Background: Newborn screening for primary carnitine deficiency (NBS) is commonly implemented worldwide; however, it has poor sensitivity. This study aimed to evaluate the feasibility of improving screening by including a second-tier genetic assay.Results: An Agena iPLEX assay was developed to identify 17 commonSLC22A5mutations in Chinese populations and was applied in NBS as a second-tier screening. From January 2017 to December 2018, 204,777 newborns were screened for PCD using tandem mass spectrometry. A total of 316 (0.15%) residual NBS-positive specimens with low free carnitine (C0) levels were subjected to this second-tier screening. The screening identified 20 screen-positive newborns who harboured biallelic mutations in theSLC22A5gene, 99 carriers with one mutation, and 197 screen-negative newborns with no mutations. Among the 99 carriers, four newborns were found to have a second disease-causingSLC22A5mutation by further genetic analysis. Among the 197 screen-negatives were four newborns with persistently low C0 levels, and further genetic analysis revealed that one newborn had two novelSLC22A5pathogenic variants. In total, 25 newborns were diagnosed with PCD, for a positive predictive value of 7.91% (25/316). Based on these data, we estimate the incidence of PCD in Quanzhou is estimated to be 1:8191.Thirteen distinctSLC22A5variants were identified, and the most common was c.760C > T, with an allelic frequency of 32% (16/50), followed by c.1400C > G (7/50, 14%), and c.51C > G (7/50, 14%).Conclusion: Data from this study revealed that 24% (6/25) of PCD cases would have been missed by conventional NBS. This high-throughput iPLEX assay is a powerful tool for PCD genotyping. The addition of this second-tier genetic screening to the current NBS program could identify missed PCD cases, thereby increasing PCD detection. However, further studies are needed to optimise the workflow of the new screening algorithm and to evaluate the cost-effectiveness of this screening approach.

Background: Preterm human milk has advantages over preterm formula (PF), but it may compromise some functions after pasteurization. Objective: To explore the effects of preterm donor milk (DM) on growth, feeding tolerance, and severe morbidity in very-low-birth-weight infants. Method: This was a single-center, prospective cohort study that included 304 preterm infants weighing <1,500 g or of gestational age 0.05). Feeding intolerance in the DM group was significantly lower than that in PF group (P < 0.05), and parenteral nutrition time and hospitalization time were also shorter than that in the PF group (P < 0.05). Moreover, the incidence of necrotizing enterocolitis and sepsis was also significantly lower in the DM group (P < 0.05). Conclusion: The study indicated that preterm DM does not affect the growth of very-low-birth-weight infants. Further, it significantly reduces feeding intolerance, helps achieve full enteral feeding early, and has protective effects against necrotizing enterocolitis and sepsis. Thus, compared with formula, preterm DM can lower the rate of infection in preterm infants and is worthy of promotion.

Background: Glutaric acidemia type 1 (GA1) is a treatable disorder affecting cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. GA1 diagnosis reports following newborn screening (NBS) are scarce in the Chinese population. This study aimed to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 identified through NBS. Results: From January 2014 to September 2020, 517,484 newborns were screened by tandem mass spectrometry, 102 newborns with elevated glutarylcarnitine (C5DC) levels were called back. Thirteen patients were diagnosed with GA1, including 11 neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated at 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderate to markedly increased C5DC levels. Notably, one neonatal patient with low free carnitine (C0) level suggest primary carnitine deficiency (PCD) but was ultimately diagnosed as GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA and 3HGA levels, and one was reported to be within the normal range. Ten distinct GCDH variants were identified. Eight were previously reported, and two were newly identified. In silico prediction tools and protein modeling analyses suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2 A>C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G>A (p.Ala421Thr) at 9.09% (2/22). Conclusions: Neonatal GA1 patients with increased C5DC levels can be identified through NBS. Maternal GA1 patients can also be detected using NBS due to the low C0 levels in their infants. Few neonatal GA1 patients may have atypical acylcarnitine profiles that are easy to miss during NBS; therefore, multigene panel testing should be performed in newborns with low C0 levels. This study indicates that the GCDH variant spectra were heterogeneous in this southern Chinese cohort.

Background: There are limited reports available on investigations into the molecular spectrum of thalassemia and hemoglobinopathy in Fujian province, Southeast China. Here, we aim to reveal the spectrum of the thalassemia mutation and hemoglobinopathy in Quanzhou prefecture, Fujian province.Methods: We collected data from a total of 17,407 subjects with the thalassemia trait in Quanzhou prefecture. Gap-PCR, DNA reverse dot blot hybridization, and DNA sequencing were utilized for common and rare thalassemia gene testing.Results: In our study, we identified 7,085 subjects who were carrying thalassemia mutations, representing a detection rate of 40.70% (7,085/17,407). Among them, 13 different α-thalassemia gene mutations were detected, with the most common mutation being –^SEA (69.01%), followed by –α^3.7 (21.34%) and –α^4.2 (3.96%). We also discovered 26 β-thalassemia gene mutations, with the mutations of IVS-II-654 (C > T) (36.28%) and CD41/42(–TCTT) (29.16%) being the most prevalent. Besides, a variety of rare thalassemia variants were identified. Among them, the –^FIL, β^Malay, β^{IVS–I–130}, and β^{IVS–II–672} mutations were identified in Fujian province for the first time. Additionally, we detected 78 cases of hemoglobinopathies, of which Hb Owari was the first reported case in Fujian province and Hb Miyashiro was the first case identified in the Chinese population.Conclusion: Our study indicates that there is a diverse range of thalassemia mutations, and it also reveals the mutation spectrum of rare thalassemia and hemoglobinopathies in Quanzhou, Fujian province. It provides valuable data for the prevention and control of thalassemia in Southeast China.

Objective: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD. Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied. Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000–1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA). Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies.