Skip to main content Accessibility help

Associations of prenatal maternal smoking with offspring hyperactivity: causal or confounded?

  • K. M. Keyes (a1) (a2), G. Davey Smith (a3) and E. Susser (a1) (a2)



The relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common.


Data were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961–1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory.


Unadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [β = 0.22, 95% confidence interval (CI) 0.11–0.33] and, to a similar degree, when the father smoked (β = 0.18, 95% CI 0.07–0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (β = 0.25, 95% CI 0.09–0.40) but father smoking was not (β = 0.02, 95% CI −0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (β = 0.26, 95% CI 0.03–0.49) or did not smoke (β = 0.30, 95% CI 0.04–0.57). By number of cigarettes, associations with hyperactivity were present for 10–19 and 20+ cigarettes per day among mothers.


In a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.


Corresponding author

* Address for correspondence: K. M. Keyes, Ph.D., Assistant Professor of Epidemiology, Columbia University, 722 West 168th Street, #503, New York, NY, 10032, USA. (Email:


Hide All
Agrawal, A, Scherrer, JF, Grant, JD, Sartor, CE, Pergadia, ML, Duncan, AE, Madden, PA, Haber, JR, Jacob, T, Bucholz, KK, Xian, H (2010). The effects of maternal smoking during pregnancy on offspring outcomes. Preventative Medicine 50, 1318.
Ball, SW, Gilman, SE, Mick, E, Fitzmaurice, G, Ganz, ML, Seidman, LJ, Buka, SL (2010). Revisiting the association between maternal smoking during pregnancy and ADHD. Journal of Psychiatric Research 44, 10581062.
Brion, MJ, Leary, SD, Davey Smith, G, Ness, AR (2007). Similar associations of parental prenatal smoking suggest child blood pressure is not influenced by intrauterine effects. Hypertension 49, 14221428.
Cornelius, MD, Ryan, CM, Day, NL, Goldschmidt, L, Willford, JA (2001). Prenatal tobacco effects on neuropsychological outcomes among preadolescents. Journal of Developmental and Behavioral Pediatrics 22, 217225.
D'Onofrio, BM, Van Hulle, CA, Waldman, ID, Rodgers, JL, Harden, KP, Rathouz, PJ, Lahey, BB (2008). Smoking during pregnancy and offspring externalizing problems: an exploration of genetic and environmental confounds. Development and Psychopathology 20, 139164.
Davey, Smith G (2008). Assessing intrauterine influences on offspring health outcomes: can epidemiological studies yield robust findings? Basic and Clinical Pharmacology and Toxicology 102, 245256.
Davey, Smith G (2012). Negative control exposures in epidemiologic studies. Epidemiology 23, 350351.
Davey, Smith G, Ebrahim, S (2003). ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? International Journal of Epidemiology 32, 122.
Denson, R, Nanson, JL, McWatters, MA (1975). Hyperkinesis and maternal smoking. Canadian Psychiatry Association Journal 20, 183187.
DiFranza, JR, Aligne, CA, Weitzman, M (2004). Prenatal and postnatal environmental tobacco smoke exposure and children's health. Pediatrics 113, 10071015.
DiPietro, JA, Hodgson, DM, Costigan, KA, Hilton, SC, Johnson, TR (1996). Fetal neurobehavioral development. Child Development 67, 25532567.
Donovan, SJ, Susser, E (2011). Commentary: advent of sibling designs. International Journal of Epidemiology 40, 345349.
Dow, WH, Rehkopf, DH (2010). Socioeconomic gradients in health in international and historical context. Annals of the New York Academy of Sciences 1186, 2436.
Eriksson, P, Ankarberg, E, Fredriksson, A (2000). Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptors and in behaviour of adult mice. Brain Research 853, 4148.
Eskenazi, B, Prehn, AW, Christianson, RE (1995). Passive and active maternal smoking as measured by serum cotinine: the effect on birthweight. American Journal of Public Health 85, 395398.
Fergusson, DM, Horwood, LJ, Lynskey, MT (1993). Maternal smoking before and after pregnancy: effects on behavioral outcomes in middle childhood. Pediatrics 92, 815822.
Foley, DL, Craig, JM, Morley, R, Olsson, CA, Dwyer, T, Smith, K, Saffery, R (2009). Prospects for epigenetic epidemiology. American Journal of Epidemiology 169, 389400.
Fried, PA, Watkinson, B, Gray, R (1992). A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marihuana, cigarettes, and alcohol. Neurotoxicology and Teratology 14, 299311.
Frisell, T, Oberg, S, Kuja-Halkola, R, Sjolander, A (2012). Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology 23, 713720.
Gilman, SE, Gardener, H, Buka, SL (2008). Maternal smoking during pregnancy and children's cognitive and physical development: a causal risk factor? American Journal of Epidemiology 168, 522531.
Graham, H, Inskip, HM, Francis, B, Harman, J (2006). Pathways of disadvantage and smoking careers: evidence and policy implications. Journal of Epidemiology and Community Health 60 (Suppl. 2), 712.
Griesler, PC, Hu, MC, Schaffran, C, Kandel, DB (2008). Comorbidity of psychiatric disorders and nicotine dependence among adolescents: findings from a prospective, longitudinal study. Journal of the Ameircan Academy of Child Adolescent Psychiatry 47, 13401350.
Hill, SY, Lowers, L, Locke-Wellman, J, Shen, SA (2000). Maternal smoking and drinking during pregnancy and the risk for child and adolescent psychiatric disorders. Journal of Studies on Alcohol 61, 661668.
Johns, JM, Louis, TM, Becker, RF, Means, LW (1982). Behavioral effects of prenatal exposure to nicotine in guinea pigs. Neurobehavioral Toxicology and Teratology 4, 365369.
Keyes, KM, Davey, Smith G, Susser, E (2013 a). On sibling designs. Epidemiology 24, 473474.
Keyes, KM, March, D, Link, BG, Chilcoat, H, Susser, E (2013 b). Do socio-economic gradients in smoking emerge differently across time by gender? Implications for the tobacco epidemic from a pregnancy cohort in California, USA. Social Science and Medicine 76, 101106.
Klebanoff, MA, Levine, RJ, Clemens, JD, DerSimonian, R, Wilkins, DG (1998). Serum cotinine concentration and self-reported smoking during pregnancy. American Journal of Epidemiology 148, 259262.
Knopik, VS (2009). Maternal smoking during pregnancy and child outcomes: real or spurious effect? Developmental Neuropsychology 34, 136.
Knopik, VS, Heath, AC, Jacob, T, Slutske, WS, Bucholz, KK, Madden, PA, Waldron, M, Martin, NG (2006). Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design. Psychological Medicine 36, 14611471.
Kramer, MS (1987). Intrauterine growth and gestational duration determinants. Pediatrics 80, 502511.
Kristjansson, EA, Fried, PA, Watkinson, B (1989). Maternal smoking during pregnancy affects children's vigilance performance. Drug and Alcohol Dependence 24, 1119.
Langley, K, Heron, J, Davey, Smith G, Thapar, A (2012). Maternal and paternal smoking during pregnancy and risk of ADHD symptoms in offspring: testing for intrauterine effects. American Journal of Epidemiology 176, 261268.
Langley, K, Rice, F, van den Bree, MB, Thapar, A (2005). Maternal smoking during pregnancy as an environmental risk factor for attention deficit hyperactivity disorder behaviour. A review. Minerva Pediatrica 57, 359371.
Leary, S, Davey, Smith G, Ness, A (2006 a). Smoking during pregnancy and components of stature in offspring. American Journal of Human Biology 18, 502512.
Leary, SD, Davey, Smith G, Rogers, IS, Reilly, JJ, Wells, JC, Ness, AR (2006 b). Smoking during pregnancy and offspring fat and lean mass in childhood. Obesity (Silver Spring) 14, 22842293.
Lindblad, F, Hjern, A (2010). ADHD after fetal exposure to maternal smoking. Nicotine and Tobacco Research 12, 408415.
Linnet, KM, Wisborg, K, Obel, C, Secher, NJ, Thomsen, PH, Agerbo, E, Henriksen, TB (2005). Smoking during pregnancy and the risk for hyperkinetic disorder in offspring. Pediatrics 116, 462467.
Little, RJ, Vartivarian, S (2003). On weighting the rates in non-response weights. Statistics in Medicine 22, 15891599.
McGee, R, Stanton, WR (1994). Smoking in pregnancy and child development to age 9 years. Journal of Paediatrics and Child Health 30, 263268.
Mick, E, Biederman, J, Faraone, SV, Sayer, J, Kleinman, S (2002). Case–control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy. Journal of the American Academy of Child and Adolescent Psychiatry 41, 378385.
Milberger, S, Biederman, J, Faraone, SV, Chen, L, Jones, J (1996). Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? American Journal of Psychiatry 153, 11381142.
Naeye, RL, Peters, EC (1984). Mental development of children whose mothers smoked during pregnancy. Obstetrics and Gynecology 64, 601607.
Nomura, Y, Marks, DJ, Halperin, JM (2010). Prenatal exposure to maternal and paternal smoking on attention deficit hyperactivity disorders symptoms and diagnosis in offspring. Journal of Nervous and Mental Disease 198, 672678.
Obel, C, Olsen, J, Henriksen, TB, Rodriguez, A, Jarvelin, MR, Moilanen, I, Parner, E, Linnet, KM, Taanila, A, Ebeling, H, Heiervang, E, Gissler, M (2011). Is maternal smoking during pregnancy a risk factor for hyperkinetic disorder?–Findings from a sibling design. International Journal of Epidemiology 40, 338345.
Olfson, M, Gameroff, MJ, Marcus, SC, Jensen, PS (2003). National trends in the treatment of attention deficit hyperactivity disorder. American Journal of Psychiatry 160, 10711077.
Pickett, KE, Rathouz, PJ, Kasza, K, Wakschlag, LS, Wright, R (2005). Self-reported smoking, cotinine levels, and patterns of smoking in pregnancy. Paediatric and Perinatal Epidemiology 19, 368376.
Power, C, Jefferis, BJ (2002). Fetal environment and subsequent obesity: a study of maternal smoking. International Journal of Epidemiology 31, 413–9.
Sexton, M, Hebel, JR (1984). A clinical trial of change in maternal smoking and its effect on birth weight. Journal of the American Medical Association 251, 911915.
Streissguth, AP, Martin, DC, Barr, HM, Sandman, B, Kirchner, GL, Darby, B (1984). Intrauterine alcohol and nicotine exposure: attention and reaction time in 4-year-old children. Developmental Psychology 20, 533541.
Susser, E, Eide, MG, Begg, M (2010). Invited commentary: The use of sibship studies to detect familial confounding. American Journal of Epidemiology 172, 537539.
Thapar, A, Fowler, T, Rice, F, Scourfield, J, van den Bree, M, Thomas, H, Harold, G, Hay, D (2003). Maternal smoking during pregnancy and attention deficit hyperactivity disorder symptoms in offspring. American Journal of Psychiatry 160, 19851989.
Thapar, A, Rice, F, Hay, D, Boivin, J, Langley, K, van den Bree, M, Rutter, M, Harold, G (2009). Prenatal smoking might not cause attention-deficit/hyperactivity disorder: evidence from a novel design. Biological Psychiatry 66, 722727.
Tuddenham, RD, Brooks, J, Milkovich, L (1974). Mothers’ reports of behavior of ten-year-olds: relationships with sex, ethnicity, and mother's education. Developmental Psychology 10, 959995.
Tyrrell, J, Huikari, V, Christie, JT, Cavadino, A, Bakker, R, Brion, MJ, Geller, F, Paternoster, L, Myhre, R, Potter, C, Hohnson, PC, Ebrahim, S, Feenstra, B, Harikainen, AL, Hattersley, AT, Hofman, A, Kaakinen, M, Lowe, LP, Magnus, P, McConnachie, A, Melbye, M, Ng, JW, Nohr, EA, Power, C, Ring, SM, Sebert, SP, Sengpiel, V, Taal, HR, Watt, GC, Sattar, N, Relton, CL, Jacobsson, B, Frayling, TM, Sorensen, TI, Murray, JC, Lawlor, DA, Pennell, CE, Jaddoe, VW, Hypponen, E, Lowe, WL, Jarvelin, MR, Davey, Smith G, Freathy, RM, Early Growth Genetics Consortium (2012). Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight. Human Molecular Genetics 21, 53445358.
United States Department of Health, Education, and Welfare (1964). Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service. Public Health Service Publication no. 1103. Public Health Service Office of the Surgeon General: Washington, DC.
van de Kamp, JL, Collins, AC (1994). Prenatal nicotine alters nicotinic receptor development in the mouse brain. Pharmacology, Biochemist, and Behavior 47, 889900.
van den Berg, BJ, Christianson, RE, Oechsli, FW (1988). The California Child Health and Development Studies of the School of Public Health University of California at Berkeley. Paediatric and Perinatal Epidemiology 2, 265282.
Weissman, MM, Warner, V, Wickramaratne, PJ, Kandel, DB (1999). Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood. Journal of the American Academy of Child Adolescent Psychiatry 38, 892899.
Weitzman, M, Gortmaker, S, Sobol, A (1992). Maternal smoking and behavior problems of children. Pediatrics 90, 342349.


Type Description Title
Supplementary materials

Keyes Supplementary Material
Table S1-S4 and Figure S1-S2

 Word (277 KB)
277 KB

Associations of prenatal maternal smoking with offspring hyperactivity: causal or confounded?

  • K. M. Keyes (a1) (a2), G. Davey Smith (a3) and E. Susser (a1) (a2)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed