Comparing Strategies for Critical Congenital Heart Disease Newborn Screening.

OBJECTIVES: An extended newborn critical congenital heart disease (CCHD) screening program using oximetry has been implemented in Taipei, Taiwan since April 2014. This study was conducted to investigate the test accuracy and efficiency of this screening protocol. METHODS: This study analyzed data from 30 birthing facilities representing 87.9% of live births in Taipei. Positive screening was defined as oxygen saturation <95% in either extremity or a preductal-postductal oxygen saturation difference of >3%. This study cohort was used to retrospectively estimate outcomes on the basis of different CCHD screening protocols. RESULTS: During the study period, 93 058 of 94 204 (98.8%) infants who had no prenatal suspicion were screened. The referral rate was 0.17% (156/93 058), and up to 90% of test-positive infants were referred within 48 hours of life. Forty-two CCHD cases without prenatal suspicion were detected and 97.6% were diagnosed within 72 hours of life. Of the screened newborns, 4 CCHD cases passed the screening. The false positive and false negative rates were 0.12% and 0.04%, respectively. In addition, applying our database to Spanish and updated American Academy of Pediatrics screening strategies led to more CCHD case detection. CONCLUSIONS: The Taipei protocol provided an efficient and effective screening referral system in a community setting. For optimal efficiency, we advocated the updated American Academy of Pediatrics algorithm/Spanish recommendation with a modification of immediate referral if oxygen saturation ≤90% in either extremity. The updated protocol would be practicable for nationwide screening in Taiwan and could also be applied to other regions with similar medical care systems.

Long-term neurodevelopmental outcomes of significant neonatal jaundice in Taiwan from 2000-2003: a nationwide, population-based cohort study.

Newborns with significant neonatal jaundice (SNJ) would admit for evaluation and/or intervention due to an earlier or more rapid increase in bilirubin level. Bilirubin-induced neurological dysfunction in this population might be underestimated. We aimed to investigate the risk of long-term neurodevelopmental sequelae of SNJ in Taiwan. An SNJ 2000-2003 follow-up cohort consisting of 66,983 neonates was extracted from the nationwide, population-based health insurance database in Taiwan to survey the accumulative incidence of long-term (7-year) neurodevelopmental sequelae in comparison to a reference general-population neonate cohort of 12,579 individuals born in 2000. The SNJ follow-up cohort was furtherly categorized into subgroups according to interventions (phototherapy, intensive phototherapy, and exchange transfusion). The SNJ follow-up cohort exhibited significantly higher cumulative rates of long-term neurodevelopmental sequelae than did the reference cohort (P < 0.05). The risks of infantile cerebral palsy, hearing loss, and developmental delay in the SNJ follow-up cohort were between twice and three times of those in the reference cohort after adjusting for gender, comorbid perinatal disorders and urbanization levels. All intervention subgroups demonstrated higher risks for long-term neurodevelopmental sequelae than the reference cohort (P < 0.05) after adjustment. Patients with SNJ are at risk of developing neurodevelopmental disorders during their growth period. A scheduled follow-up protocol of physical and neurodevelopmental assessment during early childhood for these SNJ patients would potentially be helpful for the early detection of and intervention for neurodevelopmental disorders.

Outcomes of neonatal jaundice in Taiwan.

OBJECTIVE: To investigate the burden of clinically significant neonatal jaundice (SNJ) in Taiwan, 2000-2010. STUDY DESIGN: The nationwide, population-based health insurance database in Taiwan was used to investigate the incidence, kernicterus rate and mortality rates of SNJ cohort born between 2000 and 2010. RESULTS: From 2000 to 2010, up to 242 546 patients admitted with neonatal jaundice (NJ) were identified. The incidence of SNJ was 5.9% in 2000 and increased to 13.7% in 2010 (P<0.001). The mortality rate significantly decreased from 0.51% in 2000 to 0.26% in 2010 (P<0.001) and the average incidence of kernicterus was 0.86 per 100 000 live births, indicating dramatically decreased rates compared with earlier rates in Taiwan. CONCLUSIONS: In spite of the increased incidence rates, the rates of mortality and kernicterus in patients with NJ significantly declined in Taiwan. The public health prevention programme, clinicians' awareness and effective management might contribute to the reduction of these acute severe sequelae.

Development of a Newborn Screening Program for Critical Congenital Heart Disease (CCHD) in Taipei.

BACKGROUND: Early detection of critical congenital heart disease (CCHD) can significantly reduce morbidity and mortality among newborns. We investigate the feasibility of implementing a community-based newborn CCHD screening program in Taipei. METHODS: Twelve birthing facilities in Taipei participated in a trial screening program between October 1, 2013, and March 31, 2014. Newborns underwent pulse oximetry at 24-36 h old, with probes attached to the right hand and one lower limb. Any screening saturation ≥95% in either extremity, with an absolute difference of ≤3% between the right hand and foot, was accepted as a screening pass. A screening result was considered as a fail if the oxygen saturation was <95% at either probe site, on 3 separate occasions, each separated by 30 min or the first result was <95% at either probe site, and any subsequent oxygen saturation measurement was <90%. Public health nurses would follow up all missed or refused cases. RESULTS: Of the 6,387 live births, 6,296 newborns (coverage rate: 6,296/6,387 = 98.6%) underwent appropriate pulse oximetry screening. Sixteen newborns (0.25%) were reported to have a failed screening result. Five of these screen positive newborns were confirmed with CCHD; two of them were diagnosed solely attributed to the failed screening results. The false-positive rate was 0.18%. Implementing a 6-month screening program for CCHD produced good case detection rate, while using efficient screening and referral systems. CONCLUSION: This program was successful in integrating screening, referral and public health tracking systems. The protocol outlined in this report could provide a community-based model for worldwide implementation.

The universal newborn hearing screening program of Taipei City.

OBJECTIVES: To establish a hearing screening program with high coverage, low referral rate, high follow-up rate, and early intervention in Taipei City. METHODS: From September 2009 to December 2010, 85% delivery units in Taipei City, which includes 20 hospitals and 14 obstetrics clinics, were recruited into the screening program in two stages. A total of 15,930 babies were born in these participating hospitals and clinics during the program period. Among these neonates, 15,790 underwent hearing screening test with automatic auditory brainstem response (AABR). The screening was free of charge to the parents. The hearing screening examination was performed 24-36 h after birth. The same test was repeated between 36 and 60 h of age if the baby failed the first hearing test. The neonate was referred to the diagnostic hospitals for further investigations if he failed the second test. RESULTS: The screening coverage rate was 99.1% (15,790/15,930). The incidence of bilateral moderate to severe and unilateral hearing loss was 1.4 per 1000 (22/15,790) and 1.5 per 1000 (24/15,790), respectively. Four percent (626/15,790) of newborns failed to pass the initial screening test and 1.0% of newborns failed to pass the second screening test. Therefore, 1.0% newborns were referred for diagnostic assessments. The follow-up rate was 94.4% (151/160). Sixty-four percent (14/22) of babies with bilateral hearing loss completed the full diagnostic hearing tests within 3 months of birth. CONCLUSIONS: The universal newborn hearing screening program is an adequate program for Taipei City with high coverage, low referral rate, and good follow-up rate. Screening fees covered by third parties, two-stage screening steps with AABR strategy, and the stringent monitoring system proved to be effective. LEVEL OF EVIDENCE: 2b, individual cohort study.

Saccharomyces cerevisiaeTSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex.

Saccharomyces cerevisiae TSC11/AVO3 is an essential gene encoding one component of TORC2, a multi-protein complex of yeast Tor2p that also contains Lst8p, Avo1p, and Avo2p. Despite the proven physical association among TORC2 components, little is known about the functional linkage or cellular pathways these proteins act in. Here, we present genetic data linking the function of TSC11 to the regulation of cell integrity. Mutants carrying temperature-sensitive (ts) alleles in different regions of TSC11 displayed cell wall defects, evidenced by characteristic osmotic stabilizer-remediable cell lysis, susceptibility to trypan blue staining, and sensitivity to cell wall-digesting enzymes. Dosage suppression analysis identified different groups of genes in rescuing phenotypes of different tsc11(ts) mutants. AVO1 suppressed one class of mutants, whereas active PKC1, AVO2, and SLM1 partially rescued another. Our findings demonstrate functional connections among TORC2 components and we speculate that Tsc11p exerts its function via a Pkc1p-independent mechanism mediated through Avo1p, and a Pkc1p-dependent mechanism mediated through Avo2p and Slm1p.