Behavior Genetics

, Volume 47, Issue 4, pp 383–393 | Cite as

A Family-Based Study of the Association Between Labor Induction and Offspring Attention-Deficit Hyperactivity Disorder and Low Academic Achievement

  • Kelsey K. Wiggs
  • Martin E. Rickert
  • Sonia Hernandez-Diaz
  • Brian T. Bateman
  • Catarina Almqvist
  • Henrik Larsson
  • Paul Lichtenstein
  • Anna Sara Oberg
  • Brian M. D’Onofrio
Original Research


The current study examined associations between labor induction and both (1) offspring attention-deficit hyperactivity disorder (ADHD) diagnosis in a Swedish birth cohort born 1992–2005 (n = 1,085,008) and (2) indices of offspring low academic achievement in a sub-cohort born 1992–1997 (n = 489,196). Associations were examined in the entire sample (i.e., related and unrelated individuals) with adjustment for measured covariates and, in order to account for unmeasured confounders shared within families, within differentially exposed cousins and siblings. We observed an association between labor induction and offspring ADHD diagnosis and low academic achievement in the population. However, these associations were fully attenuated after adjusting for measured covariates and unmeasured factors that cousins and siblings share. The results suggest that observed associations between labor induction and ADHD and low academic achievement may be due to genetic and/or shared environmental factors that influence both mothers’ risk of labor induction and offspring neurodevelopment.


Labor induction Attention-deficit hyperactivity disorder Academic achievement Family studies Sibling comparison Cousin comparison 



This study was supported by grants from the Indiana Clinical and Translational Sciences Institute: Pediatric Project Development Team; the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) framework Grant No 340-2013-5867; the National Institute of Health, T32 Grant No HD 07475. This study was approved by the Institutional Review Board at the Karolinska Institutet.

Compliance with Ethical Standards

Conflict of interest

H Larsson has served as a speaker for Eli-Lilly and Shire and has received research grants from Shire; all outside the submitted work. Paul Lichtenstein has served as a speaker for Medice. All other authors report no conflicts of interest.

Research Involving with Human and Animal Rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and/or with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

For this type of study, formal consent was not required. This article does not contain any studies with animals performed by any of the authors.

Supplementary material

10519_2017_9852_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 26 KB)


  1. Barker DJP (1998) Mothers, babies, and health in later life. Elsevier Health Sciences, AmsterdamGoogle Scholar
  2. Berkowitz GS, Lapinski RH, Wein R, Lee D (1992) Race/ethnicity and other risk factors for gestational diabetes. Am J Epidemiol 135(9):965–973CrossRefPubMedGoogle Scholar
  3. Bramson L, Rickert M, Class Q, Sariaslan A, Almqvist C, Larsson H, D’onofrio B (2016) The association between childhood relocations and subsequent risk of suicide attempt, psychiatric problems, and low academic achievement. Psychol Med 46(05):969–979CrossRefPubMedGoogle Scholar
  4. Cammu H, Martens G, Ruyssinck G, Amy J-J (2002) Outcome after elective labor induction in nulliparous women: a matched cohort study. Am J Obstet Gynecol 186(2):240–244CrossRefPubMedGoogle Scholar
  5. Chang Z, Lichtenstein P, D’Onofrio BM, Almqvist C, Kuja-Halkola R, Sjölander A, Larsson H (2014) Maternal age at childbirth and risk for ADHD in offspring: a population-based cohort study. Int J Epidemiol dyu204Google Scholar
  6. Chen Q, Sjölander A, Långström N, Rodriguez A, Serlachius E, D’Onofrio BM, Larsson H (2013) Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design. Int J Epidemiol dyt152Google Scholar
  7. Cnattingius S, Ericson A, Gunnarskog J, Kallen B (1990) A quality study of a medical birth registry. Scand J Soc Med 18(2):143–148. Retrieved from
  8. Coonrod DV, Bay RC, Kishi GY (2000) The epidemiology of labor induction: Arizona, 1997. Am J Obstet Gynecol 182(6):1355–1362Google Scholar
  9. Cochran D, Fallon D, Hill M, Frazier JA (2013) The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings. Harv Rev Psychiatry 21(5):219CrossRefPubMedPubMedCentralGoogle Scholar
  10. D’onofrio BM, Singh AL, Iliadou A, Lambe M, Hultman CM, Grann M, Lichtenstein P (2010) Familial confounding of the association between maternal smoking during pregnancy and offspring criminality: a population-based study in Sweden. Arch Gen Psychiatry 67(5):529–538CrossRefPubMedPubMedCentralGoogle Scholar
  11. D’Onofrio BM, Lahey BB, Turkheimer E, Lichtenstein P (2013) The critical need for family-based, quasi-experimental research in integrating genetic and social science research. Am J Public Health 103:S46–S55CrossRefPubMedPubMedCentralGoogle Scholar
  12. D’Onofrio BM, Class QA, Rickert ME et al (2016) Translational epidemiologic approaches to understanding the consequences of early-life exposures. Behav Genet 46(3):315–328CrossRefPubMedGoogle Scholar
  13. Frisell T, Öberg S, Kuja-Halkola R, Sjölander A (2012) Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology 23(5):713–720CrossRefPubMedGoogle Scholar
  14. Frost F, Starzyk P, George S, McLaughlin JF (1984) Birth complication reporting: the effect of birth certificate design. Am J Public Health 74(5):505–506CrossRefPubMedPubMedCentralGoogle Scholar
  15. Getahun D, Rhoads GG, Demissie K, Lu SE, Quinn VP, Fassett MJ, Jacobsen SJ (2013) In utero exposure to ischemic-hypoxic conditions and attention-deficit/hyperactivity disorder. Pediatrics 131(1):e53–e61CrossRefPubMedGoogle Scholar
  16. Gregory SG, Anthopolos R, Osgood CE, Grotegut CA, Miranda ML (2013) Association of autism with induced or augmented childbirth in North Carolina Birth Record (1990–1998) and Education Research (1997–2007) databases. JAMA Pediatr 167(10):959–966. doi: 10.1001/jamapediatrics.2013.2904 CrossRefPubMedGoogle Scholar
  17. Hannah ME, Hannah WJ, Hellmann J, Hewson S, Milner R, Willan A (1992) Induction of labor as compared with serial antenatal monitoring in post-term pregnancy: a randomized controlled trial. N Engl J Med 326(24):1587–1592CrossRefPubMedGoogle Scholar
  18. Heckman JJ (2012) The developmental origins of health. Health Econ 21(1):24–29. doi: 10.1002/hec.1802 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kenyon S, Tokumasu H, Dowswell T, Pledge D, Mori R (2013) High-dose versus low-dose oxytocin for augmentation of delayed labour. The Cochrane LibraryGoogle Scholar
  20. Kjos SL, Henry OA, Montoro M, Buchanan TA, Mestman JH (1993) Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management. Ame J Obstet Gynecol 169(3):611–615CrossRefGoogle Scholar
  21. Kurth L, Haussmann R (2011) Perinatal pitocin as an early ADHD biomarker: neurodevelopmental risk? J Atten Disorders 15:423–431CrossRefGoogle Scholar
  22. Lambe M, Hultman C, Torrång A, MacCabe J, Cnattingius S (2006) Maternal smoking during pregnancy and school performance at age 15. Epidemiology 17(5):524–530CrossRefPubMedGoogle Scholar
  23. Larsson H, Rydén E, Boman M, Långström N, Lichtenstein P, Landén M (2013) Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder. Br J Psychiatry 203(2):103–106CrossRefPubMedPubMedCentralGoogle Scholar
  24. Larsson H, Sariaslan A, Långström N, D’Onofrio B, Lichtenstein P (2014a) Family income in early childhood and subsequent attention deficit/hyperactivity disorder: a quasi-experimental study. J Child Psychol Psychiatry 55(5):428–435CrossRefPubMedGoogle Scholar
  25. Larsson H, Chang Z, D’Onofrio BM, Lichtenstein P (2014b) The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychol Med 44(10):2223–2229CrossRefPubMedGoogle Scholar
  26. Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A (2009) The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol 24(11):659–667. doi: 10.1007/s10654-009-9350-y CrossRefPubMedPubMedCentralGoogle Scholar
  27. Luthy DA, Malmgren JA, Zingheim RW (2004) Cesarean delivery after elective induction in nulliparous women: the physician effect. Am J Obstet Gynecol 191(5):1511–1515CrossRefPubMedGoogle Scholar
  28. Nassar AH, Adra AM, Chakhtoura N, Gómez-Marín O, Beydoun S (1998) Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol 179(5):1210–1213CrossRefPubMedGoogle Scholar
  29. National Board of Health and Welfare (2003) The Swedish Medical Birth Register—A Summary of Content and Quality. Retrieved from StockholmGoogle Scholar
  30. National Board of Health and Welfare (2009) Quality and Content in the Patient Register—Inpatient care discharges 1964–2007 and outpatient (specialized care) visits 1997–2007 [in Swedish] (2009-125-15). Retrieved from StockholmGoogle Scholar
  31. Nomura Y, Marks DJ, Grossman B, Yoon M, Loudon H, Stone J, Halperin JM (2012) Exposure to gestational diabetes mellitus and low socioeconomic status: effects on neurocognitive development and risk of attention-deficit/hyperactivity disorder in offspring. Arch Pediatr Adolesc Med 166(4):337–343CrossRefPubMedGoogle Scholar
  32. Oberg AS, D’Onofrio BM, Rickert ME, Hernandez-Diaz S, Ecker J L, Almqvist C, Bateman BT (2016) Association of Labor Induction with Offspring Risk of Autism Spectrum Disorders. JAMA Pediatr 170: e160965–e160965CrossRefPubMedGoogle Scholar
  33. Osterman MJ, Martin JA (2014) Recent declines in induction of labor by gestational age. NCHS Data Brief 155(155):1–8. Retrieved from
  34. Saade GR, Sibai BM, Silver R (2014) Induction or augmentation of labor and autism. JAMA Pediatr, 168(2):190–191. doi: 10.1001/jamapediatrics.2013.4800 CrossRefPubMedGoogle Scholar
  35. Silva D, Colvin L, Hagemann E, Bower C (2014a) Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder. Pediatrics 133(1):e14–e22. doi: 10.1542/peds.2013-1434 CrossRefPubMedGoogle Scholar
  36. Silva D, Colvin L, Hagemann E, Bower C (2014b) Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder. Pediatrics 133(1):e14–e22CrossRefPubMedGoogle Scholar
  37. Skoglund C, Chen Q, Lichtenstein P, Larsson H (2014) Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring. J Child Psychol Psychiatry 55(1):61–68CrossRefPubMedGoogle Scholar
  38. Smith JG, Merrill DC (2006) Oxytocin for induction of labor. Clin Obstet Gynecol 49(3):594–608CrossRefPubMedGoogle Scholar
  39. Spong CY, Landon MB, Gilbert S, Rouse DJ, Leveno KJ, Varner MW, Wapner RJ (2007) Risk of uterine rupture and adverse perinatal outcome at term after cesarean delivery. Obstet Gynecol 110(4):801–807CrossRefPubMedGoogle Scholar
  40. Stitely ML (2014) Induction or augmentation of labor and autism. JAMA Pediatr 168(2):189–190. doi: 10.1001/jamapediatrics.2013.4789 CrossRefPubMedGoogle Scholar
  41. Vintzileos A, Ananth C (2014) Induction or augmentation of labor and autism. JAMA Pediatr 1168:190CrossRefGoogle Scholar
  42. Vivian-Taylor J, Sheng J, Hadfield RM, Morris JM, Bowen JR, Roberts CL (2011) Trends in obstetric practices and meconium aspiration syndrome: a population-based study. BJOG 118(13):1601–1607CrossRefPubMedGoogle Scholar
  43. Wahl RU (2004) Could oxytocin administration during labor contribute to autism and related behavioral disorders?—a look at the literature. Med Hypotheses 63(3):456–460. doi: 10.1016/j.mehy.2004.03.008 CrossRefPubMedGoogle Scholar
  44. Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I (2015) Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr 169(2):154–162CrossRefPubMedPubMedCentralGoogle Scholar
  45. WHO (1992) International classification of diseases. World Health Organization WHO, GenevaGoogle Scholar
  46. WHO (2004) International statistical classification of diseases and health related problems (The) ICD-10. World Health Organization, GenevaGoogle Scholar
  47. Zhang C, Bao W, Rong Y, Yang H, Bowers K, Yeung E, Kiely M (2013) Genetic variants and the risk of gestational diabetes mellitus: a systematic review. Hum Reprod Update 19(4):376–390CrossRefPubMedPubMedCentralGoogle Scholar
  48. Statistics Sweden (2010) Multi-Generation Register 2009—a description of contents and quality (2010:13). Retrieved from Örebro, SwedenGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kelsey K. Wiggs
    • 1
  • Martin E. Rickert
    • 1
  • Sonia Hernandez-Diaz
    • 2
  • Brian T. Bateman
    • 3
    • 4
  • Catarina Almqvist
    • 5
    • 6
  • Henrik Larsson
    • 5
    • 7
  • Paul Lichtenstein
    • 5
  • Anna Sara Oberg
    • 2
    • 5
  • Brian M. D’Onofrio
    • 1
  1. 1.Department of Psychological and Brain SciencesIndiana UniversityBloomingtonUSA
  2. 2.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  3. 3.Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine at Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  5. 5.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  6. 6.Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children’s Hospital, Karolinska University HospitalKarolinska InstitutetStockholmSweden
  7. 7.School of Medical SciencesOrebro UniversityOrebroSweden

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