Background: Preterm infants with bradycardia at birth often undergo immediate cord clamping (ICC) followed by resuscitation with positive pressure ventilation (PPV), chest compressions (CCs) and umbilical venous catheter (UVC) epinephrine. Resuscitation with an intact cord (PPV during delayed umbilical cord clamping-DCC) stabilizes cardiac output but delays UVC placement. Objective: To evaluate the feasibility of direct epinephrine injection into the umbilical vein during DCC (DCC + direct-epinephrine) compared with ICC and epinephrine administered through a UVC (ICC + cath-epinephrine), and to explore differences in return of spontaneous circulation (ROSC) and need for CCs between these approaches. Methods: Eleven preterm lambs (125-127 d gestation) were asphyxiated by cord compression to decrease heart rate (HR) to <30/min. In the ICC + cath-epinephrine group, the cord was immediately cut, lambs received PPV followed by CCs if HR < 60/min, and epinephrine was administered after UVC placement. In the DCC + direct-epinephrine group, cord compression was released when HR < 30/min and PPV was initiated. If HR remained <60/min, epinephrine was injected into the UV using a 25G needle. If ROSC was achieved, DCC was continued for 2 min. If HR < 100/min, the cord was cut and resuscitation was continued as outlined above. Plasma epinephrine concentrations were analyzed. Results: All lambs required epinephrine. Time to epinephrine was shorter with DCC + direct-epinephrine, 1.0 (0.7, 1.6) vs. 3.7 min (3.2, 5.2). Fewer lambs with DCC + direct-epinephrine needed CC (2/6 vs. 5/5, p = 0.06). ROSC success and plasma epinephrine concentrations were similar. Post-ROSC, heart rates and mean blood pressures tended to be higher in the ICC + cath-epinephrine group. Conclusions: In this perinatal lamb model of asphyxial bradycardia, resuscitation with an intact cord with direct umbilical venous epinephrine injection is feasible. Larger studies are required to determine whether this approach reduces the need for CC or improves clinically meaningful outcomes.

Background Spontaneous breathing during and after delayed cord clamping (DCC) stabilizes cardiopulmonary transition at birth. Caffeine stimulates breathing and decreases apnea in premature newborns. We evaluated the pharmacokinetics and physiological effects of early caffeine administration-direct injection into the umbilical vein (UV) during DCC or administered through a UV catheter (UVC) after delivery. Methods Eighteen extremely premature lambs (125–127d, term gestation 145d) were exteriorized and instrumented. Lambs received caffeine-citrate at high (40 mg/kg) or standard-dose (20 mg/kg) via direct UV (DUV) injection during DCC, or via the UVC. Results Mean peak plasma caffeine concentrations were lower with high-dose DUV compared to UVC (18 ± 4.3 vs. 46 ± 12 mg/L, p < 0.05). With standard-dose caffeine, mean peak plasma levels were 7.48 ± 2.6 with DUV and 28.73 ± 9.4 mg/L with UVC. The volume of distribution was higher in the DUV group compared to UVC (2.5 ± 1.0 vs. 0.69 ± 0.15 L/kg) with an estimated 39 ± 18% entering the maternal circulation. Maternal peak concentrations were 0.79 ± 0.71 and 1.43 ± 0.74 mg/L with standard and high-dose DUV, respectively. Conclusions Caffeine injected directly into the UV during DCC is feasible but achieves lower concentrations due to high volume of distribution including maternal circulation. Further trials evaluating DUV caffeine injection should use higher caffeine doses. Impact Respiratory stimulation with early caffeine may reduce the need for intubation in preterm infants. In the preterm lambs, caffeine injection directly into the umbilical vein during delayed cord clamping is feasible. Plasma caffeine concentrations are less than half when administered directly into the umbilical vein during delayed cord clamping compared to administration via an umbilical venous catheter following birth likely attributed to a larger volume of distribution or injection site leak. There were no significant hemodynamic alterations following caffeine injection.

BACKGROUND:Cerebral oxygen delivery (cDO2) is low during chest compressions (CC). We hypothesized that gas exchange and cDO2 are better with continuous CC with high frequency percussive ventilation (CCC + HFPV) compared to conventional 3:1 compressions-to-ventilation (C:V) resuscitation during neonatal resuscitation in preterm lambs with cardiac arrest induced by umbilical cord compression. METHODS:Fourteen lambs in cardiac arrest were randomized to 3:1 C:V resuscitation (90CC + 30 breaths/min) per the Neonatal Resuscitation Program guidelines or CCC + HFPV (120CC + HFPV continuously). Intravenous epinephrine was given every 3 min until return of spontaneous circulation (ROSC). RESULTS:There was no difference in the incidence and time to ROSC between both groups. Median (IQR) PaCO2 was significantly lower with CCC + HFPV during CC, at ROSC and 15 min post-ROSC-[104 (99-112), 83 (77-99), and 43 (40-64)], respectively compared to 3:1 C:V-[149 (139-167), 153 (143-168), and 153 (138-178) mmHg. PaO2 and cDO2 were higher with CCC + HFPV during CC and at ROSC. PaO2 was similar 15 min post-ROSC with a lower FiO2 in the CCC + HFPV group 0.4 (0.4-0.5) vs. 1 (0.6-1). CONCLUSION:In preterm lambs with perinatal cardiac-arrest, continuous chest compressions with HFPV does not improve ROSC but enhances gas exchange and increases cerebral oxygen delivery compared to 3:1 C:V during neonatal resuscitation. IMPACT STATEMENT:Ventilation is the most important intervention in newborn resuscitation. Currently recommended 3:1 compression-to-ventilation ratio is associated with hypercarbia and poor oxygen delivery to the brain. Providing uninterrupted continuous chest compressions during high frequency percussive ventilation is feasible in a lamb model of perinatal cardiac arrest, and demonstrates improved gas exchange and oxygen delivery to the brain. This is the first study in premature lambs evaluating high frequency percussive ventilation with asynchronous chest compressions and lays the groundwork for future clinical studies to optimize gas exchange and hemodynamics during chest compressions in newborns.

Purpose: The goal of this study was to review the role of human milk in shaping the infant intestinal microbiota and the potential of human milk bioactive molecules to reverse trends of increasing intestinal dysbiosis and dysbiosis-associated diseases. Methods: This narrative review was based on recent and historic literature. Findings: Human milk immunoglobulins, oligosaccharides, lactoferrin, lysozyme, milk fat globule membranes, and bile salt-stimulating lipase are complex multifunctional bioactive molecules that, among other important functions, shape the composition of the infant intestinal microbiota. (C) 2021 Elsevier Inc.

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Wide fluctuations in partial pressure of carbon dioxide (PaCO 2 ) can potentially be associated with neurological and lung injury in neonates. Blood gas measurement is the gold standard for assessing gas exchange but is intermittent, invasive, and contributes to iatrogenic blood loss. Non-invasive carbon dioxide (CO 2 ) monitoring has become ubiquitous in anesthesia and critical care and is being increasingly used in neonates. Two common methods of non-invasive CO 2 monitoring are end-tidal and transcutaneous. A colorimetric CO 2 detector (a modified end-tidal CO 2 detector) is recommended by the International Liaison Committee on Resuscitation (ILCOR) and the American Academy of Pediatrics to confirm endotracheal tube placement. Continuous CO 2 monitoring is helpful in trending PaCO 2 in critically ill neonates on respiratory support and can potentially lead to early detection and minimization of fluctuations in PaCO 2 . This review includes a description of the various types of CO 2 monitoring and their applications, benefits, and limitations in neonates.

Objective Hypoglycemia is a significant risk factor for perinatal brain injury and adverse outcomes, particularly in infants requiring resuscitation following hypoxic ischemic (HI) insult. We aimed to study blood glucose (BG) levels in physiologically stressed infants in the presence or absence of epinephrine (Epi) administration at resuscitation in the first 24hours after birth. Study Design A retrospective chart review of all infants with heart rate (HR)<100/min at 1minute requiring positive pressure ventilation (PPV) at birth was performed. Infants were classified into two groups as follows: (1) PPV group : infants' HR improved with PPV only at resuscitation, and Epi group : infants received Epi at resuscitation for persistent bradycardia. Serial measurements of BG levels collected and glucose infusion rate (GIR) calculated at 24hours. Results By design, infants in the Epi group had lower cord pH and higher base deficit. BG was significantly lower overtime in premature infants 32 weeks of gestation in the Epi group. The BG was markedly higher in near-term and term infants in the Epi group compared with the PPV group. Hypoglycemia was more common despite administration of higher GIR in premature infants <= 32 weeks of gestation. Conclusion In the presence of physiological stress, premature infants are more at risk for hypoglycemia than term infants.

Objective: This paper intends to evaluate the association between Down Syndrome (DS) and postoperative medical and surgical complications and inpatient postoperative mortality in pediatric patients undergoing intestinal operations. Methods: The 2012 Kids' Inpatient Database was queried to compare short-term postoperative medical and surgical complications and in-patient mortality among patients with DS undergoing intestinal operations to a cohort without DS using inverse probability weighting. Subset analysis was performed for patients undergoing intestinal operations exclusive of gastrostomy placement. Adverse treatment effects were calculated for the outcomes of interest. Results: Of 17.026 pediatric patients undergoing intestinal operations, 444 had DS. In unadjusted analysis, medical complications (urinary tract infection, deep venous thrombosis, sepsis, pneumonia) occurred in 7.9% of patients with DS, compared to 14.1% of those without (p < 0.001). Surgical complications (wound disruption, hemorrhage, superficial or deep wound infection) occurred in 35% of patients with DS, compared to 4.6% of those without (p = 0.34), and in-patient mortality occurred in 0.3% of patients with DS, compared to 2.7% of those without (p = 0.009). Adverse treatment effects (ATE) calculated after inverse probability weighting demonstrated no difference for medical or surgical complications but a significantly decreased mortality with DS. Conclusions: Contrary to common perception and data extrapolated from the adult literature, pediatric patients with DS have neither higher medical nor surgical complication rates after intestinal operations. Similar to patients undergoing congenital heart surgery, pediatric patients with DS have a lower postoperative inpatient mortality after these general operations compared to those without DS. Mechanisms influencing risks in DS patient remain unknown. (C) 2018 Elsevier Inc. All rights reserved.