Risk Factors of Chylothorax After Congenital Heart Surgery in Infants: A Single-Centre Retrospective Study.

Background: Studies of chylothorax after congenital heart disease in infants are rare. Chylothorax has a higher incidence in infancy, but its risk factors are not well understood. Objective: The purpose of this study is to investigate the risk factors of chylothorax after congenital heart surgery in infants. Methods: This retrospective study included 176 infants who underwent congenital heart disease surgery at the Guangdong Cardiovascular Institute, China, between 2016 and 2020. According to the occurrence of chylothorax, the patients were divided into a control group (n = 88) and a case group (n = 88). Univariate and multivariate logistic regression were performed to analyse the incidence and influencing factors of chylothorax after congenital heart surgery in infants. Results: Between 2016 and 2020, the annual incidence rate fluctuated between 1.55% and 3.17%, and the total incidence of chylothorax was 2.02%. Multivariate logistic regression analysis showed that postoperative albumin (p = 0.041; odds ratio [OR] = 0.095), preoperative mechanical ventilation (p = 0.001; OR = 1.053) and preterm birth (p = 0.002; OR = 5.783) were risk factors for postoperative chylothorax in infants with congenital heart disease. Conclusion: The total incidence of chylothorax was 2.02% and the annual incidence rate fluctuated between 1.55% and 3.17% between 2016 and 2020. Premature infants, longer preoperative mechanical ventilation and lower albumin after congenital heart surgery may be risk factors for chylothorax. In addition, infants with chylothorax are inclined to be infected, need more respiratory support, use a chest drainage tube for longer and remain longer in hospital.

The implications of an integrated management model of prenatal diagnosis/postnatal treatment for premature infants with critical congenital heart disease-a case-control study.

Background: The high death rate and medical costs of critical congenital heart disease (CCHD) in preterm infants has resulted in significant burdens on both countries and individuals. It is unclear how this affects the mortality of the integrated management model of prenatal diagnosis/postnatal treatment. This study explored the effects of the delivery classification scale for fetal heart and postnatal infants' CCHD on prenatal and postnatal integrated treatment strategies to improve the effectiveness of disease management in CCHD. Methods: This study was a case-control study, which retrospectively analyzed the clinical data of 79 preterm infants (<37 weeks) who underwent prenatal diagnosis and postpartum treatment in Guangdong Provincial People' s Hospital (China) from June 2017 to June 2019. According to the diagnostic and exclusion criteria, the subjects were divided into prenatal and postpartum diagnostic groups. The clinical characteristics and survival outcomes of patients were collected and compared. The delivery classification scale was used for risk stratification and patient management. Results: Among the 79 patients included in this study, 48 (60.76%) were diagnosed prenatally, and 31 (39.24%) were diagnosed postpartum. The prenatal diagnosis group was born slightly earlier during the gestation period [35.00 (33.29-35.86) vs. 35.57 (34.14-36.71) weeks, P<0.05], and their mothers were older (33.23±5.22 vs. 30.43±6.37 years, P<0.05). The difference in the admission age between the groups was statistically significant [0 (0-5.5) vs. 7 (5-16) days, P<0.001]. The median survival time of the prenatal diagnosis group was higher than the postnatal diagnosis group [48 months (95% CI: 40.78-57.29) vs. 39 months (95% CI: 34.41-44.32), P<0.05]. The 3-year survival rates of the classes I, II, and III were 92.31% (12/13), 59.09% (13/22), and 38.46% (5/13), respectively. The survival of class I as denoted in the delivery classification scale was better than classes II or III (class I vs. II, P<0.05; class I vs. III, P<0.05). Unexpectedly, the hospitalisation costs were lower and total in-hospital days were shorter in the postnatal diagnosis group. Conclusions: The results indicated that the integrated management of a prenatal diagnosis/postnatal treatment approach in premature infants may be effective. Furthermore, the delivery classification scale has a particular prognostic value for CCHD. The authors anticipate that their management model will be able to contribute to the shift from a reactive monodisciplinary system to a proactive, multidisciplinary and dynamic management paradigm in premature infants with CCHD in the near future.

Abnormal placental DNA methylation variation in spontaneous preterm birth.

OBJECTIVE: Preterm birth (PTB) has become a major public health concern as the leading cause of neonatal death, but little is understood about its etiology. Children born preterm are also at increased risk of long-term consequences such as neurodevelopmental disorders, adulthood hypertension and diabetes. Recent studies have indicated that DNA methylation may be involved in the occurrence of PTB as well as related adverse outcomes. The latest Infinium EPIC BeadChip extends the coverage of the genome and provides a better tool to help investigate the involvement of DNA methylation in these conditions. METHODS: We conducted this case-control study in three Women and Children's hospitals in South China, and enrolled 32 spontaneous preterm births and 16 term births. We assessed placental DNA methylation profiling of these participants with the Infinium EPIC BeadChip. We identified PTB and gestational age (GA)-associated CpG sites with limma regression model, and applied seqlm to identify PTB-associated regions. We performed gene ontology analysis to further interpret functional enrichment of the identified differentially methylated genes in PTB. RESULTS: We identified a total of 8 differentially methylated positions (DMPs) that were significantly associated with PTB (FDR < 0.1) and a total of 15 DMPs that were associated with GA (FDR < 0.1). In the regional analysis, one differentially methylated region in the SLC23A1 gene overlapped with PTB-associated CpG site. The differentially methylated CpG sites in PTB were mapped to the genes involving in biological processes mainly regarding neurodevelopment, regulation of inflammation and metabolism. CONCLUSION: Our findings suggested that preterm placenta have distinct DNA methylation alterations, and these alteration patterns established at birth provide insight into the long-term consequences of preterm birth.

Metabolic signatures in the conversion from gestational diabetes mellitus to postpartum abnormal glucose metabolism: a pilot study in Asian women.

We aimed to identify serum metabolites related to abnormal glucose metabolism (AGM) among women with gestational diabetes mellitus (GDM). The study recruited 50 women diagnosed with GDM during mid-late pregnancy and 50 non-GDM matchees in a Singapore birth cohort. At the 5-year post-partum follow-up, we applied an untargeted approach to investigate the profiles of serum metabolites among all participants. We first employed OPLS-DA and logistic regression to discriminate women with and without follow-up AGM, and then applied area under the curve (AUC) to assess the incremental indicative value of metabolic signatures on AGM. We identified 23 candidate metabolites that were associated with postpartum AGM among all participants. We then narrowed down to five metabolites [p-cresol sulfate, linoleic acid, glycocholic acid, lysoPC(16:1) and lysoPC(20:3)] specifically associating with both GDM and postpartum AGM. The combined metabolites in addition to traditional risks showed a higher indicative value in AUC (0.92-0.94 vs. 0.74 of traditional risks and 0.77 of baseline diagnostic biomarkers) and R2 (0.67-0.70 vs. 0.25 of traditional risks and 0.32 of baseline diagnostic biomarkers) in terms of AGM indication, compared with the traditional risks model and traditional risks and diagnostic biomarkers combined model. These metabolic signatures significantly increased the AUC value of AGM indication in addition to traditional risks, and might shed light on the pathophysiology underlying the transition from GDM to AGM.

Comparison of DNA methylation profiles associated with spontaneous preterm birth in placenta and cord blood.

BACKGROUND: The etiology and mechanism of spontaneous preterm birth (sPTB) are still unclear. Accumulating evidence has documented that various environmental exposure scenarios may cause maternal and fetal epigenetic changes, which initiates the focus on whether epigenetics can contribute to the occurrence of sPTB. Therefore, we conducted the current study to examine and compare the DNA methylation changes associated with sPTB in placenta and cord blood. METHODS: This hospital-based case-control study was carried out at three Women and Children's hospitals in South China, where 32 spontaneous preterm births and 16 term births were recruited. Genome-wide DNA methylation profiles of the placenta and cord blood from these subjects were measured using the Illumina HumanMethylation EPIC BeadChip, and sPTB-associated differential methylated CpG sites were identified using limma regression model, after controlling for major maternal and infant confounders. Further Gene Ontology analysis was performed with PANTHER in order to assess different functional enrichment of the sPTB-associated genes in placenta and cord blood. RESULTS: After controlling for potential confounding factors, one differentially methylated position (DMP) in placenta and 31 DMPs in cord blood were found significantly associated with sPTB (Bonferroni corrected p < 0.05). The sPTB-associated CpG sites in placenta were mapped to genes that showed higher enrichment on biological processes including biological regulation, multicellular organismal process, and especially response to stimulus, while those in cord blood were mapped to genes that had higher enrichment on biological processes concerning cellular process, localization, and particularly metabolic process. CONCLUSION: Findings of this study indicated that DNA methylation alteration in both placenta and cord blood are associated with sPTB, yet the DNA methylation modification patterns may appear differently in placenta and cord blood.

Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls.

Background: Fibroblast growth factor receptor 2 (FGFR2) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association. Results: We conducted analyses for each of the five valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and found that per one standard deviation increase in the DNA methylation of CpG 11 at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in placental surface area (ß = - 0.18; standard error = 0.08, p = 0.02). The mediation effect of placental surface area on the association between DNA methylation and full-term low birth weight was significant in girls (OR = 1.38, 95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was 48.38%. Conclusion: Our findings suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner. Our study supported the importance of placental epigenetic changes in placental development and fetal growth.