Effect of uterine fundal pressure applied in the second stage of labor on birth outcomes and neonatal oxygen saturation.

AIM: To examine the effect of fundal pressure applied in the second stage of labor on birth outcomes and neonatal O2 saturation. METHODS: The study is of a descriptive and comparative type. Research data were collected in the obstetrics clinic of a Maternity Hospital between August 15, 2019 and February 15, 2020. The study sample consisted of 160 pregnant women who met the research criteria (80 pregnant women who received fundal pressure, 80 pregnant women who did not receive fundal pressure). RESULTS: The duration of the second and third stages of labor was found to be shorter in the nonfundal pressure group (t = -3.422, p = 0.001; t = 2.195, p = 0.030). When the groups were compared, the formation of perineal trauma and second-degree laceration, episiotomy requirement, elongation of the episiotomy incision and cervical laceration rate were found to be significantly higher in the fundal pressure group χ2  = 10.794 p = 0.001; χ2  = 8.403 p = 0.004; χ2  = 10.014, p = 0.002; χ2  = 16.579 p = 0.000; χ2  = 16.276 p = 0.000). The 1st and 5th min Apgar scores of the newborns were lower in the fundal pressure group (t = -6.377, p = 0.000; t = -3.581, p = 0.001). The 1st, 5th, 10th, and 15th min oxygen saturation of the newborns were determined to be significantly lower in the fundal pressure group (t = -4.753, p = 0.000; t = -2.427, p = 0.016; t = -2.604, p = 0.010; t = -2.492, p = 0.014). CONCLUSION: According to the study results, it was determined that the uterine fundal pressure has a negative effect on birth outcomes and neonatal oxygen saturation. Adverse effects of fundal pressure application should be revealed in different aspects.

The effect of delayed umbilical cord clamping on Newborn's oxygen saturation and sucking success in primiparous pregnant.

AIM: The objective of this study was to examine the effect of delayed umbilical cord clamping on the newborn's oxygen saturation and sucking success in primiparas. METHODS: The study was conducted based on the experimental model with a control group, between March 15-November 10, 2020. The sample of the study consisted of 101 primiparous pregnant (48 primiparous with delayed cord clamping within 1-3 min and 53 primiparous with early cord clamping within 1 min) (having no high-risk pregnancy, 38-42 weeks, vaginal birth) in Turkey. The data were collected using a personal information form, the LATCH breastfeeding tool and the pulse oximetry. Statistical analyses were conducted using percentage distribution, arithmetic means, chi-square testing, and independent samples t-testing. RESULTS: Oxygen saturation values of newborns with delayed umbilical cord clamping were higher than those of newborns with early cord clamping. The saturation was first minute 66.43 versus 74.37, fifth minute 81.90 versus 88.60, tenth minute 91.77 versus 94.50 (p < 0.05). When compared to the group with early cord clamping, oxygen saturation is higher in the first by 11.95%, in the fifth by 8.18%, and in the tenth minute by 2.97% in the group with delayed cord clamping. The LATCH breastfeeding scores were found to be higher in the group with delayed cord clamping compared to the group with early cord clamping. CONCLUSION: It was determined that delayed cord clamping positively affected oxygen saturation values and sucking success in neonatal babies. Delayed umbilical cord clamping is an important issue that needs to be addressed in its different dimensions.

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. METHODS: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. DISCUSSION: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. TRIAL REGISTRATION: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.

Alternative Progenitor Lineages Regenerate the Adult Lung Depleted of Alveolar Epithelial Type 2 Cells.

An aberrant oxygen environment at birth increases the severity of respiratory viral infections later in life through poorly understood mechanisms. Here, we show that alveolar epithelial cell (AEC) 2 cells (AEC2s), progenitors for AEC1 cells, are depleted in adult mice exposed to neonatal hypoxia or hyperoxia. Airway cells expressing surfactant protein (SP)-C and ATP binding cassette subfamily A member 3, alveolar pod cells expressing keratin (KRT) 5, and pulmonary fibrosis were observed when these mice were infected with a sublethal dose of HKx31, H3N2 influenza A virus. This was not seen in infected siblings birthed into room air. Genetic lineage tracing studies in mice exposed to neonatal hypoxia or hyperoxia revealed pre-existing secretoglobin 1a1+ cells produced airway cells expressing SP-C and ATP binding cassette subfamily A member 3. Pre-existing Kr5+ progenitor cells produced squamous alveolar cells expressing receptor for advanced glycation endproducts, aquaporin 5, and T1α in alveoli devoid of AEC2s. They were not the source of KRT5+ alveolar pod cells. These oxygen-dependent changes in epithelial cell regeneration and fibrosis could be recapitulated by conditionally depleting AEC2s in mice using diphtheria A toxin and then infecting with influenza A virus. Likewise, airway cells expressing SP-C and alveolar cells expressing KRT5 were observed in human idiopathic pulmonary fibrosis. These findings suggest that alternative progenitor lineages are mobilized to regenerate the alveolar epithelium when AEC2s are severely injured or depleted by previous insults, such as an adverse oxygen environment at birth. Because these lineages regenerate AECs in spatially distinct compartments of a lung undergoing fibrosis, they may not be sufficient to prevent disease.

Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus.

Infants born prematurely often require supplemental oxygen, which contributes to aberrant lung development and increased pulmonary morbidity following a respiratory viral infection. We have been using a mouse model to understand how early-life hyperoxia affects the adult lung response to influenza A virus (IAV) infection. Prior studies showed how neonatal hyperoxia (100% oxygen) increased sensitivity of adult mice to infection with IAV [IAV (A/Hong Kong/X31) H3N2] as defined by persistent inflammation, pulmonary fibrosis, and mortality. Since neonatal hyperoxia alters lung structure, we used a novel fluorescence-expressing reporter strain of H1N1 IAV [A/Puerto Rico/8/34 mCherry (PR8-mCherry)] to evaluate whether it also altered early infection of the respiratory epithelium. Like Hong Kong/X31, neonatal hyperoxia increased morbidity and mortality of adult mice infected with PR8-mCherry. Whole lung imaging and histology suggested a modest increase in mCherry expression in adult mice exposed to neonatal hyperoxia compared with room air-exposed animals. However, this did not reflect an increase in airway or alveolar epithelial infection when mCherry-positive cells were identified and quantified by flow cytometry. Instead, a modest increase in the number of CD45-positive macrophages expressing mCherry was detected. While neonatal hyperoxia does not alter early epithelial infection with IAV, it may increase the activity of macrophages toward infected cells, thereby enhancing early epithelial injury.

Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups. DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Evaluating enhanced pulse oximetry auditory displays for neonatal oxygen targeting: A randomized laboratory trial with clinicians and non-clinicians.

Standard pulse oximeter auditory tones do not clearly indicate departures from the target range of oxygen saturation (SpO2) of 90%-95% in preterm neonates. We tested whether acoustically enhanced tones would improve participants' ability to identify SpO2 range. Twenty-one clinicians and 23 non-clinicians used (1) standard pulse oximetry variable-pitch tones plus alarms; (2) beacon-enhanced tones without alarms in which reference tones were inserted before standard pulse tones when SpO2 was outside target range; and (3) tremolo-enhanced tones without alarms in which pulse tones were modified with tremolo when SpO2 was outside target range. For clinicians, range identification accuracies (mean (SD)) in the standard, beacon, and tremolo conditions were 52% (16%), 73% (14%) and 76% (13%) respectively, and for non-clinicians 49% (16%), 76% (13%) and 72% (14%) respectively, with enhanced conditions always significantly more accurate than standard. Acoustic enhancements to pulse oximetry clearly indicate departures from preterm neonates' target SpO2 range.

Reducing the time delay of oxygen transport to the neonate on continuous positive airway pressure support: A bench study.

Background: Premature newborns often require oxygen support as part of their therapy. Systems for oxygen administration are developed to assure adequate oxygenation of newborns. Several factors were identified in the systems that contribute to the time delay between the change in the set inspiratory oxygen fraction and its actual delivery to tissues. In this study, we aimed to reduce the physical delay in oxygen delivery to newborns. Methods: We developed an O2 Flush System (O2-FS) that brings the source of oxygen as close to a patient as possible to make oxygen available for rapid delivery that compensates for the physical delay in the ventilator circuit. The O2-FS system is built around an electromechanical on/off valve. We validated the O2-FS concept in experiments with non-invasive Continuous Positive Airways Pressure (CPAP) ventilators. Results: The O2-FS accelerated oxygen delivery with all the tested systems and arrangements, typically by 5-15 s. We also observed that the application of supplemental oxygen increased the pressure in the ventilator circuit by 3-4 cmH2O which may mitigate the apneic pauses that are common in premature newborns. Conclusions: The O2-FS system may work as a universal accessory of the CPAP lung ventilator and shorten the distribution of oxygen to the patient during oxygen desaturation events, possibly eliminating or interrupting apneic pauses in neonates, for whom oxygen therapy is an essential treatment. In clinical practice, the O2-FS could help maintain normoxemic saturation values through adequate oxygen dosing in preterm neonates, thus reducing morbidity and mortality.

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age.

Neonatal anoxia induces long-term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30-hour old pups to 100% nitrogen, represents a non-invasive and global stimulus, which simulates clinical conditions of human pre-term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety-like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious-like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia-induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyrus and CA1 subfields, but not in CA3-2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3-2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury.

Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-ß/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions.