Abstract
Purpose
Exposure to prenatal stress has been reported to affect the risk of adverse neurodevelopmental outcomes in the offspring; however, there is currently no clear consensus. The aim of this systematic review and meta-analysis was to examine the existing literature on the association between prenatal stress and autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) in the offspring.
Methods
Based on a registered protocol, we searched several electronic databases for articles in accordance with a detailed search strategy. We performed this study following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
Results
Prenatal stress was significantly associated with an increased risk of both ASD (pooled OR 1.64 [95% CI 1.15–2.34]; I2 = 90%; 15 articles) and ADHD (pooled OR 1.72 [95% CI 1.27–2.34]; I2 = 85%; 12 articles).
Conclusions
This study suggests that prenatal stress may be associated with ASD and ADHD; however, several limitations in the reviewed literature should be noted including significant heterogeneity and there is a need for carefully controlled future studies in this area.
Similar content being viewed by others
References
Charil A, Laplante DP, Vaillancourt C, King S (2010) Prenatal stress and brain development. Brain Res Rev 65(1):56–79
McDonald SW, Lyon AW, Benzies KM, McNeil DA, Lye SJ, Dolan SM, Pennell CE, Bocking AD, Tough SC (2013) The All Our Babies pregnancy cohort: design, methods, and participant characteristics. BMC Pregnancy and Childbirth 13(1):S2. https://doi.org/10.1186/1471-2393-13-s1-s2
Van den Bergh BR, Marcoen A (2004) High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8-and 9-year-olds. Child Dev 75(4):1085–1097
Ronald A, Pennell CE, Whitehouse AJ (2011) Prenatal maternal stress associated with ADHD and autistic traits in early childhood. Front Psychol 1:223
Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, Kurzius-Spencer M, Zahorodny W, Robinson C, Rosenberg C, White T, Durkin MS, Imm P, Nikolaou L, Yeargin-Allsopp M, Lee L-C, Harrington R, Lopez M, Fitzgerald RT, Hewitt A, Pettygrove S, Constantino John N, Vehorn A, Shenouda J, Hall-Lande J, Van K, Naarden K, Braun K, Dowling NF (2014) Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States. Morb Mortal wkly Rep Surveill Summ 67(6):1–23. https://doi.org/10.15585/mmwr.ss6706a1
Robel L (2009) Clinical features in autism. Arch de Pediatr Organe Officiel de la Soc Francaise de Pediatr 16(11):1507–1512
Volkmar F, Chawarska K, Klin A (2005) Autism in infancy and early childhood. Annu Rev Psychol 56:315–336
Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiat 57(11):1215–1220
Larsson J-O, Larsson H, Lichtenstein P (2004) Genetic and environmental contributions to stability and change of ADHD symptoms between 8 and 13 years of age: a longitudinal twin study. J Am Acad Child Adolesc Psychiatry 43(10):1267–1275
Geschwind DH (2011) Genetics of autism spectrum disorders. Trends Cogn Sci 15(9):409–416
Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A (2017) The heritability of autism spectrum disorder. JAMA 318(12):1182–1184. https://doi.org/10.1001/jama.2017.12141
Brikell I, Kuja-Halkola R, Larsson H (2015) Heritability of attention-deficit hyperactivity disorder in adults. Am J Med Genet Part B Neuropsychiatr Genet 168(6):406–413. https://doi.org/10.1002/ajmg.b.32335
Larsson H, Chang Z, D’Onofrio BM, Lichtenstein P (2014) The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychol Med 44(10):2223–2229
Khashan AS, Abel KM, McNamee R, Pedersen MG, Webb RT, Baker PN, Kenny LC, Mortensen PB (2008) Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Arch Gen Psychiatry 65(2):146–152
Class QA, Abel KM, Khashan AS, Rickert ME, Dalman C, Larsson H, Hultman CM, Långström N, Lichtenstein P, D‘Onofrio BM (2014) Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress. Psychol Med 44(1):71–84
Rodriguez A, Bohlin G (2005) Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? J Child Psychol Psychiatry 46(3):246–254. https://doi.org/10.1111/j.1469-7610.2004.00359.x
Li J, Vestergaard M, Obel C, Christensen J, Precht DH, Lu M, Olsen J (2009) A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement. Pediatrics 123(4):1102–1107
Li JO, Olsen J, Vestergaard M, Obel C (2010) Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark. Eur Child Adolesc Psychiatry 19(10):747–753. https://doi.org/10.1007/s00787-010-0113-9
Say GN, Karabekiroǧlu K, Babadaǧi Z, Yüce M (2016) Maternal stress and perinatal features in autism and attention deficit/hyperactivity disorder. Pediatr Int 58(4):265–269. https://doi.org/10.1111/ped.12822
Wadhwa PD, Entringer S, Buss C, Lu MC (2011) The contribution of maternal stress to preterm birth: issues and considerations. Clin Perinatol 38(3):351–384
Davis EP, Sandman CA (2010) The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev 81(1):131–148. https://doi.org/10.1111/j.1467-8624.2009.01385.x
Smith GD (2008) Assessing intrauterine influences on offspring health outcomes: can epidemiological studies yield robust findings? Basic Clin Pharmacol Toxicol 102(2):245–256
Rai D, Golding J, Magnusson C, Steer C, Lewis G, Dalman C (2012) Prenatal and early life exposure to stressful life events and risk of autism spectrum disorders: population-based studies in Sweden and England. PLoS One 7(6):e38893
Rice F, Harold G, Boivin J, Van den Bree M, Hay D, Thapar A (2010) The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences. Psychol Med 40(2):335–345
Roberts AL, Lyall K, Rich-Edwards JW, Ascherio A, Weisskopf MG (2016) Maternal exposure to intimate partner abuse before birth is associated with autism spectrum disorder in offspring. Autism 20(1):26–36
Kinney DK, Miller AM, Crowley DJ, Huang E, Gerber E (2008) Autism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana. J Autism Dev Disord 38(3):481–488
Manzari N, Matvienko-Sikar K, Baldoni F, Keeffe G, Khashan A (2019) Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol [version 2; peer review: 4 approved, 1 approved with reservations]. HRB Open Res. https://doi.org/10.12688/hrbopenres.12827.2
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097
Lee CY, Chang YY, Lung FW (2006) The marriage-related risk factors during maternal pregnancy in children with attention-deficit hyperactivity disorder. Child Care Health Dev 32(2):205–212
Martini J, Knappe S, Beesdo-Baum K, Lieb R, Wittchen H-U (2010) Anxiety disorders before birth and self-perceived distress during pregnancy: associations with maternal depression and obstetric, neonatal and early childhood outcomes. Early Human Dev 86(5):305–310. https://doi.org/10.1016/j.earlhumdev.2010.04.004
Tsuchiya K, Matsumoto K, Suda S, Miyachi T, Itoh H, Kanayama N, Hirano K, Ohzeki T, Takei N, Team HS (2010) Searching for very early precursors of autism spectrum disorders: the Hamamatsu birth cohort for mothers and children (HBC). J Dev Origins Health Dis 1(3):158–173
Higgins JP, Green S (2011) Cochrane handbook for systematic reviews of interventions, vol 4. Wiley, New York
Oerlemans AM, Burmanje MJ, Franke B, Buitelaar JK, Hartman CA, Rommelse NN (2016) Identifying unique versus shared pre-and perinatal risk factors for ASD and ADHD using a simplex-multiplex stratification. J Abnorm Child Psychol 44(5):923–935
Zhang X, Lv C-C, Tian J, Miao R-J, ** W, Hertz-Picciotto I, Qi L (2010) Prenatal and perinatal risk factors for autism in China. J Autism Dev Disord 40(11):1311–1321
L-s ZHANG, X-m JIN, Y-w ZHANG (2009) Analysis of family environment of children with attention deficit hyperactivity disorder in clinics. J Shanghai Jiaotong Univ (Med Sci) 7:008
Ward AJ (1990) A comparison and analysis of the presence of family problems during pregnancy of mothers of “autistic” children and mothers of normal children. Child Psychiatry Hum Dev 20(4):279–288
Grossi E, Veggo F, Narzisi A, Compare A, Muratori F (2016) Pregnancy risk factors in autism: a pilot study with artificial neural networks. Pediatr Res 79(2):339
Beversdorf DQ, Manning S, Hillier A, Anderson S, Nordgren R, Walters S, Nagaraja H, Cooley W, Gaelic S, Bauman M (2005) Timing of prenatal stressors and autism. J Autism Dev Disord 35(4):471–478
Lei G, ** QQ, Jun W, Yu H, Wei D, Su YY, Zhang X (2015) Association between prenatal environmental factors and child autism: a case control study in Tian**, China. Biomed Environ Sci 28(9):642–650
George B, Padmam MR, Nair M, Leena M, Russell PSS (2014) CDC Kerala 13: antenatal, Natal and postnatal factors among children (2–6 y) with autism–a case control study. Indian J Pediatr 81(2):133–137
Hamadé A, Salameh P, Medlej-Hashim M, Hajj-Moussa E, Saadallah-Zeidan N, Rizk F (2013) Autism in children and correlates in Lebanon: a pilot case-control study. J Res Health Sci 13(2):119–124
Visser JC, Rommelse N, Vink L, Schrieken M, Oosterling IJ, van der Gaag RJ, Buitelaar JK (2013) Narrowly versus broadly defined autism spectrum disorders: differences in pre-and perinatal risk factors. J Autism Dev Disord 43(7):1505–1516
Grizenko N, Fortier ME, Zadorozny C, Thakur G, Schmitz N, Duval R, Joober R (2012) Maternal stress during pregnancy, ADHD symptomatology in children and genotype: gene-environment interaction. J Can Acad Child Adolesc Psychiatry 21(1):9–15
Park S, Cho S-C, Kim J-W, Shin M-S, Yoo H-J, Oh SM, Han DH, Cheong JH, Kim B-N (2014) Differential perinatal risk factors in children with attention-deficit/hyperactivity disorder by subtype. Psychiatry Res 219(3):609–616
Kim HW, Cho SC, Kim BN, Kim JW, Shin MS, Kim Y (2009) Perinatal and familial risk factors are associated with full syndrome and subthreshold attention-deficit hyperactivity disorder in a Korean community sample. Psychiatry Investig 6(4):278–285. https://doi.org/10.4306/pi.2009.6.4.278
Motlagh MG, Katsovich L, Thompson N, Lin HQ, Kim YS, Scahill L, Lombroso PJ, King RA, Peterson BS, Leckman JF (2010) Severe psychosocial stress and heavy cigarette smoking during pregnancy: an examination of the pre- and perinatal risk factors associated with ADHD and Tourette syndrome. Eur Child Adolesc Psychiatry 19(10):755–764. https://doi.org/10.1007/s00787-010-0115-7
Sasaluxnanon C, Kaewpornsawan T (2005) Risk factor of birth weight below 2,500 grams and attention deficit hyperactivity disorder in Thai children. J Med Assoc Thai 88(11):1514–1518
Flanigan C, Sheikh A, DunnGalvin A, Brew BK, Almqvist C, Nwaru BI (2018) Prenatal maternal psychosocial stress and offspring’s asthma and allergic disease: a systematic review and meta-analysis. Clin Exp Allergy 48(4):403–414. https://doi.org/10.1111/cea.13091
St-Hilaire A, Steiger H, Liu A, Laplante DP, Thaler L, Magill T, King S (2015) A prospective study of effects of prenatal maternal stress on later eating-disorder manifestations in affected offspring: preliminary indications based on the Project Ice Storm cohort. Int J Eat Disord 48(5):512–516. https://doi.org/10.1002/eat.22391
Cole-Lewis HJ, Kershaw TS, Earnshaw VA, Yonkers KA, Lin H, Ickovics JR (2014) Pregnancy-specific stress, preterm birth, and gestational age among high-risk young women. Health Psychol 33(9):1033–1045. https://doi.org/10.1037/a0034586
Spann MN, Monk C, Scheinost D, Peterson BS (2018) Maternal immune activation during the third trimester is associated with neonatal functional connectivity of the salience network and fetal to toddler behavior. J Neurosci 38(11):2877–2886. https://doi.org/10.1523/JNEUROSCI.2272-17.2018
Torche F, Kleinhaus K (2011) Prenatal stress, gestational age and secondary sex ratio: the sex-specific effects of exposure to a natural disaster in early pregnancy. Hum Reprod 27(2):558–567
Mueller BR, Bale TL (2007) Early prenatal stress impact on co** strategies and learning performance is sex dependent. Physiol Behav 91(1):55–65
Coughlin SS (1990) Recall bias in epidemiologic studies. J Clin Epidemiol 43(1):87–91
CoCw D (2001) The pediatrician’s role in the diagnosis and management of autistic spectrum disorder in children. Pediatrics 107(5):1221–1226
Risi S, Lord C, Gotham K, Corsello C, Chrysler C, Szatmari P, Cook EH, Leventhal BL, Pickles A (2006) Combining information from multiple sources in the diagnosis of autism spectrum disorders. J Am Acad Child Adolesc Psychiatry 45(9):1094–1103
Hinshaw SP (1994) Attention deficits and hyperactivity in children, vol 29. Sage, Thousand Oaks
Kissgen R, Franke S (2016) An attachment research perspective on ADHDADHS im Fokus der Bindungsforschung. Neuropsychiatrie 30(2):63–68
Crittenden PM, Kulbotton G (2007) Familial contributions to ADHD: an attachment perspective. Tidsskrift for Norsk Psykologorening 10:1220–1229
Dipietro JA, Costigan KA, Sipsma HL (2008) Continuity in self-report measures of maternal anxiety, stress, and depressive symptoms from pregnancy through two years postpartum. J Psychosom Obstet Gynaecol 29(2):115–124
Lobel M, Cannella DL, Graham JE, DeVincent C, Schneider J, Meyer BA (2008) Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychol 27(5):604
Nast I, Bolten M, Meinlschmidt G, Hellhammer DH (2013) How to measure prenatal stress? A systematic review of psychometric instruments to assess psychosocial stress during pregnancy. Paediatr Perinat Epidemiol 27(4):313–322
Osterweis M, Solomon F, Green M (1984) Committee for the study of health consequences of the stress of bereavement, Institute of Medicine. Bereavement: reactions, consequences, and care. National Academy Press, Washington, DC
Rubin SS, Malkinson R (2001) Parental response to child loss across the life cycle: clinical and research perspectives. In: Stroebe MS, Hansson RO, Stroebe W, Schut H (eds) Handbook of bereavement research: consequences, co**, and care. American Psychological Association, Washington, DC, USA, pp 219–240. https://doi.org/10.1037/10436-009
Acknowledgements
This publication has emanated from research conducted with the financial support of the Science Foundation Ireland (SFI) in the form of a research centre grant to the Irish Centre for Fetal and Neonatal Translational Research under the grant number INFANT-12/RC/2272.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding authors state that there is no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Manzari, N., Matvienko-Sikar, K., Baldoni, F. et al. Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol 54, 1299–1309 (2019). https://doi.org/10.1007/s00127-019-01745-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00127-019-01745-3