Prenatal smoking and the risk of early childhood caries: A prospective cohort study.

1.Introduction

Dental caries is a chronic complex disease of multifactorial etiology (Chapple et al., 2017) that affects about a quarter of U.S. children (Dye et al., 2015). Widely accepted risk factors are a susceptible tooth, fermentable carbohydrates and caries bacteria. Given its multifactorial etiology and chronic complex nature, the etiology of dental caries comprises certain upstream risk factors —including prenatal exposures— that promote a favorable oral environment for caries susceptibility, development and progression. One such exposure is maternal smoking during pregnancy (prenatal smoking).

The United States is one of 10 countries comprising 2/3rds of all smokers worldwide (World Health Organization, 2013). While prenatal smoking rates continue to decline (Tong et al., 2013), a 2010 U.S. data from the World Health Organization suggests that 13.6% of women in obstetrics care smoke, with differences according to race/ethnicity and socio-economic position (Samet et al., 2010). More recent data based on the 2014 U.S. birth certificate records representing 95% of all births that year indicate that 8.4% of women smoked at any time during their pregnancy, with differences seen according to race/ethnicity and geographic location (Curtin and Matthews, 2016).

Maternal smoking during pregnancy alters fetal blood flow and protein metabolism (Zhou et al., 2014) and exposes the growing fetus to chemical toxins like nicotine through its direct metabolite (cotinine), known to cross the placenta and accumulate in fetal tissues (Maritz, 2008). Indeed, prenatal smoking is consistently reported to have negative effects on the health of the offspring. Among these are respiratory illnesses (Jurado et al., 2005, Metsala et al., 2008), cleft lip and palate (Chung et al., 2000), attention deficit hyperactivity disorders (Dong et al., 2018) as well as elevated systolic BP (Cabral et al., 2017).

Evidence linking prenatal smoking to offspring caries experience is sparse and methodologically inadequate (Williams et al., 2000, Claudia et al., 2016, Tanaka et al., 2015, Tanaka et al., 2009, Tanaka et al., 2015, Majorana et al., 2014, Iida et al., 2007, Schroth et al., 2013). In a study of 1576 women, the association between prenatal smoking and offspring dental caries was derived from multivariable adjusted models where prenatal smoking was not the main exposure variable (Iida et al., 2007). Therefore, findings may have been biased by adjusting for variables that are not confounders. In another study, reliance only on mothers self-reported offspring decay (Claudia et al., 2016) is subject to recall bias especially for teeth missing for reasons (like trauma) other than dental decay and for sealants accidentally recalled as dental restorations. For other studies, the emphasis was on post-natal exposure of the child to environmental tobacco smoke (ETS) in the home (Williams et al., 2000, Tanaka et al., 2015, Hanioka et al., 2011) and thus does not capture exposures occurring prenatally. Among studies that specifically investigated prenatal smoking, smoking during pregnancy had to be recalled several years after the pregnancy (Claudia et al., 2016, Tanaka et al., 2015, Tanaka et al., 2009, Tanaka et al., 2015, Majorana et al., 2014), and therefore also subject to under/mis-reporting and recall bias. Although a systematic review of cross-sectional studies of prenatal smoking and offspring caries was recently conducted, its findings were inconclusive and called for well-designed longitudinal studies (Kellesarian et al., 2017).

The aims of this study were two-fold: 1) to assess whether prenatal smoking and the quantity of cigarettes smoked during pregnancy were associated with offspring dental caries experience; 2) using a negative control exposure method to assess the potential causal nature of the prenatal smoking-offspring caries experience by substituting maternal smoking for partner smoking during pregnancy.

2. Methods

2.5. Statistical analysis

Data analysis was restricted to singleton births who were alive at age 1 year. Descriptive analysis began with an exploration of the distribution of selected covariates for the children-in-focus sample and children not selected for this subsample to assess if there were any meaningful differences between them. Means and SDs were reported for continuous variables while frequencies and relative frequencies were reported for categorical variables. Covariates included as confounders and outcome (offspring caries experience) risk factors were determined after analyzing a directed acyclic graph (Greenland et al., 1999, Akinkugbe et al., 2016) – Appendix B; Fig. 1. Regression analyses of the potential association between prenatal smoking and offspring caries experience were modeled in three ways: 1) we utilized log-binomial regression models to estimate the 31-month, 43-month and 5-year risks of objectively determined offspring dental caries experience (i.e. dmft > 1) and the corresponding risk ratios (RR) and 95% confidence intervals (C.I); 2) we used a discrete time hazards regression (Richardson, 2010)) to estimate the hazard odds ratio (HOR) and 95% C.I. of first caries experience occurrence (see Appendix A for more detail); 3) we used a zero-inflated negative binomial (ZINB) regression (Preisser et al., 2012, Preisser et al., 2016) to estimate the prenatal smoking association on total dmft count and evaluated the fit of the ZINB model using the Vuong’s test (see Appendix A for more detail). We assessed likely dose–response association according to number of cigarettes smoked per day (none, <half pack, >half pack) during pregnancy with offspring caries experience for the methods of analyses previously described.

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Fig. 1

Adjusted associations between prenatal smoking and quantity smoked with the 31, 43 and 61-month risk of and offspring caries experience: Avon Longitudinal Study of Parents and Children.

3. Results

Table 1 shows the distribution of selected covariates for the CIF sample and children not selected for the CIF sub-study. Mothers of the CIF sample were on average older, more likely to be aged between 25 and 35 years and to have advanced education as compared to mothers of children not selected for the CIF sample.

Overall, 22% percent of the mothers smoked during pregnancy, 14% smoked < half pack/day and 7.9% smoked >half pack/day during pregnancy. Three percent of the children had dmft > 1 at 31 months, 16% and 31% at 43 months and 61 months respectively. The average time under study was 55 months for children of mothers who reported smoking during pregnancy and 57 months for children of mothers who did not smoke during pregnancy. Thirty-three percent of the children of non-smoking mothers developed caries at some point during follow-up with a mean dmft count of 0.33 as compared to 46% of children whose mothers smoked during pregnancy with a mean dmft count of 1.58 (Table 2).

Offspring caries experience risk in the prenatal smoking group was 4%, 21% and 38% at 31, 43 and 61 months respectively (Table 3). Further, prenatal smoking was associated with 41% increased risk of offspring caries (95% CI: 1.03, 1.91) at 43 months and a 30% (95% CI: 1.08, 1.58) increased risk at 61 months as compared to the risk in non-smoking mothers. Upon covariate adjustment, prenatal smoking retained its positive association with offspring caries experience, however, the magnitudes of the associations were smaller and less precisely estimated (Fig. 1).

The adjusted hazard odds of first occurrence of offspring caries for prenatal smoking in contrast with no prenatal smoking was 1.42 (95% CI: 1.08, 1.86). Similarly, there appeared to be a dose–response increase in the hazard odds of caries experience according to the quantity of cigarettes smoked per day during pregnancy. Compared to children of non-smoking mothers, children whose mothers smoked <half pack/day were 10% more likely to experience caries while children of mothers who smoked >half pack/day were 38% (95% CI: 0.98, 1.95) more likely to experience caries (Table 4). Each additional half pack of cigarettes smoked per day increased the hazard odds of first offspring caries experience occurrence by 34% (95% CI: 1.05, 1.71). Findings from the ZINB model were consistent with increased caries experience according to prenatal smoking status as well as a dose–response association with quantity smoked (Appendix C; Table 2). Furthermore, the latent or logistic part (see Appendix A) of the ZINB model was consistent with an inverse association between prenatal smoking and offspring caries. In other words, prenatal smoking was associated with having fewer zeros (i.e. no caries experience) while the non-smoking group had more zeros. Results of complete case analysis (i.e. data analysis without imputation) were consistent in magnitude and direction as the analysis with imputed observations (Appendix D; Table 1, Table 2, Table 3).

4. Discussion

In this prospective cohort study, both maternal- and partner-smoking during pregnancy were associated with slightly increased risk of dental caries developing in the offspring. Further, we found a positive dose–response association with the quantity of cigarettes smoked per day during pregnancy with respect to offspring caries experience.

Although we were unable to assess tooth eruption patterns in this study, Ntani and colleagues (Ntani et al., 2015) reported that children whose mothers smoked during pregnancy had more teeth erupted at ages 1 and 2 years compared to similarly aged children whose mothers did not smoke. This suggests that prematurely erupted teeth are likely more susceptible to Mutan Streptococci (caries bacteria) colonization (Law and Seow, 2006, Caufield et al., 2012) by way of exposure to frequent infant feedings and the corresponding oral environment longer than teeth that are not prematurely erupted and by extension, more opportunity for caries development. Other studies indicate that prenatal smoking (Jaddoe et al., 2008) is associated with low-birth weight and prematurity, conditions reported to increase the risk for developmental enamel defects (Caufield et al., 2012, Vello et al., 2010), that are highly susceptible to cariogenic bacteria (Plonka et al., 2013, Salanitri and Seow, 2013) in the presence of fermentable carbohydrates (Caufield et al., 2012).

The positive prenatal smoking association on offspring caries experience we observed at a younger age persisted to older ages and suggest that exposures in-utero may have detrimental oral health effects later in the life of the child. This is surprising given the expectation that caries when the child is older may be largely dependent on several factors including the child’s oral hygiene habits as opposed to prenatal exposures. Nevertheless, the association in older children that we reported persisted even after adjusting for dental visit, sugar intake, fluoride supplement use and frequency of daily tooth brushing.

The magnitude of the estimates we reported for prenatal and partner smoking were dependent on the regression models we used. In our log-binomial regression estimating risk ratios and 95% C.I., the estimated risk ratios for partner smoking was of similar or of slightly higher magnitude than maternal smoking, while in the discrete time hazard regression, we found a higher magnitude for maternal smoking than for partner smoking. Nevertheless, our findings suggest that the association between prenatal smoking and offspring caries experience is not limited to events occurring in-utero. Indeed, the role of shared genetics with the partner and potential residual confounding by shared environmental factors are likely also at play.

CRediT authorship contribution statement

Aderonke A. Akinkugbe: Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing – review & editing, Funding acquisition. Tegwyn H. Brickhouse: Conceptualization, Writing – review & editing, Funding acquisition. Marcelle M. Nascimento: Methodology, Writing – review & editing. Gary D. Slade: Formal analysis, Writing – review & editing.

Acknowledgements

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