Neonatal Diagnosis of Alveolar Capillary Dysplasia via Rapid Genomic Sequencing: A New Gold Standard?

Classic alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare congenital lung disorder presenting in the early neonatal period with refractory hypoxemic respiratory failure and pulmonary hypertension. No curative treatment is currently available. Although definitive diagnosis is obtained by histology, lung biopsy is often challenging in unstable, critically ill neonates. Molecular diagnosis has been achieved with chromosomal microarray and targeted gene sequencing; however, each of these modalities can be limited by turnaround time, coverage of the genome, and inability to detect all pathogenic variant types for ACDMPV. We present a case of ACDMPV diagnosed via rapid genome sequencing and posit that rapid genomic sequencing, including both rapid exome and genome sequencing, has an expanding role in severe neonatal respiratory failure as a comprehensive and noninvasive approach to timely diagnosis.

A quality improvement initiative to reduce necrotizing enterocolitis in high-risk neonates.

OBJECTIVE: Prompted by an acute increase in necrotizing enterocolitis (NEC) rates, we aimed to decrease the rate of stage 2 or greater NEC in infants born at <1500 grams or <30 weeks gestational age from 19.5% to less than 9.7% (a 50% reduction) within 18 months, without adversely affecting central line-associated bloodstream infection (CLABSI) rates. STUDY DESIGN: We utilized Define, Measure, Analyze, Improve, and Control (DMAIC) as our improvement model. Informed by our key driver diagram and root cause analyses, six Plan-Do-Study-Act cycles were completed. RESULTS: 147 infants in the QI initiative had a median gestational age of 28.1 weeks and a median birthweight of 1070 grams. NEC rates decreased from the QI baseline of 19.5% to 6% (p = 0.03). Oral care administration increased, and maximal gavage tube dwell time decreased. CONCLUSION: NEC rates decreased during this QI initiative through a combination of multidisciplinary interventions aimed at reducing dysbiosis.

Refining interpretation of transcutaneous bilirubin measurement in newborns born late preterm.

BACKGROUND: Transcutaneous bilirubin (TCB) monitoring is widely used for jaundice screening in the newborn period. Limited data exists on adjusting TCB for bias in late preterm infants. The objective of this study was to determine the median bias between transcutaneous bilirubin and total serum bilirubin levels in newborns born at 35-36 weeks' gestation. METHODS: This was a retrospective cohort study of late preterm infants born at 35-0/7 to 36-6/7 weeks' gestation who were admitted to a level III neonatal intensive care unit from May 2018 to February 2020. Transcutaneous and total serum bilirubin levels were assessed within 2 h of each other during the first 60 h of life. Bland-Altman plots were used to evaluate transcutaneous bilirubin bias. Bilirubin risk stratification based on age (in hours) was done using an adaptation of the Bhutani nomogram for transcutaneous, adjusted transcutaneous, and total serum bilirubin measurements. RESULTS: The median bias between transcutaneous and total serum bilirubin bias was 2.4 mg/dL (IQR 1.7-3.4, 95% CI 2.2-2.7). The kappa statistic demonstrated slight agreement between the unadjusted transcutaneous bilirubin and total serum bilirubin (k = 0.033, p = 0.194. The kappa statistic demonstrated fair agreement between an adjusted transcutaneous bilirubin (subtract 1 mg/dL) and total serum bilirubin (k = 0.298, p < 0.0001) and moderate agreement between another adjusted transcutaneous bilirubin (subtract 2 mg/dL) and total serum bilirubin (k = 0.430, p < 0.0001). CONCLUSION: In a single center study of late preterm infants, transcutaneous bilirubin systematically overestimated the total serum bilirubin level. Subtracting 1 mg/dL from the transcutaneous bilirubin identified infants with total serum bilirubin levels in the high or high intermediate risk range. Adjusting the transcutaneous bilirubin prior to risk stratification may reduce unnecessary blood draws for total serum bilirubin. Studies of racially and ethnically diverse newborns using various transcutaneous bilirubin meters are needed prior to broad application of the adjusted transcutaneous bilirubin approach.

Association of outborn versus inborn birth status on the in-hospital outcomes of neonates treated with therapeutic hypothermia: A propensity score-weighted cohort study.

OBJECTIVE: To compare the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. METHODS: The association of outborn birth status with in-hospital mortality and morbidity, prior to NICU discharge or transfer, was assessed in a large historical cohort of neonates who had therapeutic hypothermia initiated on the day of birth. The cohort was restricted to neonates born at ≥35 weeks gestational age from 2007 to 2018. Since the sample was non-random, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalance in baseline maternal and neonatal characteristics between outborn and inborn neonates. Cox proportional hazards regression was used to assess the association between outborn status and in-hospital mortality. RESULTS: There were 4447 neonates included in the study (2463 outborn). Outborn status was not significantly associated with an increased risk of in-hospital mortality in the unadjusted cohort (HR = 1.17, 95% CI 0.97-1.42, p = 0.10) or IPW cohort (HR = 1.09, 95% CI 0.95-1.26, p = 0.22). However, in the IPW cohort, outborn neonates were significantly more likely to have seizures (28% vs 24%, p = 0.006), anticonvulsant exposure (46% vs 41%, p = 0.002), and gastrostomy tube placement (5.8% vs 3.8%, p = 0.009) during their newborn hospitalization. CONCLUSION: Outborn status was not significantly associated with increased in-hospital mortality among neonates treated with whole body hypothermia. However, outborn neonates were more likely to have seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement. Further study is needed to better understand the etiologies of these outcome disparities and potential implications for long-term neurodevelopmental outcomes.

Profound Hypotonia and Respiratory Failure due to Suspected Nemaline Myopathy in a Preterm Infant.

Congenital myopathies, such as nemaline myopathy, may present with hypotonia and respiratory failure in the neonatal period. Respiratory function can be further compromised in affected infants by the development of chylous effusions. We present the case of a preterm male infant born at 32 6/7 weeks' gestation, who was profoundly hypotonic and required intubation at birth. His clinical course progressed from acute to chronic respiratory failure with mechanical ventilation dependence. He developed bilateral chylous pleural effusions during the newborn period. Whole exome sequencing identified an ACTA1 gene mutation leading to the presumed diagnosis of nemaline myopathy. This case highlights the need to include congenital myopathies in the differential for a preterm newborn with hypotonia and respiratory failure.

Reducing Opioid Exposure in a Level IV Neonatal Intensive Care Unit.

INTRODUCTION: Infants in neonatal intensive care units require painful and noxious stimuli as part of their care. Judicious use of analgesic medications, including opioids, is necessary. However, these medications have long- and short-term side effects, including potential neurotoxicity. This quality improvement project's primary aim was to decrease opioid exposure by 33% in the first 14 days of life for infants less than 1,250 g at birth within 12 months. METHODS: A multidisciplinary care team used Define, Measure, Analyze, Improve, Control methodology to identify root causes of the quality gap including: (1) inconsistent reporting of objective pain scales; (2) variable provider prescribing patterns; and (3) variable provider bedside assessment of pain. These root causes were addressed by two interventions: (1) standardized reporting of the premature infant pain profile scores and (2) implementation of an analgesia management pathway. RESULTS: Mean opioid exposure, measured in morphine equivalents, in infants less than 1,250 g at birth during their first 14 days of life decreased from 0.64 mg/kg/d (95% confidence interval 0.41-0.87) at baseline to 0.08 mg/kg/d (95% confidence interval 0.03-0.13) during the postintervention period (P < 0.001). There was no statistical difference in rates of days to full feedings, unintentional extubations, or central line removals between epochs. CONCLUSIONS: Following the implementation of consistent pain score reporting and an analgesia management pathway, opioid exposure in the first 14 days of life for infants less than 1,250 g was significantly reduced by 88%, exceeding the project aim.

Improving Infant Vaccination Status in a Level IV Neonatal Intensive Care Unit.

BACKGROUND AND OBJECTIVES: Infants in NICUs are at risk for underimmunization. Adherence to the routine immunization schedule recommended by the Advisory Committee for Immunization Practices minimizes the risk of contracting vaccine-preventable illnesses in this vulnerable population. From January 2015 to June 2017, only 56% (419 of 754) of the infants in our Mayo Clinic level IV NICU were fully up to date for recommended immunizations at the time of discharge or hospital unit transfer. We aimed to increase this rate to 80% within 6 months. METHODS: Using the quality improvement methodology of Define, Measure, Analyze, Improve, Control, we analyzed baseline data, including provider and nursing surveys using a fishbone diagram, the 5 Whys, and a Pareto chart. We identified 3 major root causes of the quality gap: lack of provider knowledge of the routine immunization schedule, failure of providers to order vaccines when due, and hesitancy of parents toward vaccination. Using plan-do-study-act cycles, 5 improvement interventions were implemented. These included an intranet resource for NICU providers on the routine immunization schedule, an Excel-based checklist to track when immunizations were due, and provider education on parental vaccine hesitancy and vaccine safety. RESULTS: During the 19-month improve and control phases of the project, the fully immunized rate at the time of NICU discharge or transfer rose from a baseline of 56% (419 of 754) to 93% (453 of 488), with a P value <.001. CONCLUSIONS: Our NICU significantly improved infant immunization rates with a small number of interventions. These interventions may be generalizable to other NICUs with low infant immunization rates.

Infant male with TARP syndrome: Review of clinical features, prognosis, and commonalities with previously reported patients.

TARP syndrome (talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava) is a rare X-linked condition. As more patients are identified through genetic testing, it is increasingly clear that the original TARP acronym does not fully describe the complete phenotypic spectrum of this syndrome. The presented patient had genetically confirmed TARP syndrome and demonstrated new findings of hydronephrosis and hemodynamically significant hypertrophic obstructive cardiomyopathy. The patient also had physical findings common with previously reported individuals with TARP syndrome in the literature but not described by the TARP acronym. These features include central nervous system dysfunction, renal abnormalities, cardiac lesions other than atrial septal defect or persistent left superior vena cava, and distal limb defects other than talipes equinovarus. By adding to the known spectrum of the TARP phenotype, this report will aid clinicians as they care for patients with this rare condition.