Maternal smoking during pregnancy and risk of phacomatoses: results from a Swedish register-based study

Background and aim: Phacomatoses are genetic syndromes often associated with an increased risk of a variety of malignant and benign neoplasms, including nervous system tumors. Little is known about the causes of de novo occurrences of phacomatoses. Therefore, the aim of this study was to assess the association between maternal smoking during pregnancy and the occurrence of de novo phacomatoses.

Methods: All individuals born in Sweden between 1982 and 2014 with information on both biological parents were identified through the Medical Birth Register (MBR), n=3,132,056. The Swedish population-based health care registers were used to identify individuals with a phacomatosis and information on maternal smoking was extracted from the MBR. Logistic regression models were used to evaluate the effect of maternal smoking during pregnancy on the risk of phacomatoses.

Results: In the study population, we identified 2074 individuals diagnosed with a phacomatosis, among which 75% were regarded as de novo occurrence. While no effect of heavy maternal smoking (10+ cigarettes/day) was observed for de novo neurofibromatosis, an increased risk was found for other phacomatoses excluding neurofibromatosis (OR =1.51, 95% CI 1.13-2.03). Indications of an increased risk for specific phacomatosis subtypes were observed for tuberous sclerosis (OR =1.39, 95% CI 0.91-2.14) and Sturge-Weber syndrome (OR =1.86, 95% CI 0.83-4.19). No association was observed for familial phacomatoses.

Conclusion: This is the first study examining the risk of de novo phacomatoses associated with heavy maternal smoking during pregnancy. Further studies are needed to confirm the associations observed and elucidate potential biological mechanisms.