The study cohort comprised 338,680neonatesborn in midwifery institutions in Haidian District, Beijing from October 2010 to September 2017.
Specimen collection, preservation, and delivery
After obtaining parental permission, blood samples were collected from the heels of newborns 72 hours after birth. The samples were dripped onto a special filter paper, dried, and delivered to Haidian Maternal and Child Hospital, where they were scanned into a quality control system. They were then sent to the Beijing Neonatal Screening Center’s central laboratory by express mail. Appropriately qualified professionals were responsible for sending, receiving, and testing the samples.
Laboratory screening methods
Thyroid-stimulating hormone (TSH) concentrations were measured to screen for CH and phenylalanine (Phe) concentrations to screen for PKU. Time-resolved fluoroimmunoassays were performed to quantitate TSH and a fluorescence quantitative method was performed to quantitate Phe. A filter paper blood TSH≥10 μIU/mL was considered suspicious of CH and a blood Phe ≥2 mg/dL suspicious of PKU．
Management of neonatal screening
The Neonatal Screening Center is located in Beijing Maternal and Child Health Hospital. Twenty-four hospitals in Haidian District participated in collecting the required blood specimens. The Beijing Neonatal Screening Center is responsible for testing, diagnosis, recalls, treatment, and follow-up. In this center, neonatal screening is computerized using newborn screening management software to create files for each screened neonate.
Neonates suspected of having a metabolic disorder were recalled through the three-level network of the Beijing Neonatal Screening Center, Haidian Maternal and Child Health (MCH) Hospital, delivery hospitals and communities. The families of these neonates were notified via Short Messaging Services (SMS) and phone call by the Beijing Neonatal Screening Center (Level-1 recall). The names of neonates who were not brought in for reexamination within a certain time after receiving this message were sent to the relevant MCH Hospital by the Beijing Neonatal Screening Center management system at the beginning of each month. After receiving these names, the professional responsible for this task called the relevant neonates’ parents (Level-2recall).The delivery hospital was informed about neonates who again failed to attend for reexamination and asked to assist in ensuring a follow-up visit (Level-3recall).The local community child health doctor of the small number of neonates who failed to present for reexamination after the above three follow-up attempts was then notified. Professionals in the MCHs of the relevant districts were responsible for recording the results of Level-2 and Level-3 follow-up attempts in the district level information management system and these data were regularly reported to the Beijing Neonatal Screening Center.
Circulating T3, T4, TSH, FT3, and FT4 concentrations were measured in the neonates suspected of having CH and ultrasound examination was performed to confirm the final diagnosis. Neonates whose blood Phe concentrations continued to increase after excluding tetrahydrobiopterin deficiency were diagnosed as having PKU. The Beijing Neonatal Screening Center created a file for every neonate diagnosed with CH or PKU. Thyroid hormone replacement therapy was prescribed for those with CH, whereas those with PKU were placed on a low phenylalanine diet．
The Beijing Neonatal Screening Laboratory is monitored by the National Center for Clinical Laboratories. In addition, newborn screening laboratory quality management software has been established to monitor newborn screening laboratories’ blood spot collection, storage, delivery, testing, data-entry processes, and quality control standards．
The numbers of live births were drawn from obstetric reports submitted by 24 midwifery institutions in Haidian District to the Maternal and Child Information Department of Haidian MCH hospital. The numbers of neonates screened, suspected of having an inherited metabolic disorder, recalled, and with confirmed diagnosis were obtained from the data recorded by the Beijing Neonatal Screening Center from 2010 to 2017;data on follow-up of neonates with suspicious findings were obtained from the Quality Monitoring and Management System of that center.
Because blood for screening is collected at least 72 hours after the time of birth, the neonatal disease screening system used by midwifery institutions in Beijing is a stand-alone version. Only the district managers are connected with the screening center’s system and the proportion of live births screened is calculated by the Beijing Neonatal Screening Center as follows: identified cases/screened cases×100%. Follow-up data in the neonatal disease screening system were then entered into Excel 2007.The interval to follow-up in different years was compared by analysis of variance or independent sample t-test. Statistical significance was set at P< 0.05. Data analyses were performed using IBM SPSS, version 20.0(SPSS, Chicago, IL, USA).