Interleukin-2 gene methylation levels and interleukin-2 levels associated with environmental exposure as risk biomarkers for preterm birth.

AIM: To compare interleukin-2 levels (IL-2) and IL-2 gene site 1 methylation levels between preterm newborns (PN) and full-term newborns (FN) and investigate their association with the environmental exposure of their mothers during pregnancy. METHODS: IL-2 and IL-2 gene site 1 methylation levels were assessed in 50 PN and 56 FN. Newborns' mothers filled in questionnaires about their living and occupational environments, habits, diets, and hobbies. RESULTS: The mothers of PN were significantly more frequently agrarian/rural residents than the mothers of FN. PN had significantly higher IL-2 levels, and significantly lower methylation of IL-2 gene site 1 levels than FN. CONCLUSION: IL-2 levels, hypomethylation of the IL-2 gene site 1, and the mother's rural residence (probably due to pesticide exposure) were predictive biomarkers for preterm birth. For the first time, we present the reference values for the methylation of IL-2 gene site 1 in PN and FN, which can be used in the clinical setting and biomonitoring.

Comparison of Estradiol, Testostosterone, and CYP19 Methylation Levels between Full-Term and Preterm Newborns.

Estradiol (E), testosterone (T), and their ratio are crucial axis in life. Especially during intrauterine growth, they orchestrate the complex development of organs and their interaction, which have lifelong impact on health and an organism's capacity to respond to environmental stressors. The aim of this study was to compare for the first time E, T, and their ratio levels with aromatase (CYP19) gene methylation levels between preterm newborns (PN) and full-term newborns (FN) with respect to their mother's environmental exposure and diet. In this study, 56 FN of 37-42 weeks of gestation age (GA) and 46 PN at GA 27-36 weeks were analysed for E and T levels and CYP19A1 gene pI.3/II promoter region methylation. Results showed there was no difference in E levels between PN and FN, but there were significantly lower levels of T in PN than in FN (2.81 nmol vs. 3.76 nmol, respectively) and consequently a significantly higher E/T ratio in PN than in FN (5278.04 vs. 2891.23, respectively). CYP19A1 methylation was significantly lower in PN than in FN (86.04% vs. 90.04%, respectively). CYP19A1 methylation was significantly reduced in newborns whose mothers reported daily milk consumption. Our study is the first to provide referent values for CYP19A1 methylation levels in FN and PN and shows that PN and FN significantly differ in CYP19A1 methylation levels, T levels, and E/T ratio. Future research should further investigate the mechanisms involved in GA-dependent CYP19A1 methylation levels and mechanisms of sex hormone disturbances which may contribute to preterm birth.

The relationship between histologic chorioamnionitis and decidual macrophage polarization and their influence on outcomes of neonates born before the 32nd gestational week.

PURPOSE: To explore the relationship between histologic chorioamnionitis (HCA) and decidual macrophage (DM) polarization and their influence on outcomes of neonates born before the 32nd gestational week. MATERIALS AND METHODS: Eighty-four neonates and their placentas were included in this retrospective case-control study and divided into two groups: with and without HCA present (HCA + and HCA-). Neonatal, maternal, and placental risk factors were explored and their influence on neonatal outcomes was examined. We used CD68 and iNOS as markers for polarized DMs type 1 (M1) and CD163, CD206 and arginase (Arg-1) for polarized DMs type 2 (M2). RESULTS: HCA was present in 47 (56%) cases, and 37 (44%) cases were without the present HCA. There was no statistically significant difference in neonatal risk factors between the two groups (HCA + and HCA-). Higher rates of HCA (p = .042) were observed in mothers who received antepartum corticosteroid therapy. The frequency of vaginal deliveries in HCA + pregnancies was significantly higher than in HCA- pregnancies where deliveries by cesarean section were more frequently observed (p < .001). M2 DM were more abundant in the HCA + group (p = .035). Multiple regression model assessed the association between the presence of HCA, M1, and M2 DM with ROP stages. It has been observed that HCA is a risk factor for ROP stages (ß coefficient = 0.34, rpartial = 0.246, p = .024). With the logistic regression model, the association between the presence of HCA, M1, and M2 DM with neonatal nCPAP respiratory support and necrotizing enterocolitis (NEC) was assessed. The presence of M2 macrophages in decidua is an independent risk factor for neonatal nCPAP respiratory support (coefficient -0.07, OR = 0.928, 95% CI 0.87-0.99, p = .024) and the presence of M1 macrophages in decidua increases the risk for NEC (coefficient 0.010, OR = 1.0108, 95% CI 1.00-1.02, p = .032). CONCLUSIONS: The significantly more abundant presence of M2 DM was detected in HCA + placentas and their association with the increased risk for neonatal nCPAP respiratory support was observed. On the contrary, the presence of M1 DM increases the risk for NEC. The presence of HCA is a risk factor for ROP stages.

Successful separation of xypho-omphalopagus conjoined twins with extrauterine twin-twin transfusion syndrome: a case report.

Conjoined twining is a rare medical phenomenon, with an overall prevalence of 1.47 per 100 000 births. This report describes a successful separation of xypho-omphalopagus conjoined twins complicated by unbalanced blood shunting through the porto-systemic anastomoses within the shared liver parenchyma. Significant extrauterine twin-twin transfusion syndrome caused by unbalanced shunting is an extremely rare, and probably under-recognized, hemodynamic complication in conjoined twins necessitating urgent separation. Progressive deterioration with a poor outcome can be prevented if the condition is recognized in a timely manner.

Paths of causal influence from prenatal inflammation and preterm gestation to childhood asthma symptoms.

Introduction: Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. The aim was to investigate paths of assumed causality leading from foetal inflammatory response syndrome (FIRS) to asthma symptoms in preterms. Methods: Demographic, antenatal, delivery and outcome data were collected from 262 infants with less than 32 completed weeks of gestational age over a 10-year period in a prospective cohort study. The presence of symptoms of asthma beyond the age of 5 years was the primary outcome measure. The causal effect of FIRS on childhood asthma was tested with three different logistic regression models and two structural equation models (SEM). Results: FIRS (OR = 4.7) and subsequent chronic lung disease of prematurity (OR = 7.7) and early childhood wheezing (OR = 9.5) are the most important risk factors for development of asthma symptoms in children born with less than 32 weeks of gestational age. The path analysis showed that FIRS has a large direct (0.59), medium indirect (0.11) and large overall (0.70) effect on CLD; large negative direct effect on ECW (-0.34) and a large positive indirect effect (0.74), mediated by CLD. On the occurrence of asthma symptoms, FIRS has a medium negative direct effect (-0.18) and a medium positive indirect effect (0.26), mediated by CLD and ECW. Conclusion: Prenatal inflammation plays an important role in the development of chronic respiratory disturbances in preterm infants. This influence is mainly related to structural and developmental lung abnormalities initiated in utero as consequences of FIRS, resulting in CLD of prematurity, and overcoming the protective mechanisms of chorioamnionitis.