Background: The epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations. Results: A cross-fostering model using a/a and A^vy/a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues. Conclusion: Our findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.

A wet nurse can be used if a baby’s natural mother is unable or chooses not to breastfeed her infant. The practice of using wet nurses is ancient and common to many cultures.

High frequency oscillatory ventilation with volume-guarantee (HFOV-VG) is a promising lung protective ventilator mode for the treatment of respiratory failure in newborns. However, indicators of optimal ventilation during HFOV-VG mode are not identified yet. In this study, we aimed to evaluate optimal high-frequency tidal volume (VThf) and the dissociation coefficient of CO₂ (DCO₂) levels to achieve normocapnia during HFOV-VG after lung recruitment in very low birthweight infants with respiratory distress syndrome (RDS). Preterm babies under the 32nd postmenstrual week with severe RDS that received HFOV-VG using open-lung strategy between January 2014 and January 2019 were retrospectively evaluated. All included patients were treated with the Dräger Babylog VN500 ventilator in the HFOV-VG mode. In total, 53 infants with a mean gestational age of 26.8 ± 2.3 weeks were evaluated. HFOV mean optimal airway pressure (MAPhf) level after lung recruitment was found to be 10.2 ± 1.7 mbar. Overall, the mean applied VThf per kg was 1.64 ± 0.25 mL/kg in the study sample. To provide normocapnia, the mean VThf was 1.61 ± 0.25 mL/kg and the mean DCO₂corr was 29.84 ± 7.88 [mL/kg]²/s. No significant correlation was found between pCO₂ levels with VThf (per kg) or DCO₂corr levels. VThf levels to maintain normocarbia were significantly lower with 12 Hz frequency compared to 10 Hz frequency (1.50 ± 0.24 vs. 1.65 ± 0.25 mL/ kg, p < 0.001, respectively). A weak but significant positive correlation was found between mean airway pressure (MAPhf) and VThf levels. To our knowledge, this is the largest study to evaluate the optimal HFOV-VG settings in premature infants with RDS, using the open-lung strategy. According to the results, a specific set of numbers could not be recommended to achieve normocarbia. Following the trend of each patient and small adjustments according to the closely monitored pCO₂ levels seems logical.

Objective: To evaluate the efficacy of the MRI-based texture analysis (TA) of the basal ganglia and thalami to distinguish moderate-to-severe hypoxic-ischemic encephalopathy (HIE) from mild HIE in neonates. Methods: This study included 68 neonates (15 with mild, 20 with moderate-to-severe HIE, and 33 control) were born at 37 gestational weeks or later and underwent MRI in first 10 days after birth. The basal ganglia and thalami were delineated for TA on the apparent diffusion coefficient (ADC) maps, T 1-, and T 2 weighted images. The basal ganglia, thalami, and the posterior limb of the internal capsule (PLIC) were also evaluated visually on diffusion-weighted imaging and T 1 weighted sequence. Receiver operating characteristic curve and logistic regression analyses were used. Results: Totally, 56 texture features for the basal ganglia and 46 features for the thalami were significantly different between the HIE groups on the ADC maps, T 2-, and T 2 weighted sequences. Using a Histogram_entropy log-10 value as >1.8 from the basal ganglia on the ADC maps (p < 0.001; OR, 266) and the absence of hyperintensity of the PLIC on T 1 weighted images (p = 0.012; OR, 17.11) were found as independent predictors for moderate-to-severe HIE. Using only a Histogram_entropy log-10 value had an equal diagnostic yield when compared to its combination with other texture features and imaging findings. Conclusion: The Histogram_entropy log-10 value can be used as an indicator to differentiate from moderate-to-severe to mild HIE. Advances in knowledge: MRI-based TA may provide quantitative findings to indicate different stages in neonates with perinatal asphyxia.

Background. Hereditary bone marrow failure syndromes are a category of biologically different syndromes that can cause cytopenia in at least one hematopoietic cell lineage. Case. We present a 29-week-old male infant who had a low Apgar Score, advanced delivery room resuscitation, widespread petechial rash, and ecchymoses at birth, without any dysmorphic features. Initial laboratory tests revealed bicytopenia (platelet count 7x10 3 /uL, hemoglobin of 3.9 g/dL, neutrophil 2.0x103 /uL) with findings of disseminated intravasculer coagulation (DIC). Imaging studies demonstrated accompanying left-sided congenital pulmonary airway malformation. On the second postnatal week pancytopenia occurred and the bone marrow findings were consistent with congenital amegakaryocytic thrombocytopenia. Further evaluations for differential diagnosis of pancitopenia were performed and the results of congenital viral infections, metabolic and immunologic tests were negative. While supportive treatments were in progress, haploidentical bone marrow transplantation (BMT) was performed from the father at 84th day due to unavailability of HLA-matched relative or nonrelative donor. Whole exome sequencing revealed a novel heterozygous frameshift variation (c.1242dupT [p. Thr538fs]) in exon 8 of the MECOM gene and validated by Sanger sequencing. No variation was detected in the parents genetic analysis. Conclusions. In this report, we present a patient with congenital bone marrow failure successfully treated with haploidentic BMT and describe a novel, de novo pathogenic variant in MECOM gene.

Background. The placenta is the major regulatory element of the in-utero environment, and alterations in placental cellular functions in infection, inflammation, and hypoxemia lead to adverse preterm birth outcomes. The importance of regulation of autophagy and inflammasome activities has been shown in the pathogenesis of morbidities in immature animal models. This study aimed to determine the relationship between placental autophagy and inflammasome activities with morbidity in extremely preterm infants. Methods. Premature infants born between 24th to 29th gestational weeks were evaluated prospectively. Placental LC3B and NLRP3 immunostainings were performed to assess autophagy and inflammasome activities. Preterm morbidities including respiratory distress syndrome (RDS), patent ductus ateriosus: (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL), sepsis, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and mortality were evaluated. Results. Fifty-nine infants with a mean gestational age of 26.9 ± 1.5 weeks were included. Anti-LC3B staining scores were moderate or intense positive in 75% of the placentas. Anti-LC3B activity was not associated with the existance of evaluated neonatal morbidities or mortality. Autophagy and inflammasome coexistence were demonstrated in 35 placentas (59.3%). Anti-NLRP3 staining score was moderate or intensely positive in 75% of the placentas. Infants with BPD had a lower rate of positive anti -NLRP3 staining than infants without BPD (42.9 vs 57.1%, p=0.048). Infants who had hemodynamic significant patent ductus arteriosus (hsPDA) and surgical- NEC showed significantly intense anti-NLRP3 staining compared to infants who did not (18.8% vs 0%, p= 0.027 and 33% vs 7.5%, p=0.048 respectively). Conclusions. The results showed that autophagy and inflammatory activities were present in varying amounts in the placenta of preterm infants. Association of decreased or increased rates of inflammasome activities with certain diseases such as BPD, hsPDA and surgical-NEC indicates the role of the intrauterin inflammatory process and the importance of critical balance in inflammation. Because of the complex pathophysiology of preterm morbidities, placental autophagy and inflammasome activities seem worthy of further investigation.