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Original Article |

Familial Confounding of the Association Between Maternal Smoking During Pregnancy and Offspring Substance Use and Problems

Brian M. D’Onofrio, PhD; Martin E. Rickert, MSc, PhD; Niklas Langström, PhD; Kelly L. Donahue, BA; Claire A. Coyne, BA; Henrik Larsson, PhD; Jarrod M. Ellingson, MA; Carol A. Van Hulle, PhD; Anastasia N. Iliadou, PhD; Paul J. Rathouz, PhD; Benjamin B. Lahey, PhD; Paul Lichtenstein, PhD
Arch Gen Psychiatry. 2012;69(11):1140-1150. doi:10.1001/archgenpsychiatry.2011.2107.
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Context  Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring.

Objective  To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design.

Design  We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding.

Setting  Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2).

Patients or Other Participants  Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1 187 360).

Main Outcome Measures  Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2).

Results  The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR]moderate, 1.32 [95% CI, 1.22-1.43]; HRhigh, 1.33 [1.17-1.53]) to a narcotics-related conviction (HRmoderate, 2.23 [2.14-2.31]; HRhigh, 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant.

Conclusions  The association between maternal SDP and offspring substance use/problems is likely due to familial background factors, not a causal influence, because siblings have similar rates of substance use and problems regardless of their specific exposure to SDP.

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Figures

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Grahic Jump Location

Figure 1. Hazard and odds ratio estimates for the association between maternal smoking during pregnancy (SDP) and offspring substance use/problems in the US sample. Whiskers represent 95% CIs. Point estimates for moderate and high SDP are compared with no SDP. Model 1 presents the unadjusted associations in the entire sample. Model 2 presents the associations in the sample controlling for statistical covariates. Model 3 presents the estimated associations fitting fixed-effects models at the maternal level, which compared differentially exposed siblings. The estimated hazard ratios for adolescent use of alcohol, cigarettes, and marijuana were based on Cox proportional hazard survival models with a sandwich estimator to account for familial clustering. The estimated odds ratios for early use of alcohol, cigarettes, and marijuana were based on logistic regression models with a sandwich estimator to account for familial clustering.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Hazard ratios for the association between maternal smoking during pregnancy (SDP) and offspring substance use/problems in the Swedish sample. Whiskers represent 95% CIs. Point estimates for moderate and high levels of SDP are compared with no SDP. Model 1 presents the unadjusted associations in the entire sample. Model 2 presents the associations in the sample controlling for statistical covariates. Model 3 presents the estimated associations fitting fixed-effects models at the maternal level, which compared differentially exposed siblings. All estimated hazard ratios are based on Cox proportional hazard survival models, which used a sandwich estimator to account for familial clustering.

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