Use of Initial Endotracheal Versus Intravenous Epinephrine During Neonatal Cardiopulmonary Resuscitation in the Delivery Room: Review of a National Database.

OBJECTIVE: To assess whether initial epinephrine administration by endotracheal tube (ET) in newly born infants receiving chest compressions and epinephrine in the delivery room (DR) is associated with lower rates of return of spontaneous circulation (ROSC) than newborns receiving initial intravenous (IV) epinephrine. STUDY DESIGN: We conducted a retrospective review of neonates receiving chest compressions and epinephrine in the DR from the AHA Get With The Guidelines-Resuscitation registry from October 2013 through July 2020. Neonates were classified according to initial route of epinephrine (ET vs IV). The primary outcome of interest was ROSC in the DR. RESULTS: In total, 408 infants met inclusion criteria; of these, 281 (68.9%) received initial ET epinephrine and 127 (31.1%) received initial IV epinephrine. The initial ET epinephrine group included those infants who also received subsequent IV epinephrine when ET epinephrine failed to achieve ROSC. Comparing initial ET with initial IV epinephrine, ROSC was achieved in 70.1% vs 58.3% (adjusted risk difference 10.02; 95% CI 0.05-19.99). ROSC was achieved in 58.3% with IV epinephrine alone, and 47.0% with ET epinephrine alone, with 40.0% receiving subsequent IV epinephrine. CONCLUSIONS: This study suggests that initial use of ET epinephrine is reasonable during DR resuscitation, as there were greater rates of ROSC compared with initial IV epinephrine administration. However, administration of IV epinephrine should not be delayed in those infants not responding to initial ET epinephrine, as almost one-half of infants who received initial ET epinephrine subsequently received IV epinephrine before achieving ROSC.

Risk Factors for Admission Hyperthermia and Associated Outcomes in Infants Born Preterm.

Maternal, placental, and neonatal factors were compared between infants born at ≤29 weeks of gestational age with admission hyperthermia (>37.5○C) and euthermia (36.5-37.5○C). Admission hyperthermia was associated with longer duration of face-mask positive-pressure ventilation and infant's temperature ≥37.5○C in the delivery room. Infants born preterm with admission hyperthermia had greater odds of developing necrotizing enterocolitis and neurodevelopmental impairment.

Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Tactile Stimulation in Newborn Infants With Inadequate Respiration at Birth: A Systematic Review.

CONTEXT: For many years the International Liaison Committee on Resuscitation has recommended the use of tactile stimulation for initial management of infants born with inadequate respiratory effort at birth without systematically examining its effectiveness. OBJECTIVE: Systematic review to compare the effectiveness of tactile stimulation with routine handling in newly born term and preterm infants. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, along with clinical trial registries. STUDY SELECTION: Randomized and non-randomized studies were included based on predetermined criteria. DATA EXTRACTION: Data were extracted independently by authors. Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) was used to assess risk of bias in non-randomized studies. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. RESULTS: Among 2455 unique articles identified, 2 observational studies were eligible and qualitatively summarized. Because one of the studies was at critical risk of bias, only the other study including 243 preterm infants on continuous positive airway pressure with clinical indications for tactile stimulation was analyzed. It showed a reduction in tracheal intubation in infants receiving tactile stimulation compared with no tactile stimulation (12 of 164 vs 14 of 79, risk ratio of 0.41 [95% confidence interval 0.20 to 0.85]); however, the certainty of evidence was very low. LIMITATIONS: The available data were limited and only from observational studies. CONCLUSIONS: A potential benefit of tactile stimulation was identified but was limited by the very low certainty of evidence. More research is suggested to evaluate the effectiveness as well as the optimal type and duration of tactile stimulation.

Surgery-Associated Infections among Infants Born Extremely Preterm.

OBJECTIVE: To assess the burden of invasive infection following surgery (surgery-associated infections [SAI]) among infants born extremely premature. STUDY DESIGN: This was an observational, prospective study of infants born at gestational age 22-28 weeks hospitalized for >3 days, between April 1, 2011, to March 31, 2015, in academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. SAI was defined by culture-confirmed bacteremia, fungemia, or meningitis ≤14 days following a surgical procedure. RESULTS: Of 6573 infants, 1154 (18%) who underwent surgery were of lower gestational age (mean [SD]: 25.5 [1.6] vs 26.2 [1.6], P < .001), lower birth weight (803 [220] vs 886 [244], P < .001), and more likely to have a major birth defect (10% vs 3%, P < .001); 64% had 1 surgery (range 1-10 per infant). Most underwent gastrointestinal procedures (873, 76%) followed by central nervous system procedures (150, 13%). Eighty-five (7%) infants had 90 SAIs (78 bacteremia, 5 fungemia, 1 bacteremia and meningitis, 6 meningitis alone). Coagulase-negative staphylococci were isolated in 36 (40%) SAI and were isolated with another organism in 5 episodes. Risk of SAI or death ≤14 days after surgery was greater after gastrointestinal compared with central nervous system procedures (16% vs 7%, adjusted relative risk [95% CI]: 1.95 [1.15-3.29], P = .01). Death ≤14 days after surgery occurred in 141 of the 1154 infants; 128 deaths occurred after gastrointestinal surgeries. CONCLUSIONS: Surgical procedures were associated with bacteremia, fungemia, or meningitis in 7% of infants. The epidemiology of invasive postoperative infections as described in this report may inform the selection of empiric antimicrobial therapy and postoperative preventive care.

Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants.

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation. STUDY DESIGN: Multicenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-246/7 and 25-286/7 weeks. RESULTS: Among 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups. CONCLUSIONS: This analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.

Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age.

OBJECTIVE: To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies. STUDY DESIGN: Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression. RESULTS: Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomalacia. Among the 433 infants with cystic periventricular leukomalacia, cystic periventricular leukomalacia disappeared in 76 (18%), persisted in 87 (20%), and 270 (62%) had late cystic periventricular leukomalacia. Loss to follow-up ranged between 3% and 13%. Death or NDI was more common in infants with disappeared cystic periventricular leukomalacia compared with those with no cystic periventricular leukomalacia (38 of 72 [53%] vs 1776 of 6376 [28%]; OR [95% CI] 2.8 [1.8-4.6]). Disappeared, persistent, and late cystic periventricular leukomalacia were all also independently associated with NDI (OR 1.17, 1.21, and 1.16, respectively). CONCLUSIONS: Infants with "disappeared" cystic periventricular leukomalacia are at increased risk of adverse outcome similar to infants with persistent or late cystic periventricular leukomalacia.

Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants.

OBJECTIVE: To evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT, <29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants. STUDY DESIGN: Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared. RESULTS: MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P < .01), including the percentage <36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and >37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures >37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality. CONCLUSIONS: Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.

Impact of the Neonatal Resuscitation Program-Recommended Low Oxygen Strategy on Outcomes of Infants Born Preterm.

OBJECTIVE: To evaluate the impact of the Neonatal Resuscitation Program (NRP)-recommended low oxygen strategy (LOX) on neonatal morbidities, mortality, and neurodevelopmental outcomes in neonates born preterm. STUDY DESIGN: In March 2011, Parkland Hospital changed from a high oxygen strategy (HOX) of resuscitation with initial 100% oxygen and targeting 85%-94% oxygen saturation for delivery room resuscitation to a LOX with initial 21% oxygen and titrating oxygen to meet NRP-recommended transitional target saturations. Neonates ≤28 weeks' gestational age born between August 2009 and April 2012 were identified. In this retrospective, observational study, neonates exposed to LOX vs HOX were compared for short-term morbidity, mortality, and long-term neurodevelopmental outcomes. Regression analysis was performed to control for confounding variables. RESULTS: Of 199 neonates, 110 were resuscitated with HOX and 89 with LOX. Compared with HOX, neonates exposed to LOX had lower oxygen exposure in the delivery room (5.2 ± 1.5 vs 7.8 ± 2.8 [∑FiO2 × time min], P < .01), spent fewer days on oxygen (30 [5, 54] vs 46 [11, 82], P = .01), and had lower odds of developing bronchopulmonary dysplasia (aOR 0.4 [0.2, 0.9]). There was no difference in mortality (17 [20%] vs 20 [18%]), but neonates exposed to LOX had greater motor composite scores on Bayley Scales of Infant and Toddler Development-Third edition assessment (91 [85, 97] vs 88 [76, 94], P < .01). CONCLUSION: The NRP-recommended LOX strategy was associated with improved respiratory morbidities and neurodevelopmental outcomes with no increase in mortality. Prospective trials to confirm the optimal oxygen strategy for the resuscitation of neonates born preterm are needed.

Efficacy of Intravenous and Endotracheal Epinephrine during Neonatal Cardiopulmonary Resuscitation in the Delivery Room.

A retrospective examination is presented of intravenous vs a lower (0.03?mg/kg) and higher (0.05?mg/kg) dose of endotracheal epinephrine during delivery room cardiopulmonary resuscitation. Repeated dosing of intravenous and endotracheal epinephrine is needed frequently for successful resuscitation. Research regarding optimal dosing for both routes is needed critically.

Perinatal asphyxia with hyperoxemia within the first hour of life is associated with moderate to severe hypoxic-ischemic encephalopathy.

OBJECTIVE: To determine whether early hyperoxemia in neonates with severe perinatal acidemia is associated with the development of hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We identified 120 infants at ≥ 36 weeks gestational age with perinatal acidosis born at Parkland Hospital who qualified for a screening neurologic exam for cooling therapy. Based on a PaO2 measurement during the first hour of life, the cohort was divided into infants with hyperoxemia (PaO2 >100 mmHg) and those without hyperoxemia (PaO2 ≤ 100 mmHg). The rate of moderate-severe encephalopathy was compared between the groups using χ(2) analysis, as well as multiple logistic regression, taking into account baseline characteristics and confounding variables. RESULTS: Thirty-six infants (30%) had an initial PaO2 >100 mmHg. Infants with and without hyperoxemia had similar baseline maternal and infant characteristics. Infants with hyperoxemia had a higher incidence of HIE than those without hyperoxemia (58% vs 27%; P = .003). Admission hyperoxemia was associated with a higher risk of HIE (OR, 4; 95% CI, 1.4-10.5; adjusted P = .01). Among the neonates with moderate-severe HIE during the first 6 hours of life, those with hyperoxemia had a higher incidence of abnormal brain magnetic resonance imaging results, consistent with hypoxic ischemic injury, compared with those without hyperoxemia (79% vs 33%; P = .015). CONCLUSION: In neonates with perinatal acidemia, admission hyperoxemia is associated with a higher incidence of HIE. Among neonates with HIE, admission hyperoxemia is associated with abnormal brain magnetic resonance imaging findings. The judicious use of oxygen during and after resuscitation is warranted.

Outcome of extremely low birth weight infants who received delivery room cardiopulmonary resuscitation.

OBJECTIVE: To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NDI) in extremely low birth weight infants. STUDY DESIGN: We conducted a cohort study of infants born with birth weight of 401 to 1000 g and gestational age of 23 to 30 weeks. DR-CPR was defined as chest compressions, medications, or both. Logistic regression was used to determine associations among DR-CPR and morbidities, mortality, and NDI at 18 to 24 months of age (Bayley II mental or psychomotor index <70, cerebral palsy, blindness, or deafness). Data are adjusted ORs with 95% CIs. RESULTS: Of 8685 infants, 1333 (15%) received DR-CPR. Infants who received DR-CPR had lower birth weight (708±141 g versus 764±146g, P<.0001) and gestational age (25±2 weeks versus 26±2 weeks, P<.0001). Infants who received DR-CPR had more pneumothoraces (OR, 1.28; 95% CI, 1.48-2.99), grade 3 to 4 intraventricular hemorrhage (OR, 1.47; 95% CI, 1.23-1.74), bronchopulmonary dysplasia (OR, 1.34; 95% CI, 1.13-1.59), death by 12 hours (OR, 3.69; 95% CI, 2.98-4.57), and death by 120 days after birth (OR, 2.22; 95% CI, 1.93-2.57). Rates of NDI in survivors (OR, 1.23; 95% CI, 1.02-1.49) and death or NDI (OR, 1.70; 95% CI, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score <2 survived without NDI. CONCLUSIONS: DR-CPR is a prognostic marker for higher rates of mortality and NDI for extremely low birth weight infants. New DR-CPR strategies are needed for this population.

Naloxone during neonatal resuscitation: acknowledging the unknown.

There are no studies to support or to refute the current recommendations regarding naloxone concentration, routes for administration, and doses in neonatal resuscitation in the delivery room. Given the lack of supporting evidence, naloxone should not be given routinely in the delivery room to depressed neonates whether or not they are exposed to opioids before delivery because no important improvement has been documented and the drug may have potential short- and long-term harmful effects.