The Impact of Pulmonary Hypertension in Preterm Infants with Severe Bronchopulmonary Dysplasia through 1 Year.

OBJECTIVES: To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe bronchopulmonary dysplasia. STUDY DESIGN: This was a multicenter, retrospective cohort study of 1677 infants born <32 weeks of gestation with severe bronchopulmonary dysplasia enrolled in the Children's Hospital Neonatal Consortium with records linked to the Pediatric Health Information System. RESULTS: Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P < .001), ventilator support at 36 weeks of postmenstrual age (60% vs 40%, P < .001), duration of ventilation (72 IQR 30-124 vs 41 IQR 17-74 days, P < .001), and higher respiratory severity score (3.6 IQR 0.4-7.0 vs 0.8 IQR 0.3-3.3, P < .001). At discharge, pulmonary hypertension was associated with tracheostomy (27% vs 9%, P < .001), supplemental oxygen use (84% vs 61%, P < .001), and tube feeds (80% vs 46%, P < .001). Through 1 year of corrected age, pulmonary hypertension was associated with increased frequency of readmission (incidence rate ratio [IRR] = 1.38, 95% CI 1.18-1.63, P < .001). CONCLUSIONS: Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through 1 year of corrected age. This highlights the need for improved diagnostic practices and prospective studies evaluating treatments for this high-risk population.

Adult Outcomes After Newborn Respiratory Failure Treated With Extracorporeal Membrane Oxygenation.

OBJECTIVE: To describe the outcome of young adults treated for hypoxemic respiratory failure with extracorporeal membrane oxygenation as neonates. DESIGN: The study was designed as a multisite, cross sectional survey. SETTING: The survey was completed electronically or on paper by subjects and stored in a secure data base. SUBJECTS: Subjects were surviving neonatal extracorporeal membrane oxygenation patients from eight institutions who were18 years old or older. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A questionnaire modified from the 2011 Behavioral Risk Factor Surveillance System and the 2011 National Health Interview Survey with additional unique questions was completed by subjects. Results were compared to age-matched national Behavioral Risk Factor Surveillance System and National Health Interview Survey data. One hundred and forty-six subjects participated (8.9% of eligible candidates). The age at questionnaire submission was 23.7 ± 2.89 years. Subjects differed statistically from national cohorts by being more satisfied with life (93% vs 84.2%); more educated (some college or degree; 80.1% vs 57.7%); more insured for healthcare (89.7% vs 72.3%); less frequent users of healthcare in the last 12 months (47.3% vs 58.2%); more limited because of physical, mental, and developmental problems (19.9% vs 10.9%); and having more medical complications. Furthermore, learning problems occurred in 29.5% of the study cohort. The congenital diaphragmatic hernia group was generally less healthy and less well educated, but equally satisfied with life. Perinatal variables contributed little to outcome prediction. CONCLUSIONS: Most young adult survivors in this study cohort treated with extracorporeal membrane oxygenation as neonates are satisfied with their lives, working and/or in college, in good health and having families. These successes are occurring despite obstacles involving health issues such as asthma, attention deficit disorder, learning difficulties, and vision and hearing problems; this is especially evident in the congenital diaphragmatic hernia cohort. Selection bias inherent in such a long-term study may limit generalizability, and it is imperative to note that our sample may not be representative of the whole.

Chronic lung disease in full-term infants: Characteristics and neonatal intensive care outcomes in infants referred to children's hospitals.

OBJECTIVE: To describe characteristics, outcomes, and risk factors for death or tracheostomy with home mechanical ventilation in full-term infants with chronic lung disease (CLD) admitted to regional neonatal intensive care units. STUDY DESIGN: This was a multicenter, retrospective cohort study of infants born ≥37 weeks of gestation in the Children's Hospitals Neonatal Consortium. RESULTS: Out of 67,367 full-term infants admitted in 2010-2016, 4886 (7%) had CLD based on receiving respiratory support at either 28 days of life or discharge. 3286 (67%) were still hospitalized at 28 days receiving respiratory support, with higher mortality risk than those without CLD (10% vs. 2%, p < 0.001). A higher proportion received tracheostomy (13% vs. 0.3% vs. 0.4%, p < 0.001) and gastrostomy (30% vs. 1.7% vs. 3.7%, p < 0.001) compared to infants with CLD discharged home before 28 days and infants without CLD, respectively. The diagnoses and surgical procedures differed significantly between the two CLD subgroups. Small for gestational age, congenital pulmonary, airway, and cardiac anomalies and bloodstream infections were more common among infants with CLD who died or required tracheostomy with home ventilation (p < 0.001). Invasive ventilation at 28 days was independently associated with death or tracheostomy and home mechanical ventilation (odds ratio 7.6, 95% confidence interval 5.9-9.6, p < 0.0001). CONCLUSION: Full-term infants with CLD are at increased risk for morbidity and mortality. We propose a severity-based classification for CLD in full-term infants. Future work to validate this classification and its association with early childhood outcomes is necessary.

A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children's Hospitals Neonatal Consortium Severe BPD Group.

OBJECTIVE: To compare three bronchopulmonary dysplasia (BPD) definitions against hospital outcomes in a referral-based population. STUDY DESIGN: Data from the Children's Hospitals Neonatal Consortium were classified by 2018 NICHD, 2019 NRN, and Canadian Neonatal Network (CNN) BPD definitions. Multivariable models evaluated the associations between BPD severity and death, tracheostomy, or length of stay, relative to No BPD references. RESULTS: Mortality was highest in 2019 NRN Grade 3 infants (aOR 225), followed by 2018 NICHD Grade 3 (aOR 145). Infants with lower BPD grades rarely died (<1%), but Grade 2 infants had aOR 7-21-fold higher for death and 23-56-fold higher for tracheostomy. CONCLUSIONS: Definitions with 3 BPD grades had better discrimination and Grade 3 2019 NRN had the strongest association with outcomes. No/Grade 1 infants rarely had severe outcomes, but Grade 2 infants were at risk. These data may be useful for counseling families and determining therapies for infants with BPD.

Association of time of first corticosteroid treatment with bronchopulmonary dysplasia in preterm infants.

OBJECTIVE: To evaluate the association between the time of first systemic corticosteroid initiation and bronchopulmonary dysplasia (BPD) in preterm infants. STUDY DESIGN: A multi-center retrospective cohort study from January 2010 to December 2016 using the Children's Hospitals Neonatal Database and Pediatric Health Information System database was conducted. The study population included preterm infants <32 weeks' gestation treated with systemic corticosteroids after 7 days of age and before 34 weeks' postmenstrual age. Stepwise multivariable logistic regression was used to assess the association between timing of corticosteroid initiation and the development of Grade 2 or 3 BPD as defined by the 2019 Neonatal Research Network criteria. RESULTS: We identified 598 corticosteroid-treated infants (median gestational age 25 weeks, median birth weight 760 g). Of these, 47% (280 of 598) were first treated at 8-21 days, 25% (148 of 598) were first treated at 22-35 days, 14% (86 of 598) were first treated at 36-49 days, and 14% (84 of 598) were first treated at >50 days. Infants first treated at 36-49 days (aOR 2.0, 95% CI 1.1-3.7) and >50 days (aOR 1.9, 95% CI 1.04-3.3) had higher independent odds of developing Grade 2 or 3 BPD when compared to infants treated at 8-21 days after adjusting for birth characteristics, admission characteristics, center, and co-morbidities. CONCLUSIONS: Among preterm infants treated with systemic corticosteroids in routine clinical practice, later initiation of treatment was associated with a higher likelihood to develop Grade 2 or 3 BPD when compared to earlier treatment.

Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). STUDY DESIGN: Infants with sBPD in the Children's Hospitals Neonatal Database who had echocardiograms 34-44 weeks' postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. RESULTS: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2-3.0; RVSP OR 2.2, 95% CI 1.1-4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. CONCLUSIONS: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive.

Late Preterm Infants: Morbidities, Mortality, and Management Recommendations.

Infants born between 34 weeks 0 days and 36 weeks 6 days of gestation are termed late preterm. This group accounts for the majority of premature births in the United States, with rates increasing in each of the last 3 years. This increase is significant given their large number: nearly 280,000 in 2016 alone. Late preterm infants place a significant burden on the health care and education systems because of their increased risk of morbidities and mortality compared with more mature infants. This increased risk persists past the newborn period, leading to the need for continued health monitoring throughout life.

Late preterm infants, early term infants, and timing of elective deliveries.

Delivery of infants who are physiologically mature and capable of successful transition to the extrauterine environment is an important priority for obstetric practitioner. A corollary of this goal is to avoid iatrogenic complications of prematurity and maternal complications from delivery. The purpose of this review is to describe the consequences of birth before physiologic maturity in late preterm and term infants, to identify factors contributing to the decline in gestational age of deliveries in the United States, and to describe strategies to reduce premature delivery of late preterm and early term infants.

A recommendation for the definition of "late preterm" (near-term) and the birth weight-gestational age classification system.

Determination of gestational age is important to assess risks for morbidity and mortality in neonates. Definitions for preterm, term and postterm have been precisely defined although definitions for subgroups of infants within these categories have not been well defined. More precise definitions for the subgroup of infants born "near-term" is especially important because of the rapid increase in percentage of births attributed to this subgroup. It is recommended that "late preterm" replace "near-term" because it better reflects the higher risk for complications of preterm birth experienced by this subgroup of preterm infants. Furthermore, it is proposed that "late preterm" be defined as beginning on the 239th day (34 0/7 weeks' gestation) and ending on the 259th day (36 6/7 weeks' gestation) since the first day of the mother's last normal menstrual period.

Intraosseous access for administration of medications in neonates.

Intraosseous administration of resuscitation medications and fluids in preterm and term neonates is an alternative when intravascular access is not possible with intravenous catheters or needles. Intraosseous access is rarely needed in neonates because of the availability of clinicians with expert technical skills for placement of intravenous catheters in neonatal ICUs, the presence of the umbilical vein during the first days after birth when most resuscitations occur, and the predominance of resuscitations being responsive to positive-pressure ventilation alone. Intraosseous access is most likely to be needed in out-of-hospital settings and in hospitalized infants without intravenous access who have vascular collapse secondary to shock or when clinicians responsible for vascular access during resuscitations are more skilled in intraosseous access than intravenous access.

Primary unilateral pulmonary hypoplasia: neonate through early childhood - case report, radiographic diagnosis and review of the literature.

Unilateral pulmonary hypoplasia is a rare cause of respiratory distress in the neonate. It is usually secondary to other causes such as diaphragmatic hernia. We present a case of a newborn with primary hypoplasia of the right upper lobe who was later found to also have tracheobronchomalacia. We describe the clinical course through early childhood.

Robin sequence: mortality, causes of death, and clinical outcomes.

BACKGROUND: The authors report the cause of and risk factors for mortality in infants with Robin sequence and identify characteristics associated with quality-of-life outcomes. METHODS: The authors performed an 11-year retrospective review of all infants with Robin sequence treated at a neonatal intensive care unit. Patient characteristics were correlated to mortality and quality-of-life measures. Emergency room visits and hospital admissions were used to assess quality-of-life outcomes. Significant variables were identified by means of univariate analysis. RESULTS: One hundred eighty-one consecutive infants were identified. Patient characteristics included the following: isolated, 32.6 percent; syndromic, 31.5 percent; gastrointestinal, 38.1 percent; pulmonary, 32.6 percent; cardiac, 30.9 percent; central nervous system, 25.4 percent; and two or more organ system anomalies, 69.6 percent. Mortality was 16.6 percent; two deaths were related to airway obstruction problems. There were no deaths in isolated Robin sequence (p = 0.002). Mortality was statistically associated with cardiac anomalies (p < 0.001), central nervous system anomalies (p = 0.001), and two or more organ system abnormalities (p = 0.001). Variables associated with an increased rate of emergency room visits were cardiac anomalies (p = 0.04) and two or more organ system abnormalities (p = 0.04). The presence of two or more organ system abnormalities (p = 0.04) was associated with an increased hospital admission rate. CONCLUSIONS: Mortality and negative quality-of-life measures in Robin sequence are not directly related to respiratory obstruction. Isolated Robin sequence confers no increased risk of mortality. There is a high incidence of cardiac and central nervous system anomalies, which are significantly associated with mortality. Cardiac and cranial imaging should be performed during the initial evaluation of infants with Robin sequence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Morbidity and mortality in late preterm and early term newborns: a continuum.

Late preterm and early term infants are at higher risk for short-term and long-term morbidities and mortality than term infants. Such outcomes are influenced by many factors, the strongest of which is gestational age. Counseling and educating women and families about risks of late preterm and early term births is helpful for timing and route of delivery, managing the pregnancy and infant, and prognosticating outcomes for infants.

Safe transportation of preterm and low birth weight infants at hospital discharge.

Safe transportation of preterm and low birth weight infants requires special considerations. Both physiologic immaturity and low birth weight must be taken into account to properly position such infants. This clinical report provides guidelines for pediatricians and other caregivers who counsel parents of preterm and low birth weight infants about car safety seats.

Synchronized nasal intermittent positive-pressure ventilation and neonatal outcomes.

BACKGROUND: Synchronized nasal intermittent positive-pressure ventilation (SNIPPV) use reduces reintubation rates compared with nasal continuous positive airway pressure (NCPAP). Limited information is available on the outcomes of infants managed with SNIPPV. OBJECTIVES: To compare the outcomes of infants managed with SNIPPV (postextubation or for apnea) to infants not treated with SNIPPV at 2 sites. METHODS: Clinical retrospective data was used to evaluate the use of SNIPPV in infants

Impact of postnatal corticosteroid use on neurodevelopment at 18 to 22 months' adjusted age: effects of dose, timing, and risk of bronchopulmonary dysplasia in extremely low birth weight infants.

OBJECTIVE: Postnatal steroid use decreases lung inflammation but increases impairment. We hypothesized that increased dose is associated with increased neurodevelopmental impairment, lower postmenstrual age at exposure increases impairment, and risk of bronchopulmonary dysplasia modifies the effect of postnatal corticosteroid. METHODS: Steroid dose and timing of exposure beyond 7 days was assessed among 2358 extremely low birth weight infants nested in a prospective trial, with 1667 (84%) survivors examined at 18 to 22 months' postmenstrual age. Logistic regression tested the relationship between impairment (Bayley Mental Developmental Index/Psychomotor Developmental Index of <70, disabling cerebral palsy, or sensory impairment), total dose (tertiles: <0.9, 0.9-1.9, and >/=1.9 mg/kg), and postmenstrual age at first dose. Separate logistic regression tested effect modification according to bronchopulmonary dysplasia severity (Romagnoli risk > 0.5 as high risk, n = 2336 (99%) for days of life 4-7). RESULTS: Three hundred sixty-six (16%) neonates were steroid-treated (94% dexamethasone). Treated neonates were smaller and less mature; 72% of those treated were at high risk for bronchopulmonary dysplasia. Exposure was associated with neurodevelopmental impairment/death. Impairment increased with higher dose; 71% dead or impaired at highest dose tertile. Each 1 mg/kg dose was associated with a 2.0-point reduction on the Mental Developmental Index and a 40% risk increase for disabling cerebral palsy. Older age did not mitigate the harm. Treatment after 33 weeks' postmenstrual age was associated with greatest harm despite not receiving the highest dose. The relationship between steroid exposure and impairment was modified by the bronchopulmonary dysplasia risk, with those at highest risk experiencing less harm. CONCLUSIONS: Higher steroid dose was associated with increased neurodevelopmental impairment. There is no "safe" window for steroid use in extremely low birth weight infants. Neonates with low bronchopulmonary dysplasia risk should not be exposed. A randomized trial of steroid use in infants at highest risk is warranted.

Surfactant-replacement therapy for respiratory distress in the preterm and term neonate.

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes indications, administration, formulations, and outcomes for surfactant-replacement therapy. The impact of antenatal steroids and continuous positive airway pressure on outcomes and surfactant use in preterm infants is reviewed. Because respiratory insufficiency may be a component of multiorgan dysfunction, preterm and term infants receiving surfactant-replacement therapy should be managed in facilities with technical and clinical expertise to administer surfactant and provide multisystem support.

"Late-preterm" infants: a population at risk.

Late-preterm infants, defined by birth at 34(0/7) through 36(6/7) weeks' gestation, are less physiologically and metabolically mature than term infants. Thus, they are at higher risk of morbidity and mortality than term infants. The purpose of this report is to define "late preterm," recommend a change in terminology from "near term" to "late preterm," present the characteristics of late-preterm infants that predispose them to a higher risk of morbidity and mortality than term infants, and propose guidelines for the evaluation and management of these infants after birth.

A cluster-randomized trial of benchmarking and multimodal quality improvement to improve rates of survival free of bronchopulmonary dysplasia for infants with birth weights of less than 1250 grams.

OBJECTIVE: We tested whether NICU teams trained in benchmarking and quality improvement would change practices and improve rates of survival without bronchopulmonary dysplasia in inborn neonates with birth weights of <1250 g. METHODS: A cluster-randomized trial enrolled 4093 inborn neonates with birth weights of <1250 g at 17 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Three centers were selected as best performers, and the remaining 14 centers were randomized to intervention or control. Changes in rates of survival free of bronchopulmonary dysplasia were compared between study year 1 and year 3. RESULTS: Intervention centers implemented potentially better practices successfully; changes included reduced oxygen saturation targets and reduced exposure to mechanical ventilation. Five of 7 intervention centers and 2 of 7 control centers implemented use of high-saturation alarms to reduce oxygen exposure. Lower oxygen saturation targets reduced oxygen levels in the first week of life. Despite these changes, rates of survival free of bronchopulmonary dysplasia were all similar between intervention and control groups and remained significantly less than the rate achieved in the best-performing centers (73.3%). CONCLUSIONS: In this cluster-randomized trial, benchmarking and multimodal quality improvement changed practices but did not reduce bronchopulmonary dysplasia rates.

Age terminology during the perinatal period.

Consistent definitions to describe the length of gestation and age in neonates are needed to compare neurodevelopmental, medical, and growth outcomes. The purposes of this policy statement are to review conventional definitions of age during the perinatal period and to recommend use of standard terminology including gestational age, postmenstrual age, chronological age, corrected age, adjusted age, and estimated date of delivery.