Inflammation and oxidative stress after hypoxic-ischemic brain injury may be modified by genetic variability in addition to therapeutic hypothermia. The aim of our study was to evaluate the association between the polymorphisms in genes of antioxidant and inflammatory pathways in newborns treated with therapeutic hypothermia and the development of epilepsy or CP at two years follow-up. The DNA of 55 subjects was isolated from buccal swabs. Genotyping using competitive allele-specific PCR was performed for polymorphisms in antioxidant (SOD2 rs4880, CAT rs1001179, GPX1 rs1050450) and inflammatory (NLRP3 rs35829419, CARD8 rs2043211, IL1B rs1143623, IL1B rs16944, IL1B rs10716 76, TNF rs1800629) pathways. Polymorphic CARD8 rs2043211 T allele was less frequent in patients with epilepsy, but the association was not statistically significant. The interaction between CARD8 rs2043211 and IL1B rs16944 was associated with epilepsy after HIE: CARD8 rs2043211 was associated with lower epilepsy risk, but only in carriers of two normal IL1B rs16944 alleles (OR_adj = 0.03 95% CI = 0.00–0.55; p_adj = 0.019). Additionally, IL1B rs16944 was associated with higher epilepsy risk only in carriers of at least one polymorphic CARD8 rs2043211 (OR_adj = 13.33 95% CI = 1.07–166.37; p_adj = 0.044). Our results suggest that gene–gene interaction in inflammation pathways might contribute to the severity of brain injury in newborns with HIE treated with therapeutic hypothermia.

The role of quantitative ultrasound in diagnosing severe bone metabolic diseases in newborns

Background : From the conception onward, certain parameters associated with maternal health may affect foetal body composition, growth and bone mineral content. The objective of the study was to determine the association between maternal vitamin D and adiponectin status with the anthropometrical measures of newborns, and bone health status measured by Quantitative Ultrasound (QUS) at birth. Methods : Circulating 25OHD and adiponectin concentration were measured in 73 pregnant women. Correlations with the anthropometrical measures and bone health status in their infants were studied. Bone health was evaluated using QUS with the measurements of speed of sound (SOS, in m/s) and Z score on the right tibia. Results : There was no significant association between maternal 25OHD and newborn’s anthropometrical measures at birth (weight p=0.35, length p=0.59 and head circumference p=0.47). There was a significant negative correlation between a maternal serum adiponectin and a) weight of infants at birth (R= -0.37, p=0.002); b) birth length (R= -0.31, p=0.008) and c) head circumference (R= -0.29, p=0.014). There was no significant correlation between maternal 25OHD blood levels during pregnancy and SOS in newborns (p=0.48). Additionally, a correlation between maternal adiponectin concentration during pregnancy and SOS in newborns was not significant (p=0.82). Conclusion : Although a high prevalence of low 25OHD level among pregnant women was found, maternal vitamin D status did not influence growth and bone health of their offspring at birth. Maternal adiponectin levels in plasma showed an inverse relationship with anthropometrical measures of infants at birth, while no correlation with the newborn’s bone health was found.

Inflammation and oxidative stress are recognized as important contributors of brain injury in newborns due to a perinatal hypoxic-ischemic (HI) insult. Genetic variability in these pathways could influence the response to HI and the outcome of brain injury. The aim of our study was to evaluate the impact of common single-nucleotide polymorphisms in the genes involved in inflammation and response to oxidative stress on brain injury in newborns after perinatal HI insult based on the severity and pattern of magnetic resonance imaging (MRI) findings. The DNA of 44 subjects was isolated from buccal swabs. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1B rs16944, IL1B rs1143623, IL1B rs1071676, TNF rs1800629, CAT rs1001179, SOD2 rs4880, and GPX1 rs1050450. Polymorphism in CARD8 was found to be protective against HI brain injury detected by MRI overall findings. Polymorphisms in IL1B were associated with posterior limb of internal capsule, basal ganglia, and white matter brain patterns determined by MRI. Our results suggest a possible association between genetic variability in inflammation- and antioxidant-related pathways and the severity of brain injury after HI insult in newborns.

Background: Significant improvement in neonatal care has enabled increasing survival of preterm infants. Metabolic bone disease of prematurity is often overlooked due to other comorbidities of preterm birth. The best approach is screening and prevention of the disease in high-risk infants such as preterm infants. Aim: We followed up the clinical, radiological, and serum biochemical markers of metabolic bone disease in extremely preterm infants (<28 weeks of gestation). The clinical applicability and validation of C-terminal telopeptide of type I collagen (CTX-I) as a novel bone turnover marker were assessed. Standard and novel biochemical bone turnover markers and quantitative ultrasound were compared. Method: Patients’ data were collected from medical records. Assessments of calcium, phosphate, alkaline phosphatase, bone-alkaline phosphatase, CTX-I, and quantitative ultrasound were prospectively performed twice in 42 extremely preterm infants at postmenstrual ages of 30–32 weeks and 36–40 weeks. Bone mineral density was measured by quantitative ultrasound. Conclusion: Phosphate, alkaline phosphatase, bone alkaline phosphatase, calcium, or ionized calcium are not related to gestational age, but bone mineral density, measured by quantitative ultrasound, is related. There is no correlation between standard and novel biochemical markers and quantitative ultrasound for the identification of metabolic bone disease.