*
Author for correspondence: Sharon K. Hunter, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort.

Methods

Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age. Effects of maternal 16 weeks of gestation plasma choline concentrations ⩾7.07 μM, 1 s.d. below the mean level obtained with supplementation in the previous trial, were compared to lower levels. The Attention Problems and Withdrawn Syndrome scales on Child Behavior Checklist 1½–5 were the principal outcomes.

Results

Higher maternal plasma choline was associated with lower mean Attention Problems percentiles in children, and for male children, with lower Withdrawn percentiles. Higher plasma choline concentrations also reduced Attention Problems percentiles for children of mothers who used cannabis during gestation as well as children of mothers who had gestational infection.

Conclusions

Prenatal choline's positive associations with early childhood behaviors are found in a second, more diverse cohort. Increases in attention problems and social withdrawal in early childhood are associated with later mental illnesses including attention deficit disorder and schizophrenia. Choline concentrations in the pregnant women in this study replicate other research findings suggesting that most pregnant women do not have adequate choline in their diets.

Keywords

cholinepregnancycognitioninflammationcannabis
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 14 , October 2022 , pp. 3019 - 3028
Check for updates
Copyright
Copyright © The Author(s) 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abratte, C. M., Wang, W., Li, R., Axume, J., Moriarty, D. J., & Caudill, M. A. (2009). Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women. Journal of Nutritional Biochemistry, 20(1), 62–69. https://doi.org/10.1016/j.jnutbio.2007.12.002CrossRefGoogle Scholar
Achenbach, T. M., & Rescorla, L. (2000). Manual for the ASEBA preschool forms & profiles: An integrated system of multi-informant assessment. Burlington, VT: ASEBA.Google Scholar
ACOG (American College of Obstetricians and Gynecologists). (2017). Society for Maternal-Fetal Medicine. Guidance 700: Methods for Estimating the Due Date. Retrieved April 1, 2020, from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/methods-for-estimating-the-due-dateGoogle Scholar
Albright, C. D., Tsai, A. Y., Friedrich, C. B., Mar, M. H., & Zeisel, S. H. (1999). Choline availability alters embryonic development of the hippocampus and septum in the rat. Brain Research: Developmental Brain Research, 113(1–2), 13–20. https://doi.org/10.1016/S0165-3806(98)00183-7CrossRefGoogle ScholarPubMed
Ballard, M. S., Sun, M., & Ko, J. (2012). Vitamin A, folate, and choline as a possible preventive intervention to fetal alcohol syndrome. Medical Hypotheses, 78(4), 489–493. https://doi.org/10.1016/j.mehy.2012.01.014CrossRefGoogle ScholarPubMed
Baumgartner, H. K., Trinder, K. M., Galimanis, C. E., Post, A., Phang, T., Ross, R. G., & Winn, V. D. (2015). Characterization of choline transporters in the human placenta over gestation. Placenta, 36(12), 1362–1369. https://doi.org/10.1016/j.placenta.2015.10.001CrossRefGoogle ScholarPubMed
Birnbaum, R., Jaffe, A. E., Hyde, T. M., Kleinman, J. E., & Weinberger, D. R. (2014). Prenatal expression patterns of genes associated with neuropsychiatric disorders. American Journal of Psychiatry, 171(7), 758–767. https://doi.org/10.1176/appi.ajp.2014.13111452CrossRefGoogle ScholarPubMed
Boeke, C. E., Gillman, M. W., Hughes, M. D., Rifas-Shiman, S. L., Villamor, E., & Oken, E. (2013). Choline intake during pregnancy and child cognition at age 7 years. American Journal of Epidemiology, 177(12), 1338–1347. https://doi.org/10.1093/aje/kws395CrossRefGoogle ScholarPubMed
Brown, A. S., & Derkits, E. J. (2010). Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. American Journal of Psychiatry, 167(3), 261–280. https://doi.org/10.1176/appi.ajp.2009.09030361CrossRefGoogle ScholarPubMed
Cassidy, C. M., Joober, R., King, S., & Malla, A. K. (2011). Childhood symptoms of inattention-hyperactivity predict cannabis use in first episode psychosis. Schizophrenia Research, 132(2–3), 171–176. https://doi.org/10.1016/j.schres.2011.06.027CrossRefGoogle ScholarPubMed
Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., & Canfield, R. L. (2018). Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: A randomized, double-blind, controlled feeding study. The FASEB Journal, 32(4), 2172–2180. https://doi.org/10.1096/fj.201700692RRCrossRefGoogle Scholar
Centers for Disease Control and Prevention. (2020). If You Are Pregnant, Breastfeeding, or Caring for Young Children. Retrieved August 3, 2020, from CDC website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/pregnancy-breastfeeding.htmlGoogle Scholar
Cheatham, C. L., Goldman, B. D., Fischer, L. M., da Costa, K.-A. A., Reznick, J. S., & Zeisel, S. H. (2012). Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: A randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition, 96(6), 1465–1472. https://doi.org/10.3945/ajcn.112.037184CrossRefGoogle Scholar
Court, J. A., Lloyd, S., Johnson, M., Griffiths, M., Birdsall, N. J. M., Piggott, M. A., … Perry, R. H. (1997). Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging. Developmental Brain Research, 101(1–2), 93–105. https://doi.org/10.1016/S0165-3806(97)00052-7CrossRefGoogle ScholarPubMed
Descarries, L., Aznavour, N., & Hamel, E. (2005). The acetylcholine innervation of cerebral cortex: New data on its normal development and its fate in the hAPPSW,IND mouse model of Alzheimer's disease. Journal of Neural Transmission, 112(1), 149–162. https://doi.org/10.1007/s00702-004-0186-zCrossRefGoogle ScholarPubMed
Erlenmeyer-Kimling, L., & Cornblatt, B. (1987). The New York high-risk project: A followup report. Schizophrenia Bulletin, 13(3), 451–461. https://doi.org/https://doi.org/10.1093/schbul/13.3.451CrossRefGoogle Scholar
Fischer, L. M., da Costa, K. A., Galanko, J., Sha, W., Stephenson, B., Vick, J., & Zeisel, S. H. (2010). Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma. American Journal of Clinical Nutrition, 92(2), 336–346. https://doi.org/10.3945/ajcn.2010.29459CrossRefGoogle ScholarPubMed
Food and Drug Administration. (2016). Food labeling: Revision of the nutrition and supplement facts labels. Federal Register, 81 (May 27), 903–904. Retrieved from https://www.federalregister.gov/documents/2016/05/27/2016-11867/food-labeling-revision-of-the-nutrition-and-supplement-facts-labelsGoogle Scholar
Frazier, C. J., Rollins, Y. D., Breese, C. R., Leonard, S., Freedman, R., & Dunwiddie, T. V. (1998). Acetylcholine activates an α-bungarotoxin-sensitive nicotinic current in rat hippocampal interneurons, but not pyramidal cells. Journal of Neuroscience, 18(4), 1187–1195. https://doi.org/10.1523/jneurosci.18-04-01187.1998CrossRefGoogle Scholar
Freedman, R., Hunter, S. K., Law, A. J., Wagner, B. D., D'Alessandro, A., Christians, U., … Hoffman, M. C. (2019). Higher gestational choline levels in maternal infection are protective for infant brain development. The Journal of Pediatrics, 208, 198–206, e2. https://doi.org/10.1016/j.jpeds.2018.12.010CrossRefGoogle ScholarPubMed
Gartstein, M. A., Putnam, S., & Kliewer, R. (2016). Do infant temperament characteristics predict core academic abilities in preschool-aged children? Learning and Individual Differences, 45, 299–306. https://doi.org/10.1016/j.lindif.2015.12.022CrossRefGoogle ScholarPubMed
Gartstein, M. A., & Rothbart, M. K. (2003). Studying infant temperament via the revised infant behavior questionnaire. Infant Behavior and Development, 26(1), 64–86. https://doi.org/10.1016/S0163-6383(02)00169-8CrossRefGoogle Scholar
Goff, W. R., Williamson, P. D., VanGilder, J. C., Allison, T., & Fisher, T. C. (1980). Neural origins of long latency evoked potentials recorded from the depth and from the cortical surface of the brain in man. Progress in Clinical Neurophysiology, 7, 126–145.Google Scholar
Gossell-Williams, M., Fletcher, H., McFarlane-Anderson, N., Jacob, A., & Zeisel, S. (2005). Dietary intake of choline and plasma choline concentrations in pregnant women in Jamaica. West Indian Medical Journal, 54(6), 355–359.CrossRefGoogle ScholarPubMed
Hamilton, H. K., Williams, T. J., Ventura, J., Jasperse, L. J., Owens, E. M., Miller, G. A., … Yee, C. M. (2018). Clinical and cognitive significance of auditory sensory processing deficits in schizophrenia. American Journal of Psychiatry, 175(3), 275–283. https://doi.org/10.1176/appi.ajp.2017.16111203CrossRefGoogle ScholarPubMed
Hoffman, M. C., Hunter, S. K., D'Alessandro, A., Noonan, K., Wyrwa, A., & Freedman, R. (2020). Interaction of maternal choline levels and prenatal Marijuana's effects on the offspring. Psychological Medicine, 50(10), 1716–1726. https://doi.org/10.1017/S003329171900179XCrossRefGoogle ScholarPubMed
Hyde, T. M., Lipska, B. K., Ali, T., Mathew, S. V, Law, A. J., Metitiri, O. E., … Kleinman, J. E. (2011). Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. The Journal of Neuroscience, 31(30), 11088–11095. Retrieved from http://www.jneurosci.org/content/31/30/11088.abstractCrossRefGoogle ScholarPubMed
Jacobson, S. W., Carter, R. C., Molteno, C. D., Stanton, M. E., Herbert, J. S., Lindinger, N. M., … Jacobson, J. L. (2018). Efficacy of maternal choline supplementation during pregnancy in mitigating adverse effects of prenatal alcohol exposure on growth and cognitive function: A randomized, double-blind, placebo-controlled clinical trial. Alcoholism: Clinical and Experimental Research, 42(7), 1327–1341. https://doi.org/10.1111/acer.13769CrossRefGoogle ScholarPubMed
Jensen, H. H., Batres-Marquez, S. P., Carriquiry, A., & Schalinske, K. L. (2007). Choline in the diets of the US population: NHANES, 2003-2004. Federation of American Societies for Experimental Biology, 21(6), LB46–LB46.Google Scholar
Leppert, B., Havdahl, A., Riglin, L., Jones, H. J., Zheng, J., Davey Smith, G., … Stergiakouli, E. (2019). Association of maternal neurodevelopmental risk alleles with early-life exposures. JAMA Psychiatry, 76(8), 834. https://doi.org/10.1001/jamapsychiatry.2019.0774CrossRefGoogle ScholarPubMed
Liu, Z., Neff, R. A., & Berg, D. K. (2006). Sequential interplay of nicotinic and GABAergic signaling guides neuronal development. Science, 314(5805), 1610–1613. https://doi.org/10.1126/science.1134246CrossRefGoogle ScholarPubMed
Masih, S. P., Plumptre, L., Ly, A., Berger, H., Lausman, A. Y., Croxford, R., … O'Connor, D. L. (2015). Pregnant Canadian women achieve recommended intakes of one-carbon nutrients through prenatal supplementation but the supplement composition, including choline, requires reconsideration. Journal of Nutrition, 145(8), 1824–1834. https://doi.org/10.3945/jn.115.211300CrossRefGoogle ScholarPubMed
Matheson, S. L., Vijayan, H., Dickson, H., Shepherd, A. M., Carr, V. J., & Laurens, K. R. (2013). Systematic meta-analysis of childhood social withdrawal in schizophrenia, and comparison with data from at-risk children aged 9-14 years. Journal of Psychiatric Research, 47(8), 1061–1068. https://doi.org/10.1016/j.jpsychires.2013.03.013CrossRefGoogle ScholarPubMed
McGrath, J. J., Eyles, D. W., Pedersen, C. B., Anderson, C., Ko, P., Burne, T. H., … Mortensen, P. B. (2010). Neonatal vitamin D status and risk of schizophrenia: A population-based case-control study. Archives of General Psychiatry, 67(9), 889–894. https://doi.org/10.1001/archgenpsychiatry.2010.110CrossRefGoogle ScholarPubMed
Mednick, S. A., Machon, R. A., Huttunen, M. O., & Bonett, D. (1988). Adult schizophrenia following prenatal exposure to an influenza epidemic. Archives of General Psychiatry, 45(2), 189–192. https://doi.org/10.1001/archpsyc.1988.01800260109013CrossRefGoogle Scholar
Miller, C. L., & Freedman, R. (1995). The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated auditory stimuli. Neuroscience, 69(2), 371–381. https://doi.org/10.1016/0306-4522(95)00249-ICrossRefGoogle ScholarPubMed
Morales, M., Hein, K., & Vogel, Z. (2008). Hippocampal interneurons co-express transcripts encoding the α7 nicotinic receptor subunit and the cannabinoid receptor 1. Neuroscience, 152(1), 70–81. https://doi.org/10.1016/j.neuroscience.2007.12.019CrossRefGoogle ScholarPubMed
Orczyk-Pawilowicz, M., Jawien, E., Deja, S., Hirnle, L., Zabek, A., & Mlynarz, P. (2016). Metabolomics of human amniotic fluid and maternal plasma during normal pregnancy. PLOS ONE, 11(4), e0152740. https://doi.org/10.1371/journal.pone.0152740CrossRefGoogle ScholarPubMed
Riglin, L., Collishaw, S., Richards, A., Thapar, A. K., Maughan, B., O'Donovan, M. C., & Thapar, A. (2017). Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: A population-based cohort study. The Lancet Psychiatry, 4(1), 57–62. https://doi.org/10.1016/S2215-0366(16)30406-0CrossRefGoogle ScholarPubMed
Roncero, C., Valriberas-Herrero, I., Mezzatesta-Gava, M., Villegas, J. L., Aguilar, L., & Grau-López, L. (2020). Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders. A systematic review. Reproductive Health, 17(1), 25. https://doi.org/10.1186/s12978-020-0880-9CrossRefGoogle ScholarPubMed
Ross, R. G., Hunter, S. K., Hoffman, M. C., McCarthy, L., Chambers, B. M., Law, A. J., … Freedman, R. (2016). Perinatal phosphatidylcholine supplementation and early childhood behavior problems: Evidence for CHRNA7 moderation. American Journal of Psychiatry, 173(5), 509–516. https://doi.org/10.1176/appi.ajp.2015.15091188CrossRefGoogle ScholarPubMed
Ross, R. G., Hunter, S. K., McCarthy, L., Beuler, J., Hutchison, A. K., Wagner, B. D., … Freedman, R. (2013). Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. American Journal of Psychiatry, 170(3), 290–298. https://doi.org/10.1176/appi.ajp.2012.12070940CrossRefGoogle ScholarPubMed
Rossi, A., Pollice, R., Daneluzzo, E., Marinangeli, M. G., & Stratta, P. (2000). Behavioral neurodevelopment abnormalities and schizophrenic disorder: A retrospective evaluation with the Childhood Behavior Checklist (CBCL). Schizophrenia Research, 44(2), 121–128. https://doi.org/10.1016/S0920-9964(99)00223-6CrossRefGoogle ScholarPubMed
Roza, S. J., Van Batenburg-Eddes, T., Steegers, E. A. P., Jaddoe, V. W. V., MacKenbach, J. P., Hofman, A., … Tiemeier, H. (2010). Maternal folic acid supplement use in early pregnancy and child behavioural problems: The generation R Study. British Journal of Nutrition, 103(3), 445–452. https://doi.org/10.1017/S0007114509991954CrossRefGoogle ScholarPubMed
Susser, E. S., & Lin, S. P. (1992). Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944–1945. Archives of General Psychiatry, 49(12), 983–988. https://doi.org/10.1001/archpsyc.1992.01820120071010CrossRefGoogle Scholar
Vasistha, N. A., Pardo-Navarro, M., Gasthaus, J., Weijers, D., Müller, M. K., García-González, D., … Khodosevich, K. (2019). Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner. Molecular Psychiatry, 25(10), 2313–2329. https://doi.org/10.1038/s41380-019-0539-5Google Scholar
Volkow, N. D., Han, B., Compton, W. M., & McCance-Katz, E. F. (2019). Self-reported medical and nonmedical cannabis use among pregnant women in the United States. JAMA, 322(2), 167–169. https://doi.org/http://dx.doi.org/10.1001/jama.2019.7982CrossRefGoogle ScholarPubMed
Wald, N., Sneddon, J., Densem, J., Frost, C., & Stone, R. (1992). Prevention of neural tube defects: Results of the medical research council vitamin study. International Journal of Gynecology & Obstetrics, 338(8760), 131–137. https://doi.org/10.1016/0020-7292(92)90076-uGoogle Scholar
Walker, E. F., Savoie, T., & Davis, D. (1994). Neuromotor precursors of schizophrenia. Schizophrenia Bulletin, 20(3), 441–451. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7526446CrossRefGoogle ScholarPubMed
Wan, L., Friedman, B. H., Boutros, N. N., & Crawford, H. J. (2008). P50 sensory gating and attentional performance. International Journal of Psychophysiology, 67, 91–100. https://doi.org/10.1016/j.ijpsycho.2007.10.008CrossRefGoogle ScholarPubMed
Wu, W. L., Adams, C. E., Stevens, K. E., Chow, K. H., Freedman, R., & Patterson, P. H. (2015). The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring. Brain, Behavior, and Immunity, 46, 192–202. https://doi.org/10.1016/j.bbi.2015.02.005CrossRefGoogle ScholarPubMed
Wu, B. T. F., Dyer, R. A., King, D. J. J., Richardson, K. J., & Innis, S. M. (2012). Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS ONE, 7(8), e43448. https://doi.org/10.1371/journal.pone.0043448CrossRefGoogle ScholarPubMed
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., Ogshea, D. J., … Deisseroth, K. (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature, 477(7363), 171–178. https://doi.org/10.1038/nature10360CrossRefGoogle ScholarPubMed
Zeisel, S. H. (2000). Choline: Needed for normal development of memory. Journal of the American College of Nutrition, 19, 528S–531S. https://doi.org/10.1080/07315724.2000.10718976CrossRefGoogle ScholarPubMed
Zeisel, S. H. (2006a). Choline: Critical role during fetal development and dietary requirements in adults. Annual Review of Nutrition, 26, 229–250. https://doi.org/10.1146/annurev.nutr.26.061505.111156CrossRefGoogle ScholarPubMed
Zeisel, S. H. (2006b). The fetal origins of memory: The role of dietary choline in optimal brain development. Journal of Pediatrics, 149(Suppl. 5), S131–S136. https://doi.org/10.1016/j.jpeds.2006.06.065CrossRefGoogle ScholarPubMed
Zeisel, S. H., & da Costa, K. A. (2009). Choline: An essential nutrient for public health. Nutrition Reviews, 67(11), 615–623. https://doi.org/10.1111/j.1753-4887.2009.00246.xCrossRefGoogle ScholarPubMed
Zeisel, S. H., Epstein, M. F., & Wurtman, R. J. (1980). Elevated choline concentration in neonatal plasma. Life Sciences, 26(21), 1827–1831. https://doi.org/10.1016/0024-3205(80)90585-8CrossRefGoogle ScholarPubMed
Zeisel, S. H., Growden, J. H., Wurtman, R. J., Magil, S. G., Logue, M., Growdon, J. H., … Logue, M. (1980). Normal plasma choline responses to ingested lecitin. Neurology, 30(11), 1226–1229. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7191517CrossRefGoogle Scholar
Supplementary material: File

Hunter et al. supplementary material

Tables S1-S6

Download Hunter et al. supplementary material(File)
File 33.4 KB
Supplementary material: File

Hunter et al. supplementary material

Hunter et al. supplementary material

Download Hunter et al. supplementary material(File)
File 264.5 KB