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
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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)