Our systematic review suggests that exposure to prenatal smoking increases risk for overweight in childhood. The association was unaffected by adjustment for parental sociodemographic factors and body size, gestational weight gain, infant feeding, and child behaviors, indicating that social and behavioral differences between smokers and nonsmokers are not likely to account for the observed differences in overweight risk. In all of the studies, smoking during pregnancy was associated with increased overweight in offspring, despite a wide range of populations, smoking habits, birth years, and overweight prevalence. Compared with children of nonsmokers, children exposed to prenatal smoking may be heavier, shorter or both.
Publication bias likely exists, as smaller studies reported stronger effects than larger ones, and no published studies were null or reported an inverse association. The data in our review come from observational studies rather than registered clinical trials, so we cannot determine the number of unpublished null studies. We did not contact authors to obtain unpublished effect estimates. However, our efforts to impute the unpublished data suggest that the observed association does not entirely derive from a publication bias.
Other studies have evaluated additional endpoints related to overweight. Single studies have suggested that individuals exposed to prenatal smoking may have greater weight gain from birth to age 2 years,45
elevated risk for diabetes mellitus,54
and exhibit a high-risk cluster of low birth weight and higher attained BMI,55
or of higher BMI, blood pressure, lipids, and glucose levels.56
Several investigators have studied associations between prenatal smoking exposure and blood pressure in childhood. In the studies that accounted for sociodemographics and other characteristics including child size, systolic blood pressure was consistently about 1 mm Hg higher among children who were exposed to prenatal maternal smoking.19,36,57,58
A growing body of epidemiologic and experimental evidence indicates that the prenatal period is a sensitive period for later health outcomes.59
Early research in the field considered birth weight as a marker for intrauterine nutrition. The example of maternal smoking highlights the importance of looking at more refined measures, such as body composition, rather than birth weight alone in studying prenatal influences on later size and disease risk. Maternal smoking may result in lower fetal growth but more rapid postnatal weight gain, yet both fetal growth and weight gain in early infancy are directly associated with weight in later life.7
In our meta-analysis, associations of smoking with child overweight were independent of birth weight or fetal growth and postnatal weight gain. These apparently incongruous relationships may be explained by reports that even at birth, infants born to mothers who smoked in pregnancy have a preserved ponderal index60
(a measure of weight for length) compared with infants of nonsmokers, and have relatively more body fat but less lean body mass.61,62
These findings also reinforce the need for research aimed at understanding pathways independent of early growth by which early life experiences may influence later health and disease risk.59
Mechanisms by which maternal smoking may program child weight are not yet well characterized. Likely culprits for the physiologic effects of cigarette smoking during pregnancy are nicotine, which is transported across the placenta, and carbon monoxide, which may influence placental vascular function and cause fetal hypoxia. In both humans and animals, nicotine acts both centrally and peripherally to reduce appetite and body weight, and nicotine withdrawal results in hyperphagia and weight gain.63–65
Children of smokers tend to be less physically active and have poorer diet quality.66–68
In one study, adults with prenatal smoking exposure were more likely to report having a ‘poor appetite’, although dietary intake was not measured; since they were also heavier, appetite perception might have been influenced rather than appetite itself.20,69
In animal studies, administration of nicotine to pregnant mothers resulted in offspring that were smaller at birth but had increased body fat.70–73
In other studies, rats prenatally exposed to low doses of nicotine were not smaller at birth but became heavier by 5–10 weeks of age74,75
and had higher overall body fat as well as increased perivascular adipose tissue, resulting in decreased vascular relaxation.75
In another protocol, prenatal nicotine exposure did not influence body weight, but caused higher blood pressure only among genetically susceptible rats.76
Among humans, some researchers have studied whether hormones such as leptin may mediate associations of smoking with offspring size. Maternal smoking throughout pregnancy may be associated with lower cord blood leptin77,78
though other studies have not suggested an association.79,80
Investigations of other possible mediators, including growth hormone and IGF-1, have not been as well studied,80
and no data exist regarding levels of any of these hormones beyond the newborn period.
A recent systematic review of prenatal programming of childhood overweight and obesity also considered prenatal smoking, concluding that strong evidence linked maternal smoking with childhood obesity.81
However, those authors included only 8 studies of the 14 that we evaluated, primarily those with simultaneous collection of exposure and outcome data and with clinical height and weight measurement, did not calculate a pooled effect size, and did not consider publication bias. This present study overcomes these limitations and allows for an estimation of the public health impact on overweight risk resulting from maternal prenatal smoking.
All of the studies included in the present meta-analysis relied upon maternal self-report of smoking behaviors without biochemical validation. However, self-report of smoking during pregnancy has reasonable validity,82
and any under-reporting would likely bias results towards the null. Although some studies collected information on prenatal smoking at the same time that child outcomes were assessed, we doubt recall bias as exclusion of these studies did not substantially change estimates. All studies used measured height and weight as the endpoint, none relied on self-report. Sufficient data do not exist to determine whether quitting smoking would lower the risk of child overweight to the same degree as never having smoked.
In addition to demographic differences such as education and income, smokers and their children also tend to have less healthy lifestyle habits, including diet and physical activity.66–68,83
Residual confounding may explain the observed higher risk for overweight in exposed children. The similar pooled estimates for unadjusted and adjusted associations suggest that sociodemographic, behavioral, and dietary differences between smokers and nonsmokers did not explain the observed association. A recent publication found that associations of maternal prenatal smoking with child body fat were only slightly stronger than associations of paternal prenatal smoking, and concluded that residual confounding may explain the observed association.39
However, the evidence for dose-effect, the lack of association with smoking before or after pregnancy, the support from animal studies, and the consistency of results across populations with markedly different demographic profiles and confounding structures make it more likely that a causal association exists. Future studies following children whose mothers participated in randomized trials of smoking cessation during pregnancy might help further elucidate the role of confounding.
In conclusion, available evidence suggests that maternal smoking during pregnancy increases risk for overweight in childhood. These findings add to the recognized health burden from tobacco, already estimated at almost 5 million deaths per year.5
The overall population impact of a 50% increased risk of overweight is likely to be large. In the US, where 11% of pregnant women currently smoke4
and child overweight is highly prevalent,84
about 715 000 US children may be overweight because their mothers smoked. Individuals who are born small and later become obese are at highest risk for developing cardiovascular disease.7
This phenotype, typical of exposure to maternal prenatal smoking, is also characteristic of parts of the world undergoing the nutritional transition to high fat diets and sedentary lifestyle and the accompanying epidemiologic transition to chronic diseases associated with obesity.8
In such populations, the combination of poor maternal nutrition, lower birth weight, and increasing adoption of a western lifestyle heralds an explosion in obesity and cardiovascular disease that may well intensify if young women respond to tobacco companies’ advertisements targeting them.8,85