A preliminary study on the relationship between neural development and gut microbiota in preterm infants / 中国医师杂志

Objective:To explore the relationship between the neural development of preterm infants and gut microbiota.Methods:66 premature infants who were hospitalized in the Neonatology Department of Hunan Children′s Hospital from September 2018 to September 2019 were included in the study. Their fecal samples and clinical data from the first admission were collected. According to the neurodevelopment, the patients were divided into normal neurodevelopment group and neurodysplasia group. The bacterial DNA of fecal samples was extracted by 16S rDNA high-throughput sequencing technology and bioinformatics analysis was conducted to compare the composition and diversity of gut microbiota between the two groups.Results:(1) The Shannon index of gut microbiota in normal neurodevelopmental group and neurodysplastic group was 0.89(0.41, 1.51) and 1.01(0.47, 1.31), respectively. There was no significant difference in diversity index between the two groups ( P>0.05). (2) Bifidobacterium, veronica and negativites in the gut microbiota of the normal neurodevelopmental group were significantly higher (all P<0.05), and streptococcus in the gut microbiota of the dysplastic group were significantly higher ( P<0.05). The gut microbiota of the two groups were mainly enterococcus and escherichia shigella. Conclusions:At the genus level, enterococcus and escherichia are the dominant flora of early gut microbiota in preterm infants. Gut microbiota is related to the neural development of preterm infants. The increased abundance of streptococcus, and the decreased abundance of bifidobacterium, veronicus, and negativites may be risk factors for neurodysplasia of preterm infants. The diversity of gut microbiota in early preterm infants may not be significantly related to neural development.

Genetic analysis of unexplained neonatal encephalopathy / 中华围产医学杂志

Objective:To explore the potential genetic causes of unexplained neonatal encephalopathy.Methods:This retrospective study enrolled 113 infants diagnosed with unexplained neonatal encephalopathy and underwent genetic testing in the Children's Hospital of Hunan Province from January 2019 to May 2021. Perinatal data, clinical manifestations, electroencephalograph, brain MRI findings, genetic information, and prognosis of those patients were analyzed. T-test or Chi-square test were used for data analysis. Results:Of the 113 infants enrolled, 74 (65.5%) were males. The gestational age at birth was (38.6±1.5) weeks, and the birth weight was (2 957±561) g. The most common clinical manifestation was the disturbance of consciousness (83/113, 73.5%), followed by seizures (39/113, 34.5%). There were 38.2% (34/89) of the patients with abnormal brain MRI, and 80.4% (74/92) presented abnormal electroencephalography. Among the 113 infants, 60 (53.1%) had genetic abnormalities, including 48 with single nucleotide variations, eight with copy number variations, and four with chromosome abnormalities. Single nucleotide variations in the 48 patients were classified into syndromic ( n=18, 37.5%), metabolic ( n=16, 33.3%), epileptic ( n=11, 22.9%) and mitochondrial-related genes ( n=3, 6.3%), of which 14 were not included in any database. Among the 103 cases which were successfully followed up until December 31, 2021, 75 (72.8%) had a poor prognosis, including 52 (50.5%) death cases and 23 (22.3%) cases of development retardation. Birth weight and the incidence of seizures in the poor prognosis group were both lower than those in the non-poor prognosis group [(2 876±536) vs (3 254±554) g, t=3.15; 29.3% (22/75) vs 53.6% (15/28), χ2=5.20; both P<0.05], while the incidence of disturbance of consciousness was higher [80.0% (60/75) vs 53.6% (15/28), χ2=7.19, P<0.05]. The proportion of infants with genetic abnormalities in the poor prognosis group was higher than that in the non-poor prognosis group, but the difference was not statistically significant [53.3% (40/75) vs 46.4% (13/28), χ2=0.39, P=0.533]. Conclusions:Genetic abnormality is one of the leading causes of unexplained neonatal encephalopathy. Nucleotide variation is the most common genetic type. Syndromic, metabolic, and epileptic variants are frequently detected in these patients.

Risk factors and prognosis of pulmonary hypertension associated with bronchopulmonary dysplasia in extremely preterm infants / 中国新生儿科杂志

Objective:To study the risk factors and prognosis of pulmonary hypertension(PH) associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants(EPIs).Methods:From January 2020 to December 2021, EPIs [gestational age (GA) <32 w] with BPD admitted to NICU of our hospital were retrospectively assigned into two groups: BPD with late-onset PH(PH group) and BPD without late-onset PH(non-PH group). Their general condition, treatment and prognosis were compared and the risk factors of late-onset PH were analyzed.Results:A total of 229 EPIs with BPD were enrolled, including 24(10.5%) in the PH group and 205(89.5%) in the non-PH group. The PH group had significantly smaller GA [(27.9±2.3) w vs. (28.7±1.8) w], longer mechanical ventilation [42.0(16.0, 84.0) d vs. 9.0(2.0, 23.0) d], longer hospital stay [100.5(86.3, 142.0) d vs. 77.0(56.5, 96.5)d],higher incidence of early-onset PH(54.2% vs. 9.3%) and higher mortality rate(33.3% vs. 9.8%) than the non-PH group ( P<0.05). Multivariate logistic regression analysis showed prolonged mechanical ventilation ( OR=1.046, 95% CI 1.011~1.064), early-onset PH ( OR=5.414, 95% CI 1.796~16.323) were independent risk factors for BPD with late-onset PH. 8(33.3%) patients in the PH group died, including 2 with grade Ⅱ BPD and 6 grade Ⅲ BPD. Conclusions:Prolonged mechanical ventilation and early-onset PH are independent risk factors for late-onset PH in BPD infants. BPD infants with late-onset PH have longer hospital stay, higher mortality and worse prognosis.

Clinical analysis of severe hyperbilirubinemia caused by hemolytic disease of the newborn and G6PD deficiency / 中国新生儿科杂志

Objective:To study the clinical characteristics and differences of severe hyperbilirubinemia caused by hemolytic disease of the newborn (HDN) and glucose-6-phosphate dehydrogenase (G6PD) deficiency.Methods:From January 2014 to December 2021, newborns (gestational age ≥ 35 weeks and postnatal age ≤ 28 d) admitted to the Department of Neonatology of Hunan Children's Hospital with severe hyperbilirubinemia caused by HDN or G6PD deficiency were retrospectively analyzed. According to the etiology of hyperbilirubinemia, they were assigned into HDN group and G6PD deficiency group. The general conditions, clinical manifestations, laboratory results, treatment and prognosis of the two groups were compared using SPSS 26.0 software.Results:A total of 532 cases were in the HDN group and 413 cases in the G6PD deficiency group. The HDN group reached peak hyperbilirubinemia earlier than the G6PD deficiency group [3(2,5) d vs. 6(4,8)d, P<0.05]. The HDN group had lower peak value of total serum bilirubin [379.5(345.6,426.7) μmol/L vs. 486.4 (413.5,577.4) μmol/L] and lower incidence of anemia [37.4% (199/532) vs. 55.0% (227/413)]than the G6PD deficiency group.The incidence of anemia with elevated reticulocyte percent(Ret%) in the HDN group was higher than the G6PD deficiency group[66.3%(132/199) vs. 5.7%(13/227), P<0.05]. Compared with the G6PD deficiency group, the incidences of exchange transfusion and repeated (≥2 times) exchange transfusion, acute bilirubin encephalopathy(ABE) and the mortality rate after withdrawal of treatment in the HDN group were significantly lower ( P<0.05). Conclusions:Neonatal severe hyperbilirubinemia caused by HDN has early onset. G6PD deficiency caused hyperbilirubinemia has higher incidences of anemia, more severe jaundice and ABE, without increased Ret%.

A case of neonatal lipoprotein lipase deficiency caused by novel compound heterozygous variants of LPL gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese neonate with lipoprotein lipase deficiency.@*METHODS@#Targeted capture and next-generation sequencing (NGS) were carried out to detect variants of genes associated with inborn errors of metabolism. Suspected variants were validated by Sanger sequencing.@*RESULTS@#Genetic testing revealed novel complex heterozygous variants, namely c.347G>C (p.Arg116Pro) and c.472T>G (p.Tyr158Asp), of the LPL gene, which were respectively inherited from his father and mother.@*CONCLUSION@#Compound heterozygous variants c.347G>C and c.472T>G of the LPL gene probably underlie the lipoprotein lipase deficiency in this child.

Genetic analysis of a child affected with Crigler-Najjar syndrome type II / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutation of the UGT1A1 gene in a child affected with Crigler-Najjar syndrome type II.</p><p><b>METHODS</b>Blood samples were collected from the patient and his parents for the extraction of genomic DNA. Potential mutation of the UGT1A1 gene was detected with polymerase chain reaction (PCR) and direct sequencing. The child was followed up until the age of 3 years and 6 months.</p><p><b>RESULTS</b>The patient showed persistent unconjugated hyperbilirubinemia. Sequencing of the UGT1A1 gene has detected a rare heterozygous c.610 A>G (p.Met204Val) mutation in the exon 1, in addition with a heterozygous c.1091 C>T (p.Pro364Leu) mutation in exon 4. The two mutations were inherited from his father and mother, respectively. The patient was diagnosed with Crigler-Najjar syndrome type II and received oral phenobarbital treatment.</p><p><b>CONCLUSION</b>The compound UGT1A1 gene mutation probably accounts for the disease in the patient manifesting persistent mild unconjugated hyperbilirubinemia. Genetic counseling and prenatal diagnosis should be provided for his family.</p>