A Scoping Review of Multigenerational Impacts of Grandparental Exposures on Mental Health in Grandchildren

Overview

Journal Curr Environ Health Rep

Specialty Environmental Health

Date 2023 Nov 26

PMID 38008881

Authors

Jingyuan Xiao

Anushka Jain

Giselle Bellia

Kate Nyhan

Zeyan Liew

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: The multigenerational effects of grandparental exposures on their grandchildren's mental health and neurodevelopment are gaining research attention. We conducted a scoping review to summarize the current epidemiological studies investigating pregnancy-related and environmental factors that affected grandparental pregnancies and mental health outcomes in their grandchildren. We also identified methodological challenges that affect these multigenerational health studies and discuss opportunities for future research.

Recent Findings: We performed a literature search using PubMed and Embase and included 18 articles for this review. The most investigated grandparental pregnancy-related factors were the grandparental age of pregnancy (N = 6), smoking during pregnancy (N = 4), and medication intake (N = 3). The most frequently examined grandchild outcomes were autism spectrum disorder (N = 6) and attention-deficit/hyperactivity disorder (N = 4). Among these studies, grandparental smoking and the use of diethylstilbestrol were more consistently reported to be associated with neurodevelopmental disorders, while the findings for grandparental age vary across the maternal or paternal line. Grandmaternal weight, adverse delivery outcomes, and other spatial-temporal markers of physical and social environmental stressors require further scrutiny. The current body of literature has suggested that mental and neurodevelopmental disorders may be outcomes of unfavorable exposures originating from the grandparental generation during their pregnancies. To advance the field, we recommend research efforts into setting up multigenerational studies with prospectively collected data that span through at least three generations, incorporating spatial, environmental, and biological markers for exposure assessment, expanding the outcome phenotypes evaluated, and developing a causal analytical framework including mediation analyses specific for multigenerational research.

Citing Articles

Paternal preconception donepezil exposure enhances learning in offspring.

Fan G, Pan T, Ji X, Jiang C, Wang F, Liu X Behav Brain Funct. 2024; 20(1):25.

PMID: 39342229 PMC: 11439325. DOI: 10.1186/s12993-024-00252-z.

References

Heindel J, Skalla L, Joubert B, Dilworth C, Gray K . Review of developmental origins of health and disease publications in environmental epidemiology. Reprod Toxicol. 2016; 68:34-48. DOI: 10.1016/j.reprotox.2016.11.011. View

Wesselink A . Multigenerational effects of environmental exposures. Hum Reprod. 2020; 36(3):539-542. DOI: 10.1093/humrep/deaa361. View

Bohacek J, Gapp K, Saab B, Mansuy I . Transgenerational epigenetic effects on brain functions. Biol Psychiatry. 2012; 73(4):313-20. DOI: 10.1016/j.biopsych.2012.08.019. View

Calkins K, Devaskar S . Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care. 2011; 41(6):158-76. PMC: 4608552. DOI: 10.1016/j.cppeds.2011.01.001. View

Hagemann E, Silva D, Davis J, Gibson L, Prescott S . Developmental Origins of Health and Disease (DOHaD): The importance of life-course and transgenerational approaches. Paediatr Respir Rev. 2021; 40:3-9. DOI: 10.1016/j.prrv.2021.05.005. View

McCarthy D, Morgan Jr T, Lowe S, Williamson M, Spencer T, Biederman J . Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants. PLoS Biol. 2018; 16(10):e2006497. PMC: 6191076. DOI: 10.1371/journal.pbio.2006497. View

Choi C, Gonzales E, Kim K, Yang S, Kim J, Mabunga D . The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy. Sci Rep. 2016; 6:36250. PMC: 5098241. DOI: 10.1038/srep36250. View

Wolstenholme J, Edwards M, Shetty S, Gatewood J, Taylor J, Rissman E . Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression. Endocrinology. 2012; 153(8):3828-38. PMC: 3404345. DOI: 10.1210/en.2012-1195. View

Martini M, Corces V, Rissman E . Mini-review: Epigenetic mechanisms that promote transgenerational actions of endocrine disrupting chemicals: Applications to behavioral neuroendocrinology. Horm Behav. 2020; 119:104677. PMC: 9942829. DOI: 10.1016/j.yhbeh.2020.104677. View

10.

Zhou Y, Zhang M, Liu W, Li Y, Qin Y, Xu Y . Transgenerational transmission of neurodevelopmental disorders induced by maternal exposure to PM2.5. Chemosphere. 2020; 255:126920. DOI: 10.1016/j.chemosphere.2020.126920. View

11.

Knecht A, Truong L, Marvel S, Reif D, Garcia A, Lu C . Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish. Toxicol Appl Pharmacol. 2017; 329:148-157. PMC: 5539966. DOI: 10.1016/j.taap.2017.05.033. View

12.

Chen L, Wang X, Zhang X, Lam P, Guo Y, Lam J . Transgenerational endocrine disruption and neurotoxicity in zebrafish larvae after parental exposure to binary mixtures of decabromodiphenyl ether (BDE-209) and lead. Environ Pollut. 2017; 230:96-106. DOI: 10.1016/j.envpol.2017.06.053. View

13.

Golding J, Pembrey M, Iles-Caven Y, Watkins S, Suderman M, Northstone K . Ancestral smoking and developmental outcomes: a review of publications from a population birth cohort†. Biol Reprod. 2021; 105(3):625-631. PMC: 8444670. DOI: 10.1093/biolre/ioab124. View

14.

Buck J, Yu L, Knopik V, Stitzel J . DNA methylome perturbations: an epigenetic basis for the emergingly heritable neurodevelopmental abnormalities associated with maternal smoking and maternal nicotine exposure†. Biol Reprod. 2021; 105(3):644-666. PMC: 8444709. DOI: 10.1093/biolre/ioab138. View

15.

Mouat J, LaSalle J . The Promise of DNA Methylation in Understanding Multigenerational Factors in Autism Spectrum Disorders. Front Genet. 2022; 13:831221. PMC: 8886225. DOI: 10.3389/fgene.2022.831221. View

16.

Walker V, Boyles A, Pelch K, Holmgren S, Shapiro A, Blystone C . Human and animal evidence of potential transgenerational inheritance of health effects: An evidence map and state-of-the-science evaluation. Environ Int. 2018; 115:48-69. DOI: 10.1016/j.envint.2017.12.032. View

17.

Ambeskovic M, Roseboom T, Metz G . Transgenerational effects of early environmental insults on aging and disease incidence. Neurosci Biobehav Rev. 2017; 117:297-316. DOI: 10.1016/j.neubiorev.2017.08.002. View

18.

Tricco A, Lillie E, Zarin W, OBrien K, Colquhoun H, Levac D . PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018; 169(7):467-473. DOI: 10.7326/M18-0850. View

19.

Sampson M, McGowan J, Cogo E, Grimshaw J, Moher D, Lefebvre C . An evidence-based practice guideline for the peer review of electronic search strategies. J Clin Epidemiol. 2009; 62(9):944-52. DOI: 10.1016/j.jclinepi.2008.10.012. View

20.

Kioumourtzoglou M, Coull B, OReilly E, Ascherio A, Weisskopf M . Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits. JAMA Pediatr. 2018; 172(7):670-677. PMC: 6137513. DOI: 10.1001/jamapediatrics.2018.0727. View