Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity.

OBJECTIVE: To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). STUDY DESIGN: We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n = 118). RESULTS: For Cohort1, after adjusting for potential confounders, stage III CAM (n = 5554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (OR: 0.86; 95% CI: 0.78-0.94]. CAM of stage I (n = 3277) and II (n = 4319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05-0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01-0.93). CONCLUSIONS: After adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Transient abnormal myelopoiesis in non-Down syndrome neonate.

We encountered a case of neonatal acute megakaryoblastic leukemia not associated with Down syndrome (DS). Molecular cytogenetic analysis of leukemic blast cells indicated that increased blast cell status was caused by transient abnormal myelopoiesis with trisomy 21 and GATA1 mutation. Based on these molecular cytogenetic data, intensive chemotherapy was avoided, and the patient was successfully cured with low-dose cytarabine. Morphologically, leukemic blast cells of acute megakaryoblastic leukemia in a non-DS neonate are indistinguishable from a blast cell of transient abnormal myelopoiesis. The possibility of transient abnormal myelopoiesis should be carefully considered before intensive chemotherapy is adopted.

Case Report: A neonatal case of cryopyrin-associated periodic syndrome with severe funisitis and neonatal asphyxia.

Cryopyrin-associated periodic syndrome (CAPS) is a genetic disorder and autoinflammatory disease characterized by chronic inflammation throughout the body. The most severe form of CAPS, Chronic Infantile Neurologic Cutaneous, and Articular (CINCA) syndrome, also known as Neonatal Onset Multisystem Inflammatory Disease (NOMID), has three main features: skin rash, CNS involvement, and joint symptoms. Although these symptoms are typically reported shortly after birth, there have been a few reports of prenatal inflammation. Here, we report our experience managing a case of a CAPS infant born in severe neonatal asphyxia due to a ruptured cord associated with severe funisitis. The baby was born at 38 weeks and 6 days of gestation, weighing 2,898 g, through an ultra-emergency Caesarian section prompted by variable deceleration. The Apgar score was 1 point at 1 min and 4 points at 5 min, necessitating intensive care due to hypoxic-ischemic encephalopathy. Upon delivery, it was observed that the umbilical cord had partially ruptured at the site of attachment to the baby, accompanied by arterial hemorrhage. Umbilical cord rupture was considered to be the cause of the sudden decrease in fetal heart rate. Pathological examination also showed that the inflammation of the cord was more severe on the side attached to the fetus and on the arterial side, suggesting that the inflammation had extended from the fetus. The father carried a genetic mutation associated with CINCA syndrome/NOMID (NLRP3 c.2068G>A p.Glu690Lys Hetero), which was also found in the child. Histopathologic examination of the placenta and umbilical cord can provide crucial insights into the intrauterine onset of inflammation, which is the first manifestation of CINCA syndrome/NOMID in newborns. It should be noted that births with a genetic predisposition to CAPS may have complications related to the placenta and umbilical cord.

Transcriptome analysis of umbilical cord mesenchymal stem cells revealed fetal programming due to chorioamnionitis.

Although chorioamnionitis (CAM) has been demonstrated to be associated with numerous short- and long-term morbidities, the precise mechanisms remain unclear. One of the reasons for this is the lack of appropriate models for analyzing the relationship between the fetal environment and chorioamnionitis and fetal programming in humans. In this study, we aimed to clarify the fetal programming caused by CAM using the gene expression profiles of UCMSCs. From nine preterm neonates with CAM (n = 4) or without CAM (n = 5), we established UCMSCs. The gene expression profiles obtained by RNA-seq analysis revealed distinctive changes in the CAM group USMSCs. The UCMSCs in the CAM group had a myofibroblast-like phenotype with significantly increased expression levels of myofibroblast-related genes, including α-smooth muscle actin (p < 0.05). In the pathway analysis, the genes involved in DNA replication and G1 to S cell cycle control were remarkably decreased, suggesting that cellular proliferation was impaired, as confirmed by the cellular proliferation assay (p < 0.01-0.05). Pathway analysis revealed that genes related to white fat cell differentiation were significantly increased. Our results could explain the long-term outcomes of patients who were exposed to CAM and revealed that UCMSCs could be an in vitro model of fetal programming affected by CAM.

Prematurity at less than 24 weeks of gestation is a risk for prolonged hyperglycemia in extremely low-birth weight infants.

Hyperglycemia in extremely low-birth weight infants (ELBWIs) is frequently observed during the acute perinatal phase, (i.e., first 1-2 weeks postnatal period); however it can occasionally persists for >2 weeks, extending to the post-acute phase. Since such prolonged hyperglycemia (PH) is not typical for ELBWIs, the aim of the present study was to further understand the clinical details of PH. Twenty-five hyperglycemic ELBWIs born before 28 weeks of gestation from 2015 to 2018 were included in the study. Based on the duration of hyperglycemia, we separated the subjects into two groups: non-prolonged hyperglycemia (NPH) who achieved remission within ≤2 weeks [n = 18, median 3.0 (range, 2.0-4.0) days], and PH, whose hyperglycemia persisted for >2 weeks [n = 7, median 50.0 (range, 33.5-66.0) days]. Compared to the NPH group, glucose metabolism of the PH group was more deteriorate. The peak blood glucose level was significantly higher in the PH group [PH: median 472 mg/dL, NPH: median 275 mg/dL, p < 0.001], and a higher proportion of subjects in the PH group required insulin therapy [PH: 100% (7/7) vs. NPH: 22% (4/22)]. Multivariate analysis revealed that among perinatal factors, prematurity was the only independent risk factor for PH (glucocorticoid therapy: p = 0.884, gestational age: p = 0.006), with a cutoff of 23W4D determined by receiver operating characteristic analysis. Our data revealed distinctive clinical features of PH, suggesting a type different from the previously reported hyperglycemia in ELBWIs. Specifically, extreme prematurity, less than 24 weeks of gestation, is a risk for PH, and aggressive interventions, such as insulin would be required.