Intergenerational Effect of Maternal Exposure to Childhood Maltreatment on Newborn Brain Anatomy

BACKGROUND Childhood maltreatment (CM) confers deleterious long-term consequences, and growing evidence suggests some of these effects may be transmitted across generations. We examined the intergenerational effect of maternal CM exposure on child brain structure and also addressed the hypothesis that this effect may start during the child's intrauterine period of life. METHODS A prospective longitudinal study was conducted in a clinical convenience sample of 80 mother-child dyads. Maternal CM exposure was assessed using the Childhood Trauma Questionnaire. Structural magnetic resonance imaging was employed to characterize newborn global and regional brain (tissue) volumes near the time of birth. RESULTS CM exposure was reported by 35% of the women. Maternal CM exposure was associated with lower child intracranial volume (F1,70 = 6.84, p = .011), which was primarily due to a global difference in cortical gray matter (F1,70 = 9.10, p = .004). The effect was independent of potential confounding variables, including maternal socioeconomic status, obstetric complications, obesity, recent interpersonal violence, pre- and early postpartum stress, gestational age at birth, infant sex, and postnatal age at magnetic resonance imaging scan. The observed group difference between offspring of CM-exposed mothers versus nonexposed mothers was 6%. CONCLUSIONS These findings represent the first report to date associating maternal CM exposure with variation in newborn brain structure. These observations support our hypothesis of intergenerational transmission of the effects of maternal CM exposure on child brain development and suggest this effect may originate during the child's intrauterine period of life, which may have downstream neurodevelopmental consequences.

[1]  G. Fink,et al.  Changes in grey matter development in autism spectrum disorder , 2012, Brain Structure and Function.

[2]  C. Pariante,et al.  Intergenerational transmission of maltreatment and psychopathology: the role of antenatal depression , 2012, Psychological Medicine.

[3]  Claudia Buss,et al.  Fetal Programming of Brain Development: Intrauterine Stress and Susceptibility to Psychopathology , 2012, Science Signaling.

[4]  T. Bale,et al.  Paternal Stress Exposure Alters Sperm MicroRNA Content and Reprograms Offspring HPA Stress Axis Regulation , 2013, The Journal of Neuroscience.

[5]  John H. Gilmore,et al.  Automatic segmentation of MR images of the developing newborn brain , 2005, Medical Image Anal..

[6]  I. Evangelou,et al.  Complex Trajectories of Brain Development in the Healthy Human Fetus , 2016, Cerebral cortex.

[7]  M. Lobel,et al.  Coping and distress in pregnancy: an investigation of medically high risk women. , 1999, Journal of psychosomatic obstetrics and gynaecology.

[8]  E. Adam,et al.  Mothers’ childhood hardship forecasts adverse pregnancy outcomes: Role of inflammatory, lifestyle, and psychosocial pathways , 2017, Brain, Behavior, and Immunity.

[9]  Guido Gerig,et al.  User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability , 2006, NeuroImage.

[10]  Margaret J. Briggs-Gowan,et al.  Prevalence of DSM-IV disorder in a representative, healthy birth cohort at school entry: sociodemographic risks and social adaptation. , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[11]  M. Lepage,et al.  White Matter Injury and Autistic-Like Behavior Predominantly Affecting Male Rat Offspring Exposed to Group B Streptococcal Maternal Inflammation , 2013, Developmental Neuroscience.

[12]  L. Radloff The CES-D Scale , 1977 .

[13]  J. Soliva,et al.  Global and regional gray matter reductions in ADHD: A voxel-based morphometric study , 2005, Neuroscience Letters.

[14]  A. Chicz–DeMet,et al.  Prenatal exposure to maternal depression and cortisol influences infant temperament. , 2007, Journal of the American Academy of Child and Adolescent Psychiatry.

[15]  A. Chicz–DeMet,et al.  Maternal corticotropin-releasing hormone and habituation in the human fetus. , 1999, Developmental psychobiology.

[16]  J. Buitelaar,et al.  Short CommunicationMaternal Prenatal Stress and 4–6 Year Old Children's Salivary Cortisol Concentrations Pre- and Post-vaccination , 2004, Stress.

[17]  J. Flory,et al.  Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors , 2014, Psychoneuroendocrinology.

[18]  S Campbell,et al.  Assessment of gestational age in the second trimester by real-time ultrasound measurement of the femur length. , 1981, American journal of obstetrics and gynecology.

[19]  Daniel Rueckert,et al.  Automatic segmentation of brain MRIs of 2-year-olds into 83 regions of interest , 2008, NeuroImage.

[20]  C. Nemeroff,et al.  Neurobiological and psychiatric consequences of child abuse and neglect. , 2010, Developmental psychobiology.

[21]  S. Entringer,et al.  Prenatal stress, development, health and disease risk: A psychobiological perspective—2015 Curt Richter Award Paper , 2015, Psychoneuroendocrinology.

[22]  B. Dias,et al.  Parental olfactory experience influences behavior and neural structure in subsequent generations , 2013, Nature Neuroscience.

[23]  Martin Styner,et al.  Asymmetric bias in user guided segmentations of brain structures , 2007, NeuroImage.

[24]  E. Davis,et al.  The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. , 2010, Child development.

[25]  D. Finkelhor,et al.  Prevalence of Childhood Exposure to Violence, Crime, and Abuse: Results From the National Survey of Children's Exposure to Violence. , 2015, JAMA pediatrics.

[26]  A. Chicz–DeMet,et al.  Timing of fetal exposure to stress hormones: effects on newborn physical and neuromuscular maturation. , 2008, Developmental psychobiology.

[27]  M. Weisskopf,et al.  Association of maternal exposure to childhood abuse with elevated risk for autism in offspring. , 2013, JAMA psychiatry.

[28]  M. Mclean,et al.  A placental clock controlling the length of human pregnancy , 1995, Nature Medicine.

[29]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[30]  Kristin Bergman,et al.  Prenatal cortisol exposure predicts infant cortisol response to acute stress. , 2013, Developmental psychobiology.

[31]  Paul M. Thompson,et al.  Mapping Gray Matter Development: Implications for Typical Development and Vulnerability to Psychopathology , 2022 .

[32]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[33]  Richard Thompson Mothers' violence victimization and child behavior problems: examining the link. , 2007, The American journal of orthopsychiatry.

[34]  Jonathan B. Kotch,et al.  Child Maltreatment in the United States: Prevalence, Risk Factors, and Adolescent Health Consequences , 2006, Pediatrics.

[35]  D. Bernstein,et al.  Childhood Trauma Questionnaire: A retrospective self-report manual , 1998 .

[36]  Martin Styner,et al.  Maternal Influenza Infection During Pregnancy Impacts Postnatal Brain Development in the Rhesus Monkey , 2010, Biological Psychiatry.

[37]  B. Shahbaba,et al.  Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology , 2016, Biological Psychiatry.

[38]  W. Katon,et al.  Costs of health care use by women HMO members with a history of childhood abuse and neglect. , 1999, Archives of general psychiatry.

[39]  Sandhya Ramrakha,et al.  Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health. , 2016, Journal of child psychology and psychiatry, and allied disciplines.

[40]  Jean Golding,et al.  Maternal childhood abuse and offspring adjustment over time , 2007, Development and Psychopathology.

[41]  S. Matthews,et al.  Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects. , 2001, American journal of physiology. Endocrinology and metabolism.

[42]  B. Shahbaba,et al.  Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems , 2012, Proceedings of the National Academy of Sciences.

[43]  R. Gibbons,et al.  Prevalence rates and correlates of psychiatric disorders among preschool children. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[44]  A. Baker Adult recall of childhood psychological maltreatment: Definitional strategies and challenges , 2009 .

[45]  A. Chicz–DeMet,et al.  Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: a prospective investigation. , 2004, American journal of obstetrics and gynecology.

[46]  L. Stroud,et al.  Childhood sexual abuse is associated with cortisol awakening response over pregnancy: Preliminary findings , 2012, Psychoneuroendocrinology.

[47]  D. Rubinow,et al.  Psychiatric Symptoms and Proinflammatory Cytokines in Pregnancy , 2011, Psychosomatic medicine.

[48]  J. Mcfarlane,et al.  Assessing for abuse during pregnancy. Severity and frequency of injuries and associated entry into prenatal care. , 1992 .

[49]  Rebecca C. Knickmeyer,et al.  Regional Gray Matter Growth, Sexual Dimorphism, and Cerebral Asymmetry in the Neonatal Brain , 2007, The Journal of Neuroscience.

[50]  Martin Styner,et al.  Automatic tissue segmentation of neonate brain MR Images with subject-specific atlases , 2015, Medical Imaging.

[51]  A. Chicz–DeMet,et al.  Corticotropin-Releasing Hormone during Pregnancy Is Associated with Infant Temperament , 2005, Developmental Neuroscience.

[52]  Martin Styner,et al.  Multi-atlas segmentation of subcortical brain structures via the AutoSeg software pipeline , 2014, Front. Neuroinform..

[53]  K. Dodge,et al.  Intergenerational continuity in child maltreatment: mediating mechanisms and implications for prevention. , 2011, Child development.

[54]  S. Entringer,et al.  The association between early life adversity and bacterial vaginosis during pregnancy. , 2011, American journal of obstetrics and gynecology.

[55]  J. Buitelaar,et al.  Prenatal maternal cortisol levels and infant behavior during the first 5 months. , 2003, Early human development.

[56]  P. Gluckman,et al.  Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children , 2017, Translational Psychiatry.

[57]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[58]  C. Spielberger,et al.  Manual for the State-Trait Anxiety Inventory , 1970 .

[59]  D. Fair,et al.  Intergenerational Transmission of Maternal Childhood Maltreatment Exposure: Implications for Fetal Brain Development. , 2017, Journal of the American Academy of Child and Adolescent Psychiatry.