Evaluation of a respiratory care protocol including less invasive surfactant administration in preterm infants.

BACKGROUND: Respiratory care protocol including less invasive ssurfactant administration (LISA) in ≤29 weeks' gestational age (GA) infants introduced in October 2018. METHODS: Retrospective study of infants admitted on continuous positive airway pressure (CPAP) October 2018 to December 2021. Maternal and neonatal variables were compared between infants managed on CPAP with and without LISA. Infants who received LISA and subsequently required mechanical ventilation (MV) within 72 h of life (HOL) [LISA failure (LF)] were compared with those who required no MV [LISA success (LS)]. RESULTS: 249 infants were admitted on CPAP, 5 were intubated prior to LISA, 143 required LISA and 101 remained on CPAP without surfactant. Of those receiving LISA, 108 were LS and 35 were LF. Compared to LS, LF infants were of lower GA and birth weight, required higher fractional inspired oxygen (FiO2), and CPAP level at birth, admission, one HOL, and an hour after LISA. Moreover, LF infants had higher mortality and morbidity. Together GA ≤ 25 weeks' and FiO2 ≥ 0.3 an hour after LISA best predicted LF. CONCLUSIONS: Over 80% of infants admitted on CPAP avoided MV within 72 HOL. Early predictors of LF provide targets for future interventions to decrease need for MV in preterm infants. IMPACT: Less invasive surfactant administration (LISA) decreases the need for mechanical ventilation (MV) and improves outcomes. However, some infants require MV within 72 h of life (HOL) despite LISA (LISA failure). Over 80% of ≤29 weeks' gestational age (GA) infants can be successfully managed on CPAP with or without surfactant in the first 72 HOL. A combination of factors including ≤25 weeks' GA and fraction of inspired oxygen ≥0.3 an hour after LISA predict LISA failure. Evaluation of a noninvasive respiratory support strategy including LISA provides targets for intervention to decrease need for MV in preterm infants.

Hyperglycemia and prematurity: a narrative review.

Hyperglycemia is commonly encountered in extremely preterm newborns and physiologically can be attributed to immaturity in several biochemical pathways related to glucose metabolism. Although hyperglycemia is associated with a variety of adverse outcomes frequently described in this population, evidence for causality is lacking. Variations in definitions and treatment approaches have further complicated the understanding and implications of hyperglycemia on the immediate and long-term effects in preterm newborns. In this review, we describe the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research. IMPACT: Hyperglycemia is common and less well described than hypoglycemia in extremely preterm newborns. Hyperglycemia can be attributed to immaturity in several cellular pathways involved in glucose metabolism in this age group. Hyperglycemia has been shown to be associated with a variety of adverse outcomes frequently described in this population; however, evidence for causality is lacking. Variations in definitions and treatment approaches have complicated the understanding and the implications of hyperglycemia on the immediate and long-term effects outcomes. This review describes the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research.

Impact of Size for Gestational Age on Multivariate Analysis of Factors Associated with Necrotizing Enterocolitis in Preterm Infants: Retrospective Cohort Study.

OBJECTIVE: Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. STUDY DESIGN: Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z-score < -2. RESULTS: Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z-score < 0. CONCLUSION: NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z-score < 0. KEY POINTS: · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction..

Prompt control of an outbreak caused by extended-spectrum ß-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit.

OBJECTIVES: To assess the effectiveness of a set of multidisciplinary interventions aimed at limiting patient-to-patient transmission of extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-KP) during a neonatal intensive care unit (NICU) outbreak, and to identify risk factors associated with ESBL-KP colonization and disease in this setting. STUDY DESIGN: A 61-infant cohort present in the NICU during an outbreak of ESBL-KP from April 26, 2011, to May 16, 2011, was studied. Clinical characteristics were compared in infected/colonized infants and unaffected infants. A multidisciplinary team formulated an outbreak control plan that included (1) staff reeducation on recommended infection prevention measures; (2) auditing of hand hygiene and environmental services practices; (3) contact precautions; (4) cohorting of infants and staff; (5) alleviation of overcrowding; and (6) frequent NICU-wide screening cultures. Neither closure of the NICU nor culturing of health care personnel was instituted. RESULTS: Eleven infants in this level III NICU were infected/colonized with ESBL-KP. The index case was an 18-day-old infant born at 25 weeks' gestation who developed septicemia from ESBL-KP. Two other infants in the same room developed sepsis from ESBL-KP within 48 hours; both expired. Implementation of various infection prevention strategies resulted in prompt control of the outbreak within 3 weeks. The ESBL-KP isolates presented a single clone that was distinct from ESBL-KP identified previously in other units. Being housed in the same room as the index infant was the only risk factor identified by logistic regression analysis (P = .002). CONCLUSION: This outbreak of ESBL-KP affected 11 infants and was associated with 2 deaths. Prompt control with eradication of the infecting strain from the NICU was achieved with multidisciplinary interventions based on standard infection prevention practices.

Quality improvement project in a neonatal intensive care unit reduced the prevalence and duration of hypophosphatemia with significant and sustainable results.

BACKGROUND: Hypophosphatemia is associated with prolonged mechanical ventilation and may affect growth, bone mineralization, nephrocalcinosis, and mortality in preterm infants. Optimal nutrition practices may decrease risk for hypophosphatemia and improve outcome. METHODS: A quality improvement project was established to improve parenteral and enteral phosphorus intake with the goal to decrease prevalence and duration of hypophosphatemia in the first 14 days in infants <32 weeks' gestation. RESULTS: Among 406 preterm infants, the prevalence of moderate hypophosphatemia decreased from 44% to 19% (P < 0.01) over 4 years. The median duration of moderate hypophosphatemia decreased from 72 h (48-128) to 24 (24-53) (P < 0.01). Daily intakes of parenteral calcium and phosphorus on the fourth day of life increased from 1.5 to 2.5 mEq/kg/day (P < 0.01) and 0.6 to 1.3 mmol/kg/day (P < 0.01), respectively. The median postnatal age of first serum phosphorus concentration assessment decreased from 53 h (41-64) to 32 (24-40) (P < 0.01). CONCLUSION: During this quality improvement project, reduced prevalence and duration of hypophosphatemia in infants <32 weeks' gestation in the first 14 days of life was achieved through the optimization of parenteral and enteral phosphorus intake and improved response to acute hypophosphatemia.

Association of antenatal steroids with surfactant administration in moderate preterm infants born to women with diabetes mellitus and/or hypertension.

BACKGROUND: Randomized trials of antenatal steroid administration (ANS) for extreme or moderate preterm pregnancies excluded women with diabetes mellitus (DM) and included few with preeclampsia. METHODS: Cohort study (n = 1,813) including moderate preterm births [290/7-336/7wks' gestational age GA)] before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with hypertensive disorders (HTN) and/or DM. We compared surfactant administration in Group-1 (neither HTN nor DM), Group-2a (HTN not DM), Group-2b (DM not HTN) and Group-2c (DM and HTN). RESULTS: Surfactant administration was less frequent after ANS in Group-1 [adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.31, 0.93, P = 0.03], Group-2a (aOR 0.36, CI 0.22, 0.58, P < 0.001) and Group-2c (aOR 0.29, CI 0.12, 0.71, P = 0.007) but not Group-2b (P = 0.64). CONCLUSIONS: ANS administration was independently associated with less surfactant administration in moderately preterm neonates whose mothers had neither HTN nor DM, and those with HTN, but not those with DM without HTN.

Decreasing delivery room CPAP-associated pneumothorax at ≥35-week gestational age.

OBJECTIVE: We previously reported an increase in pneumothorax after implementing delivery room (DR) continuous positive airway pressure (CPAP) for labored breathing or persistent cyanosis in ≥35-week gestational age (GA) neonates unexposed to DR-positive pressure ventilation (DR-PPV). We hypothesized that pneumothorax would decrease after de-implementing DR-CPAP in those unexposed to DR-PPV or DR-O2 supplementation (DR-PPV/O2). STUDY DESIGN: In a retrospective cohort excluding DR-PPV the primary outcome was DR-CPAP-related pneumothorax (1st chest radiogram, 1st day of life). In a subgroup treated by the resuscitation team and admitted to the NICU, the primary outcome was DR-CPAP-associated pneumothorax (1st radiogram, no prior PPV) without DR-PPV/O2. RESULTS: In the full cohort, occurrence of DR-CPAP-related pneumothorax decreased after the intervention (11.0% vs 6.0%, P < 0.001). In the subgroup, occurrence of DR-CPAP-associated pneumothorax decreased after the intervention (1.4% vs. 0.06%, P < 0.001). CONCLUSION: The occurrence of CPAP-associated pneumothorax decreased after avoiding DR-CPAP in ≥35-week GA neonates without DR-PPV/O2.

Association of antenatal steroids with neonatal mortality and morbidity in preterm infants born to mothers with diabetes mellitus and hypertension.

BACKGROUND: Randomized trials of antenatal steroids (ANS) included women at 24-33 weeks gestational age (GA); however, few women had preeclampsia and women with diabetes mellitus (DM) were excluded. METHODS: Cohort study including preterm births at 230/7-286/7 weeks GA before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with DM and hypertensive disorders (HTN). We compared Group-A (neither DM nor HTN) and Group-B (DM and/or HTN). RESULTS: Among 747 neonates the adjusted odds ratio (aOR) for surfactant administration, in-hospital mortality, severe intraventricular hemorrhage (IVH) and death or severe IVH were lower in ANS-exposed neonates than unexposed neonates. In Group-B, ANS administration was independently associated with less severe IVH and less death or severe IVH, but not less surfactant use or mortality. CONCLUSIONS: Increased ANS administration in women with DM and/or HTN was independently associated with less severe IVH and less death or severe IVH but without decrease in surfactant administration.

Decreasing Continuous Positive Airway Pressure Failure in Preterm Infants.

BACKGROUND AND OBJECTIVES: Many preterm infants stabilized on continuous positive airway pressure (CPAP) at birth require mechanical ventilation (MV) during the first 72 hours of life, which is defined as CPAP failure. Our objective was to decrease CPAP failure in infants ≤29 weeks' gestational age (GA). METHODS: A quality improvement bundle named OPTISURF was implemented for infants ≤29 weeks' GA admitted on CPAP, consisting of stepwise escalation of CPAP and less invasive surfactant administration guided by fractional inspired oxygen concentration ≥0.3. The CPAP failure rate was tracked by using control charts. We compared practice and outcomes of a pre-OPTISURF cohort (January 2017 to September 2018) to a post-OPTISURF cohort (October 2018 to December 2019). RESULTS: Of the 216 infants ≤29 weeks' GA admitted to NICU on CPAP, 125 infants belonged to the pre-OPTISURF cohort (OSC) and 91 to the post-OSC. Compared with the pre-OSC, a higher proportion of infants in the post-OSC received CPAP 7 cm H2O within 4 hours of life (7% vs 32%; P < .01). The post-OSC also had lower rates of CPAP failure (54% vs 11%; P < .01), pneumothoraces (8% vs 1%; P < .03), need for MV (58% vs 31%; P < .01), and patent ductus arteriosus treatment (21% vs 9%; P = .02). Additionally, in a subgroup analysis, CPAP failure was lower in the post-OSC among infants 23 to 26 weeks (79% vs 27%; P < .01) and 27 to 29 weeks' GA (46% vs 3%; P < .01). CONCLUSIONS: Implementation of a quality improvement bundle including CPAP optimization and less invasive surfactant administration decreased CPAP failure and need for MV in preterm infants.

Intrauterine Transmission of SARS-COV-2 Infection in a Preterm Infant.

We present a preterm infant who developed a fever and mild respiratory disease on the second day of life. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nasopharyngeal testing was positive at 24 and 48 hours of life. Placenta histopathology revealed SARS-CoV-2 infection by electron microscopy and immunohistochemistry. Further understanding of the risk factors that lead to in utero transmission of SARS-CoV-2 infection is needed.

Decrease in the frequency of treatment for patent ductus arteriosus after implementation of consensus guidelines: a 15-year experience.

BACKGROUND: Patent ductus arteriosus (PDA) management varies widely among neonatologists. LOCAL PROBLEM: Lack of institution-specific evidence-based guidelines for therapeutic closure of PDA. METHODS: Quality improvement project among infants <30 weeks gestational age (GA) designed to determine whether the odds of therapy for closing the PDA, adjusted for GA, decreased after implementing evidence-based guidelines. INTERVENTION: Implementation of guidelines with conservative approach to PDA management. RESULTS: The frequency of PDA treatment decreased from 446/1125 (40%) in Epoch 1 to 96/482 (20%) in Epoch 2. PDA treatment was more frequent in neonates 23-26 weeks GA than those of 27-29 weeks GA (43% vs. 28%, respectively). Among 542 infants receiving indomethacin for PDA, 25% had subsequent ligation; the odds of ligation after indomethacin were lower in neonates 27-29 weeks GA and decreased during Epoch 2. CONCLUSIONS: The frequency of medical and surgical treatment for therapeutic closure of PDA decreased after implementing evidence-based treatment guidelines.

Delivery Room Continuous Positive Airway Pressure and Pneumothorax.

BACKGROUND: In 2011, the Neonatal Resuscitation Program (NRP) added consideration of continuous positive airway pressure (CPAP) for spontaneously breathing infants with labored breathing or hypoxia in the delivery room (DR). The objective of this study was to determine if DR-CPAP is associated with symptomatic pneumothorax in infants 35 to 42 weeks' gestational age. METHODS: We included (1) a retrospective birth cohort study of neonates born between 2001 and 2015 and (2) a nested cohort of those born between 2005 and 2015 who had a resuscitation call leading to admission to the NICU and did not receive positive-pressure ventilation. RESULTS: In the birth cohort (n = 200 381), pneumothorax increased after implementation of the 2011 NRP from 0.4% to 0.6% (P < .05). In the nested cohort (n = 6913), DR-CPAP increased linearly over time (r = 0.71; P = .01). Administration of DR-CPAP was associated with pneumothorax (odds ratio [OR]: 5.5; 95% confidence interval [CI]: 4.4-6.8); the OR was higher (P < .001) in infants receiving 21% oxygen (OR: 8.5; 95% CI: 5.9-12.3; P < .001) than in those receiving oxygen supplementation (OR: 3.5; 95% CI: 2.5-5.0; P < .001). Among those with DR-CPAP, pneumothorax increased with gestational age and decreased with oxygen administration. CONCLUSIONS: The use of DR-CPAP is associated with increased odds of pneumothorax in late-preterm and term infants, especially in those who do not receive oxygen in the DR. These findings could be used to clarify NRP guidelines regarding DR-CPAP in late-preterm and term infants.

Quality Improvement Project to Decrease Delivery Room Intubations in Preterm Infants.

BACKGROUND AND OBJECTIVES: Avoidance of delivery room intubation (DRI) reduces death or bronchopulmonary dysplasia (BPD) in preterm neonates. Our objective with this quality improvement project was to decrease DRI rates by improving face mask positive pressure ventilation (Fm-PPV) among infants born ≤29 weeks' gestation. METHODS: Key drivers of change were identified from a retrospective review of resuscitation records. A resuscitation bundle to optimize Fm-PPV including the use of a small round mask and end-tidal CO2 detectors, increasing peak inspiratory pressure when indicated, and debriefing after each intubation were implemented in consecutive plan-do-study-act cycles. The DRI rate was tracked by using a control chart. Resuscitation practice and outcomes of pre-quality improvement cohort (QIC) (January 2014-September 2015) were compared with post-QIC (October 2015-December 2016). RESULTS: Of the 314 infants who were resuscitated, 180 belonged to the pre-QIC and 134 to the post-QIC. The antenatal steroid administration rate was higher in the post-QIC (54% vs 88%). More infants in the post-QIC had resolution of bradycardia after Fm-PPV (56% vs 77%, P = .02). Infants in the post-QIC had lower DRI rates (58% vs 37%, P < .01), lower need for mechanical ventilation (85% vs 70%, P < .01), lower rates of BPD (26% vs 13%, P < .01), and severe retinopathy of prematurity (14% vs 5%, P = .01). Rates of DRI, BPD, and severe retinopathy of prematurity remained lower even after controlling for the potential confounders. CONCLUSIONS: Implementation of a resuscitation bundle decreased the DRI rate and improved outcomes of preterm infants.

Change in practice after the Surfactant, Positive Pressure and Oxygenation Randomised Trial.

OBJECTIVE: To test the hypothesis that the proportion of endotracheal intubation (ETI) in the delivery room (DR) decreased in Neonatal Research Network (NRN) centres after the National Institute of Child Health and Human Development NRN Surfactant, Positive Pressure, and Oxygenation Randomised Trial (SUPPORT). DESIGN: Retrospective cohort study using the prospective NRN generic database. SETTING: Eleven centres that participated in the SUPPORT trial and remained part of the NRN. Preterm neonates 24(0/7)-27(6/7) weeks' gestational age enrolled in the SUPPORT trial were randomised to: (1) DR continuous positive airway pressure or DR ETI with early surfactant administration; and (2) oxygen saturation targets of 85-89% or 91-95%. The prior NRN feasibility trial had assessed the feasibility of randomisation to continuous positive airway pressure versus ETI. PATIENTS: Infants 24(0/7)-27(6/7) weeks' gestational age, excluding infants with syndromes or major malformations and those on comfort care only. MAIN OUTCOME MEASURE: Proportion of DR ETI. RESULTS: The proportion of DR ETI decreased significantly in the group of infants from centres that had not participated in the feasibility trial (91% before vs 75% after SUPPORT, adjusted relative risk 0.86, 95% CI 0.83-0.89, p<0.0001) but not in the group of infants from the other centres, where the proportion of ETI was already lower prior to initiation of the SUPPORT trial (61% before vs 58% after SUPPORT, adjusted relative risk 0.96, 95% CI 0.89 to 1.05, p=0.40). CONCLUSION: This study shows that DR ETI changed after SUPPORT only in NRN centres that had not participated in a similar trial. TRIAL REGISTRATION NUMBER: NCT00063063 (GDB) and NCT00233324 (SUPPORT).

Change in care among nonenrolled patients during and after a randomized trial.

OBJECTIVE: Parkland Memorial Hospital (PMH) participated in Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT), an unblinded controlled trial, in which preterm neonates of 24(0/7) to 27(6/7) weeks' gestational age (GA) were randomized in the delivery room (DR) to endotracheal intubation or nasal continuous positive airway pressure. We hypothesized that DR intubation could change in nonenrolled patients at PMH and that the change would be larger than in comparable centers not participating in the trial. METHODS: The PMH Cohort included eligible but nonenrolled neonates of 24(0/7) to 27(6/7) weeks (primary) and noneligible neonates of 28 to 34(6/7) weeks (confirmatory). A subset (24(0/7)-29(6/7)weeks) of that cohort was compared with a contemporaneous cohort born in centers participating in the Vermont Oxford Network (VON). We used a Poisson regression model to obtain adjusted relative risks (RRs) of DR intubation (during/after SUPPORT versus before SUPPORT) for PMH and for VON along with the ratio of these RRs. RESULTS: In the PMH cohort (n = 3527), the proportion of DR intubation decreased during/after SUPPORT in the lower GA group (adjusted RR 0.76, 95% confidence interval [CI] 0.59-0.96) and the upper GA group (adjusted RR 0.57, 95% CI 0.46-0.70). Compared with the RR for DR intubation in VON, the RR at PMH was smaller in the lower (ratio of RR 0.76, 95% CI 0.65-0.87) and the upper GA group (ratio of RR 0.52, 95% CI 0.39-0.68). CONCLUSIONS: A center's participation in an unblinded randomized trial may affect process of care of nonenrolled patients.