Enhanced Vasoconstriction Mediated by α1-Adrenergic Mechanisms in Small Femoral Arteries in Newborn Llama and Sheep Gestated at Low and High Altitudes

The authors previously demonstrated that newborn llama (NBLL) express high levels of α1 adrenergic receptors, which provide a potent vasoconstriction response when compared with newborn sheep (NBSH) gestated at sea level. However, data regarding the impact of chronic gestational hypobaric hypoxia on α-adrenergic vasoconstriction in the neonatal life has not been studied. We evaluated if gestation under chronic hypobaric hypoxia modifies α1-adrenergic vasoconstrictor function in NBLL and NBSH. We compared the vasoconstrictor response induced by potassium and α-adrenergic stimuli in isolated small femoral arteries of NBLL and NBSH gestated at high altitude (HA; 3,600 m) or low altitude (LA; 580 m). The maximal contraction (RMAX) and potency (EC50) to potassium, noradrenaline (NA), and phenylephrine (PHE) were larger in HA-NBLL than LA-NBLL. RMAX to potassium, NA, and PHE were lower in HA-NBSH when compared with LA-NBSH and potency results were similar. Competitive blockade with prazosin showed that RNLL LA/HA have a similar pA2. In contrast, NBSH had increased pA2 values in HA when compared with LA. Finally, small femoral arteries denudated or treated with LNAME in LA and HA lacked NO or endothelium participation in response to PHE stimulation. In contrast, NBSH displayed that denudation or blockade with LNAME support NO or endothelium participation in response to PHE activation. In conclusion, HA chronic hypoxia enhances α1 adrenergic receptor activity in small femoral arteries in NBLL to a higher degree than NBSH, implying a higher vasoconstriction function.

Severe thrombocytopenia is sufficient for fetal and neonatal intra-cerebral hemorrhage to occur

Intra-cerebral hemorrhage (ICH) has a devastating impact on the neonatal population. Whether thrombocytopenia is sufficient to cause ICH in neonates is debated. In this study we have comprehensively investigated the consequences of severe thrombocytopenia on the integrity of the cerebral vasculature using two orthogonal approaches: genetically, by studying embryogenesis in the Nfe2-/- mouse line; and using biologics (anti-GP1Ba antibodies) to induce severe thrombocytopenia at defined times during development. Using a mouse model, we present data herein that not only demonstrate that platelets are required throughout fetal development and into neonatal life to maintain the integrity of the cerebral vasculature to prevent hemorrhage, but also that the location of cerebral hemorrhage is dependent on the timing during development when thrombocytopenia occurs. Importantly, this study demonstrates that thrombocytopenia-associated fetal/neonatal ICH occurs within regions of the brain which, in humans, could lead to neurological damage.

Prematurity alters the progenitor cell program of the upper respiratory tract of neonates

The impact of prematurity on human development and neonatal diseases, such as bronchopulmonary dysplasia, has been widely reported. However, little is known about the effects of prematurity on the programs of stem cell self-renewal and differentiation of the upper respiratory epithelium, which is key for adaptation to neonatal life. We developed a minimally invasive methodology for isolation of neonatal basal cells from nasopharyngeal (NP) aspirates and performed functional analysis in organotypic cultures to address this issue. We show that preterm NP progenitors have a markedly distinct molecular signature of abnormal proliferation and mitochondria quality control compared to term progenitors. Preterm progenitors had lower oxygen consumption at baseline and were unable to ramp up consumption to the levels of term cells when challenged. Although they formed a mucociliary epithelium, ciliary function tended to decline in premature cells as they differentiated, compared to term cells. Together, these differences suggested increased sensitivity of preterm progenitors to environmental stressors under non-homeostatic conditions.

Improvement in knowledge of healthcare professionals attending Neonatal Life Support(NeoLiS) training workshop

Objective:Pakistan ranks among the countries with highest neonatal mortality rate. Birth related event (Asphyxia neonatorum) is one of the three most common causes of neonatal mortality worldwide. Effective resuscitation during the Golden Minute can improve the mortality and morbidity. In Pakistan, a training programme NeoLiS (Neonatal Life Support) was developed in 2008 which was based on guidelines of ILCOR. The objective of this study was to assess the improvement in knowledge of healthcare professionals attending Neonatal Life Support training workshop. Methods:It was a retrospective cross sectional study that was conducted in the Neonatology Department of the Children’s Hospital, Lahore. A total of 52 workshops were conducted in 2017-18 in which 1350 health professionals were participated including doctors, nurses and paramedics. Data of all the training workshops were analysed in the study. Knowledge was tested through true/false questionnaires. The results of pre-course test were compared with respective post-course test by entering the data in SPSS and significance in improvement of knowledge was calculated by applying paired t-test. p-value <0.05 was considered significant. Results: Mean of pre-course and post-course results of all the participants were calculated and post-course results showed significant improvement in knowledge as compared to pre-course tests. Similarly, paired t-test was performed for all the results of doctors,nurses and paramedics on individual basis. The p-value in all groups was < 0.01 which was statistically significant. Conclusion: Neonatal Life Support (NeoLiS) training course resulted in significant gain in knowledge about neonatal resuscitation by healthcare professionals when assessed Continuous...

Fluid Status Changes During the Transition in Infants of Diabetic Mothers.

BackgroundIn animal and human neonates, expansion of the extracellular fluid volume is associated with “wet” lung and poor respiratory outcomes.MethodsTo define fluid status changes during the transition from fetal to neonatal life in infants of diabetic mothers (IDM), we conducted a single centre (Policlinico Abano Terme, Abano Terme, Italy) study of 66 IDM and a 1:2 matched control group from January 1 to September 30, 2020. Fluid status changes were assessed by computing Δ Hct from umbilical cord blood at birth and capillary heel Hct at 48h, accounting for body weight decrease.ResultsIDM presented with significantly lower cord blood Hct levels in comparison to controls (47.33±4.52 vs 50.03±3.51%, p<0.001), mainly if delivered by elective cesarean section (45.01±3.77 vs 48.43±3.50%, p=0.001). Hct levels at 48h were comparable (55.18±5.42 vs 54.62±7.41%, p=0.703), concurrently with similar body weight decrease (-217.21±113.34 vs-217.51±67.28 g, p=0.614). This supports significantly higher ∆ Hct in IDM (5.13±5.24 vs 7.29±6.48, p<0.01) and extra circulating fluid loss of 2-3%.ConclusionGestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung.