Fetal Exposure to Maternal Smoking and Neonatal Metabolite Profiles

Fetal tobacco exposure has persistent effects on growth and metabolism. The underlying mechanisms of these relationships are yet unknown. We investigated the associations of fetal exposure to maternal smoking with neonatal metabolite profiles. In a population-based cohort study among 828 mother-infant pairs, we assessed maternal tobacco use by questionnaire. Metabolite concentrations of amino acids, non-esterified fatty acids, phospholipids and carnitines were determined by using LC-MS/MS in cord blood samples. Metabolite ratios reflecting metabolic pathways were computed. Compared to non-exposed neonates, those exposed to first trimester only tobacco smoking had lower neonatal mono-unsaturated acyl-alkyl-phosphatidylcholines (PC.ae) and alkyl-lysophosphatidylcholines (Lyso.PC.e) 18:0 concentrations. Neonates exposed to continued tobacco smoking during pregnancy had lower neonatal mono-unsaturated acyl-lysophosphatidylcholines (Lyso.PC.a), Lyso.PC.e.16:0 and Lyso.PC.e.18:1 concentration (False discovery rate (FDR) p-values < 0.05). Dose-response associations showed the strongest effect estimates in neonates whose mothers continued smoking ≥5 cigarettes per day (FDR p-values < 0.05). Furthermore, smoking during the first trimester only was associated with altered neonatal metabolite ratios involved in the Krebs cycle and oxidative stress, whereas continued smoking during pregnancy was associated with inflammatory, transsulfuration, and insulin resistance markers (p-value < 0.05). Thus, fetal tobacco exposure seems associated with neonatal metabolite profile adaptations. Whether these changes relate to later life metabolic health should be studied further.