Background Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. Methods We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. Results We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. Conclusions We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.

Background: The relationships between vascular endothelial growth factor (VEGF) + 936C/T and − 634C/G gene polymorphisms and certain diseases have been widely reported. According to reported data, there may be geographical and/or ethnic differences in VEGF + 936C/T and − 634C/G allele frequencies. Xinjiang is a multi-ethnic region in China in which the distributions of the + 936C/T and − 634C/G allele frequencies in various ethnic groups and their correlations with common complications during pregnancy (preeclampsia (PE), gestational hypertension (GH) and gestational diabetes mellitus (GDM)) have not been studied. Methods: A total of 2161 women (1551 controls with normal pregnancy, 232 patients with PE, 59 patients with GH and 319 patients with GDM) were recruited for this study. Sanger sequencing was used to screen VEGF + 936C/T and − 634C/G genotypes. The Pearson chi-square test was used to test the associations between diseases and + 936C/T and − 634C/G polymorphisms. Results: We investigated the distributions of VEGF + 936C/T and − 634G/C allele frequencies in healthy pregnant women in different regions of the world and found significant differences. Our data showed that the distributions of + 936C/T and − 634G/C allele frequencies between healthy Han and Uygur women in the Xinjiang area were significantly different. We found that VEGF + 936C/T and − 634G/C gene polymorphisms were not correlated with mild PE (mPE), severe PE (sPE), GH or GDM. Ethnic subgroup analysis revealed that the + 936C/T and − 634G/C gene polymorphisms in the Han, Uygur and Hui populations were also not related to PE, GH or GDM. Conclusions: The results showed that VEGF + 936C/T and − 634G/C gene polymorphisms had significant regional and ethnic distribution differences. In Xinjiang, VEGF + 936C/T and − 634G/C gene polymorphisms do not confer susceptibility to PE, GH or GDM.