Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective:To summarize the clinical characteristics of congenital chylothorax (CC) in neonates, and to analyze the effects of conservative treatment and the prognosis.Methods:A case control study was conducted.Clinical data of neonates with CC treated in the Department of Neonatal Surgical Intensive Care Unit, Guangzhou Women and Children′s Medical Center Guangzhou Medical University, from January 2015 to April 2023 were collected.The patients were divided into a survival group and a death group according to the outcome.SPSS 26.0 software was used for statistical analysis, and binary Logistic regression was used for the analysis of risk factors for death.Results:A total of 55 patients were included in this study, including 35 males and 20 females.The gestational age at birth and birth weight were 37.1 (34.7, 38.7) weeks and 3 250 (2 640, 3 540) g, respectively.Among the patients included, 30 cases had bilateral pleural effusion, 25 cases had unilateral pleural effusion, and 22 cases had hydrops fetalis; 50 cases were prenatally diagnosed with pleural effusion, with the mean gestational age at diagnosis being 31.0(26.0, 34.6) weeks.Additionally, 21 cases had polyhydramnios, and 18 cases had mediastinal displacement.Ten cases received intrauterine treatment and 17 cases were treated with octreotide.The maximum daily amount of pleural effusion was 31.7(12.0, 62.5) mL/kg, and pleural effusion resolved within 14 (6, 22) days.The length of hospital stay was 23 (12, 36) days.Forty-four cases survived, while 11 cases died.The differences in polyhydramnios, gestational age, bilateral pleural effusion, hydrops fetalis and Apgar score were significant between the survival and death groups (all P<0.05).Binary Logistic regression analysis revealed that bilateral pleural effusion and a low 5-minute Apgar score were independent risk factors for early death in neonates with CC (all P<0.05).A total of 38 children were followed up at the age of 2.30 (1.24, 3.46) years.There was 1 case of recurrence, and none of the patients experienced recurrent respiratory infections. Conclusions:CC is most common in full-term infants and has a predominantly bilateral effusion, its long-term prognosis with conservative treatment is promising.However, neonates with CC who present with bilateral pleural effusion or low 5-minute Apgar scores have an increased risk of early mortality.

Objective:To summarize the clinical characteristics of congenital chylothorax (CC) in neonates, and to analyze the effects of conservative treatment and the prognosis.Methods:A case control study was conducted.Clinical data of neonates with CC treated in the Department of Neonatal Surgical Intensive Care Unit, Guangzhou Women and Children′s Medical Center Guangzhou Medical University, from January 2015 to April 2023 were collected.The patients were divided into a survival group and a death group according to the outcome.SPSS 26.0 software was used for statistical analysis, and binary Logistic regression was used for the analysis of risk factors for death.Results:A total of 55 patients were included in this study, including 35 males and 20 females.The gestational age at birth and birth weight were 37.1 (34.7, 38.7) weeks and 3 250 (2 640, 3 540) g, respectively.Among the patients included, 30 cases had bilateral pleural effusion, 25 cases had unilateral pleural effusion, and 22 cases had hydrops fetalis; 50 cases were prenatally diagnosed with pleural effusion, with the mean gestational age at diagnosis being 31.0(26.0, 34.6) weeks.Additionally, 21 cases had polyhydramnios, and 18 cases had mediastinal displacement.Ten cases received intrauterine treatment and 17 cases were treated with octreotide.The maximum daily amount of pleural effusion was 31.7(12.0, 62.5) mL/kg, and pleural effusion resolved within 14 (6, 22) days.The length of hospital stay was 23 (12, 36) days.Forty-four cases survived, while 11 cases died.The differences in polyhydramnios, gestational age, bilateral pleural effusion, hydrops fetalis and Apgar score were significant between the survival and death groups (all P<0.05).Binary Logistic regression analysis revealed that bilateral pleural effusion and a low 5-minute Apgar score were independent risk factors for early death in neonates with CC (all P<0.05).A total of 38 children were followed up at the age of 2.30 (1.24, 3.46) years.There was 1 case of recurrence, and none of the patients experienced recurrent respiratory infections. Conclusions:CC is most common in full-term infants and has a predominantly bilateral effusion, its long-term prognosis with conservative treatment is promising.However, neonates with CC who present with bilateral pleural effusion or low 5-minute Apgar scores have an increased risk of early mortality.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to confirm the epigenetic mechanisms in IUGR. METHODS: IUGR models were established in Sprague-Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and PPAR gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF)1-4 binding sites of the IGF2/H19 imprinting control region (ICR). The methylation states of CTCF1-4 binding sites were studied by pyrosequencing. RESULTS: The IUGR models were constructed successfully. IGF2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group (P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group (P <0.05). In addition, knocking down IGF2 reduced the protein expression levels of AKT2-P and PGC-1α (P <0.05). In CTCF binding sites 1-4 of the IGF2/H19 ICR, AcH3 enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. H3K4me3 enrichment was significantly lower in the CTCF1-4 of newborn and 8-week-old IUGR groups (P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group (P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly (P <0.05). CONCLUSION The methylation status and histone modification in the IGF2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective:To study the risk factors of surgical therapy in neonates with necrotizing enterocolitis (NEC).Methods:From January 2016 to July 2020, neonates with a confirmed diagnosis of NEC (Bell's Stage Ⅱ and above) admitted to our hospital were retrospectively enrolled. They were assigned into surgical group and conservative group according to whether surgeries were performed. The conditions during perinatal period, clinical characteristics and laboratory examinations at the onset of NEC were compared between the two groups. Multivariate Logistic regression analysis was used to determine the risk factors of surgical therapy.Results:A total of 177 neonates with NEC were identified, including 62 cases (35.0%) in the surgical group and 115 cases (65.0%) in the conservative group. Multivariate Logistic regression analysis showed that male gender ( OR=3.178,95% CI 1.457~6.929, P=0.004), comorbidity with shock ( OR=3.434, 95% CI 1.112~10.607, P=0.032), mechanical ventilation>7 d before NEC onset ( OR=3.663, 95% CI 1.098~12.223, P=0.035) and lymphocytes <2.0×10 9/L ( OR=4.121, 95% CI 1.801~9.430, P=0.001) at the onset of NEC were independent risk factors for surgical therapy. Conclusions:Male gender, comorbidity with shock, mechanical ventilation >7 d before NEC and lymphocytopenia at the onset are independent risk factors for surgical therapy in neonates with NEC (Stage Ⅱ and above).

Objective:To investigate the clinical features and outcomes of giant fetal hepatic hemangioma (GFHH).Methods:In this retrospective study, patients with GFHH from Guangzhou Women and Children's Medical Centre who received conservative management or medical intervention with a minimum of one year's follow-up after birth from August 2012 until March 2020 were enrolled. Prenatal and postnatal data were collected to analyze the pathological (size, location, and lesion type) and clinical manifestations, treatment, and prognosis of GFHH using independent sample t-test or Chi-square (or Fisher's exact) test. Results:(1) A total of 22 subjects were enrolled, including one preterm infant (4.5%), with an average gestational age of (38.9±1.5) weeks at birth, ranging from 33 +4 to 40 +3 weeks. Among them, 17 were male (77.3%), and five were female (22.7%). The gestational age at the first diagnosis was (35.0±2.8) weeks, ranging from 30 to 40 +1 weeks. Fifteen babies (68.2%) were born vaginally and seven (31.8%) by cesarean section due to fetal distress. Focal type accounted for 21 of the 22 (95.5%) patients, and multifocal type in one patient (4.5%). All the patients received B-ultrasonography on an average of 2.5 times (2-4 times) prenatally, which showed that the diameter of hepatic hemangioma increased with gestational age and reached its maximum at birth [56 mm (42-99 mm)]. Nine fetuses (40.9%) were diagnosed with GFHH with prenatal ultrasonography, and 12 with MRI. Among them, six fetuses were diagnosed with both ultrasonography and MRI. The other cases showed space-occupying lesions. (2) Ten babies received conservative management (conservative group), and 12 received drug therapy (treatment group). There was no significant difference between the two groups in gestational age at diagnosis or birth, birth weight, the maximum diameter of the tumor before birth, and location and classification of the lesions (all P>0.05). The incidence of thrombocytopenia in the treatment group was significantly lower than that in the conservative group (7/12 vs 0/10, Fisher's exact test, P=0.014). No abnormality of heart function or pulmonary hypertension was found in the conservative group, while two patients were complicated with pulmonary hypertension in the treatment group. The outcomes between the two groups were similar ( P>0.05). (3) During a median followed-up of 3.3 years (1.2-7.0 years), all patients survived, and none of the children in the conservative group received drug therapy. One of the ten patients in the conservative group had a complete tumor involution at two years old without recurrence, and the other nine had the tumor regressed in size. Besides oral propranolol, three of 12 cases in the treatment group also had dexamethasone at the early stage, two had rapamycin, and two received invasive therapy due to progressive enlargement of lesions at the early stage, with the lesions completely involuted in two cases at 1.7 and 5.5 years of age and regressed in the other ten cases. Conclusions:The diameter of GFHH increases with gestational age. Conservative management conservative is recommended for asymptomatic GFHH cases. For those affected with dyspnea and abdominal distention resulting in repeated vomiting, drugs therapy can be considered regardless of the test results, and invasive therapy is an option when drugs are ineffective. Some fetuses may have unsignificant imaging manifestations. Most children prenatally detected with giant hepatic hemangiomas can survive, and the tumor begins to regress after birth with a good long-term prognosis.

Objective:To explore the complications and nutritional outcomes of Home Enteral Nutritional (HEN) in newborn surgical patients.Method:The medical records of neonates with HEN after surgery between 2017 and 2020 were retrospectively reviewed and complications of HEN and the nutritional status before and after HEN were analyzed.Results:A total of 66 neonates were included. The average gestational age at delivery and birth weight were (35.7 ± 3.0) weeks and (2426 ± 709) g, respectively. Diagnoses were mainly congenital esophageal atresia and intestinal diseases, such as intestinal atresia, intestinal torsion and necrotizing enterocolitis. The median age at HEN initiation was 92 (50, 112) days and HEN duration was 64 (41,95) days. HEN was conducted with tube feeding, with 14 patients (21.2%) through gastrostomy, 52 (78.8%) through nasal feeding tube, 20 (30.3%) through intermittent bolus infusion and 46 (69.7%) through continuous infusion. As for the formulas, 19 patients (28.8%) were given whole protein formula, 33 (50%) extensively hydrolyzed formula and 14 (21.2%) free amino acid-based formula. During the follow-up, 10 patients (71.4%) in gastrostomy group experienced 18 cases of catheter-related complications, including accidental removal (6 patients, 42.8%), catheter displacement (4 patients, 18.6%) and excessive granulation tissue at the gastrostomy site (4 patients, 18.6%). In nasal tube feeding group, 14 patients (26.9%) experienced 21 cases of catheter-related complications, including accidental tube removal (19 cases in 12 patients, 23.1%) and tube breakage (2 patients, 3.8%). Both the weight for age Z score and the height for age Z score were improved after HEN.Conclusions:HEN can help to improve the nutrition status in postoperative neonates. Management of catheter-related complications is challenging and warrants team work to improve the outcome of HEN.

This article reported a case of neonatal CHARGE syndrome complicated by congenital esophageal atresia. A prenatal ultrasound examination at 30 weeks of gestation revealed polyhydramnios and a small magenblase of the fetus, then fetal MRI suggested congenital esophageal atresia. The infant was born with severe asphyxia at 37 +5 gestational weeks by cesarean section due to placental abruption with a birth weight of 2 310 g. Gastric tube could not be placed after resuscitation. Congenital esophageal atresia complicated by tracheoesophageal fistula was diagnosed by esophageal imaging. Bilateral choanal atresia was detected by electronic nasopharyngoscopy and MRI. Moreover, skull defect, suspected meningocele were also observed. CHARGE syndrome was confirmed by whole exome sequencing, revealing a frameshift deletion of c.2155delA (p.Thr719GlnfsTer9) in the CHD7 gene. The infant died after withdrawing treatment.

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

Objective:To study the incidences of postoperative complications and nutritional status following different timings of stoma reversal in necrotizing enterocolitis (NEC).Method:From January 2017 to December 2019, NEC patients receiving enterostomy surgery and later stoma reversal in our hospital were retrospectively analyzed. They were assigned into three groups according to the timing of stoma reversal: early group (reversal within 8 weeks of stoma formation), middle group (reversal at 8~12 weeks from stoma formation) and late group (reversal after 12 weeks from stoma formation). Weight-for-age-Z-score (WAZ) was used to evaluate nutritional status.Result:A total of 56 infants were enrolled, including 6 cases in the early group, 11 cases in the middle group, and 39 cases in the late group. The gestational age and birth weight were (33.4±3.4) weeks and (1 894±640) g, respectively. The median age of stoma formation and the interval between stoma formation and reversal were 16.5 (8.0, 28.2) days and 94.0 (76.5, 126.5) days. No significant differences existed on gestational age, birth weight, age of stoma formation and complications of stoma reversal among the three groups ( P>0.05). The incidence of growth retardation (WAZ<-2) was 14.3% at stoma formation, and significantly increased to 62.5% at stoma reversal ( P<0.05). The WAZ at stoma reversal in early, middle and late groups were (-3.2±1.9), (-3.0±1.6) and (-2.3±1.5), without significant differences( P>0.05). The WAZ gradually increased to (-0.7±1.2), (-0.1±2.0) and (-0.1±0.8) at 42~48 weeks after reversal, respectively. Conclusion:The timing of stoma reversal may not influence the complications of reversal. Growth retardation are common in NEC infants with stoma formation and stoma reversal may improve the nutritional status of the infants. Early reversal of stoma is suggested to improve the nutritional status of patients with poor weight gain after stoma formation.