Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates.

Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T- and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 - from patients with Nijmegen breakage syndrome, 1 - with X-linked agammaglobulinemia, 2 - with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (TlowB+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the method on DNA samples of children with ataxia-telangiectasia and Nijmegen syndrome showed a high sensitivity of TRECs (a total of 95.2% with cut-off 2000 copies per 106 cells) for the detection of these diseases. Thus, the tested method has shown its effectiveness for the detection of T- and B-lymphopenia and can be used for implementation of newborn screening for SCID in Ukraine.

AWARENESS OF FOLIC ACID USE AND ITS EFFECTS AMONG MEDICAL STUDENTS IN UKRAINE.

OBJECTIVE: The aim: To evaluate the awareness of folic acid, its use and effects, general knowledge about neural tube defects among medical students in Ukraine. PATIENTS AND METHODS: Materials and methods: This cross-sectional survey was conducted by questioning 114 fourth and fifth years' students of the Faculty of Medicine. The questionnaire contained questions about folic acid, its dietary sources, effects and periconceptional uses; spina bifida and its main symptoms. RESULTS: Results: Overall, 96.5% of students knew that folic acid was a vitamin and 95.6% were aware of the one natural product which had a high folate level. However, awareness of its amount in different products was insufficient. Overall, 86.8% of surveyed knew that folic acid deficiency during pregnancy caused the congenital malformations. The knowledge of the synthetic folic acid supplementation before and during pregnancy was low (67.5% and 53.5% respectively). Only 10 % of women among medical students consumed folic acid regularly. CONCLUSION: Conclusions: Despite the high level of general knowledge about folic acid and its effects among medical students in Ukraine, there is a poor awareness of the pre-conception administration of folic acid, and the number of people who regularly take folic acid among the respondents was very low.

Evaluation of awareness about primary immunodeficiencies among physicians before and after implementation of the educational program: A longitudinal study.

Increasing physicians' awareness is one of the main ways to improve early diagnosis of rare diseases. A survey among physicians of different specialties to evaluate the knowledge about primary immunodeficiencies (PID) was conducted in 2016 and in 2019 -before and after the implementation of an educational program. We compare responses from 82 doctors who participated in the 2016 survey, and 67 doctors who have taken part in the survey in 2019: pediatricians, general practitioners / family physicians and physicians of pediatric sub specialties. The percentage of correct answers to all survey questions after the implementation of the educational program has significantly increased (79.0% in 2019 versus 58.3% in 2016, P<0.0001). This increase in the percentage of correct answers was noted among the surveyed doctors of all specialties. Particular progress was found among pediatricians, who have achieved more than 80% of correct answers. In 2019 the doctors demonstrated better knowledge on the warning signs of PID and specific features of Nijmegen breakage syndrome, DiGeorge syndrome and ataxia-telangiectasia syndrome. Thus, the implementation of an educational program improved physicians' awareness of PIDs, and will contribute to early detection of PIDs and their medical care.

The impact of combining educational program with the improving of infrastructure to diagnose on early detection of primary immunodeficiencies in children.

Early detection of primary immunodeficiency diseases (PID) is vital for adequate prevention and management of PID infectious complications. The objective of this study was to evaluate the impact of a model combining physician education and public awareness with the infrastructure to diagnose PID to improve its early detection in children. Three approaches were combined and the results were followed from February 2017 to February 2019 in Ternopil region, Ukraine: the education of primary care physicians and other specialists on early PID detection using workshops, trainings, and targeted publications; organization of public events and media appearances to raise PID awareness; performing immunological testing for patients with suspected PID. Among the 150 individuals that were screened, PID was diagnosed in 19 patients (12.7%). The majority of diagnosed PID cases were combined immunodeficiency with associated or syndromic features, followed by antibody deficiencies. Patients referred by the specialist doctors had the highest percentage of confirmed PID compared with those referred by primary care physicians (p = 0.0273) and risk group patients (p = 0.0447). Among warning signs in patients with PID, two or more pneumonias within 1 year occurred most often (26.3%), followed by failure of an infant to gain weight or grow normally (21.1%). Among other signs of PID, dysmorphic features and microcephaly were the most prevalent (31.6%). In conclusion, a program combining physician education and public awareness with infrastructure needed to diagnose primary immunodeficiency diseases is an effective tool for early PID diagnosis. Physician education was a more effective tool compared with rising public awareness.