Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T05:22:22.303Z Has data issue: false hasContentIssue false
  • English
  • Français

Interaction of maternal choline levels and prenatal Marijuana's effects on the offspring

Published online by Cambridge University Press:  31 July 2019

M. Camille Hoffman ,
Sharon K. Hunter ,
Angelo D'Alessandro ,
Kathleen Noonan ,
Anna Wyrwa  and
Robert Freedman Open the ORCID record for Robert Freedman [Opens in a new window]
M. Camille Hoffman
Affiliation:
Department of Obstetrics and Gynecology, Division of Maternal and Fetal Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA Department of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Sharon K. Hunter
Affiliation:
Department of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Angelo D'Alessandro
Affiliation:
Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Kathleen Noonan
Affiliation:
Department of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Anna Wyrwa
Affiliation:
Department of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Robert Freedman*
Affiliation:
Department of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
*
Author for correspondence: Robert Freedman, E-mail: Robert.freedman@ucdenver.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors.

Methods

Marijuana use was assessed during pregnancy from women who later brought their newborns for study. Mothers were informed about choline and other nutrients, but not specifically for marijuana use. Maternal serum choline was measured at 16 weeks gestation.

Results

Marijuana use for the first 10 weeks gestation or more by 15% of mothers decreased newborns' inhibition of evoked potentials to repeated sounds (d’ = 0.55, p < 0.05). This effect was ameliorated if women had higher gestational choline (rs = −0.50, p = 0.011). At 3 months of age, children whose mothers continued marijuana use through their 10th gestational week or more had poorer self-regulation (d’ = −0.79, p < 0.05). This effect was also ameliorated if mothers had higher gestational choline (rs = 0.54, p = 0.013). Maternal choline levels correlated with the children's improved duration of attention, cuddliness, and bonding with parents.

Conclusions

Prenatal marijuana use adversely affects fetal brain development and subsequent behavioral self-regulation, a precursor to later, more serious problems in childhood. Stopping marijuana use before 10 weeks gestational age prevented these effects. Many mothers refuse to cease use because of familiarity with marijuana and belief in its safety. Higher maternal choline mitigates some of marijuana's adverse effects on the fetus.

Keywords

Cannabischolinefetal developmentmarijuanapregnancyreceptors nicotinic
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 10 , July 2020 , pp. 1716 - 1726
Copyright
Copyright © Cambridge University Press 2019

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

Abidin, RR (2012) Parenting Stress Index, 3rd Edn. Odessa, FL: Psychological Assessment Resources.Google Scholar
Abratte, CM, Wang, W, Li, R, Axume, J, Moriarty, DJ and Caudill, MA (2009) Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women. The Journal of Nutritional Biochemistry 20, 62–69.CrossRefGoogle Scholar
Adler, LE, Pachtman, E, Franks, RD, Pecevich, M, Waldo, MC and Freedman, R (1982) Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biological Psychiatry 17, 639–654.Google Scholar
Agulhon, C, Abitbol, M, Bertrand, D and Malafosse, A (1999) Localization of mRNA for CHRNA7 in human fetal brain. Neuroreport 10, 2223–2227.Google ScholarPubMed
Ahadi, SA, Rothbart, MK and Ye, R (1993) Children's temperament in the US and China: similarities and differences. European Journal of Personality 7, 359–378.CrossRefGoogle Scholar
Alkondon, M, Pereira, EFR, Cortes, WS, Maelicke, A and Albuquerque, EX (1997) Choline is a selective agonist at alpha7 nicotinic acetylcholine receptors in rat brain neurons. European Journal of Neuroscience 9, 2734–2742.CrossRefGoogle ScholarPubMed
American College of Obstetricians and Gynecologists (2016) Refusal of Medically Recommended Treatment During Pregnancy. Committee Opinion 664. https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Ethics/Refusal-of-Medically-Recommended-Treatment-During-Pregnancy?IsMobileSet=false (Accessed 12 May 2019).Google Scholar
American College of Obstetricians and Gynecologists (2018) Committee Opinion 722: Marijuana use during pregnancy and lactation. https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Marijuana-Use-During-Pregnancy-and-Lactation, October 2017 (Accessed 13 June 2018).Google Scholar
American Medical Association (2017) Proceedings of the 2017 Annual Meeting House of Delegates. Downloaded from (https://www.ama-assn.org/about/proceedings-2017-annual-meeting-house-delegates). 27 November 2017.Google Scholar
Anders, T, Emde, R and Parmelee, A (1971) A Manual of Standardized Terminology, Techniques and Criteria for Scoring of States of Sleep and Wakefulness in Newborn Infants. Los Angeles: UCLA Brain Information Service, NINDS Neurological Information Network.Google Scholar
Baumgartner, HK, Trinder, KM, Galimanis, CE, Post, A, Phang, T, Ross, RG and Winn, VD (2015) Characterization of choline transporters in the human placenta over gestation. Placenta. 36, 1362–1369.CrossRefGoogle ScholarPubMed
Bayatti, N, Moss, JA, Sun, L, Ambrose, P, Ward, JFH, Lindsay, L and Clowry, GJ (2008) A molecular neuroanatomical study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone. Cerebral Cortex 18, 1536–1548.CrossRefGoogle ScholarPubMed
Beaudin, AE and Stover, PJ (2009) Insights into metabolic mechanisms underlying folate-responsive neural tube defects: a minireview. Birth Defects Research Part A: Clinical and Molecular Teratology 85, 274–284.CrossRefGoogle ScholarPubMed
Biegon, A and Kerman, IA (2001) Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain. NeuroImage 14, 1463–1468.CrossRefGoogle ScholarPubMed
Birnbaum, R, Jaffe, AE, Hyde, TM, Kleinman, JE and Weinberger, DR (2014) Prenatal expression patterns of genes associated with neuropsychiatric disorders. American Journal of Psychiatry 171, 758–767.CrossRefGoogle ScholarPubMed
Boeke, CE, Gillman, MW, Hughes, MD, Rifas-Shiman, SL, Villamor, E and Oken, E (2013) Choline intake during pregnancy and child cognition at age 7 years. American Journal of Epidemiology 177, 1338–1347.CrossRefGoogle ScholarPubMed
Bosquet-Enlow, M, White, MT, Hails, K, Cabrera, I and Wright, RJ (2016) The infant behavior questionnaire-revised: factor structure in a culturally and sociodemographically diverse sample in the United States. Infant Behavior and Development. 43, 24–35.CrossRefGoogle Scholar
Brown, QL, Sarvet, AL, Shmulewitz, D, Martins, SS, Wall, MM and Hasin, DS (2017) Trends in marijuana use among pregnant and nonpregnant reproductive-aged women, 2002–2014. Journal of the American Medical Association 317, 207–209.CrossRefGoogle Scholar
Cabrera, A (2016) Colorado marijuana's potency getting ‘higher’. Cable Network News. https://www.cnn.com/2016/10/21/health/colorado-marijunana-potency-above-national-average/index.html (Accessed 14 July 2018).Google Scholar
Calvigioni, D, Hurd, YL, Harkany, T and Keimpema, E (2014) Neuronal substrates and functional consequences of prenatal cannabis exposure. European Child & Adolescent Psychiatry 23, 931–941.CrossRefGoogle ScholarPubMed
Caudill, MA, Strupp, BJ, Muscalu, L, Nevins, JEH and Canfield, RL (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, 2172–2180.CrossRefGoogle ScholarPubMed
Cheatham, CL, Goldman, BD, Fischer, LM, da Costa, K-AA, Reznick, JS and Zeisel, SH (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, 1465–1472.CrossRefGoogle Scholar
Court, JA, Lloyd, S, Johnson, M, Griffiths, M, Birdsall, NJM, Piggott, MA, Oakley, AE, Ince, PG, Perry, EK and Perry, RH (1997) Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging. Developmental Brain Research 101, 93–105.CrossRefGoogle ScholarPubMed
de Salas-Quiroga, A, Díaz-Alonso, J, García-Rincón, D, Remmers, F, Vega, D, Gómez-Cañas, M, Lutz, B, Guzman, M and Galve-Roperh, I (2015) Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB 1 receptors on developing cortical neurons. Proceedings of the National Academy of Sciences 112, 13693–13698.CrossRefGoogle Scholar
Descarries, L, Aznavour, N and Hamel, E (2008) The acetylcholine innervation of cerebral cortex: new data on its normal development and its fate in the hAPP(SW,IND) mouse model of Alzheimer's disease. Journal of Neural Transmission 112, 149–162.CrossRefGoogle Scholar
El Marroun, H, Tiemeier, H, Steegers, EAP, Jaddoe, VWV, Hofman, A, Verhulst, FC, van den Brink, W and Huizink, AC (2009) Intrauterine cannabis exposure affects fetal growth trajectories: the generation R study. Journal of the American Academy of Child and Adolescent Psychiatry 48, 1173–1181.CrossRefGoogle ScholarPubMed
El Marroun, H, Tiemeier, H, Steegers, EAP, Roos-Hesselink, JW, Jaddoe, VWV, Hofman, A, Verhulst, FC, van den Brink, W and Huizink, AC (2010) A prospective study on intrauterine cannabis exposure and fetal blood flow. Early Human Development 86, 231–236.CrossRefGoogle ScholarPubMed
El Marroun, H, Tiemeier, H, Jaddoe, VWV, Hofman, A, Verhulst, FC, Van Den Brink, W, van den Brink, W and Huizink, AC (2011) Agreement between maternal cannabis use during pregnancy according to self-report and urinalysis in a population-based cohort: the generation R study. European Addiction Research 17, 37–43.CrossRefGoogle Scholar
El Marroun, H, Tiemeier, H, Franken, IH, Jaddoe, VW, van der Lugt, A, Verhulst, FC, Lahey, BB and White, T (2016) Prenatal cannabis and tobacco exposure in relation to brain morphology: a prospective neuroimaging study in young children. Biological Psychiatry 79, 971–979.CrossRefGoogle ScholarPubMed
Food and Drug Administration (2016) Food Labeling: Revision of the Nutrition and Supplement Facts Labels. Federal Register, May 27, 903–904.Google Scholar
Freedman, R (2014) Alpha7-nicotinic receptor agonists for cognitive enhancement in schizophrenia. Annual Review of Medicine 65, 245–261.CrossRefGoogle Scholar
Freedman, R, Hunter, SK, Law, AJ, Wagner, BD, D'Allesandro, A, Christians, U, Noonan, KQ, Wywra, A and Hoffman, MC (2019) Higher gestational choline levels in maternal infection are protective for infant brain development. Journal of Pediatrics 208, 198–206e2.CrossRefGoogle ScholarPubMed
Freund, RK, Graw, S, Choo, KS, Stevens, KE, Leonard, S and Dell'Acqua, ML (2016) Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner. Neuroscience Letters 627, 1–6.CrossRefGoogle Scholar
Fried, PA and Watkinson, B (2001) Differential effects on facets of attention in adolescents prenatally exposed to cigarettes and marihuana. Neurotoxicology and Teratology 23, 421–430.CrossRefGoogle ScholarPubMed
Fried, PA, Watkinson, B and Gray, R (2003) Differential effects on cognitive functioning in 13- to 16-year-olds prenatally exposed to cigarettes and marihuana. Neurotoxicology and Teratology. 25, 427–436.CrossRefGoogle ScholarPubMed
Gartstein, MA and Rothbart, MK (2003) Studying infant temperament via the revised infant behavior questionnaire. Infant Behavior and Development 26, 64–86.CrossRefGoogle Scholar
Gartstein, MA, Putnam, S and Kliewer, R (2016) Do infant temperament characteristics predict core academic abilities in preschool-aged children? Learning and Individual Differences. NIH Public Access 45, 299–306.CrossRefGoogle ScholarPubMed
Goldschmidt, L, Richardson, GA, Willford, JA, Severtson, SG and Day, NL (2012) School achievement in 14-year-old youths prenatally exposed to marijuana. Neurotoxicology and Teratology 34, 161–167.CrossRefGoogle ScholarPubMed
Greenwood, TA, Lazzeroni, LC, Murray, SS, Cadenhead, KS, Calkins, ME, Dobie, DJ, Green, MF, Gur, RE, Gu, RC, Hardiman, G, Kelsoe, JR, Leonard, S, Light, GA, Nuechterlein, KH, Olincy, A, Radant, AD, Schork, NJ, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Swerdlow, NR, Tsuang, DW, Tsuang, MT, Turetsky, BI, Freedman, R and Braff, DL (2011) Analysis of 94 candidate genes and 12 endophenotypes for schizophrenia from the consortium on the genetics of schizophrenia. American Journal of Psychiatry 168, 930–946.CrossRefGoogle Scholar
Griffith, JM and Freedman, R (1995) Normalization of the auditory P50 gating deficit of schizophrenic patients after non-REM but not REM sleep. Psychiatry Research 56, 271–278.CrossRefGoogle Scholar
Hoffman, MC, Olincy, A, D'Alessandro, A, Reisz, JA, Hansen, KC, Hunter, SK, Freedman, R and Ross, RG (2019) Effects of phosphatidylcholine and betaine supplements on women's serum choline. Journal of Nutrition & Intermediary Metabolism 16, 100094.CrossRefGoogle Scholar
Holm, PI, Ueland, PM, Kvalheim, G and Lien, EA (2003) Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clinical Chemistry 49, 286–294.CrossRefGoogle ScholarPubMed
Huang, H, Xue, R, Zhang, J, Ren, T, Richards, LJ, Yarowsky, P, Miller, MI and Mori, S (2009) Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging. Journal of Neuroscience 29, 4263–4273.CrossRefGoogle ScholarPubMed
Huizink, AC (2015) Prenatal maternal substance use and offspring outcomes: overview of recent findings and possible interventions. European Psychologist 20, 90–101.CrossRefGoogle Scholar
Hunter, SK, Corral, N, Ponicsan, H and Ross, RG (2008) Reliability of P50 auditory sensory gating measures in infants during active sleep. Neuroreport 19, 79–82.CrossRefGoogle ScholarPubMed
Hunter, SK, Kisley, MA, McCarthy, L, Freedman, R and Ross, RG (2011) Diminished cerebral inhibition in neonates associated with risk factors for schizophrenia: parental psychosis, maternal depression, and nicotine use. Schizophrenia Bulletin 37, 1200–1208.CrossRefGoogle ScholarPubMed
Hunter, SK, Gillow, SJ and Ross, RG (2015) Stability of P50 auditory sensory gating during sleep from infancy to 4 years of age. Brain Cognition 94, 4–9.CrossRefGoogle ScholarPubMed
Ilcol, YO, Uncu, G and Ulus, IH (2002) Free and phospholipid-bound choline concentrations in serum during pregnancy, after delivery, and in newborns. Archives of Physiology and Biochemistry 110, 393–399.CrossRefGoogle Scholar
Ilcol, YO, Yilmaz, Z and Ulus, IH (2003) Serum free and phospholipid-bound choline decrease and surgery and methylprednisolone administration in dogs. Neuroscience Letters 339, 195–198.CrossRefGoogle ScholarPubMed
Iwao, B, Yara, M, Hara, N, Kawai, Y, Yamanaka, T, Nishihara, H, Inoue, T and Inazu, M (2016) Functional expression of choline transporter like-protein 1 (CTL1) and CTL2 in human brain microvascular endothelial cells. Neurochemistry International 93, 40–50.CrossRefGoogle ScholarPubMed
Jacobson, SW, Carter, RC, Molteno, CD, Stanton, ME, Herbert, JS, Lindinger, NM, Lewis, CE, Dodge, NC, Hoyme, HE, Zeisel, SH, Meintjes, EM, Duggan, CP and Jacobson, JL (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, 1327–1341.CrossRefGoogle ScholarPubMed
Kertz, SJ, Belden, AC, Tillman, R and Luby, J (2016) Cognitive control deficits in shifting and inhibition in preschool age children are associated with increased depression and anxiety over 7.5 years of development. Journal of Abnormal Child Psychology 44, 1185–1196.CrossRefGoogle ScholarPubMed
Kisley, MA, Polk, SD, Ross, RG, Levisohn, PM and Freedman, R (2003) Early postnatal development of sensory gating. Neuroreport 14, 693–697.CrossRefGoogle ScholarPubMed
Knight, EM, James, H, Edwards, CH, Spurlock, BG, Oyemade, UJ, Johnson, AA, West, WL, Cole, OJ, Westney, LS and Westney, OE (1994) Relationships of serum illicit drug concentrations during pregnancy to maternal nutritional status. Journal of Nutrition 124, 973S–980S.Google ScholarPubMed
Kunii, Y, Zhang, W, Xu, Q, Hyde, TM, McFadden, W, Shin, JH, Deep-Soboslay, A, Ye, T, Li, C, Kleinman, JE, Wang, KH and Lipska, BK (2015) CHRNA7 and CHRFAM7AmRNAs: co-localized and their expression levels altered in the postmortem dorsolateral prefrontal cortex in major psychiatric disorders. American Journal of Psychiatry 172, 1122–1130.CrossRefGoogle ScholarPubMed
Lin, B, Ostlund, BD, Conradt, E, Lagasse, LL and Lester, BM (2018) Testing the programming of temperament and psychopathology in two independent samples of children with prenatal substance exposure. Development & Psychopathology 30, 1023–1040.CrossRefGoogle ScholarPubMed
Liu, Z, Neff, RA and Berg, DK (2006) Sequential interplay of nicotinic and GABAergic signaling guides neuronal development. Science 314, 1610–1613.CrossRefGoogle ScholarPubMed
Mato, S, Del Olmo, E and Pazos, A (2003) Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain. European Journal of Neuroscience 17, 1747–1754.CrossRefGoogle ScholarPubMed
Metz, TD, Allshouse, AA, Hogue, CJ, Goldenberg, RL, Dudley, DJ, Varner, MW, Conway, DL, Saade, GR and Sliver, RM (2017) Maternal marijuana use, adverse pregnancy outcomes, and neonatal morbidity. American Journal of Obstetrics and Gynecology 217, 478.e1–478.e8.CrossRefGoogle ScholarPubMed
Miller, CL and Freedman, R (1995) The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated auditory stimuli. Neuroscience 69, 371–381.CrossRefGoogle ScholarPubMed
Morales, M, Hein, K and Vogel, Z (2008) Hippocampal interneurons co-express transcripts encoding the α7 nicotinic receptor subunit and the cannabinoid receptor 1. Neuroscience 152, 70–81.CrossRefGoogle ScholarPubMed
Olson, SL, Choe, DE and Sameroff, AJ (2017) Trajectories of child externalizing problems between ages 3 and 10 years: contributions of children's early effortful control, theory of mind, and parenting experiences. Development & Psychopathology 29, 1333–1351.CrossRefGoogle ScholarPubMed
Orczyk-Pawilowicz, M, Jawien, E, Deja, S, Hirnle, L, Zabek, A and Mlynarz, P (2016) Metabolomics of human amniotic fluid and maternal plasma during normal pregnancy. PLOS ONE 11, e0152740.CrossRefGoogle ScholarPubMed
Pine, DS and Fox, NA (2015) Childhood antecedents and risk for adult mental disorders. Annual Review of Psychology 66, 459–485.CrossRefGoogle ScholarPubMed
Putnam, SP, Helbig, AL, Gartstein, MA, Rothbart, MK and Leerkes, E (2014) Development and assessment of short and very short forms of the infant behavior questionnaire-revised. Journal of Personality Assessment 96, 445–458.CrossRefGoogle Scholar
Richardson, GA, Day, NL and Goldschmidt, L (1995) Prenatal alcohol, marijuana, and tobacco use: infant mental and motor development. Neurotoxicology and Teratology 17, 479–487.CrossRefGoogle ScholarPubMed
Roberson, EK, Patrick, WK and Hurwitz, EL (2014) Marijuana use and maternal experiences of severe nausea during pregnancy in Hawai'i. Hawai'i Journal of Medicine and Public Health 73, 283–287.Google ScholarPubMed
Ross, RG, Hunter, SK, McCarthy, L, Beuler, J, Hutchison, AK, Wagner, BD, Leonard, S, Stevens, KE and Freedman, R (2013) Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. American Journal of Psychiatry 170, 290–298.CrossRefGoogle ScholarPubMed
Ross, RG, Hunter, SK, Hoffman, MC, McCarthy, L, Chambers, BM, Law, AJ, Leonard, S, Zerbe, GO and Freedman, R (2016) Perinatal phosphatidylcholine supplementation and early childhood behavior problems: evidence for CHRNA7 moderation. American Journal of Psychiatry 173, 509–516.CrossRefGoogle ScholarPubMed
Rutter, M, Kim-Cohen, J and Maughan, B (2006) Continuities and discontinuities in psychopathology between childhood and adult life. Journal of Child Psychology and Psychiatry 47, 276–295.CrossRefGoogle ScholarPubMed
Slobodskaya, HR and Kozlova, EA (2016) Early temperament as a predictor of later personality. Personality and Individual Differences 99, 127–132.CrossRefGoogle Scholar
Smith, DA, Boutros, NN and Schwarzkopf, SB (1994) Reliability of P50 auditory event-related potential indices of sensory gating. Psychophysiology 31, 495–502.CrossRefGoogle ScholarPubMed
Smith, E, Crawford, T, Thomas, M and Reid, V (2018 a). Schizotypy and sensory gating: a 6-month-old EEG study. Schizophrenia Bulletin 44, S301–S302.CrossRefGoogle Scholar
Smith, MJ, Alden, EC, Herrold, AA, Roberts, A, Stern, D, Jones, J, Barnes, A, O'Connor, KP, Huestis, MA and Breiter, HC (2018 b) Recent self-reported cannabis use is associated with the biometrics of delta-9-tetrahydrocannabinol. Journal of Studies on Alcohol and Drugs 79, 441–446.CrossRefGoogle ScholarPubMed
Stephenson, J, Heslehurst, N, Hall, J, Schoemaker, DAJM, Hutchinson, J, Cade, JE, Barrett, G, Crozier, SR, Barker, M, Kumaran, K, Yajnik, CS, Baird, J and Mishra, GD (2018) Before the beginning: nutrition and lifestyle in the preconception period and its importance for future health. The Lancet 391, 1830–1841.CrossRefGoogle ScholarPubMed
Stevens, KE, Choo, KS, Stitzel, JA, Marks, MJ and Adams, CE (2014) Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice. Brain Research 1552, 26–33.CrossRefGoogle ScholarPubMed
Vanhatalo, S, Palvas, JM, Andersson, S, Rivera, C, Voipio, J and Kaila, K (2005) Slow endogenous activity transients and developmental expression KCC2 in the immature human cortex. European Journal of Neuroscience 22, 2799–2804.CrossRefGoogle Scholar
Vargish, GA, Pelkey, KA, Yuan, X, Chittajallu, R, Collins, D, Fang, C and McBain, CJ (2017) Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure. Molecular Psychiatry 22, 56–67.CrossRefGoogle ScholarPubMed
Volkow, ND, Compton, WM and Wargo, EM (2017) The risks of marijuana use during pregnancy. Journal of American Medical Association 317, 129–130.CrossRefGoogle ScholarPubMed
Wang, X, Dow-Edwards, D, Keller, E and Hurd, YL (2003) Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain. Neuroscience 118, 681–694.CrossRefGoogle ScholarPubMed
Wu, BTF, Dyer, RA, King, DJJ, Richardson, KJ and Innis, SM (2012) Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS ONE 7, e43448.CrossRefGoogle ScholarPubMed
Zecevic, N, Hu, F and Jakovcevski, I (2011) Interneurons in the developing human neocortex. Developmental Neurobiology 71, 18–33.CrossRefGoogle ScholarPubMed
Zeisel, SH, Growden, JH, Wurtman, RJ, Magil, SG and Logue, M (1980) Normal plasma choline responses to ingested lecitin. Neurology 30, 1226–1229.CrossRefGoogle Scholar
Supplementary material: File

Hoffman et al. supplementary material

Hoffman et al. supplementary material 1

Download Hoffman et al. supplementary material(File)
File 98.1 KB