Results Of Neonatal Screening Research Articles

Results of neonatal screening for spinal muscular atrophy in Hungary in 2023

Bevezetés: A gerincvelői izomsorvadással született betegek optimális egészségügyi ellátása csak az újszülöttkori szűréssel érvényesülhet. Ennek a gyógyíthatatlan, progresszív, gyermekkorban a leggyakrabban halált okozó genetikai betegségnek az újszülöttkori szűrését számos országban bevezették, és bizonyították hasznosságát a korai diagnózis és terápiakezdet jelentős eredményeivel. Célkitűzés: A betegség újszülöttkori szűrése hazai kutatási programjának értékelése a választott szűrőmódszer megbízhatóságának, lakossági igényének, költséghatékonyságának és a korai kezelés egészségnyereségének vizsgálatára; eredményessége esetén javaslattétel az újszülöttkori szűrővizsgálatok közé történő automatikus felvételére. Módszer: Az izomsorvadás szűrése a szülők önkéntes beleegyezése és ingyenes részvétele esetén a rutinszerű szűrésekre levett vérmintából. Pozitív szűrőteszt esetén megerősítő molekuláris genetikai vizsgálat a szűrőteszt ellenőrzésére és a választható terápiát befolyásoló paralóg gén kópiaszámának meghatározására. A terápia- és kezelőközpont megválasztása genetikai tanácsadás keretében, a szülőkkel hozott közös döntés alapján. A választott gyógyszer kontraindikációjának kizárásához és a finanszírozás egyedi méltányosságának elbírálásához szükséges vizsgálatok után az engedély birtokában a gyógyszeres kezelés elvégzése, majd a betegek tartós követése. Eredmények: A program 14 hónapja alatt a szűrés lakossági népszerűsége kimagasló volt, az újszülöttek 75,45%-ára kiterjedt. 9 gyermeknél újszülöttkorban, tünetmentes stádiumban igazolódott a betegség, és átlagosan 36,2 napos életkorban megtörtént a gyógyszeres kezelés: 8 betegnél tünetmentes, 1-nél tünetes állapotban. Tünetmentes terápiakezdet után átlag 218,5 (93–346) napos életkorban a gyermekek szomatomotoros és mentális fejlődése az életkoruknak megfelelő volt, nem következett be technológiafüggőség légzés- vagy nyelészavar miatt, nem szorulnak segédeszközökre. 1 betegnél a terápiakezdet előtt megjelent tünetek miatt részleges respirátorfüggőség következett be. A szűrőteszt megbízhatónak bizonyult, a kutatási időszak alatt álpozitív eredmény nem volt, és álnegatív eredményről sincs tudomásunk. Megbeszélés: A hazai szűrési program a nemzetközi adatokhoz hasonló eredményeket mutatott, igazolta a gerincvelői izomsorvadáshoz társuló egészségnyereséget. Következtetés: Az eredmények alapján indokoltnak tartjuk az újszülöttkori gerincvelői izomsorvadás szűrésének az újszülöttkori szűrőprogramba történő automatikus beiktatását Magyarországon. Orv Hetil. 2024; 165(29): 1122–1129

Insights into Central Congenital Hypothyroidism: A Multicenter Retrospective Analysis.

Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse. To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes. Multicenter cross-sectional retrospective chart review. Nine pediatric endocrine units throughout Israel. Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset. CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis. Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary.

Meconium Peritonitis in the Newborn with Cystic Fibrosis and Negative Neonatal Screening for Immunoreactive Trypsinogen: Clinical Case

Background. Meconium ileus is one of the manifestations of cystic fibrosis. It is characterized by intestinal obstruction with viscous meconium leading to perforation and peritonitis. The issues of early diagnosis of cystic fibrosis, management of newborns with meconium ileus and negative neonatal screening for immunoreactive trypsinogen (IRT), as well as IRT decrease causes and mechanisms in patients with meconium ileus require further study. Clinical case description. Routine ultrasound examination at the 33rd week of gestation has shown signs of colon obstruction and meconium peritonitis in the intrauterine child. Surgical treatment of peritonitis was performed urgently on the 1st day after birth. The child was on mechanical ventilation from the 1st day of life. The child has shown signs of intrahepatic cholestasis with direct hyperbilirubinemia (up to 100 μmol/L) and signs of hemorrhagic syndrome (bleeding from injection sites) on the 8th day of life. Negative IRT blood test was received (21.6 ng/mL, normal value < 70 ng/mL) on the 10th day. The fecal elastase concentration was 45 μg/g (normal value > 200 μg/g) (on the same day). Sweat tests were performed on the 21st and 23rd days of life. They have shown high levels of sweat chlorides (112 mmol/L in both samples, normal value — 30–59 mmol/L). The diagnosis of «cystic fibrosis» was established, thus, dornase alfa (dosage — 2.5 mg/day) was added to the therapy. Conclusion. Meconium ileus is one of the specific intestinal manifestations of cystic fibrosis and it commonly can be complicated with intestinal perforation in the intrauterine child with further peritonitis. Children with meconium ileus require sweat tests regardless the neonatal screening results.

Genetic Information to Share with Parents when Newborn Screening Reveals the Presence of Sickle Cell Trait.

The primary purpose of newborn screening for sickle cell disease is to diagnose the disease before the appearance of symptoms and to initiate early treatment. To answer the question "What genetic information needs to be communicated to parents when newborn screening reveals the presence of a sickle cell trait," we conducted a survey using a self-administered online questionnaire. We received responses from 122 healthcare workers and members of sickle cell disease associations, in France and French overseas departments. Our results showed similar positions on this issue. The information conveyed is not consistent and is the result of grassroots initiatives. The negative consequences generated by this information could be reduced when this information is delivered by a multidisciplinary team, within the framework of a dedicated consultation. This information on sickle cell trait status should be given in at least three key periods: the neonatal period, early adolescence, and later adolescence, when reproductive implications become important. Neonatal screening programs should develop systems that allow referring physicians to easily access the results of neonatal screening electronically. Harmonization of practices should allow a better analysis of the consequences of this counselling on family projects.

Preliminary Results of Neonatal Screening of 19 Genetic and Metabolic Disorders in Qalyubia Governorate

Preliminary Results of Neonatal Screening of 19 Genetic and Metabolic Disorders in Qalyubia Governorate

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022.

To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.

Assessment of the effectiveness of a new neonatal screening algorithm for cystic fibrosis

Relevance All over the world, neonatal screening protocols are being improved in order to reduce the time of diagnosis, simplify the examination procedure, and reduce the number of false positive and false negative results of neonatal screening. In most European countries, the best neonatal screening algorithm is molecular genetic testing. Objective: Evaluate the effectiveness of the new cystic fibrosis screening protocol algorithm, which, in the first step, determines the immunoreactive trypsin (IRT) level from one dry spot and performs DNA diagnostics (36 most frequent mutations) in patients with increased IRT. Compare the economic costs of screening by two algorithms (existing and alternative). Materials and methods: two parallel algorithms were used for neonatal screening. Which was performed on 56,534 infants in the Moscow Region from March to November 2022. The current three-stage algorithm was used, which involves re-blood sampling from newborns at risk 3-4 weeks after the first blood sampling and a sweat test. In the new algorithm, newborns with an elevated IRT 1 level at the 1st week of life underwent a molecular genetic study (search for frequent mutations in the CFTR-36 variants gene, sequencing of individual locus of the CFTR gene for control purposes) in the same dry blood spot used for screening. Results: out of 56,534 test forms received, 607 (1.07%) newborns with a positive test for IRT were identified for neonatal screening in a laboratory from the Moscow region, of which 501 (82.5%) samples were selected, where the level of RTI1 exceeded the cut-off level (65 ng / ml), which were sent for molecular genetic research in order to search for pathogenic variants in the CFTR gene. 106 (17.5%) newborns did not complete the examination. Positive results of confirmatory diagnosis were obtained in 6 infants, which accounted for 0.01% of the number of children who underwent screening and 1.2% of the number of children with neonatal hypertrypsinogenemia. Conclusion: the positive effects of the new algorithm are to reduce psychological tension in families during examination by reducing the time of diagnosis, no need for repeated blood sampling on the 21st-28th day of life, reduction of the time of diagnosis, prevention of nutritional deficiencies in children during the first months of life and life-threatening complications. Reducing the number of children with incomplete testing for cystic fibrosis, economic benefit. The negative effects of the new algorithm are that it is possible to miss a patient with cystic fibrosis who does not have any of the common pathogenic variants in the CFTR gene.

The Effects of the Coronavirus Disease 2019 Epidemic on the Applicability and Results of Neonatal Hearing Screening

The Effects of the Coronavirus Disease 2019 Epidemic on the Applicability and Results of Neonatal Hearing Screening

Effect of Neonatal Hearing Screening Results on the Lost to Follow-Up at the Diagnostic Level.

(1) Background: An important part of any neonatal hearing screening program is monitoring diagnostic visits to confirm or exclude the presence of hearing loss. In addition, time plays an important role in the diagnosis. We identified the number of children who came for a diagnostic visit and analyzed the time of the first audiological visit, depending on the result of the hearing screening test performed in the first days of a child's life and the presence or absence of risk factors of hearing impairment. (2) Methods: We analyzed 6,580,524 children, of which 8.9% required further diagnostics. The mean time of follow-up diagnostic visit in the analyzed group was 130 days and differed due to the presence or absence of risk factors for hearing loss before and after the neonatal period. (3) Results: Although the risk of hearing loss in children with risk factors is 2.31 to 6.38 times higher than in children without risk factors depending on the result of the screening test, more than 40% of parents do not report to scheduled audiological visits. (4) Conclusions: Doctors, nurses, and midwives who screen hearing at the neonatological level play an important role in educating parents about the possibility of hearing loss in a child and the need for an audiological examination.

The Effects of Mode of Delivery on Neonatal Screening Evaluated by Automated Auditory Brainstem Response

Background/Purpose: Neonatal hearing screening results are affected by several perinatal and neonatal factors. It is known that false positivity (FP) in the failure of newborn hearing screening increases parental concern and anxiety and has a negative impact on healthcare costs. There are conflicting reports on the effect of the mode of delivery on hearing screening results. This study aimed to investigate the role of mode of delivery on neonatal hearing by comparing the automated auditory brainstem (ABR) results of newborns born with vaginal delivery (VD) or cesarean section (CS) and to identify perinatal and neonatal factors associated with failure of the first neonatal hearing screening test results.
 Methods: This retrospective case-control study was conducted at our obstetrics clinic between December 2018 and June 2019. Following the exclusion of newborns with incomplete data, with congenital and chromosomal anomalies, with CMV infection, with anatomical deformities involving the face and the ears, and who received their hearing screening

Thyroid function and long-term outcomes of children born to mothers with Graves' disease: A 20-year review.

Thyroid dysfunction in infants born to mothers with Graves' disease (GD) is influenced by maternal factors including thyroid status, thyroid-stimulating hormone (TSH) receptor antibody (TRAb) concentration and antithyroid drug use. Thyroid dysfunction during early life could affect growth and development later in life. The aim of this study is to evaluate thyroid function tests (TFTs), and long-term growth and development of children born to mothers with GD. A retrospective chart review of children born to mothers with GD at the Faculty of Medicine Ramathibodi Hospital, Mahidol University, between January 2000 and December 2019 was performed. Clinical data including age of children at enrolment, sex, gestational age, birthweight, maternal thyroid status, maternal TRAb level, maternal GD treatment during pregnancy, neonatal TSH screening and TFT results, and growth and development outcomes of children were collected. There were 262 children (148 males) enrolled. Twelve (4%) infants had neonatal GD. Five (2%) infants had hypothyroidism requiring levothyroxine treatment: four had secondary hypothyroidism and one patient had congenital primary hypothyroidism. Seven (3%) infants had transient TSH elevation, which fell to normal by 2 weeks of age. The remaining 238 children had normal TFT results. Three out of 12 children with neonatal GD had either delayed growth or development. A number of infants born to mothers with GD had abnormal TFTs requiring specific management, and some of them had abnormal growth and development. Careful evaluation of TFTs and long-term follow-up are mandatory for those children.

Impact of Newborn Screening Programme for Congenital Heart Disease in Shanghai: a five-year observational study in 801,831 newborns

Newborn Screening Programme for Congenital Heart Disease (CHD) in Shanghai has been in operation for over 5 years, and its feasibility and effectiveness still lack a systematic and comprehensive evaluation. This study aimed to detail the implementation of the programme and evaluate its results, benefits, and reliability in clinical practice. This study was an observational study involving all newborns received CHD screening in Shanghai from 2017 to 2021. Pulse oximetry (POX) plus cardiac murmur auscultation (namely the dual-index method) was used for CHD screening in newborns aged 6-72h. Newborns who screened positive was recommended for echocardiography, and those diagnosed with CHD would be planned for further evaluation and intervention. Data were aggregated by birth year and district of birth. Results of neonatal CHD screening, diagnosis and treatment, and temporal trends of infant mortality rate (IMR) and the proportion of under-five mortality (U5M) attributed to CHD were analysed. A retrospective cohort study was also conducted to assess the reliability of the dual-index method in clinical practice. In total, 801,831 (99.48%) newborns were screened for CHD, 16,489 (2.06%) were screened positive, and 3541 (21.47%) of the screened-positive newborns were identified with CHD. Seven hundred and fifty-two patients with CHD received surgical or interventional treatment with a successful rate of 94.81%. The period from 2015 to 2021 witnessed an approximately twofold decrease in IMR from 4.58‰ to 2.30‰, and a downtrend in the proportion of U5M attributed to CHD from 25.93% to 16.61%. High sensitivity and specificity of the dual-index method in clinical practice were observed for both critical (100.00% and 97.72%) and major CHD (98.47% and 97.76%). Newborn screening programme for CHD has been well implemented in Shanghai, and this programme is a successful public health intervention to reduce infant death. Our study provides encouraging evidence and experience for implementing newborn screening programme for CHD nationwide in China. This study was supported by the National Key Research and Development Programme of China (2021YFC2701004 and 2016YFC1000506), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-002), and Three-Year Planning for Strengthening the Construction of Public Health System in Shanghai (No. GWIV-24).

Results of Neonatal Genetic Screening for Hearing Loss in Peking Union Medical College Hospital in the Past 10 Years

Results of Neonatal Genetic Screening for Hearing Loss in Peking Union Medical College Hospital in the Past 10 Years

Psychosocial Issues Related to Newborn Screening: A Systematic Review and Synthesis.

Genomic advances have contributed to a proliferation of newborn screening (NBS) programs. Psychosocial consequences of NBS have been identified as risks to these public health initiatives. Following PRISMA guidelines, this systematic review synthesizes findings from 92 evidence-based, peer-reviewed research reports published from 2000 through 2020 regarding psychosocial issues associated with NBS. Results describe parents’ knowledge of and attitudes towards NBS, reactions to and understanding of positive NBS results, experiences of communication with health providers, decisions about carrier testing, and future pregnancies. Findings also explain the impact of positive NBS results on parent–child relationships, child development, informing children about carrier status, family burden, quality of life, and disparities. In conclusion, psychosocial consequences of receiving unexpected neonatal screening results and unsolicited genetic information remain significant risks to expansion of NBS. Findings suggest that risks may be mitigated by improved parent NBS education, effective communication, individualized genetic counseling, and anticipatory developmental guidance. Clinicians need to take extra measures to ensure equitable service delivery to marginalized subpopulations. Future investigations should be more inclusive of culturally and socioeconomically diverse families and conducted in low-resource countries. Providing these countries with adequate resources to develop NBS programs is an essential step towards achieving international health equity.

Neonatal Hearing Screening Results with Screening ABR Protocol

Aim:The study aimed to present the results of our universal newborn hearing screening results at a secondary care hospital in Mardin by ABR and review with the literature. Materials and method: A total of 7134 newborns were screened between January 2021 and December 2021using ABR as first, second, third steps. Newborns who failed and at risk are referred to reference hospital and the results were obtained from the records. Result:Of the 7134 newborns,6179 are first test, 955 were retested. Failure in first test was 13.3%. 235(3.2%) of patients were referred to reference center. 0.5% were referred due to test failure, 2.7% were referred due to risk. 27 patients(3.7%) were obtained from records of reference center as abnormal results in clinical Automated Brain stem Response(ABR).16 of them (0.5%) were congenital hearing loss(CHL) who need rehabilitation. Conclusion: Incidence of hearing loss and the rate of failure in first and second test were consistent with the literature. However, reference rate increased due to reference caused by risk factors.

Neonatal thyrotropin - indicatior of monitoring of iodine deficiency severity. What's level is considered a «cutoff point»?

The issues of monitoring the effectiveness of iodine deficiency prevention programs are an important component in the process of iodine elimination. Neonatal thyrotropin (TSH) has been used as a criterion for the severity of iodine deficiency since 1994, however, the question of the "cut-off point" of the neonatal TSH level has been widely discussed in the recent literature. Evaluate the criterion for neonatal hyperthyroidism above 5 mIU/l from the perspective of monitoring iodine deficiency and establish a «cut-off point» on the model of healthy pregnant women with adequate iodine status. A prospective study was conducted in a population of pregnant women in the city of Tyumen, with the formation of observation groups according to the level of iodine excretion in the urine - the main group (with adequate iodine status throughout the entire gestation period) and the comparison group (women with iodine levels less than 150 μg/l). The results of neonatal screening for congenital hypothyroidism in children of women participating in the study were evaluated. The frequency of neonatal TSH above 5mIU/l was assessed in the observation groups. ROC-analysis was performed and a «cut-off point» of the level of neonatal TSH was established as an indicator of iodine deficiency. The median urinary iodine concentration in the population of pregnant women in Tyumen was 159.05 μg/l, the incidence of goiter was 0.38%, the incidence of neonatal hyperthyroidism above 5 mIU/l was 2.88%, which characterizes adequate iodine intake in the pregnant population women. The frequency of neonatal TSH above 5 mIU/l in newborns from women from the main group was 1.47%, and in the comparison group - 9.3% (p = 0.076). ROC analysis revealed a threshold value of neonatal TSH of 2.77 mIU/l at the cut-off point, which corresponded to the highest value of the Youden index. Urinary iodine concentrations greater than 150 μg/l were predicted for nTSH values below this value. Analysis of databases of neonatal screening for congenital hypothyroidism makes it possible to effectively, quickly and at minimal cost annually assess the iodine status in the population. The established «cut-off point» of neonatal TSH in the model of healthy pregnant women with adequate iodine intake in our work is 2.77 mIU/l, the absence of statistically significant differences in the incidence of neonatal hyperthyroidism above 5 mIU/l from women with different iodine status during pregnancy indicate the need to revise the existing threshold of 5 mIU/l and may be an incentive to conduct large-scale studies in regions with different iodine supply.

Incorporation of second-tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program.

BackgroundNowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non‐invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC‐MS/MS) for the evaluation of the baby's risk of certain metabolic disorders.MethodsThis retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second‐tier tests and secondary biomarkers to improve positive predictive value (PPV).ResultsStatistical data were recorded via call interviewing in 6–8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false‐positive rate was 0.15%.ConclusionThis study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second‐tier tests and secondary biomarkers improves PPV of neonatal screening programs.

The importance of plasma amino acid profiling in the diagnosis of inborn errors of metabolism: analytical – prospective study

Introduction. Inborn errors of metabolism (IEM) make up a large group of disorders caused by an inherited defect of proteins that have enzymatic, carrier, receptor or structural roles. The cumulative prevalence of IEM in different populations is around 1:500 – 800 newborns, despite the fact that some of these disorders are extremely rare when taken individually. Early recognition and intervention are essential to avoiding disastrous consequences associated with IEM. The phenotype of IEM patients is very heterogeneous and only in combination with specialized metabolic test it can lead to a correct diagnosis. The aim of the study was defined as evaluation of importance of plasma amino acid profile in the diagnosis of IEM. Material and methods. Plasma amino acids quantification have been performed by high performance liquid chromatography on Shimadzu LC-20 with post column derivatization with OPA in 15 patients aged from 0 to 13 years old, selected through medical genetic counseling, based on inclusion and exclusion criteria. Inform consent has been signed by parents after receiving all necessary information regarding the study. Additionally, liquid chromatography-tandem mass spectrometry (LC-MS/MS) on dried blood spots and Nuclear Magnetic Resonance Spectroscopy (H1-NMR) on urine has been done as complementary tests. Results. The first line investigations showed acid-base imbalance (33,3%), hypoglycemia (46,6%), high lactate level (46,6%) and high ammonia level (20%). Plasma amino acid concentrations were abnormal in 4 patients (27%). Increased glycine (544 μmol/L, reference values 70,72 – 256,36 μmol/L), along with elevated glycine in cerebrospinal fluid (CSF) / plasma ratio (0,147, normal < 0.02) was detected in a patient with seizures, coma, and respiratory arrest indicating non-ketotic hyperglycinemia. High level of phenylalanine (Phe 1568µmol/L, reference values 26.52 – 221 µmol/L) has been identified in a patient suspected for Phenylketonuria after neonatal screening results (Phe > 3mg/dL). Also the ratio Phe / Tyr around 17 was specifically appreciated as for classical form of PKU. High alanine concentration (> 450 µmol/L) has been observed in two patients presenting severe metabolic acidosis and high lactate level, suggesting for a metabolic error with mitochondrial involvement. The results from extended newborn screening and NMR spectroscopy narrowed the spectrum of suspected diseases, facilitating the diagnosis. Molecular genetic tests are required for the confirmation of disease in all cases. Conclusions. Quantitative amino acids analysis is an important tool for the diagnosis of “intoxication type” of IEMs and nutritional monitoring of individuals with already established diagnosis.

Evaluation of neonatal hearing screening results of newborns with premature retinopathy

ObjectivesTo reveal the risk situations of ROP patients in terms of hearing loss by examining the newborn hearing screening test results. MethodsHearing screening test results of ROP patients and newborns with similar congenital risk factors(control group) treated in our hospital were retrospectively screened. Both groups were compared in terms of newborn hearing screening test results. ResultsIn the first screening test, the rate of ‘’refer’’ result in the ROP group was significantly higher than the control group (p < 0.05). There was no significant difference between the two groups in terms of second hearing screening test results (p > 0.05). In the second screening test, 100% of stage 3 ROP patients failed from the right ear and 80% in the left ear, and this difference was statistically significant compared to the other two groups (p < 0.05). ConclusionNewborn hearing screenings of patients with advanced stage ROP patients should be followed up more sensitively, since stage 3 ROP patients had more failure results from the screening test in our study.

Ectopic thyroid gland: clinical features and diagnostics in children

The frequency of ectopia of thyroid gland among all types of dysgenesis varies from 30 to 70%, its most common localization is the root of the tongue. Otorhinolaryngologists, oncologists, pediatricians can take lingual ectopia for hypertrophy of the lingual tonsil or fibroma of the tongue root, which leads to unreasonable surgical treatment. Thyroid scintigraphy plays a key role in the diagnosis of ectopia. To assess the etiological structure of congenital hypothyroidism (CH) and demonstrate the clinical course in patients with ectopic thyroid tissue in the root of the tongue. A group of patients with CH was examined. All patients underwent neck ultrasound and radionuclide imaging. The examination was carried out against the background of the abolition of hormone replacement therapy for 14 days or before its initiation. Patients with ectopia in the root of the tongue underwent videofibrolaryngoscopy. Some patients underwent a genetic study with using genes panel of a panel of candidate genes responsible for the development of CH using the NGS method. The molecular genetic study was conducted to some patients, next-generation sequencing with the genes panel. The study included 73 patients with primary CH aged from 2 weeks to 17.3 years: 69 children were diagnosed based on the results of neonatal screening, 4 children with thyroid ectopia were first examined older than 6 years. Themedian age of patients at the time of the examination was 6.9 years [4.8; 10.0]. By data of ultrasound aplasia was diagnosed in 47.9% of patients, one child had hemiagenesis and ectopic thyroid tissue of various localization was detected in 26.0%of children. In24.7% of children thyroid tissue was found in a typical location. Scintigraphy confirmed thyroid aplasia in 65.7%of children. Examination revealed various variants of ectopically located thyroid tissue in 31 children (42.4%): thyroid ectopia in the root of the tongue in 25 children (80.6%), ectopia in the sublingual region in 5 children (16.2%), double ectopia was detected in 1 child. The median level of TSH in newborns with ectopic thyroid gland was 124 IU/ml and was significantly lower than in children with aplasia - 219 IU/ml, p&lt;0.05. On the other side the level of TG in children with ectopia was significantly higher than in children with aplasia - 37.12 ng/ml versus 0.82 ng/ml, p&gt;&lt;0.05. Combination of two methods is the best diagnostic approach to determine the etiology of CH - ultrasound and scintigraphy studies compensates deficiencies of each other. Our study demonstrates the importance of scintigraphy in children with CH and patients with the formation of the root of the tongue and the anterior surface of the neck in order to avoid unnecessary removal of the thyroid gland. In case of confirmation of thyroid ectopia in the root of the tongue and in the absence of symptoms of obstruction or bleeding, it is recommended to refer the patient to an endocrinologist for conservative treatment. &gt;&lt;0.05. On the other side the level of TG in children with ectopia was significantly higher than in children with aplasia - 37.12 ng/ml versus 0.82 ng/ml, p&lt; 0.05. Combination of two methods is the best diagnostic approach to determine the etiology of CH - ultrasound and scintigraphy studies compensates deficiencies of each other. Our study demonstrates the importance of scintigraphy in children with CH and patients with the formation of the root of the tongue and the anterior surface of the neck in order to avoid unnecessary removal of the thyroid gland. In case of confirmation of thyroid ectopia in the root of the tongue and in the absence of symptoms of obstruction or bleeding, it is recommended to refer the patient to an endocrinologist for conservative treatment.