Normal Newborn Screening Research Articles

Support for the Reliability and Validity of a Six-Item State Anxiety Scale Derived From the State-Trait Anxiety Inventory

Identifying the most efficient and theoretically appropriate methods to assess patient anxiety in fast-paced medical environments may be beneficial for clinical purposes as well as for research. The purpose of this study was to examine the reliability and validity of two previously published six-item versions of the State form of the State-Trait Anxiety Inventory (STAI) and to identify the version that would be most appropriate to use with a sample of parents who had infants with normal or abnormal newborn screens. In the current study, confirmatory factor analyses were conducted to evaluate the fit of the two six-item forms with STAI data collected at three time points from 288 parents of 150 infants. Study groups of parents were based upon infant newborn screens and subsequent diagnostic testing to include cystic fibrosis (CF; n = 26), congenital hypothyroidism (CH; n = 39), CF Carriers (CF-C; n = 45), and healthy infants (H; n = 40). The results showed the version containing items 1, 3, 6, 15, 16, and 17 of the State form of the STAI to be a better fitting model across all three time points, and it had better internal consistency than the version containing items 5, 9, 10, 12, 17, and 20. Both short forms were highly correlated with the 20-item STAI score, and all internal consistency reliabilities were greater than .90. It was concluded that the version containing items 1, 3, 6, 15, 16, and 17 of the State Anxiety scale was a reliable and valid instrument for this study sample.

Pitfalls in Screening Programs for Congenital Hypothyroidism in Premature Newborns

Sick premature infants may display transient hypothyroxinemia secondary to immaturity of the hypothalamic-pituitary axis. Therefore, early screening programs of such infants may be misleading. We present such a case report, with review of the literature and the following suggested recommendations. (1) Screening programs should report thyroid-stimulating hormone (TSH) as well as thyroxine (T(4)) levels in premature infants, which will allow the treating physicians to be aware of possible abnormality that needs to be followed. (2) Sick premature infants and other populations at risk should undergo a full serum thyroid function evaluation including free T(4) and TSH beyond the screening program at discharge or at 30 days of age, whichever comes first. (3) Physicians should use their clinical judgment and experience even in the face of normal newborn thyroid screening test and reevaluate for hypothyroidism when there is a clinical suspicion. Our case report is a reminder of the American Academy of Pediatrics guidelines with practical suggestions for extra caution to avoid missing primary hypothyroidism in sick premature infants.

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency: An examination of the medical and neurodevelopmental characteristics of 14 cases identified through newborn screening or clinical symptoms

The medical and neurodevelopmental characteristics of 14 children with short-chain acyl-CoA dehydrogenase deficiency (SCADD) are described. Eight were detected as neonates by newborn screening. Three children diagnosed on the basis of clinical symptoms had normal newborn screening results while three were born in states that did not screen for SCADD. Treatment included frequent feedings and a low fat diet. All children identified by newborn screening demonstrated medical and neuropsychological development within the normative range on follow-up, although one child had a relative weakness in the motor area and another child exhibited mild speech delay. Of the three clinically identified children with newborn screening results below the cut-off value, two were healthy and performed within the normal range on cognitive and motor tests at follow-up. Four clinically identified children with SCADD experienced persistent symptoms and/or developmental delay. However, in each of these cases, there were supplementary or alternative explanations for medical and neuropsychological deficits. Results indicated no genotype–phenotype correlations. These findings suggest that SCADD might be benign and the clinical symptoms ascribed to SCADD reflective of ascertainment bias or that early identification and treatment prevented complications that may have occurred due to interaction between genetic susceptibility and other genetic factors or environmental stressors.

Citrin Deficiency: A Novel Cause of Failure to Thrive That Responds to a High-Protein, Low-Carbohydrate Diet

The proband was born at 36 weeks, appropriate for gestational age, to nonconsanguineous white parents. There was no evidence of hyperbilirubinemia or intrahepatic cholestasis in the neonatal period, and she had normal newborn screen results. She presented with 3 episodes of life-threatening bleeding and anemia. The diagnostic evaluation for her bleeding diathesis revealed an abnormal clotting profile with no biochemical evidence for hepatocellular damage. She was incidentally noted to have severe growth deceleration that failed to respond to 502 kJ/kg (120 kcal/kg) per day of protein-hydrolyzed formula. An extensive diagnostic workup for failure to thrive, which was otherwise normal, included plasma amino acid analysis that revealed hyperglutaminemia and citrulline levels within the reference range. Testing of a repeat sample revealed isolated hypercitrullinemia. No argininosuccinic acid was detected. Her ammonia level and urine orotic acid were within the reference ranges. Subsequent plasma amino acid analysis exhibited a profile suggestive of neonatal intrahepatic cholestasis caused by citrin deficiency with elevations in citrulline, methionine, and threonine. Western blotting of fibroblasts demonstrated citrin deficiency, and a deletion for exon 3 was found in the patient's coding DNA of the SLC25A13 gene. On the basis of the experience with adults carrying this condition, the patient was given a high-protein, low-carbohydrate diet. The failure to thrive and bleeding diathesis resolved. When compliance with the dietary prescription was relaxed, growth deceleration was again noted, although significant bleeding did not recur. This is the first report of an infant of Northern European descent with citrin deficiency. The later age at presentation with failure to thrive and bleeding diathesis and without obvious evidence of neonatal intrahepatic cholestasis expands the clinical spectrum of citrin deficiency. This case emphasizes the importance of continued dietary control and growth monitoring in children with neonatal intrahepatic cholestasis caused by citrin deficiency and identifies a new metabolic entity responsible for failure to thrive.

“Silent” Tyrosinemia Presenting as Hepatocellular Carcinoma in a 10‐year‐old Girl

“Silent” Tyrosinemia Presenting as Hepatocellular Carcinoma in a 10‐year‐old Girl

Hypothyroidism Caused by Chronic Autoimmune Thyroiditis in Very Young Children

Hypothyroidism in neonates or young infants is usually the result of congenital rather than acquired aberrations. Developmental defects of the thyroid gland cause 80% to 90% of cases. The remaining 10% to 20% of patients have functional defects in thyroid hormone synthesis. Chronic autoimmune thyroiditis is rarely seen in children less than 3 years. Less than 12 patients have been described in the literature. We describe here 2 children, both less than 3 years of age, who had hypothyroidism secondary to autoimmune thyroiditis. One is a 2-year 7-month-old boy referred for short stature. Evaluation revealed a low thyroxine level with an elevated thyrotropin (TSH) along with elevated antithyroglobulin and antithyroid peroxidase antibodies. The second child is a 2-year 4-month-old girl with Down syndrome presenting with failure to thrive. She, too, had an elevated TSH, antithyroglobulin, and antithyroid peroxidase antibodies. Both children had normal newborn screens. Autoimmune thyroiditis was confirmed by positive antithyroid antibodies. Hypothyroidism in young children can be a component of several autoimmune syndromes, but our patients had isolated autoimmune thyroiditis. It is important to remember that autoimmune thyroiditis can occur in children younger than 3 years.

Neonatal Screening by Tandem Mass Spectrometry

After completing this article, readers should be able to: 1. List the major categories of diseases detectable by expanded newborn screening. 2. Give examples of the benefits and limitations of screening by tandem mass spectrometry. 3. Describe the appropriate follow-up for an abnormal screening result. The screening of newborns for inherited metabolic disorders is a well-established public health activity, first implemented in the early 1960s for the presymptomatic identification of patients who have phenylketonuria (PKU). Since then, significant technological advances, most importantly the development of tandem mass spectrometry (MS/MS), have enabled the detection of an increasing number of metabolic disorders in newborn blood. This article reviews the basic technology of MS/MS and its application to newborn screening, with the aim of highlighting the benefits and pointing out some limitations of this powerful technology. Early screening for PKU used the bacterial inhibition assay of Guthrie, in which inhibition of bacterial growth on an agar medium, introduced by the addition of a phenylalanine analog, was overcome by the presence of dried blood discs containing high levels of phenylalanine (such as from a PKU patient). This approach later was adapted for the detection of leucine in patients who have maple syrup urine disease (MSUD), methionine in patients who have classic homocystinuria, and tyrosine in patients who have tyrosinemia. Over the years, other techniques have been implemented to screen for additional disorders, including congenital hypothyroidism, biotinidase deficiency, galactosemia, hemoglobinopathies, and congenital adrenal hyperplasia. The classic criteria used to determine whether a disorder is suitable for screening include: 1) the disorder is clinically and biochemically well defined, 2) it is associated with significant morbidity or mortality, 3) an effective treatment is available, and 4) there is a simple and safe screening test. (1) By the early 1990s, all states offered screening for at least PKU and congenital hypothyroidism, …

Genotypic differences of MCAD deficiency in the Asian population: Novel genotype and clinical symptoms preceding newborn screening notification

PurposeIn contrast to its high prevalence in Caucasians, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is reported to be an extremely rare metabolic disorder in the Asian population. The common MCAD gene (ACADM) mutation 985A>G (p.K329E), accounting for the majority of cases in Caucasians, has not been detected in this ethnic group, and the spectrum of ACADM mutations has remained unknown.Method: Biochemical genetic testing including plasma acylcarnitine and urine acylglycine analyses, as well as sequencing of ACADM was performed in a Korean family with a newborn who had an elevated octanoyl (C8) carnitine concentration by newborn screening (NBS). Genotyping of 50 Korean newborns with normal NBS results was performed.Result: We report the identification of the first Korean patient with MCAD deficiency, caused by a novel missense mutation in ACADM, 843A>T (R281S), and a 4-bp deletion, c.449_452delCTGA. The patient became symptomatic before notification of the abnormal NBS result. Both the father and a brother who were identified as carriers for the 4-bp deletion had mildly elevated plasma C8 and C10:1 carnitine concentrations, whereas the acylcarnitine profile was normal in the mother who carries the missense mutation. ConclusionThe 4-bp deletion may represent a common Asian ACADM mutation, considering that it recently has also been found in two of the three Japanese patients in whom genotyping was performed. Greater availability of MCAD mutation analysis is likely to unravel the molecular basis of MCAD deficiency in the Asian population that might differ from Caucasians.

Metabolic Disorders Associated With Neonatal Hypoglycemia

After completing this article, readers should be able to: 1. Describe four sources of glucose available to the neonate in the first 24 postnatal hours. 2. Select the best routine diagnostic test to recognize fatty acid oxidation defects. 3. List three or more metabolic disorders that can be identified by newborn screening performed using tandem mass spectrometry. Hypoglycemia is a common problem in neonates that has many causes. This review focuses on metabolic disorders that may be associated with hypoglycemia in the neonatal period. During intrauterine life, the fetus derives fuel, as glucose, from the mother via the placenta. After birth, the energy demands on the former fetus increase dramatically. The baby now must maintain its own body temperature and must undertake the work of breathing and other activities. Further, the maintenance of blood glucose levels requires glycogenolysis and gluconeogenesis. Postnatally, there are four sources of glucose: dietary glucose; glucose derived from the cleavage of more complex sugars in the gut (eg, lactose to glucose and galactose); glucose released from glycogen stores (primarily in the liver); and gluconeogenesis, in which glucose is synthesized from carbon skeletons derived from certain amino acids using energy derived from catabolism of fatty acids. Most term infants have sufficient glycogen stores to maintain blood glucose levels for several hours before gluconeogenesis is required. Infants who are breastfed in the United States typically are offered only water as a supplement to human milk during the first few postnatal days, a period when the mother’s milk supply is not yet established. In contrast, formula-fed babies receive calories by mouth by the end of the first postnatal day. Consequently, the metabolic stress of prolonged fasting occurs more frequently in breastfed than in formula-fed babies. Although breastfed babies have higher levels of ketone bodies that appear to provide adequate energy during this …

Schaeffer's Diseases of the Newborn

Taeusch has joined Avery to edit the fifth edition of this text. Twenty-nine additional authors, many of whom are new since the publication of the fourth edition in 1977, have contributed one or more chapters in this revision. The general format and scope of the book remain as in previous editions, ie, a comprehensive systems approach to diseases of the newborn. In addition, sections on perinatology, general aspects of the newborn (the normal newborn, newborn screening, neonatal behavior, prematurity, etc), and neonatal pharmacology are included. Several chapters in the sections on perinatology and general aspects of the newborn represent valuable new additions, including chapters on maternal conditions and exogenous influences that affect the fetus or newborn, the assessment of fetal risk in the third trimester, the normal newborn, newborn screening, and resuscitation. In the section on disorders of the respiratory system, concise and easily readable new chapters on persistent fetal

Clinical Evaluation of One-Year-Old Infants: Possible Predictors of Risk for the “Hyperactivity Syndrome”

One hundred and twenty-three infants selected from a normal newborn screening of 933 on the basis of minor physical anomalies of face, head, hands, and feet were evaluated at one year of age. At that time parents rated infant temperament and responded to a structured pediatric interview. Developmental testing was performed by a psychologist, who also rated infant behavior. Some significant associations found between these separate ratings indicate the usefulness of the temperament scale for infant behavior studies and suggest the need for a combined approach to behavioral evaluation. The total score of minor anomalies also showed low but significant association with irritable, fussy behavior as rated at the pediatric interview and by parent questionnaire. The usefulness of temperament and anomaly measures for prediction of later behavior problems is currently being assessed by longitudinal follow-up.