The lack of a national policy on newborn screening (NBS) in the United States has resulted in 51 state-specific NBS policies (including 50 states and the District of Columbia). In 2000, a working group of the American Academy of Pediatrics provided a national NBS blueprint for the future. Using this guidance, the Health Resources and Services Administration contracted with the American College of Medical Genetics to: (i) develop a decision-making algorithm for states to use in selecting conditions for screening panels, and (ii) recommend a panel of tests to guide states in their screening requirements. This report outlines and summarises the processes and outcomes leading to the current NBS recommendations in the United States.
Humans ; Infant, Newborn ; Neonatal Screening ; methods ; standards ; United States

OBJECTIVETo plot a hour-specific transcutaneous bilirubin (TCB) nomogram for healthy neonates, and to evaluate its value for prediction of the risk of neonatal hyperbilirubinemia.

METHODSA total of 5,250 healthy full-term or near-term neonates (gestational age≥35 weeks, birth weight≥2 000 g) were enrolled as subjects. Their TCB values were continuously recorded for 168 hours after birth. The TCB values in the high-risk zones of three time periods, 24-48, 49-72, and 73-96 hours after birth, were used as predictors. The hour-specific TCB nomogram combined with the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of hour-specific TCB nomogram for hyperbilirubinemia.

RESULTSAccording to the hour-specific TCB nomogram, the TCB value dramatically increased during 16-72 hours after birth, and the increase slowed down gradually during 72-144 hours. Finally, the curve reached a plateau after 144 hours. Particularly, the P95 of TCB had been stabilized at 96 hours. The P40, P75, and P95 peak values of TCB were 173, 217, and 248 µmol/L, respectively. For the prediction of hyperbilirubinemia, the areas under the ROC curve of TCB at 24-48, 49-72, and 73-96 hours after birth were 0.77, 0.85, and 0.87, respectively. The high-risk zones at 24-48, 49-72, and 73-96 hours after birth predicted the incidence rates of neonatal hyperbilirubinemia as 35.03%, 43.35%, and 79.95%, respectively, with positive likelihood ratios of 3.35, 4.75, and 22.70, respectively.

CONCLUSIONSThe hour-specific TCB nomogram and the division of TCB risk zones can give a satisfactory prediction of the incidence of neonatal hyperbilirubinemia. The neonate with a bilirubin level in the high-risk zone within 73-96 hours after birth is likely to have hyperbilirubinemia after 73-96 hours.

Bilirubin ; analysis ; Female ; Humans ; Hyperbilirubinemia, Neonatal ; diagnosis ; Infant, Newborn ; Male ; Neonatal Screening ; methods ; Nomograms ; ROC Curve

BACKGROUNDIt has been 11 years since newborn screening started in Zhejiang in 1999. The aim of this study was to analyze and summarize the status of newborn screening in Zhejiang from 1999 to 2009.

METHODSBlood samples were collected from the heels of newborns 72 hours after birth. We have conducted laboratory tests that the congenital hypothyroidism (CH) and circulating levels of thyroid-stimulating hormone (TSH) was detected. Blood phenylalanine (Phe) was detected for phenylketonuria (PKU). Dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) was used for detection.

RESULTSFrom 1999 to 2009, 3 875 228 newborns were screened and 2309 cases were confirmed as CH and 155 cases were confirmed as PKU. The incidence of CH and PKU were 1:1678 and 1:25 001 respectively.

CONCLUSIONIn 11 years, the Zhejiang newborn screening center screened more than 3.8 million newborns, and helped more than 2000 CH and PKU patients to obtain early treatment in order to prevent physical disability and mental retardation.

China ; Congenital Hypothyroidism ; diagnosis ; Humans ; Infant, Newborn ; Neonatal Screening ; methods ; Phenylketonurias ; diagnosis

OBJECTIVETo study how to perform the hearing screening on the infants in the rural area.

METHODSThree thousand nine hundreds and twenty-two infants, about 84% of them from rural, were born in the People Hospital of LaiZhou City from January to December in 2004. The infants were performed fast hearing screening by transient evoked otoacoustic emission (TEOAE) after the birth in 2-7 days. The fail cases were checked again after 4-6 weeks, and then were diagnosed if they still failed after following-up.

RESULTSThe infants (3612/3922, 92.1%) have been checked by TEOAE, and the examination was free in the poverty cases. The rate passed on the first check was 69.96% (2527/3922), but 1085 infants failed (30.4%), while 310 infants have not been checked (7.9%). In the 1085 cases that should be rechecked, there was only 633 cases (58.34%) accepted the check on time, while 452 cases (41.66%) missed. In the 163 cases with high-risk infants in 2004, 114 infants (69.96%) were checked, but 49 infants (29.04%) were not checked. Fourteen cases failed in the recheck, and 11 of them were checked by ABR. Two cases were found to be moderate and severe hearing loss in binaural respectively and 4 cases with mild hearing loss in monaural while 3 cases were normal.

CONCLUSIONSIt is necessary and viable for the infants on hearing screening in the rural area It should be set up and perfected the model for infants on hearing screening in rural area as soon as possible; it should be free for the poor infants to make sure everyone enjoy the health care.

China ; Hearing Tests ; Humans ; Infant, Newborn ; Neonatal Screening ; methods ; Otoacoustic Emissions, Spontaneous ; Rural Population

Child ; Humans ; Infant ; Infant, Newborn ; Neonatal Screening ; methods ; Phenylalanine ; blood ; Phenylketonurias ; diagnosis ; genetics ; prevention & control ; Prognosis

Blood Glucose ; analysis ; Capillaries ; metabolism ; Humans ; Hypoglycemia ; diagnosis ; Infant, Newborn ; Neonatal Screening ; methods ; Reference Standards

OBJECTIVELife-threatening critical congenital heart disease (cCHD) is often not detected in the neonatal period. Unrecognized cCHD results in high morbidity and mortality rates. As a non-invasive, convenient, quick and accurate measuring method, pulse oximetry is considered to be a promising strategy to screen for cCHD in neonates. This article is a review on the neonatal pulse oximetry screening for cCHD.

DATA SOURCESArticles on neonatal pulse oximetry screening for cCHD were accessed from PubMed, using keywords including congenital heart defects, neonatal screening and oximetry.

STUDY SELECTIONOriginal articles and critical reviews selected were relevant to the review's theme.

RESULTSThe factors in the course of implementation, including threshold for positive pulse-oximetry screening results, the pulse oximeters used, timing of the screening, and the measuring position, influence the accuracy of the screening. It is recommended that the screening is completed on the second day of life, before hospital discharge. Motion-tolerant pulse oximeters, which can also be applied to measure the saturation in low-perfusion conditions, should be used. The probe should be put on both the right hand and on one foot. Thresholds of < 95% in either limb or a difference of > 3% between the limbs as a positive result may be appropriate. It should be emphasized that pulse-oximetry screening cannot be used as the only way to detect cCHD, clinical examination is also important in this situation. Cost-benefit analysis in the United Kingdom revealed it was plausible to use pulse oximetry as an adjunct to clinical examination. However, it is still controversial as to whether pulse oximetry can be used as a routine screening method for cCHD in neonates.

CONCLUSIONSNeonatal pulse oximetry screening improves detection of cCHD. Further studies should be carried out before it becomes one of the routine newborn screening programs.

Cost-Benefit Analysis ; Heart Defects, Congenital ; diagnosis ; Humans ; Infant, Newborn ; Neonatal Screening ; Oximetry ; methods

OBJECTIVE: This study aims at investigating tympanogram in newborns who passed hearing screening using 226 and 1 000 Hz probe tones in order to interpret the test results correctly and find out its clinical value in audiological evaluation and diagnosis in this population. METHOD: Tympanogram was conducted using 226 and 1000 Hz probe tones in 206 newborns between 2 and 7 days of age (3.92 +/- 1.24) in both ears that passed the DPOAE screening and without any of the high risk register (HRR) factors associated with hearing loss according to the Joint Committee on Infant Hearing in 2007. RESULT: The tympanogram results tested in 408 ear were as following: the percentage of single-peaked, double-peaked, and none-peaked tympanograms using 226 Hz were 52.20% (213 ears), 47.55% (194 ears) and 0.25% (1 ear) respectively. The percentage of single-peaked and other morphological type tympanograms using 1000 Hz were 94.85%(387 ears) and 5.15% (21 ears) respectively. The parameters of 1000 Hz single-peaked tympanogram in this study were as following: the average tympanometric peak pressure was 33.24 +/- 44.37 dapa, the average peak compensated static acoustic admittance was 0.52 +/- 0.25 mmho, the average tympanometric width for right and left ears were 121.38 +/- 28.79 and 108.63 +/- 26.00 dapa respectively with a statistically significant difference between them (P < 0.01). The average volume of ear canal (Vec, using 226 Hz probe tone) at boys and girls were 0.44 +/- 0.10 and 0.43 +/- 0.08 ml respectively with a statistically significant difference between them (P < 0.05). CONCLUSION The morphology of tympanogram using a 226 Hz probe tone in newborns usually includes two main types: single-peaked and double-peaked, while it is primarily the single-peaked tympanogram while using a 1000 Hz probe tone. It is more appropriate to use a 1000 Hz probe tone than 226 Hz when testing newborns' tympanogram. The parameters obtained in this study using 1000 Hz and 226 Hz could be tried and applied to interpret clinical tympanogram test results and evaluate middle ear function. However, more studies with bigger sample size are necessary in this field.
Acoustic Impedance Tests ; Ear, Middle ; physiology ; Female ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; methods

OBJECTIVE: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. METHODS: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. RESULTS: Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. CONCLUSION SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.
Humans ; Infant, Newborn ; Amino Acid Metabolism, Inborn Errors/genetics* ; Carnitine ; Neonatal Screening/methods*

OBJECTIVE: To explore the disease spectrum for abnormal 3-hydroxyisovalerylcarnitine (C5OH) metabolism identified through newborn screening and clinical diagnosis patients and the key points for differential diagnosis so as to raise the awareness of pediatricians for such diseases. METHODS: Clinical data of 85 neonates with abnormal C5OH metabolism identified from February 2004 to January 2022 at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected. Their clinical manifestations and results of tandem mass spectrometry (MS/MS), gas chromatography mass spectrometry (GC-MS) and genetic testing were retrospectively analyzed. RESULTS: Among the 85 cases, 46 (54.1%) were identified by neonate screening, whilst 39 (45.9%) were clinically diagnosed patients. Five diseases were diagnosed, including 28 cases with multiple carboxylase deficiency (MCD, 32.9%), 29 cases with 3-methylcrotonyl-coenzymeAcarboxylasedeficiency (MCCD, 34.1%), 4 cases with 3-methylglutaconic acid (3-MGA, 4.7%), 7 cases with 3-hydroxy-3-methylglutaric acid (3-HMG, 8.2%), and 17 cases with beta-ketothiolase deficiency (BKD, 20.0%). The disorders were characterized by sudden onset, anorexia, vomiting, diarrhea, abnormal breathing, consciousness disorder, spasm and developmental delay. CONCLUSION Among newborns with abnormal C5OH metabolism, MCCD is the most common disorder, which was followed by BKD and MCD. For patients with abnormal C5OH metabolism, MCD is the most common, followed by BKD and 3-HMG. C5OH related diseases have great heterogeneity. Combination of blood acylcarnitine levels, urinary organic acid levels and genetic testing based on clinical characteristics can help to attain the diagnosis.
Humans ; Infant, Newborn ; China ; Neonatal Screening ; Retrospective Studies ; Tandem Mass Spectrometry/methods*