The Landscape of Resource Utilization After Resuscitation of 22-, 23-, and 24-Weeks' Gestation Infants.

OBJECTIVE: To compare estimated healthcare resources needed to care for 22 through 24 weeks' gestation infants. STUDY DESIGN: This multicenter, retrospective cohort study included 1505 live in-born and out-born infants 22 through 24 weeks' gestational age at delivery from 6 pediatric tertiary care hospitals from 2011 through 2020. Median neonatal intensive care unit (NICU) length of stay (LOS) for each gestational age was used as a proxy for hospital resource utilization, and the number of comorbidities and medical technology use for each infant were used as estimates of future medical care needs. Data were analyzed using Kruskal-Wallis with Nemenyi's posthoc test and Fisher's exact test. RESULTS: Of the identified newborns, 22-week infants had shorter median LOS than their 23- and 24-week counterparts due to low survival rates. There was no significant difference in LOS for surviving 22-week infants compared with surviving 23-week infants. Surviving 22-week infants had similar proportions of comorbidities and medical technology use as 23-week infants. CONCLUSIONS: Compared with 23- and 24-week infants, 22-week infants did not use a disproportionate amount of hospital resources. Twenty-two-week infants should not be excluded from resuscitation based on concern for increased hospital care and medical technology requirements. As overall resuscitation efforts and survival rates increase for 22-week infants, future research will be needed to assess the evolution of these results.

Ethical Cultures in Perinatal Care: Do They Exist? Correlation of Provider Attitudes with Periviability Practices at Six Centers.

OBJECTIVE: This study aimed to compare attitudes of providers regarding perinatal management and outcomes for periviable newborns of caregivers at centers with higher resuscitation (HR) and lower resuscitation (LR) rates in the delivery room. STUDY DESIGN: All obstetric and neonatal clinical providers at six U.S. sites were invited to complete an anonymous online survey. Survey responses were compared with clinical data collected from a previous retrospective study comparing centers' rates of planned resuscitation. Responses were analyzed by multivariable logistic and linear regression to assess how HR versus LR center respondents differed in management preferences and outcome predictions. RESULTS: Paradoxically, HR versus LR respondents, when adjusting for other variables, were less likely to respond that interventions such as antenatal steroids (odds ratio: 0.61, 95% confidence interval [CI]: 0.42-0.88, p < 0.009) and resuscitation (OR: 0.59, 95% CI: 0.44-0.78, p < 0.001) should be given at 22 weeks. HR versus LR respondents also reported lower likelihood of survival and acceptable quality of life (OR: 0.7, 95% CI: 0.53-0.93, p = 0.012) at 23 weeks. CONCLUSION: Despite higher rates of planned resuscitation at 22 and 23 weeks, steroid usage and survival rates did not differ between HR and LR sites. In this subsequent survey, respondents from HR centers had a less favorable outlook on interventions for these newborns than those at LR centers, suggesting that instead of driving practices, attitudes may be more closely associated with experiences of clinical outcomes.

Antenatal Periviability Counseling and Decision Making: A Retrospective Examination by the Investigating Neonatal Decisions for Extremely Early Deliveries Study Group.

OBJECTIVE: To describe periviability counseling practices and decision making. STUDY DESIGN: This is a retrospective review of mothers and newborns delivering between 22 and 24 completed weeks from 2011 to 2015 at six U.S. centers. Maternal and fetal/neonatal clinical and maternal sociodemographic data from medical records and geocoded sociodemographic information were collected. Separate analyses examined characteristics surrounding receiving neonatology consultation; planning neonatal resuscitation; and centers' planned resuscitation rates. RESULTS: Neonatology consultations were documented for 40, 63, and 72% of 498 mothers delivering at 22, 23, and 24 weeks, respectively. Consult versus no-consult mothers had longer median admission-to-delivery intervals (58.7 vs. 8.7 h, p < 0.001). Consultations were seen more frequently when parental decision making was evident. In total, 76% of mothers had neonatal resuscitation planned. Resuscitation versus no-resuscitation newborns had higher mean gestational ages (24.0 vs. 22.9 weeks, p < 0.001) and birthweights (618 vs. 469 g, p < 0.001). Planned resuscitation rates differed at higher (HR) versus lower (LR) rate centers at 22 (43 vs. 7%, p < 0.001) and 23 (85 vs. 58%, p < 0.001) weeks. HR versus LR centers' populations had more socioeconomic hardship markers but fewer social work consultations (odds ratio: 0.31; confidence interval: 0.15-0.59, p < 0.001). CONCLUSION: Areas requiring improvement included delivery/content of neonatology consultations, social work support, consideration of centers' patient populations, and opportunities for shared decisions.

Improving Staff Knowledge and Attitudes Toward Providing Psychosocial Support to NICU Parents Through an Online Education Course.

BACKGROUND: Provider-parent communication is a critical determinant of how neonatal intensive care unit (NICU) parents cope, yet staff feel inadequately trained in communication techniques; many parents are not satisfied with the support they receive from hospital providers. PURPOSE: This study evaluated whether NICU staff would demonstrate improved knowledge and attitudes about providing psychosocial support to parents after taking an online course. METHODS: After providing demographic information, staff at 2 NICUs took a 33-item survey both before and after taking a 7-module online course "Caring for Babies and Their Families," and again at 6-month follow-up. Scores (means ± standard deviation) from all time periods were compared and effect sizes calculated for each of the course modules. RESULTS: NICU staff participants (n = 114) included nurses (88%), social workers (7%), physicians (4%), and occupational therapists (1%). NICU staff showed significant improvement in both knowledge and attitudes in all modules after taking the course, and improvements in all module subscores remained significant at the 6-month follow-up mark. Night staff and staff with less experience had lower pretest scores on several items, which improved on posttest. IMPLICATIONS FOR PRACTICE: This course, developed by an interprofessional group that included graduate NICU parents, was highly effective in improving staff knowledge and attitudes regarding the provision of psychosocial support to NICU parents, and in eliminating differences related to shift worked and duration of work experience in the NICU. IMPLICATIONS FOR RESEARCH: Future research should evaluate course efficacy across NICU disciplines beyond nursing, impact on staff performance, and whether parent satisfaction with care is improved.

Neonatal nurse practitioner ethics knowledge and attitudes.

BACKGROUND: Neonatal nurse practitioners have become the frontline staff exposed to a myriad of ethical issues that arise in the day-to-day environment of the neonatal intensive care unit. However, ethics competency at the time of graduation and after years of practice has not been described. RESEARCH AIM: To examine the ethics knowledge base of neonatal nurse practitioners as this knowledge relates to decision making in the neonatal intensive care unit and to determine whether this knowledge is reflected in attitudes toward ethical dilemmas in the neonatal intensive care unit. RESEARCH DESIGN: This was a prospective cohort study that examined decision making at the threshold of viability, life-sustaining therapies for sick neonates, and a ranking of the five most impactful ethical issues. PARTICIPANTS AND RESEARCH CONTEXT: All 47 neonatal nurse practitioners who had an active license in the State of Mississippi were contacted via e-mail. Surveys were completed online using Survey Monkey software. ETHICAL CONSIDERATIONS: The study was approved by the University of Mississippi Medical Center Institutional Review Board (IRB; #2015-0189). FINDINGS: Of the neonatal nurse practitioners who completed the survey, 87.5% stated that their religious practices affected their ethical decision making and 76% felt that decisions regarding life-sustaining treatment for a neonate should not involve consultation with the hospital's legal team or risk management. Only 11% indicated that the consent process involved patient understanding of possible procedures. Participating in the continuation or escalation of care for infants at the threshold of viability was the top ethical issue encountered by neonatal nurse practitioners. DISCUSSION: Our findings reflect deficiencies in the neonatal nurse practitioner knowledge base concerning ethical decision making, informed consent/permission, and the continuation/escalation of care. CONCLUSION: In addition to continuing education highlighting ethics concepts, exploring the influence of religion in making decisions and knowing the most prominent dilemmas faced by neonatal nurse practitioners in the neonatal intensive care unit may lead to insights into potential solutions.

Variability of Care Practices for Extremely Early Deliveries.

OBJECTIVES: Assess temporal changes, intercenter variability, and birthing person (BP) factors relating to interventions for extremely early deliveries. METHODS: Retrospective study of BPs and newborns delivered from 22-24 completed weeks at 13 US centers from 2011-2020. Rates of neonatology consultation, antenatal corticosteroids, cesarean delivery, live birth, attempted resuscitation (AR), and survival were assessed by epoch, center, and gestational age. RESULTS: 2028 BPs delivering 2327 newborns were included. Rates increased in epoch 2-at 22 weeks: neonatology consultation (37.6 vs 64.3%, P < .001), corticosteroids (11.4 vs 29.5%, P < .001), live birth (66.2 vs 78.6%, P < .001), AR (20.1 vs 36.9%, P < .001), overall survival (3.0 vs 8.9%, P = .005); and at 23 weeks: neonatology consultation (73.0 vs 80.5%, P = .02), corticosteroids (63.7 vs 83.7%, P < .001), cesarean delivery (28.0 vs 44.7%, P < .001), live birth (88.1 vs 95.1%, P < .001), AR (67.7 vs 85.2%, P < .001), survival (28.8 vs 41.6%, P < .001). Over time, intercenter variability increased at 22 weeks for corticosteroids (interquartile range 18.0 vs 42.0, P = .014) and decreased at 23 for neonatology consultation (interquartile range 23.0 vs 5.2, P = .045). In BP-level multivariate analysis, AR was associated with increasing gestational age and birth weight, Black BP race, previous premature delivery, and delivery center. CONCLUSIONS: Intervention rates for extremely early newborns increased and intercenter variability changed over time. In BP-level analysis, factors significantly associated with AR included Black BP race, previous premature delivery, and center.

Dexamethasone induces apoptosis of progenitor cells in the subventricular zone and dentate gyrus of developing rat brain.

The use of dexamethasone in premature infants to prevent and/or treat bronchopulmonary dysplasia adversely affects neurocognitive development and is associated with cerebral palsy. The underlying mechanisms of these effects are multifactorial and likely include apoptosis. The objective of this study was to confirm whether dexamethasone causes apoptosis in different regions of the developing rat brain. On postnatal day 2, pups in each litter were randomly divided into the dexamethasone-treated (n = 91) or vehicle-treated (n = 92) groups. Rat pups in the dexamethasone group received tapering doses of dexamethasone on postnatal days 3-6 (0.5, 0.25, 0.125, and 0.06 mg/kg/day, respectively). Dexamethasone treatment significantly decreased the gain of body and brain weight and increased brain caspase-3 activity, DNA fragments, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and cleaved caspse-3-positive cells at 24 hr after treatment. Dexamethasone increased cleaved caspse-3-positive cells in the cortex, thalamus, hippocampus, cerebellum, dentate gyrus, and subventricular zone. Double-immunofluorescence studies show that progenitor cells in the subventricular zone and dentate gyrus preferentially undergo apoptosis following dexamethasone exposure. These results indicate that dexamethasone-induced apoptosis in immature cells in developing brain is one of the mechanisms of its neurodegenerative effects in newborn rats.

Dexamethasone decreases insulin-like growth factor-I and -II via a glucocorticoid receptor dependent mechanism in developing rat brain.

OBJECTIVES: Dexamethasone (Dex) causes neurodegeneration in developing brain. Insulin-like growth factor-I (IGF-I) and -II (IGF-II) are potent neurotrophic and differentiation factors and play key roles in the regulation of growth and development of CNS. Current project evaluated the effects of Dex on IGF-I and -II in developing rat brains. MATERIAL AND METHODS: Sprague-Dawley rat pups in each litter were divided into vehicle (n=230) or Dex-treated (n=234) groups. Rat pups in the Dex group received one of the 3 different regimens of i.p. Dex: tapering doses (DexTD) on postnatal days (PD) 3 to PD 6 or repeated doses on PD 4 to PD 6 or single dose on PD 6. To quantify the glucocorticoid receptor (GR) blockade effect, rat pups in the DexTD group on PD 3 and 5 received vehicle or RU486 (GR blocker, 60 mg/kg) s.c., twenty minutes prior to Dex treatment. RESULTS: Dex decreased the gain of body and brain weight while RU486 inhibited these effects. RU486 also prevented the DexTD-induced increase in caspase-3 activity and reduction in IGF-I and -II proteins. Compared to the vehicle, the expression of mRNA of IGF-I and -II decreased at 24 h after DexTD treatment, while RU486 prevented this decrease on IGF-II but not IGF-I. CONCLUSIONS: Our findings indicate that Dex via GR decreases IGF-I and -II and causes neurodegeneration in the neonatal rat brain.

Intention to treat: obstetrical management at the threshold of viability.

BACKGROUND: Despite medical advances in the care of extremely preterm neonates and growing acceptance of resuscitation at 23 and even 22 weeks gestation, controversy remains concerning the use of antepartum obstetric intervention s that are intended to improve outcomes in the setting of anticipated extremely preterm birth. In the absence of demonstrated benefit at <23 weeks gestation and with uncertain benefit at 23 weeks gestation, previous obstetric committee opinions have advised against their use at these gestational ages. OBJECTIVE: The purpose of this study was to review the use of obstetric intervention s at the threshold of viability based on neonatal resuscitation plan and to review the odds of survival to neonatal intensive care unit discharge based on use of obstetric intervention s with adjustment for neonatal factors. STUDY DESIGN: This retrospective study of 6 study centers reviewed pregnant patients who were admitted between 22+0/7 and 24+6/7 weeks gestation facing delivery from 2011-2015. Patients with known anomalies or missing data were excluded. Records were reviewed for demographics, resuscitation plan, and obstetric intervention s. Mode of delivery, delivery room care, and final infant dispositions were recorded. Multiple gestations were included as 1 pregnancy in regard to the use of obstetric intervention s and were excluded from survival analysis. RESULTS: Four hundred seventy-eight mothers met the inclusion criteria. When resuscitation was planned, mothers were more likely to receive all conventional obstetric intervention s (antenatal steroids, magnesium sulfate for neuroprotection, tocolytics, and Group Beta Streptococcus prophylaxis), regardless of gestational age at admission, and were more likely to be delivered by cesarean section (P<.05). Analyzed as a group, when antenatal steroids, magnesium sulfate, tocolytics and Group Beta Streptococcus prophylaxis were administered, the odds of survival to neonatal intensive care unit discharge increased for newborn infants who were born at 22 (odds ratio, 11.33; 95% confidence interval, 1.405-91.4) and 23 weeks gestation (odds ratio, 15.5; 95% confidence interval, 3.747-64.11; P<.05). In singletons, the odds of survival to neonatal intensive care unit discharge was not improved by cesarean delivery vs vaginal delivery, even after adjustment for the use of additional interventions, weight, gender, and gestational age (odds ratio, 1.0; 95% confidence interval, 0.59-1.8; P=.912). CONCLUSION: In this study, when postnatal resuscitation was planned at 22 and 23 weeks gestation, women were more likely to receive antenatal steroids, magnesium sulfate, and antibiotics; provision of this bundle imparted survival benefit at 23 weeks gestation but could not be demonstrated at 22 weeks gestation because of the small sample size. These findings support of neonate-oriented obstetric interventions in the setting of delivery at 23 weeks gestation when resuscitation is planned and further exploration of optimal obstetric care when resuscitation of infants who were born at 22 weeks gestation is anticipated.

Aerosolized Calfactant for Newborns With Respiratory Distress: A Randomized Trial.

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

Surfactant protein-A limits Ureaplasma-mediated lung inflammation in a murine pneumonia model.

Ureaplasma respiratory tract colonization stimulates prolonged, dysregulated inflammation in the lungs of preterm infants, contributing to bronchopulmonary dysplasia (BPD) pathogenesis. Surfactant protein-A (SP-A), a lung collectin critical for bacterial clearance and regulating inflammation, is deficient in the preterm lung. To analyze the role of SP-A in modulating Ureaplasma-mediated lung inflammation, SP-A deficient (SP-A-/-) and WT mice were inoculated intratracheally with a mouse-adapted U. parvum isolate and indices of inflammation were sequentially assessed up to 28 d postinoculation. Compared with infected WT and noninfected controls, Ureaplasma-infected SP-A-/- mice exhibited an exaggerated inflammatory response evidenced by rapid influx of neutrophils and macrophages into the lung, and higher bronchoalveolar lavage TNF-alpha, mouse analogue of human growth-related protein alpha (KC), and monocyte chemotactic factor (MCP-1) concentrations. However, nitrite generation in response to Ureaplasma infection was blunted at 24 h and Ureaplasma clearance was delayed in SP-A-/- mice compared with WT mice. Coadministration of human SP-A with the Ureaplasma inoculum to SP-A-/- mice reduced the inflammatory response, but did not improve the bacterial clearance rate. SP-A deficiency may contribute to the prolonged inflammatory response in the Ureaplasma-infected preterm lung, but other factors may contribute to the impaired Ureaplasma clearance.

Surfactant protein-A enhances ureaplasmacidal activity in vitro.

BACKGROUND: Persistent respiratory tract colonization with Ureaplasma spp. in preterm infants is a significant risk factor for the development of the chronic lung disorder, bronchopulmonary dysplasia (BPD). Surfactant protein-A (SP-A), a lung collectin critical for bacterial clearance and regulating inflammation, is deficient in the preterm lung. In an experimental Ureaplasma-pneumonia model, infected SP-A deficient mice exhibited delayed bacterial clearance and an exaggerated inflammatory response compared to infected wild-type mice. The objective was to analyze the role of SP-A in Ureaplasma clearance in vitro. SUBJECTS AND METHODS: We analyzed SP-A binding to Ureaplasma isolates and SP-A-mediated ureaplasmal phagocytosis and killing by cultured RAW 264.7 macrophages. RESULTS: Calcium-dependent SP-A binding was similar among Ureaplasma isolates tested. Pre-incubation of RAW 264.7 cells with SP-A (10-50 µg/ml) enhanced phagocytosis of fluorescein-isothiocyanate (FITC)-labeled Ureaplasma. Surfactant protein-A also increased ureaplasmacidal activity of RAW 264.7 cells by 2.1-fold over 4 h. Pre-incubation of RAW 264.7 cells with 10 µg/ml SP-A reduced lipopolysaccharide (LPS) (100 ng/ml) and Ureaplasma (10(6) color changing units/ml)-stimulated release of tumor necrosis factor-α (TNF-α) by 46% and 43%, respectively, but did not affect transforming growth factor ß(1) (TGFß(1)) release. CONCLUSIONS: These in vitro data confirm that SP-A is important in host defense to perinatally-acquired Ureaplasma infection.