Cobalamin deficiency in the maternal-newborn dyad identified by neonatal screening: preliminary data from an observational study

Cobalamin (Cbl) is essential for fetal and post-natal neurological development. It cannot be synthesized by the human body and its nutritional requirement increases during pregnancy and lactation. Extensive newborn screening can identify acquired Cbl deficiency, secondary to maternal depletion, preventing clinical signs and symptoms. The aim of this observational study is to describe the neuro-metabolic and biochemical phenotype at birth, to identify main causes of maternal Cbl deficiency and to assess the relationship between maternal and neonatal values of Cbl and its indirect metabolites, plasmatic methylmalonic acid (MMA) and homocysteine (HCY). From November 2021 to November 2023, 93 newborns (57% boys, 43% girls) with acquired Cbl deficiency secondary to maternal depletion were referred by the Neonatal Screening Laboratory to the Metabolic Diseases Centre of our Hospital for the administration of hydroxocobalamin 1000 mcg to child and mother and regular clinical, nutritional and neurological follow-up. Fifty-five% of patients were exclusively breastfed, 13,8% mixed-fed and 31,2% exclusively formula fed. Newborn biochemical levels of Cbl, plasmatic MMA and HCY before and after the administration of hydroxocobalamin, with respective normal values (n.v.), are reported in Figure 1. Neurological examinations were normal in all patients. At first access, 90% of mothers had Cbl values below 400 ng/L and only 37% of them achieved the recommended Cbl intake of 2,6 mcg/die during pregnancy, representing the first cause of deficiency. During pregnancy, 58% of the mothers were omnivorous, 22% lacto-ovo-vegetarian and 20% lacto-vegetarian. The most frequent non-nutritional causes of deficiency were anti-parietal cell antibodies positivity and hyperemesis gravidarum. Preliminary results show that after hydroxocobalamin administration, Cbl and indirect metabolites of deficiency status improved. A multidisciplinary diagnostic-therapeutic management model, actually lacking, is needed. The prevention of nutritional deficiencies, frequent causes of maternal and neonatal Cbl deficiency, should start from pregnancy onwards, through the implementation of clinical alliances among gynecologists, neonatologists and pediatricians.