Objective:To summarize the clinical and genetic characteristics of children with Menkes disease(MD).Methods:The clinical manifestations, auxiliary examinations and genetic testing results of 15 MD children admitted to the Department of Pediatrics of the Third Affiliated Hospital of Zhengzhou University, Children′s Hospital Affiliated of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from June 2016 to October 2022 were analyzed retrospectively.These children were followed up.Results:All the 15 children were male.The age at onset was ranging from 9 days to 5.5 months.White skin, curly hair, skin laxity, hypotonia and severe developmental delay were found in all children, with epilepsy in 13 children, anemia in 11 children and granulocytopenia in 4 children.The concentration of ceruloplasmin in the serum of MD children was lower than that in healthy children of the same age.The concentration of ceruloplasmin in MD children younger than 3 months was significantly lower than that in healthy children of the same age and MD children older than 3 months.The brain magnetic resonance imaging showed abnormalities in all 15 children.Twelve children showed tortuous intracranial vessels in brain magnetic resonance angiography examinations.All the 15 children had ATP7A gene pathogenic variants, including 4 missense variants(2 cases with c. 2179G>A), 3 frameshift variants, 3 nonsense variants, 3 exon deletions and 2 splice site variants.Among these children, 1 had a novel gene variant that had not been reported so far(c.2968C>T). Conclusions:MD has early onset age and diverse clinical manifestations, but also has characteristic clinical manifestations and applicable auxiliary examinations.Its diagnosis depends on genetic testing.The c. 2179G>A and exon deletions may be hot mutations in Chinese MD patients.

Objective:To study the clinical characteristics and risk factors of necrotizing enterocolitis (NEC) in one of the premature twins.Methods:A retrospective study was conducted on twin premature infants who were admitted to the Department of Neonatology at the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2022 and only one got NEC. The twins were divided into NEC group and control group, the clinical data were collected and analyzed by SPSS 26.0 statistical software.Results:This study enrolled 109 pairs of premature twins, 109 cases in the NEC group, and 109 cases in the control group. Univariate analysis showed that birth weight, pre NEC white blood cell count were lower in NEC group than those in the control group, while the proportion of smaller than gestational age (SGA), donor of twin-to-twin transfusion syndrome, feeding intolerance, incomplete enteral feeding, start feeding time >48 h, red blood cell transfusion 72 h before NEC onset and the neutrophils ratio were higher in the NEC group than that of the control group, the difference was statistically significant ( P<0.05). Multivariate logistic analysis showed that low birth weight ( OR=1.558, 95% CI1.197-2.142), SGA ( OR=1.721, 95% CI 1.217-2.536), feeding intolerance ( OR=3.798, 95% CI 1.347-10.706), and incomplete enteral feeding ( OR=4.319, 95% CI 1.673-11.149) were independent risk factors for NEC ( P<0.05). Conclusions:Low birth weight, small for gestational age, feeding intolerance, and incomplete enteral feeding are independent risk factors for NEC in one of the premature twins.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective:To explore the relationship between preterm labor with different causes and cerebral perfusion in different regions of interest in very preterm infants.Methods:This was a prospective cohort study. A total of 145 preterm infants with gestational age of 28-31 +6 weeks who were hospitalized in the Neonatology Department of the Third Affiliated Hospital of Zhengzhou University within 24 h after birth from April 2022 to May 2023 were selected for the study, and were categorized into the iatrogenic preterm labor group ( n=55), spontaneous preterm labor with premature rupture of the membranes (PROM) group ( n=47), and spontaneous preterm labor with intact membranes group ( n=43) according to the cause of preterm labor. Cerebral blood flow (CBF) values in the cortex and deep gray matter of different regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) were measured using the arterial spin labeling technique in the very preterm infants in each group. One-way analysis of variance, Kruskal-Wallis H test and Bonferroni correction, Chi-square test or Fisher's exact probability method, analysis of covariance, and LSD test were used to compare the differences in CBF among the groups. Results:The differences in the incidence of complications such as cerebral white matter injury, Ⅰ-Ⅱ grade intracranial hemorrhage, and late-onset sepsis during hospitalization among the three groups of preterm infants were not statistically significant (all P>0.05). In the iatrogenic preterm labor group, compared with the spontaneous preterm labor with PROM group, CBF [in units of ml/ (100 g·min)] was higher in regions of interest such as the right temporal lobe [20.5 (16.1-24.6) vs. 17.1 (14.5-23.0)], bilateral parietal lobe [left side: 22.4 (17.1-25.3) vs. 16.9 (14.4-24.1); right side: 23.0 (18.2-27.4) vs. 17.0 (14.0-22.2)], right occipital lobe [22.1 (18.6-29.5) vs. 19.4 (13.7-24.5)], bilateral basal ganglia [left side: 33.0 (29.1-36.3) vs. 24.9 (22.9-33.1); right side: 32.8 (29.0-37.0) vs. 26.1 (22.3-35.0)], and bilateral thalamus [left side: 39.2 (36.0-45.0) vs. 32.6 (25.1-42.2); right side: 38.6 (34.6-44.1) vs. 32.0 (25.4-44.9)] (Bonferroni corrected, all P<0.017). Compared with the spontaneous preterm labor group with intact membranes, CBF in the iatrogenic preterm labor group was higher in the cortex and deep gray matter of regions of interest such as bilateral frontal lobe [left side: 21.4 (18.3-25.3) vs. 17.0 (12.0-22.2); right side: 22.1 (16.7-25.0) vs. 15.9 (12.0-23.3)], temporal lobe [left side: 21.4 (17.0-24.8) vs. 18.4 (14.0-22.0); right side: 20.5 (16.1-24.6) vs. 17.3 (13.3-22.3)], parietal lobe [left side: 22.4 (17.1-25.3) vs. 15.3 (10.4-20.8); right side: 23.0 (18.2-27.4) vs. 15.7 (11.1-23.6)], occipital lobe [left side: 22.7 (18.8-28.4) vs. 18.2 (11.4-23.4); right side: 22.1 (18.6-29.5) vs. 19.6 (14.0-25.8)], basal ganglia [left side: 33.0 (29.1-36.3) vs. 27.7 (19.1-32.4); right side: 32.8 (29.0-37.0) vs. 27.7 (21.5-33.0)] and thalamus [left side: 39.2 (36.0-45.0) vs. 33.9 (26.0-43.7); right side: 38.6 (34.6-44.1) vs. 33.3 (27.8-40.4)] (Bonferroni corrected, all P<0.017). Analysis of covariance revealed that the cause of preterm birth had a significant effect on CBF values in the cortex and deep gray matter of very preterm infants ( P=0.007), and that iatrogenic preterm birth elevated CBF perfusion in the localized cerebral cortex and deep gray matter of very preterm infants as compared to the spontaneous preterm births with PROM group and spontaneous preterm births with intact membranes group (LSD test, all P<0.05). Conclusion:Cerebral blood perfusion in very preterm infants is related to the causes leading to preterm birth, and local cortical and deep gray matter blood perfusion levels in the brain are increased in those with iatrogenic preterm birth compared to spontaneous preterm birth.

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia (XLAG). METHODS: A child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the result was analyzed by using bioinformatic software. RESULTS: The child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene, which as a frameshifting variant has resulted in a truncated protein. His mother was found to be heterozygous for the variant, whilst his father was of wild type. The variant was unreported previously. CONCLUSION The hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient. Above finding has provided a basis for the diagnosis and genetic counseling for this family.
Humans ; Child ; Classical Lissencephalies and Subcortical Band Heterotopias ; Exons ; Computational Biology ; Genetic Counseling ; Genitalia ; Transcription Factors ; Homeodomain Proteins

Objective:To study the neurodevelopmental prognosis and risk factors for adverse outcomes of neonatal seizure.Methods:From December 2019 to November 2020, infants with neonatal seizure diagnosed in our hospital were enrolled in this retrospective study. Based on survival or not, mental development index (MDI), psychomotor development index (PDI) and seizure episodes at the age of 12 months, the infants were assigned into adverse outcome group and normal outcome group. The risk factors for adverse outcomes were statistically analyzed.Results:A total of 75 infants were enrolled,including 39 cases in adverse outcome group and 36 in normal outcome group. 69 cases showed abnormal amplitude-integrated electroencephalogram(aEEG), including 38 mildly abnormal cases,23 moderately abnormal cases and 8 severely abnormal cases, The incidences of adverse outcomes and mortality rates were significantly different ( P<0.05) among infants with different severity levels of aEEG abnormalities and the severity levels of aEEG abnormalities were positively correlated with adverse outcomes ( r=0.367, 0.471, P<0.05).Univariate analysis showed that adverse outcome group had significantly higher incidences of chorioamnionitis, seizure onset age ≤3 d, 5 min Apgar score ≤3, cranial ultrasound abnormalities, brain MR abnormalities and aEEG abnormalities than normal outcome group ( P<0.05).Logistic regression analysis showed that seizure onset age ≤3 d ( OR=3.988, 95% CI 1.376-11.674), abnormal brain MR ( OR=3.296, 95% CI 2.383-17.377) and bilirubin encephalopathy ( OR=3.792,95% CI 2.110-13.216) were independent risk factors for adverse outcomes of neonatal seizure. Conclusions:For neonatal seizure, the infants with more severe abnormal aEEG will have higher incidences of adverse outcomes and mortality. Seizure onset age ≤3 d, brain MR abnormalities and bilirubin encephalopathy were independent risk factors for adverse outcomes of neonatal seizure.

Objective:To study the clinical characteristics and imaging features of neonatal ovarian cysts and to analyze treatment and prognosis of ovarian torsion.Methods:From January 2011 to December 2021,neonates with ovarian cysts admitted to the department of neonatology and pediatric surgery of our hospital were retrospectively studied. They were assigned into ovarian torsion group and non-torsion group. Their clinical manifestations, imaging features, pathological results, treatment and prognosis were reviewed and compared.Results:A total of 44 neonates with ovarian cysts were included, all without specific clinical manifestations. 10 neonates were treated with conservative therapy and 34 received surgery. Ovarian torsion were confirmed during surgery in 23 patients. All 34 patients received abdominal ultrasound preoperatively and 31 (91.2%, 31/34) were diagnosed with ovarian cysts. The accuracy rates of ultrasound for cyst location and ovarian torsion were 85.3% (29/34) and 82.6% (19/23),respectively. 30 patients received abdominal CT scan and 23 (76.7%, 23/30) were diagnosed with ovarian cysts. The accuracy rates of CT scan for cyst location and ovarian torsion were 53.3% (16/30) and 47.8% (11/23), respectively. Among the 34 patients treated with surgery, ovarian cyst dissection was performed in 11 patients and cyst resection in 23 patients with torsion necrosis. 24 patients had simple cysts including 15 torsion necrosis (62.5%, 15/24) and 10 had complicated cysts including 8 torsion necrosis(80.0%, 8/10). The average diameter of ovarian cysts was significantly larger in the torsion group [(8.4±1.6) cm] than the non-torsion group [(4.7±1.2) cm] ( P<0.05). Conclusions:Neonatal ovarian cysts are mostly unilateral without specific clinical manifestations. Large, bilateral and complex cysts are prone to torsion necrosis. Abdomen ultrasound has advantages than CT scan for the localization of the ovarian cyst and diagnosis of ovarian torsion. Surgical treatment is necessary after diagnosis.

Objective:To study the clinical characteristics and risk factors of intrauterine Ureaplasma urealyticum (UU) infection in very low birth weight preterm infants.Methods:From March 2019 to February 2022, very low birth weight preterm infants with gestational age 28~32 weeks admitted to our hospital were enrolled in this single-center retrospective study. According to the UU test results of respiratory tract samples obtained within 24 h after admission, the infants were assigned into the UU group (UU-PCR positive) and the non-UU group (UU-PCR negative). SPSS 26.0 statistical software was used to compare the clinical characteristics, laboratory indices, and complications between the two groups. Risk factors of UU infection were calculated.Results:A total of 327 preterm infants were included: 45 in the UU group and 282 in the non-UU group. No significant differences existed in gender, gestational age, birth weight and delivery pattern between the two groups ( P>0.05). Compared with the non-UU group, the UU group had significantly higher incidences of premature rupture of membranes (PROM) and chorioamnionitis, elevated white blood cell and platelet counts, procalcitonin and C-reactive protein levels, total duration of oxygen use and ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and metabolic osteopathy ( P<0.05). Multivariate logistic regression analysis showed that PROM ( OR=5.444, 95% CI 2.749-10.781, P<0.001) and chorioamnionitis ( OR=2.161, 95% CI 1.048-4.454, P=0.037) were independent risk factors for UU infection. Conclusions:PROM and chorioamnionitis are risk factors for UU infection in very low birth weight preterm infants. For high-risk premature infants, the UU test should be completed as soon as possible after birth.

Objective:To study the effects of recombinant human erythropoietin (rhEPO) on cerebral blood flow (CBF) in preterm infants using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From September 2021 to June 2022, preterm infants (gestational age ≤32 weeks, birth weight ≤1 500 g) admitted to NICU of our hospital within 24 h after birth were randomly assigned into rhEPO group and control group for this prospective study. The rhEPO group was given rhEPO (500 IU/kg iv, once every other day for 2 weeks) within 72 h after birth plus symptomatic supportive treatment. The control group received same amount of normal saline injection. Both groups received brain MRI, diffusion-weighted imaging and ASL at adjusted gestational age of 35~37 weeks and CBF values of interested areas were measured.Results:A total of 85 infants were enrolled, including 40 in the rhEPO group and 45 in the control group. No significant differences existed in the incidences of periventricular-intraventricular hemorrhage, periventricular leukomalacia, focal white matter injury and extensive white matter injury between the two groups ( P>0.05). The CBF values [ml/(100 g·min)] of frontal cortex [left 15.1±3.9 vs. 17.9±3.1, right 15.9 (12.5, 17.8) vs. 18.1(16.1,20.2)], temporal cortex [left 15.8±4.3 vs. 18.6±3.8, right 16.3(13.2,19.4) vs. 18.1(15.7,19.7)], occipital cortex (left 15.8±6.1 vs. 18.8±3.3, right 16.8±5.5 vs. 19.3±4.8), basal ganglia (left 24.7±7.2 vs. 28.7±6.2, right 26.0±7.9 vs. 29.3±6.4) and thalamus (left 32.7±11.8 vs. 37.9±8.6, right 32.1±11.6 vs. 37.6±10.2) in the rhEPO group were significantly lower than the control group ( P<0.05). No significant differences existed of CBF value at the parietal cortex between the two groups ( P>0.05). Conclusions:Early application of rhEPO can reduce CBF in premature infants, which may be related to the neuro-protective effects of EPO.

Objective:To study the complications and prognosis of extremely premature infants(EPIs) with gestational age (GA) <28 w.Methods:From January 2016 to December 2020, EPIs with GA <28 w admitted to NICU of our hospital were retrospectively studied. Clinical data of the infants and their mothers during pregnancy were reviewed. According to the prognosis, the infants were assigned into the survival group, the death group and the withdrawal group. According to GA, the infants were assigned into <26 w goup, 26~26 +6 w group, ≥27 w group. According to birth weight (BW), the infants were assigned in to ≤750 g group, 750~999 g group and ≥1 000 g group. SPSS 26.0 was used for data analysis. Results:A total of 265 EPIs were included, 122 (46.0%) in the survival group, 47 (17.7%) in the death group and 96 (36.2%) in the withdrawal group. GA and BW of the survival group were significantly higher than the death group and the withdrawal group ( P<0.05). The incidences of tracheal intubation (92.2%) and pulmonary hemorrhage (42.2%) in the death group were the highest among the three groups. The survival group had the highest application of prenatal glucocorticoids (80.3%) and pulmonary surfactants (99.2%) ( P<0.05). In the survival group, the top 3 common complications were bronchopulmonary dysplasia (BPD) (68.0%), pulmonary infections (65.6%) and neonatal sepsis (34.4%). The survival rate increased with GA and BW. Conclusions:The survival rate of EPIs is closely correlated with GA and BW. EPIs with pulmonary hemorrhage and tracheal intubation have poor prognosis. Prenatal glucocorticoids and pulmonary surfactant may improve clinical outcome. BPD and pulmonary infections are common complications of surviving EPIs.