Association between cobalamin deficiency detected through newborn screening and creatine levels in mothers and their offspring in the first age stages

Introduction: Creatine is primarily consumed from meat, fish, eggs, and dairy products. For this reason, its intake is reduced in vegan or vegetarian subjects. Creatine is also produced endogenously, through processes involving the amino acids arginine, glycine and methionine in the kidneys and liver. However, a deficiency in cobalamin (a cofactor of methionine synthase), which is common in vegans and vegetarians, leads to an altered production of methionine and may therefore contribute to a reduction in creatine blood levels. The expanded newborn screening (ENS) allows to detect a cobalamin deficiency in mothers and their offspring through the dosage of specific metabolites. A diet poor in foods of animal origin during pregnancy and breastfeeding may cause suboptimal creatine levels in addition to cobalamin deficiency. This study aims to evaluate creatine levels in newborns in whom ENS resulted altered, because of cobalamin deficiency, and in their mothers. Methods: Creatine concentration was assessed on dried blood spot (DBS) by tandem mass spectrometry in 35 newborns during the first visit at 20 days of life (T0). Afterwards, creatine values were compared with those from 36 healthy newborns and respective mothers. After an adequate nutritional counseling and intramuscular supplementation with hydroxocobalamin 1000 µg in both newborns and mothers, another sample of DBS was collected one month later (T1) in 18 patients. Results: Mean creatine levels in patients (180,11 μM/l, SD 109,05) resulted significantly lower in comparison to mean creatine levels in controls (221,91 μM/l, SD 51,22) with a high data dispersion in the patients’ group. Creatine values increased significantly in T1 (209,96 μM/l, SD 76,51) compared to T0 (145,78 μM/l, SD 38,26) (p-value 0,0217). No significant difference was observed between patients’ and mothers’ values (p > 0,05). Discussion and conclusion: Significantly lower creatine levels in breastfed newborns, whose mother followed a prevalent vegetarian diet and in whom ENS detected a cobalamin deficiency, may be secondary both to a reduced creatine availability during pregnancy and breastfeeding and to a postnatal reduced endogen synthesis due to cobalamin deficiency. Creatine may represent an easily detectable marker of cobalamin deficiency. Further studies are needed to define its reliability and eventual age-based cut-offs.