Newborn screening is used primarily for diseases that develop after birth and for which treatment can improve the prognosis of the infant. These disorders occur when the newborn is no longer protected by maternal-infant exchange after birth and has abnormal biochemical functions. For example, in phenylketonuria, the blood phenylpropionic acid level is normal at birth but is significantly elevated a few hours after birth, and in congenital hypothyroidism, the child can receive maternal T4 from the placenta in utero. these disorders, although very low in incidence, if left uncontrolled, can result in growth retardation and eventually mental retardation, whereas if treated and controlled by diet within the first week of life, mental retardation can be avoided. Intellectual backwardness can be avoided if treated and controlled by diet within the first week of life. PKU, congenital hypothyroidism (CH), glucose-6-phosphate dehydrogenase deficiency (G6PD), congenital adrenocortical hyperplasia (CAD), and hearing screening are some of the diseases that are routinely screened for in China. In 1962, Guthrie invented a screening method in which only a small drop of whole blood on filter paper was used to determine phenylpropanoid levels using simple bacterial analysis. With current advances in molecular genetics, more advanced techniques are available for newborn screening, making it possible to screen for more diseases, such as the more than 50 diseases screened for in the United States. Specimen collection Blood specimens are often collected from the heel of the infant, a method invented by Guthrie and Susi (1963), which is simple and easy to use and plays a huge role in newborn screening. The specimen is collected without side effects and there are no problems such as bleeding infections. The blood collection site is the lateral and medial heel, squeeze the blood on one side of the test paper and fill each circle. The test paper will affect the screening result if contaminated by iodine, alcohol, petroleum, colloid, fecal urine, milk and oil, etc. Too high temperature or humid environment will reduce the enzyme activity and produce wrong result. Dry the test strips at room temperature for at least 3 hours before placing them in the envelope. Blood specimens are also sometimes collected through the dorsal foot vein or central placement with a capillary tube. The method of collection does not affect the screening results, but drawing blood from the central placement may bring amino acids from the rehydration solution into the blood specimen, resulting in a false positive amino acid screen. In conclusion, it is recommended that blood be collected from the heel of the foot. Timing of collection Newborn screening includes a wide range of disorders, and each disorder has its own optimal screening time; therefore, it is important to emphasize that the recommended screening time is not optimal for all disorders to be screened. For example, symptoms of congenital adrenal hyperplasia may appear as early as 1 week after birth, so the optimal screening time is 24-48 hours after birth. The choice of thyroid stimulating hormone (TSH) as a first-line marker to screen for congenital hypothyroidism, or a second-line marker after T4, again makes early screening more reliable. The timing of specimen collection has not been standardized; in Europe and Australia, the common time of collection is 48-72 hours after birth, while in the UK it is 5-8 days of age. In the United States, specimens are mostly collected 24-72 hours after birth. In China, specimens are usually collected before discharge or within 3 days (60 hours after birth) for each newborn. There are special requirements for screening in some cases. For example, for children requiring blood transfusion, the screening test should be collected before the transfusion or repeated once 2 months after the transfusion (when the red blood cells of the blood donor have been metabolized). What to do if you have a positive screening result Most positive screening results do not indicate the presence of disease. Most abnormal values are only slightly above the threshold, and the child does not have the associated disease. Uniform emergency intervention or series of tests for all children with a positive screening result would add unnecessary anxiety and medical costs to parents. Positive screening results need to be treated differently, and when a positive screening result occurs, primary care providers can refer to an individually categorized information card based on the disease associated with the test marker, the likelihood of having the disease, the clinical manifestations of the disease, factors influencing the false positive, and next steps for intervention. Next steps of intervention include urgent hospitalization to refine screening treatment without delay, or a review in a few days. History taking and physical examination must be performed as soon as possible. When a review is not performed and the child is critically ill and progressing rapidly, he or she should be quickly transferred to the appropriate specialty for consultation. If the child responds well during the initial examination, cries loudly, completes breastfeeding, and no obvious abnormalities are found, no urgent treatment is needed and the child can be referred to a metabolic disease clinic if the second screening result is positive or a confirmatory test is performed. Missed diagnoses In newborn screening, patients with PKU, patients with congenital hypothyroidism, and other conditions are missed. Laboratory and institutional errors are the most common cause of missed diagnoses. In some cases, specimens were missed due to referral of newborns to other hospitals. In some cases, it is because the laboratory did not perform quality control, so the clinician should base the diagnosis on the clinical situation and not exclude it because the screening has been done by default. For metabolic and endocrine disorders, confirmatory tests should be performed regardless of screening results, as long as symptoms are present.