The impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study

BMC Medicine, Feb 2015

Background Maternal smoking during pregnancy (MSDP) is associated with multiple adverse childhood outcomes including externalizing behaviors. However, the association between MSDP and internalizing (anxiety and depressive) behaviors in offspring has received less investigation. We aimed to assess the association between MSDP and childhood internalizing (anxiety and depressive) behaviors in a very large, well-characterized cohort study. Methods We assessed the association between MSDP and internalizing behaviors in offspring utilizing information drawn from 90,040 mother-child pairs enrolled in the Norwegian Mother and Child Cohort Study. Mothers reported smoking information, including status and frequency of smoking, twice during pregnancy. Mothers also reported their child’s internalizing behaviors at 18 months, 36 months, and 5 years. Associations between MSDP and childhood internalizing behaviors, including dose-response and timing of smoking in pregnancy, were assessed at each time point. Results MSDP was associated with increased internalizing behaviors when offspring were aged 18 months (B = 0.11, P <0.001) and 36 months (B = 0.06, P <0.01), adjusting for numerous potential confounders. Higher rates of smoking (e.g., >20 cigarettes per day) were associated with higher levels of internalizing behaviors. Maternal smoking during early pregnancy appeared to be the critical period for exposure. Conclusions We found evidence supporting a potential role for MSDP in increasing internalizing (anxiety and depressive) behaviors in offspring. We also found evidence supportive of a possible causal relationship, including dose-dependency and support for a predominant role of early pregnancy exposure. Further investigation utilizing genetically informed designs are warranted to assess this association.

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The impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study

Moylan et al. BMC Medicine The impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study Steven Moylan 0 1 Kristin Gustavson Simon verland Evalill Blstad Karevold Felice N Jacka 0 Julie A Pasco 0 Michael Berk 0 1 0 School of Medicine, Deakin University , Geelong, Victoria 3220 , Australia 1 Barwon Health , Geelong, Victoria 3220 , Australia Background: Maternal smoking during pregnancy (MSDP) is associated with multiple adverse childhood outcomes including externalizing behaviors. However, the association between MSDP and internalizing (anxiety and depressive) behaviors in offspring has received less investigation. We aimed to assess the association between MSDP and childhood internalizing (anxiety and depressive) behaviors in a very large, well-characterized cohort study. Methods: We assessed the association between MSDP and internalizing behaviors in offspring utilizing information drawn from 90,040 mother-child pairs enrolled in the Norwegian Mother and Child Cohort Study. Mothers reported smoking information, including status and frequency of smoking, twice during pregnancy. Mothers also reported their child's internalizing behaviors at 18 months, 36 months, and 5 years. Associations between MSDP and childhood internalizing behaviors, including dose-response and timing of smoking in pregnancy, were assessed at each time point. Results: MSDP was associated with increased internalizing behaviors when offspring were aged 18 months (B = 0.11, P <0.001) and 36 months (B = 0.06, P <0.01), adjusting for numerous potential confounders. Higher rates of smoking (e.g., >20 cigarettes per day) were associated with higher levels of internalizing behaviors. Maternal smoking during early pregnancy appeared to be the critical period for exposure. Conclusions: We found evidence supporting a potential role for MSDP in increasing internalizing (anxiety and depressive) behaviors in offspring. We also found evidence supportive of a possible causal relationship, including dose-dependency and support for a predominant role of early pregnancy exposure. Further investigation utilizing genetically informed designs are warranted to assess this association. Anxiety; Depression; Cigarette smoking; Pregnancy; Obstetrics; Psychiatry - Background Maternal smoking during pregnancy (MSDP) is associated with numerous adverse outcomes in children. These occur in physical, cognitive, and behavioral domains, including stillbirth [1], lowered birth weight [2], childhood asthma [3], obesity [4], intelligence [5], hyperactivity, impulsivity, and conduct problems [6-10]. Hypotheses explaining these associations include direct causation (e.g., cigarette components directly damaging developing fetal structures and physiological systems) and shared vulnerability [11-13] (e.g., genetic and/or environmental factors increasing rates of MSDP and childhood outcomes). In the realm of childhood behavioral outcomes, consistent findings from multiple prospective observational studies [14], controlling for plausible confounders, support an argument for a direct causal relationship (e.g., via physiological effects) rather than one solely underpinned by shared vulnerability. This is complimented by animal and human research [15] demonstrating that MSDP can disrupt neurodevelopment via effects on maturing neurotransmitter systems and brain architecture in regions associated with stress and mood regulation (e.g., the hippocampus [16] and somatosensory cortex [17]). Despite these findings, however, debate continues regarding whether these associations represent causal relationships [18-20]. As noted by several authors [19,21], MSDP is associated with numerous social and environmental factors (e.g., teenage motherhood, lower maternal education [11], increased single motherhood [22]) that influence childhood outcomes. In addition, genes that influence the likelihood of MSDP [23] may also affect childhood outcomes through maternal-child genetic inheritance. For this reason, studies utilizing quasi-experimental designs [19] (e.g., siblings with discordant exposures [24], children from in vitro fertilization [25]), predominantly investigating MSDP-childhood externalizing behavior associations, have been undertaken in an attempt to control for unmeasured genetic and environmental confounders. These studies have generally demonstrated attenuation of previously observed MSDP-childhood externalizing behavior associations [11,21,26], though exceptions exist [27]. Although these approaches have advantages over traditional observational methods [19] and should be pursued further [19,28], they are not without problems [29]. For example, most studies utilizing discordant sibling and in vitro fertilization analysis have fewer participants, reducing power to detect true associations. Additionally, discordant samples are a highly selected group [29], with factors that underpin maternal behavi (...truncated)


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Steven Moylan, Kristin Gustavson, Simon Øverland, Evalill Karevold, Felice N Jacka, Julie A Pasco, Michael Berk. The impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study, BMC Medicine, 2015, pp. 24, 13, DOI: 10.1186/s12916-014-0257-4