Behavior Genetics

, Volume 46, Issue 3, pp 353–364 | Cite as

Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters

  • Valerie S. Knopik
  • Kristine Marceau
  • Rohan H. C. Palmer
  • Taylor F. Smith
  • Andrew C. Heath
Original Research


Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the fetus. There is considerable debate about the best method of assessing SDP, including birth/medical records, timeline follow-back approaches, multiple reporters, and biological verification (e.g., cotinine). This is particularly salient for genetically-informed approaches where it is not always possible or practical to do a prospective study starting during the prenatal period when concurrent biological specimen samples can be collected with ease. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we: (1) compare rates of agreement across different types of report—maternal report of SDP, paternal report of maternal SDP, and SDP contained on birth records from the Department of Vital Statistics; (2) examine whether SDP is predictive of birth weight outcomes using our best SDP report as identified via step (1); and (3) use a sibling-comparison approach that controls for genetic and familial influences that siblings share in order to assess the effects of SDP on birth weight. Results show high agreement between reporters and support the utility of retrospective report of SDP. Further, we replicate a causal association between SDP and birth weight, wherein SDP results in reduced birth weight even when accounting for genetic and familial confounding factors via a sibling comparison approach.


Birth weight Genetics Sibling comparison design Multiple reporters Smoking during pregnancy 



This work supported by NIH Grants: DA023134 (Knopik), DA17671 (Knopik), AA07728 (Heath), AA09022 (Heath), AA11998 (Heath), HD049024 (Heath), AA017688 (Heath), AA021492 (Heath). Dr. Marceau is supported by T32 DA016184. Dr. Palmer is supported by K01 AA021113 and L30 TR001045. Dr. Smith is supported by T32 MH19927.

Compliance with ethical standards

Conflicts of interest

Valerie S. Knopik, Kristine Marceau, Rohan H.C. Palmer, Taylor F. Smith, and Andrew C. Heath declare that they have no conflicts of interest.

Human and animal rights and informed consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.


  1. Agrawal A, Knopik VS, Pergadia ML, Waldron M, Bucholz KK, Martin NG, Heath AC, Madden PA (2008) Correlates of cigarette smoking during pregnancy and its genetic and environmental overlap with nicotine dependence. Nicotine Tob Res 10(4):567–578CrossRefPubMedGoogle Scholar
  2. Agrawal A, Scherrer JF, Grant JD, Sartor CE, Pergadia ML, Duncan AE, Xian H (2010) The effects of maternal smoking during pregnancy on offspring outcomes. Prev Med 50(1–2):13–18CrossRefPubMedCentralPubMedGoogle Scholar
  3. Benjamin-Garner R, Stotts A (2013) Impact of smoking exposure change on infant birthweight among a cohort of women in a prenatal smoking cessation study. Nicotine Tob Res 15(3):685–692CrossRefPubMedCentralPubMedGoogle Scholar
  4. Bidwell LC, Palmer RHC, Brick L, Heath AC, Madden PAF, Knopik VS (under review) A propensity scoring approach to characterizing the effects of maternal smoking during pregnancy on offspring’s initial responses to cigarettes and alcohol. Behav Genet Google Scholar
  5. Buka SL, Goldstein JM, Spartos E, Tsuang MT (2004) The retrospective measurement of prenatal and perinatal events: accuracy of maternal recall. Schizophr Res 71(2–3):417–426CrossRefPubMedGoogle Scholar
  6. Castles A, Adams EK, Melvin CL, Kelsch C, Boulton ML (1999) Effects of smoking during pregnancy. Five meta-analyses. Am J Prev Med 16(3):208–215CrossRefPubMedGoogle Scholar
  7. Chatterji P, Lahiri K, Kim D (2014) Fetal growth and neurobehavioral outcomes in childhood. Econ Hum Biol 15:187–200CrossRefPubMedCentralPubMedGoogle Scholar
  8. Cook DG, Strachan DP (1999) Health effects of passive smoking-10: summary of effects of parental smoking on the respiratory health of children and implications for research. Thorax 54(4):357–366CrossRefPubMedCentralPubMedGoogle Scholar
  9. 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. Dev Psychopathol 20(1):139–164PubMedCentralPubMedGoogle Scholar
  10. D’Onofrio BM, Singh AL, Iliadou A, Lambe M, Hultman CM, Grann M, Neiderhiser JM, Langstrom N, 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 67:529–538CrossRefPubMedCentralPubMedGoogle 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–S55CrossRefPubMedCentralPubMedGoogle Scholar
  12. Datta Gupta N, Deding M, Lausten M (2013) The effect of low birth weight on height, weight, and behavioral outcomes in the medium run. Econ Hum Biol 11:42–55CrossRefPubMedGoogle Scholar
  13. Dempsey D, Jacob P III, Benowitz NL (2002) Accelerated metabolism of nicotine and cotinine in pregnant smokers. J Pharmacol Exp Ther 301(2):594–598CrossRefPubMedGoogle Scholar
  14. Doherty SP, Grabowski J, Hoffman C, Ng SP, Zelikoff JT (2009) Early life insult from cigarette smoke may be predictive of chronic diseases later in life. Biomarkers 14(Suppl 1):97–101CrossRefPubMedGoogle Scholar
  15. D’Onofrio BM, Turkheimer EN, Eaves LJ, Corey LA, Berg K, Solaas MH, Emery RE (2003) The role of the Children of Twins design in elucidating causal relations between parent characteristics and child outcomes. J Child Psychol Psychiatry 44(8):1130–1144CrossRefPubMedGoogle Scholar
  16. Dwyer JB, McQuown SC, Leslie FM (2009) The dynamic effects of nicotine on the developing brain. Pharmacol Ther 122(2):125–139CrossRefPubMedCentralPubMedGoogle Scholar
  17. Einarson A, Riordan S (2009) Smoking in pregnancy and lactation: a review of risks and cessation strategies. Eur J Clin Pharmacol 65(4):325–330CrossRefPubMedGoogle Scholar
  18. Hanrahan JP, Tager IB, Segal MR, Tosteson TD, Castile RG, Van Vunakis H et al (1992) The effect of maternal smoking during pregnancy on early infant lung function. Am Rev Respir Dis 145:1129–1135CrossRefPubMedGoogle Scholar
  19. Hebel JR, Fox NL, Sexton M (1988) Dose-response of birth weight to various measures of maternal smoking during pregnancy. J Clin Epidemiol 41:483–489CrossRefPubMedGoogle Scholar
  20. Hewson D, Bennett A (1987) Childbirth research data: medical records or women’s reports. Am J Epidemiol 125:484–491PubMedGoogle Scholar
  21. Huizink AC, Mulder EJH (2006) Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. Neurosci Behav Rev 30:24–41CrossRefGoogle Scholar
  22. Hutter D, Kingdom J, Jaeggi E (2010) Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: a review. Int J PediatrGoogle Scholar
  23. Joya X, Manzano C, Álvarez AT, Mercadal M, Torres F, Salat-Batlle J, Garcia-Algar O (2014) Transgenerational exposure to environmental tobacco smoke. Int J Environ Res Public Health 11(7):7261–7274CrossRefPubMedCentralPubMedGoogle Scholar
  24. Knopik VS (2009) Maternal smoking during pregnancy and child outcomes: real or spurious effect? Dev Neuropsychol 34(1):1–36CrossRefPubMedCentralPubMedGoogle Scholar
  25. Knopik VS, Sparrow EP, Madden PAF, Bucholz KK, Hudziak JJ, Reich W, Slutske WS, Grant JD, McLaughlin TL, Todorov A, Todd RD, Heath AC (2005) Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study. Psychol Med 35(5):625–635CrossRefPubMedGoogle Scholar
  26. Knopik VS, Heath AC, Bucholz KK, Madden PAF, Waldron M (2009) Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: a female twin study. Pharmacol Biochem Behav 93(3):313–321CrossRefPubMedCentralPubMedGoogle Scholar
  27. Knopik VS, Maccani MA, Francazio S, McGeary JE (2012) The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Dev Psychopathol 24(4):1377–1390CrossRefPubMedCentralPubMedGoogle Scholar
  28. Knopik VS, Heath AC, Marceau K, Palmer RHC, McGeary JE, Todorov A, Evans A (2015) Missouri mothers and their children (MO-MATCH): a family study of the prenatal environment. Twin Res Hum Genet 18(5):485–496CrossRefPubMedCentralPubMedGoogle Scholar
  29. Kotrlik JW, Williams HA, Jabor MK (2011) Reporting and interpreting effect size in quantitative agricultural education research. J Agric Edu 52(1):132–142CrossRefGoogle Scholar
  30. Kuja-Halkola R, D’Onofrio BM, Larsson H, Lichtenstein P (2014) Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and environmental sources of covariance. Behav Genet 44(5):456–467CrossRefPubMedCentralPubMedGoogle Scholar
  31. Lambers DS, Clark KE (1996) The maternal and fetal physiologic effects of nicotine. Semin Perinatol 20(2):115–126CrossRefPubMedGoogle Scholar
  32. Land TG, Landau AS, Manning SE, Purtill JK, Pickett K, Wakschlag L, Dukic VM (2012) Who underreports smoking on birth records: a Monte Carlo predictive model with validation. PLoS One 7(4):e34853CrossRefPubMedCentralPubMedGoogle Scholar
  33. Lin C, Yon JM, Hong JT, Lee JK, Jeong J, Baek IJ, Lee BJ, Yun YW, Nam SY (2014) 4-O-methylhonokiol inhibits serious embryo anomalies caused by nicotine via modulations of oxidative stress, apoptosis, and inflammation. Birth Defects Res B 101(2):125–134CrossRefGoogle Scholar
  34. Liu J, Tuvblad C, Li L, Raine A, Baker LA (2013) Medical record validation of maternal recall of pregnancy and birth events from a twin cohort. Twin Res Hum Genet 16:845–860CrossRefPubMedCentralPubMedGoogle Scholar
  35. Marceau K, Palmer RHC, Neiderhiser JM, Smith TF, Knopik VS (under review) Passive rGE or developmental gene-environment cascade? An investigation of the role of xenobiotic genes in the association between smoking during pregnancy and child birthweight. Behav Genet Google Scholar
  36. Morales-Suarez-Varela MM, Bille C, Christensen K, Olson J (2006) Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol 107:51–57CrossRefPubMedGoogle Scholar
  37. Muthén LK, Muthén BO (1998–2012) Mplus user’s guide, 7th edn. Muthén & Muthén, Los AngelesGoogle Scholar
  38. Neiderhiser JM, Marceau K, De Araujo-Greecher M, Ganiban JM, Mayes LC, Shaw DS, Reiss D, Leve LD (under review) Refining measurement to examine how genetic and prenatal environmental factors influence early childhood behavioral outcomes. Behav Genet Google Scholar
  39. Palmer RHC, Bidwell LC, Heath AC, Brick L, Madden PAF, Knopik VS (under review) Maternal smoking during pregnancy and offspring externalizing problems: a propensity score approach. Behav Genet Google Scholar
  40. Pickett KE, Kasza K, Biesecker G, Wright RJ, Wakschlag LS (2009) Women who remember, women who do not: a methodological study of maternal recall of smoking in pregnancy. Nicotine Tob Res 11(10):1166–1174CrossRefPubMedCentralPubMedGoogle Scholar
  41. Pringle KG, Rae K, Weatherall L, Hall S, Burns C, Smith R, Lumbers ER, Blackwell CC (2015) Effects of maternal inflammation and exposure to cigarette smoke on birth weight and delivery of preterm babies in a cohort of indigenous Australian women. Front Immunol 10(6):89Google Scholar
  42. Reich W, Todd RD, Joyner CA, Neuman RJ, Heath AC (2003) Reliability and stability of mothers’ reports about their pregnancies with twins. Twin Res 6:85–88CrossRefPubMedGoogle Scholar
  43. Rice F, Harold GT, Bolvin J, Hay DF, Van den Bree M, Thapar A (2009) Disentangling prenatal and inherited influences in humans with an experimental design. PNAS 106(7):2464–2467CrossRefPubMedCentralPubMedGoogle Scholar
  44. Shah NR, Bracken MB (2000) A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery. Am J Obstet Gynecol 182(2):465–472CrossRefPubMedCentralPubMedGoogle Scholar
  45. Smith TF, Schmidt-Kastner R, McGeary JE, Kaczorowski JA, Knopik VS (under review) Prenatal ischemia-hypoxia, the ischemia-hypoxia response pathway, and ADHD risk. Behav Genet Google Scholar
  46. Snijders TA, Bosker RJ (1999) Multilevel analysis: An introduction to basic and advanced multilevel modeling. Sage, Thousand OaksGoogle Scholar
  47. StataCorp. (2015) Stata Statistical Software: Release 14. StataCorp LP, College StationGoogle Scholar
  48. Stone WL, Bailey B, Khraisha N (2014) The pathophysiology of smoking during pregnancy: a systems biology approach. Front Biosci 6:318–328CrossRefGoogle Scholar
  49. Tager IB, Ngo L, Hanrahan JP (1995) Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life. Am J Respir Crit Care Med 152:977–983CrossRefPubMedGoogle Scholar
  50. 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. Biol Psychiatry 66(8):722–727CrossRefPubMedCentralPubMedGoogle Scholar
  51. Thielen A, Klus H, Muller L (2008) Tobacco smoke: unraveling a controversial subject. Exp Toxicol Pathol 60(2–3):141–156CrossRefPubMedGoogle Scholar
  52. Todd RD, Joyner CA, Heath AC, Neuman RJ, Reich W (2003) Reliability and stability of a semi-structured DSM-IV interview designed for family studies. J Am Acad Child Adolesc Psychiatry 42(12):1460–1468CrossRefPubMedGoogle Scholar
  53. Tong VT, Dietz PM, Morrow B, D’Angelo DV, Farr SL, Rockhill KM, England LJ (2013) Trends in smoking before, during, and after pregnancy: pregnancy risk assessment monitoring system, United States, 40 Sites, 2000–2010. Morb Mortal Wkly Rep 62(SS06):1–19Google Scholar
  54. US Department of Health and Human Services (2010) A report of the surgeon general: how tobacco smoke causes disease: what it means to you. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and HealthGoogle Scholar
  55. Wakschlag LS, Kistner EO, Pine DS, Biesecker G, Pickett KE, Skol AD, Dukic V, Blair RJ, Leventhal BL, Cox NJ, Burns JL, Kasza KE, Wright RJ, Cook EH Jr (2010) Interaction of prenatal exposure to cigarettes and MAOA genotype in pathways to youth antisocial behavior. Mol Psychiatry 15(9):928–937CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Division of Behavioral Genetics, Department of PsychiatryRhode Island HospitalProvidenceUSA
  2. 2.Department of Psychiatry and Human BehaviorBrown UniversityProvidenceUSA
  3. 3.Center for Alcohol and Addiction StudiesBrown UniversityProvidenceUSA
  4. 4.Department of Psychology and Child DevelopmentCalifornia Polytechnic State UniversitySan Luis ObispoUSA
  5. 5.Midwest Alcoholism Research Center, Department of PsychiatryWashington University School of MedicineSt LouisUSA

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