The effects of modifiable maternal pregnancy exposures on offspring molar-incisor hypomineralisation: A negative control study

Objectives Explore associations between modifiable maternal pregnancy exposures: pre-pregnancy body mass index (BMI), pregnancy smoking and alcohol consumption with offspring molar-incisor hypomineralisation (MIH). Use negative control analyses to explore for the presence of confounding. Methods Using prospectively collected data from Avon Longitudinal Study of Parents and Children (ALSPAC), we performed logistic regression to explore confounder adjusted associations between maternal pre-pregnancy BMI and smoking and alcohol consumption during pregnancy with MIH. We compared these with negative control exposure (paternal BMI, smoking and alcohol) and outcome (offspring dental trauma) analyses. Results 5,536 mother/offspring pairs were included (297 MIH cases [5.4%]). We found a weak, positive association between maternal mean BMI and offspring MIH (OR per 1□kg/m 2 difference in BMI: 1.04, 95%CI: 1.00, 1.08). Results of subsequent analyses suggested this effect was non-linear and being driven by women in the highest BMI quintile (OR for women in the highest BMI quintile versus the lowest: 1.61 95%CI: 1.02, 2.60). Negative control analyses showed no evidence of an association between paternal BMI and offspring MIH (OR: 0.94, 95%CI: 0.89,1.00) and maternal BMI and offspring dental trauma (OR: 0.99, 95%CI: 0.96, 1.02). There was no clear evidence of an association for maternal smoking (OR: 0.76, 95%CI: 0.46,1.22) or alcohol consumption (OR: 0.79, 95%CI: 0.56, 1.21) with offspring MIH with results imprecisely estimated. Conclusion We found evidence of a possible intrauterine effect for high maternal pre-pregnancy BMI on offspring MIH, but no robust evidence of an intrauterine effect for maternal pregnancy smoking or alcohol consumption. A key limitation includes possible misclassification of MIH. Replication of these results is warranted.