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Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals. [ABSTRACT FROM AUTHOR]

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, prenatal, neonatal and later in life. Screening should only be offered if the advantages outweigh the disadvantages. Technical innovations in testing and treatment are driving changes in the field of prenatal and neonatal screening, where many jurisdictions have organized population-based screening programs. As a result, a greater number and wider range of conditions are being added to the programs, which can benefit couples' reproductive autonomy (preconception and prenatal screening) and improve early diagnosis to prevent irreversible health damage in children (neonatal screening) and in adults (cancer and cascade screening). While many developments in screening are technology-driven, citizens may also express a demand for innovation in screening, as was the case with non-invasive prenatal testing. Relatively new emerging issues for genetic screening, especially if testing is performed using DNA sequencing, relate to organization, data storage and interpretation, benefit–harm ratio and distributive justice, information provision and follow-up, all connected to acceptability in current healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inborn error of mitochondrial fatty acid metabolism with autosomal recessive pattern of inheritance. Its phenotype is highly variable (neonatal, infantile, and adult onset) on the base of mutations of the CPT II gene. In affected subjects, long-chain acylcarnitines cannot be subdivided into carnitine and acyl-CoA, leading to their toxic accumulation in different organs. Neonatal form is the most severe, and all the reported patients died within a few days to 6 months after birth. Hereby, we report on a male late-preterm newborn who presented refractory cardiac arrhythmias and acute multiorgan (hepatic, renal, muscular) injury, leading to cerebral hemorrhage, hydrocephalus, cardiovascular failure and early (day 5 of life) to death. Subsequently, extended metabolic screening and target next generation sequencing (NGS) analysis allowed the CPT II deficiency diagnosis. Case presentation: The male proband was born at 36+ 4 weeks of gestation by spontaneous vaginal delivery. Parents were healthy and nonconsanguineous, although both coming from Nigeria. Family history was unremarkable. Apgar score was 9/9. At birth, anthropometric measures were as follows: weight 2850 g (47th centile, -0.07 standard deviations, SD), length 50 cm (81st centile, + 0.89 SD) and occipitofrontal circumference (OFC) 35 cm (87th centile, + 1.14 SD). On day 2 of life our newborn showed bradycardia (heart rate around 80 bpm) and hypotonia, and was then transferred to the Neonatal Intensive Care Unit (NICU). There, he subsequently manifested many episodes of ventricular tachycardia, which were treated with pharmacological (magnesium sulfate) and electrical cardioversion. Due to the critical conditions of the baby (hepatic, renal and cardiac dysfunctions) and to guarantee optimal management of the arrythmias, he was transferred to the Pediatric Cardiology Reference Center of our region (Sicily, Italy), where he died 2 days later. Thereafter, the carnitines profile evidenced by the extended metabolic screening resulted compatible with a fatty acid oxidation defect (increased levels of acylcarnitines C16 and C18, and low of C2); afterwards, the targeted next generation sequencing (NGS) analysis revealed the known c.680 C > T p. (Pro227Leu) homozygous missense mutation of the CPTII gene, for diagnosis of CPT II deficiency. Genetic investigations have been, then, extended to the baby's parents, who were identified as heterozygous carriers of the same variant. When we meet again the parents for genetic counseling, the mother was within the first trimester of her second pregnancy. Therefore, we offered to the couple and performed the prenatal target NGS analysis on chorionic villi sample, which did not detect any alterations, excluding thus the CPT II deficiency in their second child. Conclusions: CPTII deficiency may be suspected in newborns showing cardiac arrhythmias, associated or not with hypertrophic cardiomyopathy, polycystic kidneys, brain malformations, hepatomegaly. Its diagnosis should be even more suspected and investigated in cases of increased plasmatic levels of creatine phosphokinase and acylcarnitines in addition to kidney, heart and liver dysfunctions, as occurred in the present patient. Accurate family history, extended metabolic screening, and multidisciplinary approach are necessary for diagnosis and adequate management of affected subjects. Next generation sequencing (NGS) techniques allow the identification of the CPTII gene mutation, essential to confirm the diagnosis before or after birth, as well as to calculate the recurrence risk for family members. Our report broads the knowledge of the genetic and molecular bases of such rare disease, improving its clinical characterization, and provides useful indications for the treatment of patients. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a chronic and potentially life-threatening condition, wherein timely diagnosis assumes paramount significance for the prompt initiation of therapeutic interventions, thereby ameliorating pulmonary function, addressing nutritional deficits, averting complications, mitigating morbidity, and ultimately enhancing the quality of life and extending longevity. This review aims to amalgamate existing knowledge to provide a comprehensive appraisal of contemporary diagnostic modalities pertinent to CF in the 21st century. Deliberations encompass discrete delineations of each diagnostic modality and the elucidation of potential diagnostic quandaries encountered in select instances, as well as the delineation of genotype–phenotype correlations germane to genetic counseling endeavors. The synthesis underscores that, notwithstanding the availability and strides in diagnostic methodologies, including genetic assays, the sweat test (ST) retains its position as the preeminent diagnostic standard for CF, serving as a robust surrogate for CFTR functionality. Prospective clinical investigations in the realm of CF should be orchestrated with the objective of discerning novel diagnostic modalities endowed with heightened specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Background: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth. Methods: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR). Results: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95%CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1). Discussion: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination. [ABSTRACT FROM AUTHOR]

Developmental hip dysplasia or developmental dysplasia of the hip (DDH) includes a wide range of deformities of the hip, such as congenital dysplasia, subluxation, and dislocation. It is usually identified through neonatal screening during the first 6–8 weeks of life. The incidence of DDH ranges from 1–7% in neonates among some populations, but this may vary among different ethnicities and countries. A consensus about the ideal age for screening has not been reached to date. The aim of this study is to summarize the existing data regarding the incidence of congenital hip dysplasia and screening tests among European countries. The authors conducted a systematic search in PubMed/Medline and Scopus and collected original studies published in English, French or German. The incidence of DDH presents fluctuations, not only among European countries, but also within the same country. There is no unanimity regarding the screening methods of DDH; in some countries, universal ultrasound is proposed as the basic screening method for neonates for DDH; in other countries screening is performed only in high-risk cases. More robust data are needed to conclude which screening approach is associated with improved long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: High blood lead levels (BLLs) in pregnant women are associated with poor outcome in neonates. One of the newest non-occupational sources of lead contamination is opium consumption. Accordingly, this study aimed to assess BLLs in mothers addicted to opium and their neonates in Kerman. Methods: This cross-sectional was conducted in Afzalipour hospital in Kerman, from February 2019 to February 2020. The BLLs were measured in 100 opium-addicted and non-addicted mothers and their newborns, and the lead levels higher than 5 μg/dL were considered contamination. Then, the demographic and anthropometric data were compared. Findings: Based on the results of the present study, the BLLs of opium-addicted mothers (33.40 ± 9.22 μg/dL vs 3.2 ± 1.5 μg/dL) and their neonates (13.46 ± 4.86 vs 1.1 ± 0.9) were significantly higher (P = 0.001) than those of non-addicts. Moreover, the average birth weight of the newborns in the addicted group was significantly lower than in the non-addicted group (2572.8 ± 77.49 vs 2946 ± 46.87) (P = 0.001). Besides, there was a significant relationship between the average birth weight and the BLL of the mother and baby, and the average weight of the babies was significantly lower at higher levels of lead. However, no correlation was observed regarding the average height and head circumference of the neonates (P > 0.05). Conclusion: It seems that the serum level of lead in neonates of opium-addicted mothers contaminated with lead is significantly higher than that of non-addicts, but their anthropometric characteristics at birth were not different from those of the nonaddicted group. [ABSTRACT FROM AUTHOR]

The identification of cystic fibrosis screening-positive, inconclusive diagnosis (CFSPID) in infants is a controversial outcome of newborn screening for cystic fibrosis (CF). Today, despite improvements in the knowledge of CFSPID and the description of several cohorts, little data are available on cohorts with a follow-up period of more than 6 years. In this study, we report the outcomes of an Italian cohort of CFSPID individuals with CFSPID or formerly CFTR-related disorders (CFTR-RD) (CFSPID > CFTR-RD) or diagnosed with CF (CFSPID > CF). This was an observational and multicentre Italian study collecting clinical data on CFSPID born between the period January 1, 2011, and December 13, 2019. A total of 268 participants were included: 243 with persistent CFSPID, 7 with CFSPID > CFTR-RD, and 18 with CFSPID > CF. The trend of sweat chloride (SC) values, percentage of definitive diagnoses, lung function in school-aged children, and development of CF-related complications were evaluated. At the end of the observation period, almost 80% of the individuals with CFSPID did not have a conclusive diagnosis. A total of 29 children (10.8%) transitioned to a diagnosis of CF for pathological SC values (≥ 60 mmol/L) or multi-organ involvement, and 18 (6.7%) to CFTR-RD. Children who were followed up for > 6 years (median age, 7.5 years; range, 6.04–10.5) had normal lung function and were pancreatic sufficient, and the evolution in CF was only present in two cases. Conclusion: Most Italian preschool and school-aged children with CFSPID did not have a conclusive diagnosis, and progression to CF was unlikely in children > 6 years of age. An annual follow-up could be indicated to identify early evolution in clinical features consistent with a CFTR-RD. What is Known: • Cystic Fibrosis newborn screening identifies also subjects with an inconclusive diagnosis (CFSPID). • Over time a variable percentage of CFSPIDs will be diagnosed as CF. • Little data is available on CFSPIDs with a follow-up period of more than six years. What is New: • 80% of Italian preschool and school-age CFSPIDs not have a conclusive diagnosis. • Italian preschool and school-age CFSPIDs have normal lung function and are pancreatic sufficient. • Annual follow-up after 6 years is recommended in CFSPID with abnormal LCI2.5 or with a CF-causing variant in trans with a VVCC. [ABSTRACT FROM AUTHOR]

Background: The standard treatment for congenital adrenal hyperplasia (CAH) in children is still hydrocortisone. Improved strategies for timing of the dose during the day and the dose per square meter body surface area used in children of different ages and developmental phases have improved the situation and outcome for the patients. Neonatal screening enables an earlier diagnosis and initiation of treatment, prevents from adrenal crisis, and improves growth and development also for children with the less severe forms of CAH. Summary: This review describes the current treatment strategies for children with CAH and discusses some potential treatment options that have been developed with the primary aim to decrease the adrenal androgen production. Novel modified release glucocorticoid therapies are also discussed. Key Messages: The long-term effects of the new adjunct therapies are unknown, and some are not suitable for use in children and adolescents. The effects of the new therapies on bone mineral density, gonadal functions, and long-term cognitive development are yet to be assessed. It is not known what levels of adrenal androgens are optimal for normal growth, puberty, and bone health. The basis of using glucocorticoids and mineralocorticoids in the treatment of CAH remains, and in some individuals, it may be beneficial to add therapies to reduce the androgen load during certain life stages. [ABSTRACT FROM AUTHOR]

Despite the lack of nationwide epidemiological studies, congenital hypothyroidism (CH) incidence in China has increased. We aimed to evaluate the trends of CH and the possible reasons behind them. Data from screened newborns from the Chinese Newborn Screening Information System from 2012 to 2019 was collected. We applied the Bayesian hierarchical Poisson regression model and meta-analysis to estimate incidence or proportion over the years. The estimated CH incidence increased from 4.01 per 10,000 births in 2012 to 5.77 per 10,000 births in 2019. The average annual growth rate (ARG) of CH incidence for all provinces varied from 0.59 to 20.96%. The most rapid rise in incidence was observed in cases with an initial thyroid stimulating hormone (TSH) concentration of < 10 mIU/L. The meta-analysis results showed that the proportion of permanent CH increased by 0.024% (95%CI: 0.011%, 0.037%) annually. Each 1 mIU/L decrease in TSH cutoff value was associated with a 2.96% increase in CH incidence. In the same period, the proportion of premature CH cases increased from 6.60 to 9.10%, which was much higher than the increase in preterm births. A significant relationship was not found between provincial growth rates in screening coverage and provincial baseline incidences of CH. Conclusion: CH incidence has substantially increased in China. The slight adjustment of the TSH cutoff value and increasing preterm birth rate contribute to such a trend; however, the contribution is limited. What is Known: • An uptrend in congenital hypothyroidism (CH) incidence has been reported in many European and American countries in the last two decades; however, no studies have been conducted in China to explain the increased CH incidence. • We provide a detailed epidemiological report on the trends of CH during 2012–2019 in China, with an attempt to explore the reasons behind it. What is New: • This first-ever national-wide epidemiological report in China showed an uptrend in CH incidence with variations over regions and CH subtypes. The mild lowering of TSH cutoff values and the increasing preterm birth rate contributed to this uptrend. [ABSTRACT FROM AUTHOR]

Objective This study aimed to identify extremely premature infants (< 31 weeks of gestation and/or <1,500 g) affected by congenital hypothyroidism (CH) with delayed elevation of thyrotropin (TSH) and to evaluate the detection strategy for this pathology in our reference screening population. Study Design A descriptive and retrospective study was carried out with samples collected from western Andalusia and the autonomous city of Ceuta. Results This protocol allowed us to detect six neonates with delayed TSH elevation. One of them, due to serious heart problems, died without being able to confirm CH. In two neonates, however, it was possible to detect CH, another two presented a persistent TSH elevation but normal free T4, and another one presented a temporary TSH elevation. Conclusion It is essential to repeat the CH screening in extremely premature infants, not only at the age of 15 days but also with a third sample at the moment of hospital discharge to detect cases with delayed TSH elevation. Key Points The Newborn Screening Programs are an essential activity of preventive medicine. Extremely preterm infants have a very high risk of CH. Optimal management of thyroid dysfunction in this population remains to be established. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether preeclampsia and gestational diabetes mellitus is a risk factor for cochlear damage and sensorineural hearing impairment in infants. Materials and Methods: Longitudinal study was conducted in 2 tertiary referral centers. 1068 neonates were included, who were born to preeclampsia, gestational diabetes mellitus, and healthy mothers. The hearing evaluation was done using DPOAE on day 2 and for those who failed the initial DPOAE on day 2, underwent repeat DPOAE on day 15, ABR was done on day 30 if repeat DPOAE was Refer. The results were compared between the groups and analyzed. Results: On initial DPOAE, bilateral ear absent DPOAE rates were 19.5%, 15.8%, and 3.5% among preeclampsia, Gestational Diabetes Mellitus (GDM), control groups respectively. The difference was statistically significant (P <.001). Also it was noted that absent DPOAE was significantly high at low and mid frequencies (1000, 2000, 3000, and 4000 Hz) in bilateral ear. However the difference in repeat DPOAE among the groups were not significant (Right ear P =.17, Left ear P =.31). Infants who failed repeat DPOAE test underwent ABR test in which 3 of GDM group, 2 infants of preeclampsia group and 1 infant of control group had absent ABR test. Conclusion: This study reveals that GDM and preeclampsia showed remarkable association of hearing loss at lower and mid frequencies which was transient. The prevalence of absent DPOAE was corresponding to the severity of the maternal conditions under the study. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of hearing loss and identify the high-risk factors among neonates with hearing loss. Methods: Retrospective study done on 1054 infants in a tertiary care centre in Eastern India from 2020 to 2021 and approved by the Institutional Ethics Committee. A two-step protocol is used for screening. In the well-nursed group, OAE and BOA were performed. In the case of REFER results for automated ABR following OAE evaluation in well-nursed babies, a detailed audiological evaluation was scheduled to be carried out using diagnostic ABR within one month of age. In the high-risk group, hearing screening includes OAE, BOA, and AABR evaluations. AABR evaluation was performed as a part of the screening protocol irrespective of the results of OAE screening as PASS or REFER. Results: In our study among 1053 neonates screened, 375 were in the risk category, and 679 were without risk factors. The overall prevalence of hearing loss in neonates was 22.78 per 1000 screened neonates and 56 per 1000 among high-risk neonates. In the high-risk group, we were able to identify 4 cases of Auditory spectrum neuropathy disorder with the use of AABR during 1st step of screening. In multivariate regression analysis, the risk factors for hearing loss identified were NICU stay (OR = 3.6, 95% CI = 1.1-12.03) and Craniofacial anomalies (OR = 55.37, 95% CI = 16.48- 186.01). Conclusion: Early neonatal screening helps in the detection, intervention, and rehabilitation of hearing loss. The use of AABR in risk infant screening enhanced the chance of detection of auditory spectrum neuropathy disorder (ASND) cases. [ABSTRACT FROM AUTHOR]

Cerebral Palsy (CP) is the most common physical disability in childhood and is associated with sensory alterations and cognitive limitations. Early diagnosis is crucial, based on a specific assessment, with a view to appropriate intervention that promotes motor and cognitive gains during a period of great neural plasticity. To this end, identifying risk factors for the development of CP is essential. Aim: to assess and detect the risk of CP in babies discharged from the NICU. Method: cross-sectional study with 35 babies who were assessed using the HINE neurological assessment. Results: 68.6% of the sample was male, 85.7% were premature, 54.3% had low birth weight. Cesarean delivery was the most prevalent (68.6%), and 31.4% of the sample were identified as being at risk of CP in the standardized neurological examination. Specifically, all the babies at risk were premature, 81.8% were male and 45.5% had a low birth weight. Conclusion: Babies coming out of the NICU are more likely to have unfavorable developmental outcomes, and the risk of developing CP can be identified early when neurological examination, MRI and HINE assessment are combined. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the clinical suspicion and where patients were when they received the positive result of the neonatal screening for CAH 21OHD. The present data derived from a retrospective analysis of a relatively large group of patients with classical CAH 21OHD patients nosed by newborn screening in Madrid, Spain. During the period from 1990 to 2015 of this study 46 children were diagnosed with classical 21OHD [36 with the salt-wasting (SW) form and 10 with simple virilizing (SV)]. In 38 patients, the disease had not been suspected before the neonatal screening result (30 SW and 8 SV). Thirty patients (79%) were at home without suspicion of any disease, as healthy children, 3 patients (8%) were at home pending completion of the study due to clinical suspicion of any disease (ambiguous genitalia, cryptorchidism) and 5 patients (13%) were admitted to the hospital for reasons unrelated to CAH (sepsis, jaundice, hypoglycemia). It is relevant to note that 69.4% of patients (25/36) with SW form were at home with potential risk of adrenal crisis. Six females had been incorrectly labeled as male at birth. The most frequent reason for clinical suspicion was genital ambiguity in women followed by family history of the disease. Neonatal screening provided better results than clinical suspicion. In the majority of patients with 21OHD the diagnosis by screening was anticipated to the clinical suspicion of the disease even in female patients with ambiguous genitalia. [ABSTRACT FROM AUTHOR]

Objective: Pregnant and lactating women are particularly at higher risk of iodine deficiency due to their increased iodine requirements. Iodine is necessary for normal growth and brain development. In regions with moderate iodine deficiency, such as Turkey, the fate of newborn babies is a critical issue.This study evaluated the relationship between maternal iodine deficiency and the frequency of recall due to high TSH value in newborn screening programs. Methods: 78 mothers who volunteered for the research were included in the study with their newborn babies. Thyroid function tests were examined in the blood serum of newborns with high heel blood TSH value (5.5-20mIU/L) who were referred to the pediatric endocrine with the suspicion of congenital hypothyroidism Urinary iodine levels of healthy mothers without any thyroid disease and iodine exposure were evaluated. Results: The median urinary iodine in mothers was 56.04 μg/l. Only 8 (10.2%) of the recalled newborns had subclinical hypothyroidism and recovered at the follow-up 1 week later, while all the rest had normal thyroid functions. In addition, there was a weak negative correlation between maternal age, the number of children, and urinary iodine levels (respectively, r=0.35,r= 0.33; p=0.001,p=0.003). Conclusion: Only 9%(7 people) of the mothers participating in the study had adequate urinary iodine excretion and almost half (38 people) of the mothers (48.7%) had severe urinary iodine deficiency. Low maternal iodine values are effective in the prolonging transient TSH elevation in newborns, and iodine supplementation to mothers during pregnancy may reduce recall rates of newborn TSH screening. [ABSTRACT FROM AUTHOR]

Objective: Congenital cytomegalovirus infection is the most common congenital infection. Although screening of congenital cytomegalovirus infection with polymerase chain reaction studies in blood, urine, and saliva samples has been developed in recent years, it is not yet in routine use in any country. Materials and Methods: In our study, cytomegalovirus deoxyribonucleic acid analysis was performed by real-time polymerase chain reaction method in saliva samples taken before the first feeding during the first day following birth in neonates born in a university hospital between January 2021 and January 2022. To support the diagnosis, additionally, cytomegalovirus deoxyribonucleic acid positivity in urine and blood samples was investigated in newborns with cytomegalovirus deoxyribonucleic acid positivity in saliva. Results: Cytomegalovirus deoxyribonucleic acid was investigated in saliva samples of 545 neonates by real-time polymerase chain reaction method in 1-year period and positivity was found in 6 neonates. Since cytomegalovirus deoxyribonucleic acid was found negative by the real-time polymerase chain reaction method in the urine and blood samples of 5 of these neonates, the positivity in the saliva sample was interpreted as false positivity. In 1 case, cytomegalovirus deoxyribonucleic acid positivity was detected in urine and blood samples 5 weeks later. As a result, definite congenital cytomegalovirus infection could not be diagnosed in 545 cases, while possible congenital cytomegalovirus infection was diagnosed in 1 case. Conclusion: It has been concluded that the frequency of congenital cytomegalovirus infection is low in our study group and studying saliva samples showed high false-positive rates. It is seen that saliva is not a suitable sample for detecting cytomegalovirus deoxyribonucleic acid by real-time polymerase chain reaction method. [ABSTRACT FROM AUTHOR]

Aim: Previous studies have not described separate positive predictive values for Ortolani and Barlow tests in clinical hip screening. We aimed to determine the positive predictive values at discharge following birth, in predicting dysplasia or instability in the subsequent hip ultrasound examinations. Methods: We included all infants with suspected or diagnosed DDH at the study hospital from 2015 to 2017 in this retrospective study. Infants with positive Ortolani or Barlow test after birth were referred for a hip ultrasound, without treatment being started. The positive predictive value of the tests to predict Graf type ≥ IIC morphology, ≥5 mm displacement in a dynamic ultrasound, or either one or both findings at the hip ultrasound examination was calculated. Results: There were 33 Ortolani‐positive hips and 103 Barlow‐positive hips in 105 referred infants (30% male) at the screening. They received ultrasound examination at mean 21.7 days of age (SD 4.8, range 11–35). The positive predictive value was 39–61% for the Ortolani test and 4%–16% for the Barlow test depending on the true positive definition. Conclusion: The Ortolani test, performed by a specialist at the maternity ward, has a high positive predictive value for developmental dysplasia of the hip. [ABSTRACT FROM AUTHOR]

Introduction The newborn hearing screening (NHS) test aims the early diagnostic of hearing deficits that may also harm the full development of communication and learning of the affected child. Objective Trace the clinical and epidemiological profile of children born between July 2016 and July 2019; in addition to the outcome of the NHSs and factors related to failure in the hearing tests at a maternity of a tertiary hospital in Santa Catarina, Brazil. Methods The present is a cross-sectional study. A census of those born in the period defined for study was performed and a script was developed for the review of medical records, based on the literature. Results The sample can be considered homogeneous in relation to gender and age. The pregnant women had an average of 30.9 years. There were 30 neonates (1.9%) that did not undergo NHS. New evaluations were required in 288 patients (18.2%). Finally, 24 (1.5% of the population) remained with insufficient results in the retest. The following variables achieved statistical relevance with higher failure rates in tests and/or retests: natural delivery (p = 0.007), arterial hypertension present (p = 0.002), use of hydralazine (p = 0.038), and use of dipyrone in the test (p = 0.041) and retest (p = 0.003). Younger mothers had higher levels of normality in the test (p = 0.003) and retest (p = 0.161). The correlations between the other variables and the outcomes were not statistically significant. Conclusion False positives (62.8%) in the first test showed a value higher than the ideal goal; those who did not undergo the NHS (1.9%) and who needed evaluation by a specialist, due to failure in the retest (1.5%), are within the quality goals defined by the Joint Committee on Infant Hearing (JCIH) in 2007. [ABSTRACT FROM AUTHOR]

Background: Neonatal hearing loss is more prevalent than other routinely screened new-born disorders like congenital hypothyroidism. Auditory deprivation during early phase of life causes developmental disorders with poor language, speech& education leading to lack of job opportunities and financial dependence. Early diagnosis is essential for suitable auditory rehabilitation of such children. Any delays in detection of hearing loss ensure an inferior quality of rehabilitation and a handicap for life. Objectives: To find the incidence of hearing loss in neonates, compare the incidence of hearing loss in the "at risk" & "not at risk" neonates and to document the risk factors associated with neonatal hearing loss. Methods: A prospective study was carried out where neonates underwent a two-step screening with OAE and BERA as per JCIH guidelines. Results: Overall incidence of neonatal hearing loss was 2.85%, incidence being higher in the "at risk" group babies (4.80%). A statistically significant association between the presence of risk factors and hearing loss was observed, p <0.05.Conclusion: Universal neonatal screening for hearing loss in all new-borns will ensure the inclusion of apparently normal neonates who form a large chunk of the "invisible burden of hearing impairment". [ABSTRACT FROM AUTHOR]

• Machine learning has the potential to improve the positive predictive value of neonatal screening for primary and central congenital hypothyroidism. • Currently, detection of central congenital hypothyroidism is accompanied by a high number of false-positives. • In order of importance, variables determining detection of congenital hypothyroidism were TSH, T4/TBG, (gestational) age, TBG, T4, and age at NBS sampling. • From the current routine screening parameters, T4/TBG is the most important parameter to detect central congenital hypothyroidism with a low positive predictive value. • New screening parameters are needed to improve the detection of central congenital hypothyroidism. The Dutch Congenital hypothyroidism (CH) Newborn Screening (NBS) algorithm for thyroidal and central congenital hypothyroidism (CH-T and CH-C, respectively) is primarily based on determination of thyroxine (T4) concentrations in dried blood spots, followed by thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) measurements enabling detection of both CH-T and CH-C, with a positive predictive value (PPV) of 21%. A calculated T4/TBG ratio serves as an indirect measure for free T4. The aim of this study is to investigate whether machine learning techniques can help to improve the PPV of the algorithm without missing the positive cases that should have been detected with the current algorithm. NBS data and parameters of CH patients and false-positive referrals in the period 2007–2017 and of a healthy reference population were included in the study. A random forest model was trained and tested using a stratified split and improved using synthetic minority oversampling technique (SMOTE). NBS data of 4668 newborns were included, containing 458 CH-T and 82 CH-C patients, 2332 false-positive referrals and 1670 healthy newborns. Variables determining identification of CH were (in order of importance) TSH, T4/TBG ratio, gestational age, TBG, T4 and age at NBS sampling. In a Receiver-Operating Characteristic (ROC) analysis on the test set, current sensitivity could be maintained, while increasing the PPV to 26%. Machine learning techniques have the potential to improve the PPV of the Dutch CH NBS. However, improved detection of currently missed cases is only possible with new, better predictors of especially CH-C and a better registration and inclusion of these cases in future models. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the neonatal screening for congenital hypothyroidism (CH) and the diagnosis CH in the national health registers and to study the effects of lowering screening thyroid-stimulating hormone (TSH) threshold on the incidence of CH and birth characteristics of screening positive and negative CH children. Design: This is a nationwide register-study of all children (n = 3 427 240) in the Swedish Medical Birth Register (MBR) and national cohort for screening positive infants (n = 1577) in 1980-2013. Methods: The study population was further linked to several other Swedish health registers. Evaluation of the CH screening and CH diagnosis was performed with levothyroxine use in the first year of life as reference. The incidence of CH was estimated by the Clopper-Pearson method. Regression models were used to study associations between CH and birth characteristics. Results: The neonatal CH screening had high efficacy, but 50% of all children with a CH diagnosis were screening negative. The incidence of screening positive CH increased (1/3375 to 1/2222), and the incidence of screening negative CH decreased (1/2563 to 1/7841) after lowering the TSH screening threshold in 2009. Screening negative CH was associated with female sex, twinning, prematurity, low birth weight, birth defects, and need of neonatal intensive care, and 42% had transient disease. Conclusions: Despite high efficacy of the CH screening, 50% of children diagnosed as CH was screening negative. Although other factors influencing the incidence of the CH diagnosis cannot be ruled out, the incidence of screening negative CH decreased with lowering of the TSH threshold. Birth characteristics differed between screening positive and negative CH. [ABSTRACT FROM AUTHOR]

Introduction: neonatal seizures represent a challenge in establishing their causes. Maple syrup urine disease (MSUD) is a rare inborn error of metabolism. These patients may present certain types of seizures that are distinctive from other diseases. Case description: seven-day-old female patient with feeding problems and "swordsman" and "cycling" seizures. After ruling out multiple causes, the diagnosis of MSUD was established by neonatal metabolic screening. Conclusions: in neonates with seizures, their correct clinical characterization is important to guide laboratory and imaginology studies, to achieve the etiological diagnosis, such as inborn errors of metabolism. [ABSTRACT FROM AUTHOR]

Objective: To explore the prevalence rate of maple syrup urine disease (MSUD) in newborns, and to analyze the mutation characteristics of related genes in Shijiazhuang area, China. Methods: A total of 185 683 newborns born from January 2014 to December 2021 in Shijiazhuang area were screened for MSUD by tandem mass spectrometry, and BCKDHA, BCKDHB and DBT mutations were detected in newborns with positive screening. Results: Two children with MSUD were confirmed, with a prevalence rate of 1∶92 842. In two confirmed cases, the levels of blood leucine (Leu) and valine (Val) were elevated during initial screening. The levels of case 2 were also elevated in the review of tandem mass spectrometry, while case 1 died prematurely before being recalled for review and was not performed the review of tandem mass spectrometry. Two children with MSUD were all classic with gene complex heterozygous mutations of BCKDHB and DBT, and four mutations were found including c.331C>T, c.289G>T, c.75_76delAT and c.1359_1360delAG. Two unreported gene mutations were found, c.289G>T and c.1359_1360delAG. No mutations in the BCKDHA gene were detected. Case 1 died prematurely 10 days after birth. Case 2 began to develop symptoms 8 days after birth, and improved after timely intervention and treatment. Conclusions: Tandem mass spectrometry technology can be applied in newborn disease screening to detect early newborns with MSUD. The genetic testing can identify genetic causes and provide a basis for genetic counseling. The prevalence rate of MSUD in Shijiazhuang area was 1 ∶92 842. Four gene mutations, two of which were unreported gene mutations, were found in this study, enriching the gene mutation spectrum of MSUD. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of an online continuing education course on infant hearing health for primary care professionals. A prospective longitudinal study with interrupted time series pre-test/post-test design. The effectiveness of the online course was assessed by comparing pre- vs. post-training performance and analysing responses to evaluations of the quality of the course. The sample comprised individuals enrolled between September 2018 and August 2019 in a Ministry of Health course, "Actions in primary care for the early identification of hearing impairment" offered on the AVASUS platform. Of the 2908 individuals registered, 1842 (63.3%) completed the course. Their ages ranged from 18 to 77 years, and 67.4% of them were females. Students and doctors were overrepresented among the enrollees. All Brazilian states were included in the sample. Comparisons of pre- and post-training performances showed a significant improvement in knowledge, and 99.3% of the participants provided positive comments regarding the quality of the course. The course is an effective distance learning tool on infant hearing health for primary care professionals. The online course circumvents the limitations posed by geographical barriers and also facilitates decentralisation. [ABSTRACT FROM AUTHOR]

Background: Premature infants are at higher risk of developing congenital hypothyroidism (CH) but the neonatal screening strategy for this population is still debatable. The purpose of this retrospective study is to describe the results of a screening program for CH in a preterm infant cohort. Materials and Methods: All preterm newborns who underwent neonatal screening in the Italian region of Piedmont in the period January 2019–December 2021, were included in this retrospective cohort study. The first thyrotropin (TSH) measurement was performed at 72 hours, whereas the second at 15 days of life. Infants with TSH >20 mUI/L at first detection and >6 mUI/L at second were recalled for a full evaluation of thyroid function. Results: During the study period, 5930 preterm newborns were screened. Based on birthweight (BW), the mean TSH was 2.08 ± 0.15 for BW <1000 g, 2.01 ± 0.02 for BW 1001–1500 g, 2.28 ± 0.03 for BW 1501–2499 g, and 2.41 ± 0.03 mUI/L in normal-weight newborns (p < 0.005) at the first detection, with a significant difference observed at the second measurement (p < 0.005). Based on gestational age, the mean TSH at first detection was 1.71 ± 0.09 mUI/L for extremely preterm babies and 1.87 ± 0.06, 1.94 ± 0.05, and 2.42 ± 0.02 mUI/L for very preterm, moderately, and late preterm infants (p < 0.005), respectively. Significant between-group differences of TSH measurements were also at the second and third detections (p < 0.005 and p = 0.01). The 99% reference range in this cohort overlapped with the recommended TSH cutoffs for screening recall (8 mUI/L for first detection and 6 mUI/L for second detection). CH incidence was 1:156. Of the 38 patients diagnosed with CH, a eutopic gland was present in 30 (87.9%), with CH transient in 29 (76.8%). Conclusions: We observed no significant difference in the recall rate between preterm and at term infants screened in this study. Our current screening strategy therefore appears effective in avoiding misdiagnosis. CH screening approaches vary among countries. Development and testing of a uniform multinational screening strategy is needed. [ABSTRACT FROM AUTHOR]

Introduction: cystic fibrosis (CF) is an autosomal recessive inherited disease. Objective: to describe the benefit of determination of immunoreactive trypsin (IRT) for the detection of CF, as part of neonatal screening. Case presentation: eight-month-old infant with two episodes of hyponatremic dehydration. With this history, CF was suspected since he had also high serum levels of IRT (130 ng/L). A genetic study confirmed CF, identifying a probably pathogenic variant in the CFTR gene. Conclusions: elevated TIR levels can help identify CF cases, from the neonatal period. [ABSTRACT FROM AUTHOR]

The diagnosis of cystic fibrosis has improved in the last few years due to greater access to diagnostic tools and the evolution of molecular biology; the knowledge obtained has contributed to the understanding of its death profile. In this context, an epidemiological study was developed focusing on deaths from cystic fibrosis in Brazil from 1996 to 2019. The data were collected from the Data-SUS (Unified National Health System Information Technology Department from Brazil). The epidemiological analysis included patients' age groups, racial groups, and sex. In our data, between 1996 and 2019, Σ3050 deaths were recorded, totaling a ≅330% increase in the number of deaths resulting from cystic fibrosis. This fact might be related to a better diagnosis of the disease, mainly in patients from racial groups that are not commonly associated with cystic fibrosis, such as Black individuals, Hispanic or Latino (mixed individuals/Pardos) individuals, and American Indians (Indigenous peoples from Brazil). Regarding of race, the Σ of deaths was: nine (0.3%) in the American Indian group, 12 (0.4%) in the Asian group, 99 (3.6%) in the Black or African American group, 787 (28.6%) in the Hispanic or Latino group, and 1843 (67.0%) in the White group. The White group showed the highest prevalence of deaths, and the increase in mortality was ≅150 times in this group, while, in the Hispanic or Latino group, it was ≅75 times. Regarding sex, the numbers and percentage of deaths of both male (N = 1492; 48.9%) and female (N = 1557; 51.1%) patients were seen to be relatively close. As for age groups, the >60-year-old group presented the most significant results, with an increase of ≅60 times in the registered deaths. In conclusion, in Brazil, despite the number of deaths from cystic fibrosis being prevalent in the White group, it increased in all racial groups (Hispanic or Latino, Black or African American, American Indian, or Asian individuals) and was associated with older age. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a disease that is part of neonatal screening. There are many causes of false-positive results on neonatal screening, and maternal opioid consumption during pregnancy is suspected to increase 17-hydroxyprogesterone (17-OHP) levels at birth. The aim of this study was to determine the effect of maternal drug consumption on 17-OHP values on neonatal screening. We studied 17-OHP levels of term newborns with reported maternal drug consumption born at the Maternity Hospital of Nancy between 2002 and 2018. These infants were matched with newborns of mothers without drug addiction. The 17-OHP levels, withdrawal syndromes, birth parameters, and maternal characteristics were compared between the two groups. The study included 241 patients (121 in the drug-exposed group, 120 in the control group). The mean 17-OHP levels in newborns of mothers with substance addiction were 9.83 nmol/L compared to 4.90 nmol/L (p =0.0001) in the control group. Newborns exposed to drugs were smaller (p= 0.0001), lighter (p =0.0001), had smaller head circumference (p =0.0001), and had lower Apgar scores (p =0.004 at 1 min and p =0.0001 at 5 min). The 17-OHP level did not differ in cases of withdrawal syndrome in drug-exposed newborn (p =0.911). A significant increase in 17-OHP levels was observed in newborns exposed to drugs, with no influence of withdrawal syndrome on 17-OHP levels. Maternal substance addiction may be associated with moderately increased 17-OHP levels during neonatal screening. [ABSTRACT FROM AUTHOR]

Objective: to verify the frequency of congenital infections in newborns and their possible associations with the universal-neonatal-hearing-screening (UNHS) results, and evaluate a reference UNHS service in the Unified Health System (Sistema Único de Saúde—SUS), according to quality indicators. Methods: Historical cohort study with data analysis of newborns attending prestigious hearing-health SUS services from January 2017 to December 2021, in Santa Catarina, Brazil. The quality of screening coverage was assessed based on the quality indicators proposed by the Brazilian neonatal-hearing-screening-care guidelines (Diretrizes de Atenção da Triagem Auditiva Neonatal—DATAN). Logistic-regression analysis, crude OR calculations, Cochran–Mantel–Haenszel OR calculation, and chi-square test were performed to estimate the association between risk indicators for hearing loss and UNHS failure. Results: In the last five years, the prestigious services performed UNHS on 34,801 newborns and met the DATAN quality indicators. Congenital syphilis was the most frequent (1.59%) congenital infection in newborns, followed by HIV (0.87%), whereas the least frequent was rubella (0.029%). Conclusion: Prestigious UNHS services reached ≥95% hearing screening coverage. Considering all congenital infections, the prevalence was 2.87%, with congenital syphilis the most frequent. Newborns with congenital syphilis or HIV are more likely to fail UNHS. [ABSTRACT FROM AUTHOR]

Neonatal screening (NS) programs represent one of the most effective public health strategies in Mexico and the world. Its purpose is to identify asymptomatic newborns with conditions that can cause illness, disability or even death, so that they can receive timely treatment, improve their quality of life and reduce their morbidity and mortality. In Mexico, the first national metabolic screening program began to operate in 1989 and in the last 2 decades, universal hearing screening, ophthalmological screening and recently cardiac screening have been added to the general health law. These programs have managed to reduce disability and death in thousands of Mexican children, however, it is still necessary to increase efforts and assign greater human and economic resources for their consolidation. [ABSTRACT FROM AUTHOR]

Introduction The Brazilian neonatal screening program established in 2001 included the investigation of cystic fibrosis (CF) in the phase III of the program. For this purpose, the immunoreactive trypsin (IRT) measurement was added to the newborn screening test. The purpose of National Neonatal Screening Program is to reach 100% of live births in Brazil. The aim of this study was to analyze the coverage of neonatal Screening for Cystic Fibrosis (CF) in Brazil from 2008 to 2017. Materials and methods This is an ecological study design based on data collected from the Brazilian Outpatient Information System regarding the detection of IRT as a component of the heel stick test from 2008 to 2017. Moreover, we gathered data from the Brazilian Live Birth Information System referring to live births from 2008 to 2017. We calculated the coverage of IRT measurement for every 100 live births, using the number of IRT measurement procedures as the numerator and the number of live births stratified by federative units (states), as well as by the Brazilian regions as the denominator. These regions correspond to the divisions of the national territory based on criteria such as natural, social, cultural and economic aspects. Results From 2008 to 2017, the regions presented the following coverage medians: South (84.1%), Southeast (71.4%), Midwest (47.3%) Northeast (12.3%) and North (10.9%). In the analysis of federative units, in the years 2013 to 2017, Paraná and Distrito Federal presented the highest median of coverage (100%), while the states with the lowest median were Rio Grande do Norte (12.1%), Amazonas (16.8%) and Paraíba (27.5%). Highest coverage was found in the South region, where are located most of the states with high socioeconomic development and high supply of health services, while the lowest coverage was found in the North region, where are located manly the states with low socioeconomic development and low supply of health services. According to data from the Brazilian Ministry of Health, the universalization of neonatal screening for cystic fibrosis occurred in 2013, however, at the end of this year, most states in the North and Northeast regions had not registered IRT measurements in the Outpatient Information System. Conclusion Although the coverage of neonatal screening for CF has improved nationwide over the years of the study, the disparity in the coverage of IRT measurements at the interregional and interstate levels is notable. Systematic implementation of neonatal screening for cystic fibrosis with equity and access to the entire population is suggested, leading to a greater number of children benefiting from treatment and a better quality of life. [ABSTRACT FROM AUTHOR]

Background and aims: Although the significance of primary congenital hypothyroidism (CH) is supported by an increasing amount of evidence, the clinical and genetic characteristics of this condition are still poorly understood. This study aimed to explore the underlying genetic etiologies in a cohort of primary CH patients. Subjects and Methods: The clinical data of 33 patients with primary CH were collected and analyzed via a cross-sectional study. Genetic analysis was performed by high-throughput sequencing and Sanger verification, and the pathogenicity of the novel missense variants was predicted using a variety of comprehensive bioinformatic tools. Results: Among the 33 patients, 22 (22/33, 66.7%) harbored pathogenic variants in the causative genes of thyroid dysgenesis or dyshormonogenesis, with DUOX2 (15/33, 45.5%) topping the list, followed by TG, TPO, DUOXA2 and PAX8. Four novel genetic variants were detected, including a pathogenic frameshift and three likely pathogenic missense variants. Positive neonatal screening for TSH, neonatal jaundice and abnormal thyroid morphology were the main positive findings among all cases. Although 31 of the total 33 CH patients exhibited normal anthropometric and social performance, the other 2 had poor prognosis in this study. Conclusions: This study reported 33 new CH patients bearing four novel genetic variants, which enriched the variant spectrum of CH genes. In this cohort, genetic factors causing thyroid dyshormonogenesis were the main etiologies of CH development. Most patients exhibited a favorable prognosis; however, systematic management remains a challenge in achieving improved clinical outcomes for CH patients. [ABSTRACT FROM AUTHOR]

Objectives Sickle cell disease (SCD) is an inherited multisystem disorder with complications starting in the first year of life. Newborn screening (NBS) can identify infants with SCD and is associated with decreased morbidity and mortality. Variation in availability of NBS in Canada, and lack of standardized screening for immigrant children, may lead to delayed diagnosis. Methods This was a retrospective cohort study of 126 children aged 0–18 years with SCD registered with the SCD clinic at the Alberta Children's Hospital between January 2003 and January 2018, prior to province-wide universal NBS for SCD. Patient demographic information, circumstances of diagnosis, and other contextual information were collected from patient health records. Descriptive statistics were used to summarize data, with Mood's median test used to compare medians between groups. Results Forty-three (35%) patients were born in Alberta. Patients were mostly (95.3%) of African descent. Of patients born in Alberta, 63% (26/43) were diagnosed at >12 months of age, with a median age at diagnosis of 18 months (IQR = 4–39). This was significantly older (P < 0.001) than children born in the USA or in Canadian provinces with SCD NBS programs, where the median age at diagnosis was zero months (N = 36). Of the 42% of patients born outside North America, 64% were diagnosed following an acute complication. Conclusions This study highlights the importance of NBS for early detection and management of SCD, and the importance of screening at-risk immigrants who may not have received NBS for SCD. [ABSTRACT FROM AUTHOR]

Background: The newborn screening program has been evaluated in several parts of the world, with varying outcomes (1). In terms of incidence, severity, age of onset, and diagnostic and therapeutic techniques, they vary greatly. The program screens a group of conditions that causes major metabolic abnormalities in newborns, resulting in irreversible damage and illness. There is a treatment for some of them that, if given soon after birth, can prevent such damage. Many countries have suggested, developed, and implemented population-based newborn screening for these illnesses, although at differing rates and using various criteria(2). Materials and Methods: This evaluation study was conducted between the first of September 2021 and the end of June 2022. This research was carried out in the Holy Karbala Governorate, to assess a pilot program implemented by the Governorate Directorate of Health in Karbala Children's Teaching Hospital and Al-Hindiya General Hospital. A checklist has been used to evaluate hospitals after reviewing the "National Guideline of Newborn Screening for Care Providers in Primary Health Care Centers in Iraq". The list was built and developed by the researchers. Results: It was documented that the program worked in only one hospital, where the trained medical staff. However, there was untrained health staff available, in addition to the lack of the program's needs for laboratory testing follow-up, food, and milk needed for the program patients. Conclusion: Although, this program could contribute to "reducing the rate of under-five mortality by two-thirds", the necessary tools to meet these objectives were not found in the hospitals. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism (CH) is the commonest preventable cause of mental retardation in human species. It is so important for clinician to know its etiology epidemiology, clinical manifestation and treatment strategies. Since it is one of the rare serious diseases that should not be diagnosed clinically because late clinical features corresponds to advanced mental retardation, the neonatal screening detection is the best and preferable way of early diagnosis of this congenital disease. Confirmatory laboratory and radiological diagnostic tests should be performed immediately after the positive neonatal screening test. In order to prevent mental defects and to maintain long term clinical as well as biochemical euthyroidism in affected children its diagnosis approach, medical treatment and follow-up should be well established knowledge to all pediatricians during the childhood period and later on to general practitioners when these individuals grow up as adults. Congenital hypothyroidism is a potentially serious disease that we need to emphasize on early detection, using proper diagnostic tools and early and planned therapeutic approach. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the implementation of France's neonatal hearing loss screening programme years after its launch, and to estimate permanent bilateral neonatal hearing loss (PBNHL) prevalence and distribution by severity. Methods: This descriptive study used aggregated regional data on all births in France in 2015–2016. Screening coverage, refusal rate, positive predictive value (PPV), proportion of children with suspected PBNHL, PBNHL prevalence and distribution by severity were calculated. Results: Eight hundred thousand neonates were eligible for the screening programme per year. Between 2015 and 2016, screening coverage increased (83.3% vs. 93.8%; p < 0.001), and the refusal rate remained stable (0.1%). In 2016, when considering the additional tests performed several weeks after birth, the proportion of suspected PBNHL neonates decreased (1.4% vs. 0.9%) while the PPV increased (4.7% vs. 7.6%). In 2015, the estimated prevalence of PBNHL (moderate to profound) was 0.09% (95% CI 0.08–0.10). Among neonates with >= 41 decibels deficit, 56.8%, 16.6%, and 26.6% had moderate, severe and profound hearing loss, respectively. Conclusion: The national target of 90% screening coverage was exceeded. The additional test could be useful to avoid overcrowding in diagnostic structures. Diagnostic data quality must be improved to confirm PBNHL prevalence and distribution by severity. [ABSTRACT FROM AUTHOR]

Awareness regarding consanguineous marriage and other risk factors of infantile hearing loss is essential for prevention, early detection and timely intervention which can save deaf children from lifelong consequences of hearing disability. A pre-post study was done among the general population of Puducherry, India to evaluate the effect of health education on knowledge and behaviour towards consanguineous marriage and infantile hearing loss. Individual direct interviews were done using a questionnaire to assess their awareness about consanguineous marriage and other risk factors of infantile hearing loss, its early detection and intervention. The assessment was repeated after a health education given for the same by direct interaction and pamphlets. The study showed that 65% participants were unaware of consanguinity being a risk factor for congenital hearing loss. More than half of them were unaware of other risk factors, neonatal hearing screening and treatment. Only 35.3% were aware that early identification and intervention enables a deaf child to learn optimum speech and language. Prior to health education, 33.7% were in support of consanguineous marriage whereas, after the health education, only 6.7% supported it showing significant improvement in their attitude towards consanguineous marriage. Post health education, there was overwhelming 100% improvement in their knowledge regarding infantile hearing loss. The study shows the poor awareness among the population of Puducherry regarding consanguineous marriage and infantile hearing loss, thus requiring a widespread sensitization about infantile hearing loss which can prevent lifelong consequences of the hearing disability. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a rare condition usually referred to as a group of genetic disorders resulting due to a deficiency of steroid enzymes required by adrenal glands to produce cortisol and mineralocorticoid hormones. It has an autosomal recessive mode of inheritance and is further categorized into two types—Classic and Non‐Classic. Non‐Classic CAH is a more common milder form that presents late after puberty. Classic CAH, although more severe, is rare and detected at birth and is associated with the life‐threatening adrenal crisis in both sexes and virilization of the external genitalia in females (46, XX) patients, whereas in males, no overt abnormality of the external genitalia is present. We present a case of a four‐month‐old male child with the classic form of CAH who was brought with complaints of loose stools, projectile non bilious vomiting, decreased urine output, and failure to feed for 3 days. The child had a clinical presentation of salt wasting with hypoglycemia and hyperpigmentation of his genitalia. The USG findings revealed increased anteroposterior diameter of renal pelvis indicative of a growth in the suprarenal area. 17‐hydroxyprogesterone (17‐OHP) was found to be elevated confirming the diagnosis. He was treated with hydrocortisone with gradual improvement in his glucose and electrolytes. The patient was discharged home on replacement therapy consisting of oral prednisolone and fludrocortisone acetate and followed up as outpatient with significant improvement in the clinical findings. The fact that the child was not screened for CAH at birth led to the critical consequences of the disease in this case. To prevent life‐threatening adrenal crisis and help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH should be made mandatory even in low‐ and middle‐income countries. [ABSTRACT FROM AUTHOR]

Objective. To carry out a cost-effectiveness analysis of pulse oximetry as a newborn screening test for critical congenital heart defects (CCHD) in Mexico. Materials and methods. Economic evaluation study was conducted from the perspective of the health care provider. A decision tree model was used to compare between physical examination alone and pulse oximetry screening (POS) as an additional test to physical examination. Results. For every 10 000 newborns, the alternative with POS detected an additional 32 cases of CCHD, with an incremental cost-effectiveness ratio of USD 1 219, and at a willingness-to-pay threshold of USD 25 000 for each early detection, the probability of cost-effectiveness is more than 90%. Conclusion. The cost-effectiveness of POS, as a newborn screening for CCHD, is higher in Mexico than in high-income countries, and represents a cost-effective investment to gain years of life in the child population of Mexico. [ABSTRACT FROM AUTHOR]

Objectives: to verify the quality indicators of neonatal hearing screening programs, identify the most prevalent risk factors for hearing loss and analyze access to the Hearing Health Care Network. Methods: cross-sectional study using secondary data. The population are children born in public maternity hospitals from 2015 to 2019. Data collection was carried out in the database of programs and hearing health service. The absolute and relative frequencies of all variables collected and the median, the interquartile range and the Mann-Whitney test were calculated to analyze the access. Results: universality increased during the study period, but was not reached (71.9%; CI95%=70.4-73.3) and the referral rate for auditory diagnosis was within the recommended range (0.9%; CI95%=0.8-0.9). The most prevalent risk factors were congenital infections and heredity. There was an evasion of children to the hearing health service of 85.1% and the type of referral interfered with the age of the child at access. Eight children with hearing loss were diagnosed, in which seven had access to therapeutic interventions. Conclusions: hearing screening was not universal. Access to the Hearing Health Care Network presents high evasion and interventions were offered to children with hearing loss. [ABSTRACT FROM AUTHOR]

Purpose: Gestational SARS-Cov-2 infection can impact maternal and neonatal health. The virus has also been reported of causing sensorineural hearing loss. The objective of this study was to determine the possible effect of maternal SARS-COV-2 infection on neonatal hearing as identified during universal hearing screening. Methods: Retrospective cohort study in two tertiary referral centers including all neonates born from November 2020 through April 1st, 2021 and undergoing the universal hearing screening program. Maternal Covid-19 infection was recorded (timing and severity) and the results of hearing screening of their neonates compared to the incidence of neonatal hearing loss results of the national universal screening program during the same period. Results: A total of 984 neonates were included (508 males and 476 females). Sixty-three neonates were excluded due to comorbidities which could cause hearing loss. The incidence of failed responses in the community at large was 2.3%. Twenty-seven failed both steps of screening (2.9%; p < 0.2). There were 34 Covid-19 positive mothers (17 in the first trimester, 8 in the second and 9 in the third). Twenty-nine neonates failed the first screening (p < 0.00001) but on further testing only one neonate failed (2.9%). Conclusion: In this study, neonates born to Covid-19 positive mothers do not seem to have an increased risk of hearing loss. However longer follow-up of these neonates is mandatory to detect any possible delayed effects of the virus. [ABSTRACT FROM AUTHOR]

Canavan disease is a devastating neurometabolic disorder caused by accumulation of N acetylaspartate in brain and body fluids due to genetic defects in the aspartoacylase gene (ASPA). New gene therapies are on the horizon but will require early presymptomatic diagnosis to be fully effective. We therefore developed a fast and highly sensitive liquid chromatography mass spectrometry (LC-MS/MS)-based method for quantification of N -acetylaspartate in dried blood spots and established reference ranges for neonates and older controls. With this test, we investigated 45 samples of 25 Canavan patients including 8 with a neonatal sample. Measuring N -acetylaspartate concentration in dried blood with this novel test, all Canavan patients (with variable severity) were well separated from the control group (median; range: 5.7; 1.6–13.6 μmol/L [ n = 45] vs 0.44; 0.24–0.99 μmol/L [ n = 59] (p < 0.05)). There was also no overlap when comparing neonatal samples of Canavan patients (7.3; 5.1–9.9 μmol/L [ n = 8]) and neonatal controls (0.93; 0.4–1.8 μmol/L [ n = 784]) (p < 0.05). We have developed a new LC-MS/MS-based screening test for early postnatal diagnosis of Canavan disease that should be further evaluated in a population-based study once a promising treatment becomes available. The method meets the general requirements of newborn screening and should be appropriate for multiplexing with other screening approaches that combine chromatographic and mass spectrometry techniques. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Dried blood spot samples are suitable for diagnosing some congenital errors of metabolism; however, they provide limited benefit in the regular monitoring of amino acids. Objectives: The present study aimed to evaluate alanine (Ala), arginine (Arg), citrulline (Cit), glutamic acid (Glu), glycine (Gly), isoleucine (Ileu), leucine (Leu), methionine (Met), ornithine (Orn), phenylalanine (Phe), tyrosine (Tyr), and valine (Val) amino acid concentrations in dried blood and plasma samples obtained simultaneously. Methods: Amino acid concentrations were determined in the plasma, and dried blood spot samples obtained simultaneously from 145 patients (50 females and 95 males). Amino acid concentrations in the plasma and dried blood spot samples were studied by LC-MS/MS using original kits. Results: There were significant differences between dried blood spots and plasma in all amino acid concentrations, except for Met and Val. Bland-Altman analysis revealed the highest mean differences in Glu (-148.1), Gly (-70.1), and Ala (-58.1). Deming regression analysis showed that plasma and dried blood spot samples were consistent concerning Cit, Met, Phe, and Tyr concentrations. Conclusions: Differences in methodology and sample can influence amino acid concentrations. Dried blood spot samples might cause errors in amino acid screening programs. [ABSTRACT FROM AUTHOR]

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial β-oxidation of fatty acids resulting in hypoketotic hypoglycemia, hepatopathy, and often fatal outcome in undiagnosed children. Introduction of tandem mass spectrometry–based newborn screening programs in the late 1990s has significantly reduced morbidity and mortality in MCAD deficiency; however, neonatal death in individuals with early disease manifestation and severe hypoglycemia may still occur. We describe the fatal disease course in eight newborns with MCAD deficiency, aiming to raise awareness for early clinical symptoms and the life-saving treatment, and promote systematic post-mortem protocols for biochemical and genetic testing, necessary for correct diagnosis and counselling of the family if unexpected death occurred in the neonatal period. Conclusion: Early newborn screening and awareness for clinical symptoms is lifesaving in MCAD deficiency, which may present with fatal neonatal crisis. Systematic post-mortem diagnostic protocols are needed for sudden neonatal deaths. What is Known: • Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency identified by newborn screening has an excellent outcome. • Fatal neonatal crises occur in the first days prior to screening. What is New: • Poor feeding, no monitoring of blood glucose, and homozygosity of the common gene variant (c.985A > G) are major risk factors for fatal neonatal crisis in MCAD deficiency. • Post-mortem diagnostic protocols are indispensable for correct diagnosis and counselling of the family if unexpected death occurred in the neonatal period. [ABSTRACT FROM AUTHOR]

Objectives: To bring out the diagnostic attitude of hearing professionals in Cameroon towards congenital hearing impairment (CHI), assess availability of tests, neonatal screening, and create a national map of availability of treatment opportunities. Methods: We conducted a cross-sectional online-based survey from June to December 2021, concerning ear–nose–throat (ENT) specialists, hearing care professionals, speech therapists and ENT nurses. A Google Forms online questionnaire was used to collect data, filled by eligible professionals involved in hearing care in Cameroon. Results: A total of 93 professionals working in 31 different health facilities participated. A cumulative percentage of 79.9% of ENTs were found in just two out of 10 regions. Specialists sought by ENTs for assessment of patients with CHI included neurologists/neuro-pediatricians (96.8%), pediatricians (47.6%), other ENTs (34.9%), and psychologists (3.2%). Investigations requested included auditory-evoked brainstem response (ABR; 87.3%), otoacoustic emissions recording (OAE; 71.4%), and tympanometry (66.7%). There were eight OAE and nine ABR machines in the country. Twenty-five (88.6%) out of 31 facilities with otolaryngologists did not carry out systematic neonatal screening. Reasons included unavailability of equipment (21; 84%), and administrative delays (14; 56%). Sixteen (51.6%) facilities had ENTs with additional training in otologic surgery and 11 (35.5%) were equipped to perform ear surgery. Three centers (9.7%) specialized in hearing aid provision and maintenance services. Three hospitals (9.7%) had performed cochlear implantation. Conclusion: Our results show scarcity and overt unevenness in distribution of specialists, equipment and solutions to CHI in Cameroon. A serious negative health care consequence of this shortage is the unavailability of universal newborn hearing screening and implementation programs. [ABSTRACT FROM AUTHOR]

Neonatal screening for congenital hypothyroidism (CH) is based on the measurement of thyroid-stimulating hormone (TSH) in whole dried blood samples on filter paper in all newborns. The objective of screening for CH is to prevent mental retardation, which is irreversible in the event of a late diagnosis, by setting up prompt treatment (before day 15) with levothyroxine. The threshold value of TSH on filter paper on day 3 is 17 mIU/L in France in the GSP method (GSP, Genetic Screening Processor, Perkin Elmer): It is one of the highest thresholds used in the world. In many countries, the TSH threshold is between 6 and 12 mIU/L. Studies have found that a threshold of > 17 mIU/L may miss as much as 30% of cases of CH, with 30–80% of these being permanent CH. Recent studies suggest that mild CH (currently missed by the French TSH threshold) is associated with cognitive consequences if left untreated. An inverse relationship between TSH at screening (below the current threshold) and cognitive development at preschool or school age has been shown. These studies advocate for the evaluation of a lowering of the threshold of TSH on filter paper in France: (a) to determine the number of CH diagnoses with the new threshold and whether these "new cases" would be transitory or permanent; and (b) to analyze the cost-effectiveness of the strategy. [ABSTRACT FROM AUTHOR]

Aim: We observed wide variation in the management of babies at risk of hypoglycaemia who participated in the hPOD (hypoglycaemia Prevention with Oral Dextrose gel) multicentre trial of prophylactic dextrose gel. The aim of this study was to identify whether this may be due to variations in the clinical guidelines used by participating hospitals.Methods: Guidelines for management of neonatal hypoglycaemia used by participating hospitals were reviewed. Recommendations regarding definition, risk factors, monitoring and treatment were compared between countries, hospital type (tertiary or secondary) and neonatal intensive care unit size (≤12 cots and >12 cots).Results: The 18 hospitals used 20 guidelines. The recommended diagnostic threshold for hypoglycaemia ranged from <2.0 mmol/L to <2.6 mmol/L, and glucose oxidase method of testing was recommended in seven (47%) of 15 guidelines. There was broad agreement about which infants should be monitored. Oral dextrose was the recommended first line of treatment in 17 of 20 guidelines, but the glucose threshold at which this should be used varied (≤2.6 mmol/L in New Zealand, 1.5-2.6 mmol/L in Australia). Re-checking blood glucose concentrations after oral dextrose was recommended at 30 min in most (10/11, 91%) New Zealand guidelines but at 60 min in most (4/6, 67%) Australian guidelines. There was greatest variation in recommended thresholds for referral to paediatric services or neonatal intensive care unit, and administration of intravenous dextrose. There were no significant differences between guidelines used by tertiary and secondary hospitals, or large and small hospitals.Conclusion: There is wide variation in guideline recommendations for the management of neonatal hypoglycaemia across New Zealand and Australian neonatal units. [ABSTRACT FROM AUTHOR]

• This study investigates the association of cystic fibrosis or CFTR-Related disorders (CFTR-RD) in babies with inconclusive diagnosis at newborn screening. • We performed whole CFTR gene sequencing, in vivo CFTR function measurement, and in vitro studies of variants of unknown significance. • This workflow differentiated children at high likelihood of evolving to CF, those at extremely low risk of developing a CFTR-RD and those with partial CFTR dysfunction who might develop CFTR-RD later on. Newborn screening for Cystic Fibrosis (CF) is associated with situations where the diagnosis of CF or CFTR related disorders (CFTR-RD) cannot be clearly ruled out. We report a case series of 23 children with unconclusive diagnosis after newborn screening for CF and a mean follow-up of 7.7 years (4–13). Comprehensive investigations including whole CFTR gene sequencing, in vivo intestinal current measurement (ICM), nasal potential difference (NPD), and in vitro functional studies of variants of unknown significance, helped to reclassify the patients. Extensive genetic testing identified, in trans with a CF causing mutation, variants with varying clinical consequences and 3 variants of unknown significance (VUS). Eighteen deep intronic variants were identified by deep resequencing of the whole CFTR gene in 13 patients and were finally considered as non-pathogenic. All patients had normal CFTR dependent chloride transport in ICM. NPD differentiated 3 different profiles: CF-like tracings qualifying the patients as CF, such as F508del/D1152H patients; normal responses, suggesting an extremely low likelihood of developing a CFTR-RD such as F508del/TG11T5 patients; partial CFTR dysfunction above 20% of the normal, highlighting a remaining risk of developing CFTR-RD such as F508del/F1052V patients. The 3 VUS were reclassified as variant with defective maturation (D537N), defective expression (T582I) or with no clinical consequence (M952T). This study demonstrates the usefulness of combining genetic and functional investigations to assess the possibility of evolving to CF or CFTR-RD in babies with inconclusive diagnosis at neonatal screening. [ABSTRACT FROM AUTHOR]

Background: Following delivery, blood tests are performed on umbilical cord blood (CB) to avoid neonatal venipuncture. Despite widespread and longstanding CB testing, no guidelines exist to suggest which immunohematology tests should be performed on CB. Study design and methods: We performed a scoping review, surveyed national practice, and developed guidance statements concerning CB testing. Database searches identified relevant articles. A survey was sent to all Canadian hospitals and transfusion laboratories that perform perinatal testing. A national panel of experts was convened to develop guidance statements. Results: A total of 116 articles met the inclusion criteria and were summarized. Literature on CB testing is limited; few studies have investigated laboratory testing methodologies or validated CB test results with peripheral samples. The survey was completed by 580/597 institutions (97%); 85% were community hospitals and 16% had a neonatal intensive care unit. There is diversity in the types of CB tests performed and variability in practice. While most centers order appropriately, some laboratories routinely perform CB tests that are not clinically indicated (e.g., direct antiglobulin testing for all neonates) and other do not perform CB tests when results would be beneficial (e.g., phenotype on CB when mother has a clinically significant antibody). Fifteen guidance statements were developed. Discussion: This study highlights variability in CB testing, likely reflecting evidence gaps, methodology differences between studies, and lack of guidelines. CB tests should only be performed when indicated and validated on this sample type. The presented guidance statements aim to standardize practice and encourage judicious CB sampling. [ABSTRACT FROM AUTHOR]