Placental Transfusion, Timing of Plastic Wrap or Bag Placement, and Preterm Neonates.

OBJECTIVE: Compare delivery room practices and outcomes of infants born at less than 32 weeks' gestation or less than 1,500 g who have plastic wrap/bag placement simultaneously during placental transfusion to those receiving plastic wrap/bag placement sequentially following placental transfusion. STUDY DESIGN: Retrospective analysis of data from a multisite quality improvement initiative to refine stabilization procedures pertaining to placental transfusion and thermoregulation using a plastic wrap/bag. Delivery room practices and outcome data in 590 total cases receiving placental transfusion were controlled for propensity score matching and hospital of birth. RESULTS: The simultaneous and sequential groups were similar in demographic and most outcome metrics. The simultaneous group had longer duration of delayed cord clamping compared with the sequential group (42.3 ± 14.8 vs. 34.1 ± 10.3 seconds, p < 0.001), and fewer number of times cord milking was performed (0.41 ± 1.26 vs. 0.86 ± 1.92 seconds, p < 0.001). The time to initiate respiratory support was also significantly shorter in the simultaneous group (97.2 ± 100.6 vs. 125.2 ± 177.6 seconds, p = 0.02). The combined outcome of death or necrotizing enterocolitis in the simultaneous group was more frequent than in the sequential group (15.3 vs. 9.3%, p = 0.038); all other outcomes measured were similar. CONCLUSION: Timing of plastic wrap/bag placement during placental transfusion did affect duration of delayed cord clamping, number of times cord milking was performed, and time to initiate respiratory support in the delivery room but did not alter birth hospital outcomes or respiratory care practices other than the combined outcome of death or necrotizing enterocolitis. KEY POINTS: · Plastic bag placement during placental transfusion is effective in stabilization of preterms.. · Plastic bag placement after placental transfusion is effective in stabilization of preterms.. · Plastic bag placement during placental transfusion and risk of death or necrotizing enterocolitis needs additional study..

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.

Home Oxygen Use and 1-Year Readmission among Infants Born Preterm with Bronchopulmonary Dysplasia Discharged from Children's Hospital Neonatal Intensive Care Units.

OBJECTIVE: To determine associations between home oxygen use and 1-year readmissions for preterm infants with bronchopulmonary dysplasia (BPD) discharged from regional neonatal intensive care units. STUDY DESIGN: We performed a secondary analysis of the Children's Hospitals Neonatal Database, with readmission data via the Pediatric Hospital Information System and demographics using ZIP-code-linked census data. We included infants born <32 weeks of gestation with BPD, excluding those with anomalies and tracheostomies. Our primary outcome was readmission by 1 year corrected age; secondary outcomes included readmission duration, mortality, and readmission diagnosis-related group codes. A staged multivariable logistic regression was adjusted for center, clinical, and social risk factors; at each stage we included variables associated at P < .1 in bivariable analysis with home oxygen use or readmission. RESULTS: Home oxygen was used in 1906 of 3574 infants (53%) in 22 neonatal intensive care units. Readmission occurred in 34%. Earlier gestational age, male sex, gastrostomy tube, surgical necrotizing enterocolitis, lower median income, nonprivate insurance, and shorter hospital-to-home distance were associated with readmission. Home oxygen was not associated with odds of readmission (OR, 1.2; 95% CI, 0.98-1.56), readmission duration, or mortality. Readmissions for infants with home oxygen were more often coded as BPD (16% vs 4%); readmissions for infants on room air were more often gastrointestinal (29% vs 22%; P < .001). Clinical risk factors explained 72% of center variance in readmission. CONCLUSIONS: Home oxygen use is not associated with readmission for infants with BPD in regional neonatal intensive care units. Center variation in home oxygen use does not impact readmission risk. Nonrespiratory problems are important contributors to readmission risk for infants with BPD.

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.

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.

Evaluation of Early Transcutaneous Bilirubinometry to Predict Subsequent Hyperbilirubinemia in Neonates Admitted to a Well-Baby Nursery.

OBJECTIVE: The aim of this study is to determine whether a transcutaneous bilirubin (TcB) value obtained within 6 hours of birth (early transcutaneous bilirubin [ETcB]) either alone, or used to calculate an early rate of rise (E-ROR) in TcB, will identify those neonates who are at a higher risk for subsequent jaundice. STUDY DESIGN: ETcB values were obtained from a convenience sample of neonates admitted to the newborn nursery. E-ROR was calculated as the average hourly increase between ETcB and subsequent TcB obtained at 18 to 36 hours of age. TcB percentile values at various ages were obtained from a previously published and cross-validated nomogram. The predictive values relating ETcB, E-ROR, and TcB at 18 to 36 hours of age to TcB at 42 to 66 hours of age were determined, and receiver-operator characteristic curves were compared. RESULTS: A total of 516 late preterm and term neonates were studied. ETcB was higher (p = 0.003) in those neonates who subsequently received phototherapy (n = 15), and negative predictive value was always ≥ 0.96; positive predictive value (PPV) ranged from 0.04 to 0.06. Compared with ETcB, TcB at 18 to 36 hours was more likely to predict significant jaundice at 42 to 66 hours of age. CONCLUSION: Given the observed low PPV, ETcB is not useful in identifying infants who develop subsequent hyperbilirubinemia. However, it may be helpful in identifying those neonates at a low risk of subsequent hyperbilirubinemia.

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.

Transcutaneous bilirubinometry.

Although the modern era of transcutaneous bilirubin monitoring (TcB) began only about 35 years ago, this screening tool is now widely used in newborn nurseries and outpatient clinics, offices, and emergency departments to obtain a rapid and non-invasive estimate of the degree of hyperbilirubinemia. TcB devices have become more sophisticated, and major breakthroughs include the following: (a) ability to report a bilirubin value rather than an index value, (b) enhanced correction for chromophores other than bilirubin, and (c) technologic improvements including interface with electronic medical records. Good agreement with laboratory bilirubin measurement has been demonstrated, and the ability of TcB screening to predict and decrease the incidence of subsequent hyperbilirubinemia has been well-documented. To date, it has not been shown that this screening results in improved long-term outcomes.

Circulating blasts and associated hematologic disorders in neonates with Down syndrome.

We analyzed complete blood count (CBC) data obtained from neonates with Down syndrome (DS) in a primarily Hispanic population over a 10-year period to determine the incidence of hematologic abnormalities and the relationship of abnormalities to the presence of circulating blasts (CB). Hematologic values obtained during the first 10 days were analyzed. Definitions were: CB, ≥ 1% blasts manually counted on peripheral smear; elevated white blood cell count (WBC), >30,000 cells/mm(3); thrombocytopenia, platelet count < 150,000/mm(3); polycythemia, hematocrit >65%. Two hundred thirty-two neonates (88% Hispanic) with DS had 692 CBCs available for analysis. The presence of CB (11.6%) and the incidence of thrombocytopenia (60.2%) were significantly higher in DS neonates than in the reference group. Elevated WBC (33.3%) and thrombocytopenia (84.6%) were more common in DS neonates with CB versus those with no CB. No relationship between thrombocytopenia and polycythemia was observed. Unlike previous reports, we did not observe a male predominance in those DS neonates with CB. Thrombocytopenia occurred frequently in DS neonates and was significantly more likely in those with CB than in those with no CB. CBC screening should be performed routinely in DS neonates.

Hospital course and short-term outcomes of term and late preterm neonates following exposure to prolonged rupture of membranes and/or chorioamnionitis.

Our objective was to characterize the hospital course and short-term outcomes of neonates exposed to prolonged rupture of membranes (PROM), chorioamnionitis (CH), or both PROM and CH. Outcomes were positive blood culture and/or clinical signs of infection (+BC/CSI) prompting >4 days of antibiotics. Six neonates had a positive BC, 2 (0.6%) in the CH group and 4 (2.7%) in the PROM + CH group (P = 0.05); none of the neonates exposed to PROM alone had a +BC. These results support our current approach of withholding routine antibiotic therapy in neonates exposed to PROM alone.

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.

Neonatal Graves' disease associated with severe metabolic abnormalities.

Neonatal Graves' disease is a rare condition that is sometimes associated with multisystem abnormalities that can mimic infection or inborn errors of metabolism. Here we describe the cases of 2 infants who had serious metabolic derangements including conjugated hyperbilirubinemia and hyperammonemia.

Growth and neurodevelopment in extremely low-birth-weight neonates exposed to postnatal steroid therapy.

We compared postnatal growth and neurodevelopment in extremely low-birth-weight (<1000 g) neonates who did or did not receive postnatal steroid (PNS) therapy for bronchopulmonary dysplasia (BPD). One hundred seventy-three neonates with Bayley Scales of Infant Development II (BSID II) testing performed at 18- to 22-month adjusted age were studied. Growth parameters and BSID II scales were compared among three groups: group I, no BPD; group II, BPD, no PNS; group III, BPD and PNS exposure. A subset of 77 neonates' growth parameters were retrieved at 12-month adjusted age. Psychomotor Development Index (PDI) and Mental Development Index (MDI) scales were lower in group III versus groups I and II. Growth velocity (GV) was lower in group III versus group I and II during the initial hospital stay. In the subset, GV from birth to 1-year adjusted age and weight, length, and head circumference determined at 1-year adjusted age were similar among the groups. Multivariate analysis revealed a significant effect of group membership and cystic periventricular leukomalacia on PDI. These results suggest that a deleterious effect of PNS therapy on neurodevelopment can occur by a mechanism that does not impair overall growth or growth of head circumference.

Anterior fontanel size in term and late preterm Hispanic neonates: description of normative values and an alternative measurement method.

We sought to determine anterior fontanel size (AFS) in Hispanic neonates and to compare two methods of measurement. The traditional method (TRAD) was defined as the sum of the longitudinal and transverse dimensions, divided by 2. Diagonal measurements (DIAG) were obtained between the estimated midpoints of the edges of the frontal and parietal bones, and the sum was divided by 2. Interobserver reliability was assessed in a subset of the study population. One hundred seventy neonates with gestational age 38.9 +/- 1.5 weeks were studied at a median age of 32 hours. Measurements by TRAD and DIAG (mean +/- standard deviation) were 22.5 +/- 7.9 mm and 20.9 +/- 6.7 mm, respectively ( P = 0.12). AFS was greater in males and in neonates whose mothers had longer duration of labor. Interobserver reliability was excellent for both methods. This study provides normative data for AFS using two methods in Hispanic neonates. A modest trend toward less variability with the DIAG method was noted. Male gender and longer duration of labor were associated with larger AFS.

Transcutaneous bilirubin nomograms: a systematic review of population differences and analysis of bilirubin kinetics.

OBJECTIVES: To compare available nomograms in the literature defining trends in bilirubin levels across populations with different risk factor profiles and to study a mathematical bilirubin kinetics model describing the natural course of jaundice and the bilirubin rate of rise needed to cross percentile curves. DATA SOURCES: We searched PubMed for publications between March 1999 and March 2009 that created transcutaneous nomograms. We performed the same search among abstracts presented in the past 2 years at meetings of the Pediatric Academic Societies or the European Society for Paediatric Research. STUDY SELECTION: Inclusion criteria were gestational age of at least 35 weeks among study subjects, the use of an electronic transcutaneous bilirubinometer, and creation of a nomogram based on hour-specific bilirubin values. Four articles met the selection criteria. DATA EXTRACTION: Jaundice risk factors were analyzed, and raw data were analyzed using nonlinear regression to describe trends in bilirubin levels and kinetics. The bilirubin exaggerated rate of rise needed to cross percentile curves was calculated. DATA SYNTHESIS: Significant differences in bilirubin values exist across populations, and there is substantial variability in rates of rise. Hispanic neonates demonstrate higher rates of rise and later plateaus. Bilirubin rates of rise tend to plateau and become null (equilibrium between bilirubin production and elimination) at about 96 hours of life. Rates of rise needed to cross percentile curves decrease over time but are lower (approximately 0.11 mg/dL/h [to convert bilirubin level to micromoles per liter, multiply by 17.104]) in the first 48 hours of life than previously thought. CONCLUSIONS: Transcutaneous bilirubin levels plateau and then decrease after about 96 hours of life in healthy neonates, with some differences across populations. A bilirubin rate of rise higher than in the previous period implies that bilirubin production exceeds elimination and indicates high risk for subsequent hyperbilirubinemia in neonates.