COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients. METHODS: Data were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test. RESULTS: Sixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored. CONCLUSIONS: Severe disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.

Prognostic neurodevelopmental testing of preterm infants: do we need to change the paradigm?

Longitudinal follow-up with assessment of developmental status at about 2 years of age is routine for high-risk newborns. The results of these assessments can be used for many purposes, including helping physicians, parents, and teachers plan educational or developmental interventions. These assessments also provide outcome measures for clinical research studies. Outcome results may also serve as a source of information for clinicians when counseling parents regarding provision of care for extreme preterm infants. Consideration should be given to use of different outcome metrics based on the purpose for testing. Categorization of composite cognitive, motor and neurosensory findings to define levels of impairment should be limited to research. Planning for individual interventions is better guided by descriptive findings. Current tools for assessing neurodevelopmental status at 2 years of age have important limitations. First, outcomes at early ages do not always predict function later in life. They are, at best, an estimate of longer-term outcomes, with important individual variation. For infants without severe neurologic injury, postnatal environmental factors play a predominant role in determining long-term cognitive and academic outcomes. Further investigations should assess quality of life and other considerations that are important for parents when making decisions about neonatal intensive care unit care for their infant.

Does diagnosis influence end-of-life decisions in the neonatal intensive care unit?

OBJECTIVE: To determine the influence of physiological status and diagnosis at the time of death on end-of-life care. STUDY DESIGN: Retrospective descriptive study in a regional referral level IV neonatal intensive care unit (NICU) of infants who died from 1 January 1999 to 31 December 2008. Infants were categorized based on diagnosis (very preterm, congenital anomalies or other) and level of stability. Primary outcome was level of clinical service provided at end of life (care withheld, care withdrawn or full resuscitation). RESULT: From 1999 to 2008, there were 414 deaths in the NICU. Congenital anomaly was the leading diagnosis at the time of death, representing 45% of all deaths. Comparing mode of death, very preterm newborns were more likely than infants with congenital anomalies to have received cardio-pulmonary resuscitation (CPR) at the time of death (26% vs 13%, P < 0.01) and were significantly more unstable (75% vs 52%, P < 0.01). Infants aged 22 to 24 weeks were mostly unstable and significantly more likely to receive CPR than infants with any other diagnosis. CONCLUSION: Over the 10-year period, very preterm infants were more likely to be physiologically unstable and to receive CPR at the time of death than infants with any other diagnosis. This finding was especially true for infants at the edge of viability (22 to 24 weeks). These differences in end-of-life care suggest that the quality of life and medical futility may be viewed differently for the least mature infants.

Prenatal ductal thrombosis presenting as cyanotic heart lesion.

We present a case of a late-preterm infant admitted for suspected cyanotic heart disease who was found to have a thrombosed ductus arteriosus. Maternal history was significant for heterozygosity for Factor V Leiden, treated with enoxaparin during her pregnancy, and congenital hearing loss. The neonate did not have a Factor V Leiden mutation detected, but was found to have a heterozygous mutation within the MFTHR gene. He was treated with anticoagulation, with improving hemodynamics measured by echocardiogram. This case presents a rare disease, which is potentially fatal if diagnosis is delayed.

Congenital duodenal obstruction: timing of diagnosis during the newborn period.

OBJECTIVE: To determine age at diagnosis for congenital duodenal obstruction in the neonatal period and the relationship to clinical outcomes. STUDY DESIGN: A children's hospital database reflecting a 7 (1/2)-year period was reviewed to identify infants with the diagnosis of duodenal obstruction in the neonatal period. Infants were grouped according to time of diagnosis: antepartum, postpartum in-hospital or after hospital discharge. Clinical descriptors and outcome variables were assessed between infants in these three groups. RESULT: In total, 27/51 (53%) infants were diagnosed antenatally. Infants with prenatal diagnosis were less mature, more likely to have Down syndrome or other birth defects and the pregnancy was more likely to be complicated by polyhydramnios. Of the 24 infants diagnosed postnatally, 8 (33%) were diagnosed after hospital discharge. These infants tended to be breast fed and discharged before 48 h of age. They had greater weight loss and more metabolic disturbances at readmission for surgery. One infant in the late diagnosis group died. CONCLUSION: Infants with congenital duodenal obstruction, particularly if breast fed, may not present with classical findings of upper gastrointestinal obstruction in the first days of life. Careful in-hospital evaluation of infants with persistent regurgitation, even low volume, is recommended to avoid missing this diagnosis.

Hypoxic respiratory failure: etiology and outcomes at one referral center 2000 through 2005.

OBJECTIVE: We calculated in a referral population of term and near-term infants with hypoxic respiratory failure (HRF) as a primary presenting problem the overall survival rate, the need for extracorporeal membrane oxygenation (ECMO) and the incidence of apparently irreversible disorders. STUDY DESIGN: All infants >or=36-week gestation admitted at 25. A total of 32 infants received ECMO, including all four who died, two with histologic evidence of pulmonary malformations and two with septic shock. CONCLUSION: Term or near-term infants with isolated HRF are likely to survive, given the low incidence of pulmonary disorders not supportable by inhaled nitric oxide or ECMO.

Neonatal complications of preterm premature rupture of membranes. Pathophysiology and management.

Midtrimester PROM is an infrequent, yet potentially disastrous complication of pregnancy. The most likely neonatal complication is preterm delivery with associated morbidity and mortality risks. Unique neonatal complications following PPROM include skeletal deformations and pulmonary hypoplasia related to prolonged oligohydramnios exposure. A systematic approach to an infant with respiratory insufficiency following PPROM delivery is possible with an understanding of the pathophysiology of pulmonary hypoplasia. Neonatal management should include immediate resuscitation including surfactant replacement, with careful attention to techniques of mechanical ventilation to avoid early volutrauma. Adjunctive therapies directed at pulmonary hypertension may now permit survival of some infants with less severe forms of pulmonary hypoplasia.

Thirty-six-month outcome of prenatal cocaine exposure for term or near-term infants: impact of early case management.

Gestational cocaine use is associated with serious pregnancy complications having fetal and neonatal implications. However, many cocaine-abusing women deliver uneventfully at term. The purpose of this study was to assess the neurodevelopmental outcome for term or near-term infants after prenatal cocaine exposure and to determine whether that outcome would be modified by early, intensive family case management. Cocaine-exposed infants identified after delivery at an urban hospital were alternately assigned to receive case management (n = 70) or routine follow-up (n = 48). A matched, non-drug-exposed group of infants was identified for comparison (n = 41). Infants aged up to 36 months were serially evaluated in a multidisciplinary clinic with cognitive, psychomotor, and language testing. Group comparisons were performed using one-way analysis of variance. There were no statistical differences in mean cognitive, psychomotor, or language quotients between cocaine-exposed and non-drug-exposed infant groups aged up to 36 months. At 6 months of age, case-managed cocaine-exposed infants had a significantly higher mean Bayley Mental Developmental Index score than those who were routinely managed. However, no differences were present at subsequent assessments. Among cocaine-exposed infants who remained with their mothers at 36 months, verbal scores were significantly higher for case-managed compared with routine-managed infants. The negative effects of urban, low socioeconomic status may overshadow the impact of prenatal cocaine exposure on early childhood outcome for those infants born without prenatal complications.

Developmental care teams in the neonatal intensive care unit: survey on current status.

Developmental Care Teams (DCT) have evolved in Neonatal Intensive Care Units (NICUs) in response to mounting evidence that developmental care is cost-effective and improves outcomes of critically ill newborns. Lack of national practice guidelines and standardized roles for DCT members prompted formulation and distribution of a questionnaire to obtain information regarding staff membership of DCTs, budgeting for DCTs, utilization of developmental care in practice, and education and developmental training of NICU staff. Questionnaires were sent to 50 NICUs in 30 states, with a return rate of 62% (31 of 50), representing 18 different states. Of those who responded, 64% had a DCT, and an additional 24% were in various phases of starting a team. Forty-three percent of the teams meeting on a regular basis did so monthly. Only 30% of those with a DCT had a dedicated budget to cover operating costs of their developmental program. Fifty-two percent of respondents had Neonatal Individualized Developmental Care and Assessment Program (NIDCAP)-certified staff at their institutions; however, nine other types of developmental specialists were also listed. Only four respondents indicated utilization of set criteria for initiation of a DCT consult, and 74% of those with DCTs initiated consults "when the need arises." NIDCAP assessments were used for parent teaching (54%), care plans (69%), care recommendations (46%), and at caregiver "discretion" (39%). The results of the survey validated an intense interest in developmental care. Approach to developmental care is variable between NICUs and implementation as outlined by NIDCAP is unusual. Practical guidelines for utilization and funding of DCTs are needed.

Survival and subsequent outcome to five years of age for infants with birth weights less than 801 grams born from 1983 to 1989.

OBJECTIVE: To determine the neurodevelopmental status for 5-year-old survivors with birth weights (BW) <801 gm born in the 1980s and to assess differences in outcome for those born from 1986 to 1989 compared with those born from 1983 to 1985. STUDY DESIGN: This investigation was a longitudinal follow-up of all infants with BW from 450 to 800 gm born at one of two hospitals in Kansas City, Mo., between January 1983 and December 1989. Medical records were reviewed at discharge to determine obstetric and neonatal interventions and complications. Neurodevelopmental outcome was assessed by a multidisciplinary evaluation at 60 +/- 3 months old. Multiple logistic regression analyses were used to determine factors statistically associated with survival and long-term outcome. RESULTS: The percentage of infants surviving to hospital discharge was not different between periods. From 1986 to 1989, there were more infants with BW <601 gm and <26 weeks' gestational age. Survival was greater for gestational age categories > or = 24 weeks. BW, gestational age, female gender (p < 0.0001), and birth era (p < 0.01) were each independently significantly associated with improved survival. At 5 years of age, there were no significant outcome differences between birth era cohorts. Overall, approximately 21% of infants had severe disabilities. Long-term outcome was significantly influenced by the occurrence of intracranial hemorrhage and socioeconomic status. CONCLUSION: For infants with BW <801 gm, survival of infants > or = 24 weeks' gestational age was greater in 1986 to 1989 compared with 1983 to 1985, although the 5-year neurodevelopmental outcome was not different between groups. The significant impact of social risk status on outcome suggests that factors outside the intensive care nursery must be addressed to improve long-term outcome.

Increased acinar arterial wall muscle in preterm infants with PROM and pulmonary hypoplasia.

Pulmonary hypoplasia (PH), secondary to premature rupture of fetal membranes (PROM), is a frequent cause of pulmonary insufficiency in preterm infants. Pulmonary hypoplasia of diverse causes is usually associated with pulmonary hypertension. The objective of this study was to quantitate the acinar arterial wall thickness and muscularization in preterm infants with PROM that died with PH in comparison to age-matched controls. The left lung and pulmonary vasculature were perfused and fixed in a standard method in 16 infants with PROM and PH, and in 16 controls. In infants with PH, the alveolar ductal artery walls were nearly twice as thick as those of controls, 15.1 +/- 5.1% versus 7.4 +/- 1.3%, p < 0.0001. Ninety-one percent had muscle in the wall compared to 18% of controls. We conclude that infants with PROM and PH have increased pulmonary arterial muscularization, placing them at significant risk to have pulmonary hypertension. For these infants, therapy to reduce pulmonary vascular resistance should be instituted early.

Defining limits of survival: lethal pulmonary hypoplasia after midtrimester premature rupture of membranes.

OBJECTIVE: Our purpose was to determine prospectively whether sequential ultrasonographic assessment of amniotic fluid volume (< 1 cm vertical pocket constitutes severe oligohydramnios), in conjunction with other readily available clinical data, could predict the occurrence of pulmonary hypoplasia and neonatal mortality in pregnancies complicated by second-trimester premature rupture of membranes. STUDY DESIGN: Singleton pregnancies complicated by premature rupture of membranes at < 29 weeks' gestation were prospectively monitored by weekly ultrasonographic assessments. Stepwise multiple logistic regression analysis was used to determine the independent predictive value of ultrasonographically determined factors in the development of lethal pulmonary hypoplasia, neonatal mortality, and skeletal deformations. RESULTS: Neonatal mortality and pulmonary hypoplasia were statistically predicted by gestational age at rupture of membranes and interaction of premature rupture of membranes of > 14 days' duration with severe oligohydramnios. The occurrence of skeletal deformations was related to the interaction of duration of premature rupture of membranes and severe oligodramnios (p < 0.0001). Fetal breathing, fetal movements, and thoracic circumference/abdominal circumference ratios were not predictive of outcome. CONCLUSIONS: Both duration of severe oligohydramnios exposure and gestational age at premature rupture of membranes were independent significant predictors of increased neonatal risk. Severe oligohydramnios > 14 days after premature rupture of membranes at < 25 weeks' gestation has a predicted neonatal mortality of > 90%.

Cocaine detection in neonatal gastric aspirate samples.

We prospectively analyzed the feasibility and sensitivity of gastric fluid detection of cocaine compared with standard meconium analysis. Cocaine was detected in nearly half (45.5%) of gastric aspirate samples tested from infants in whom meconium was positive for cocaine. The time to sample acquisition was substantially shorter for gastric aspirate sampling versus meconium analysis. The possible ramifications of the presence of cocaine in amniotic fluid are discussed.

Evaluation of airway complications in high-risk preterm infants: application of flexible fiberoptic airway endoscopy.

OBJECTIVES: We sought to determine factors that would predict the development of subglottic stenosis (SGS) and tracheomalacia (TM) in preterm infants. The utility of a semiquantitative measurement of airway dimensions was assessed in relation to signs of airway complications. We also sought to determine from a high-risk population of infants those likely to have abnormal findings identified by bronchoscopic examination. METHODS: Prospective airway endoscopy was performed for preterm infants who were intubated for 7 days or more or who demonstrated chronic oxygen needs beyond 28 days after birth and 36 weeks postconceptional age. Subjects were 117 preterm (less than 36 weeks' gestation) infants from two level III intensive care nurseries. Endoscopy was used to classify the type and degree of airway injury. Subglottic stenosis was defined subjectively and compared with an objective measurement using subglottic spatial relations described as a trans-subglottic/vocal cord ratio (TSG/VC). Clinical signs and symptoms and other risk factors were evaluated as significant predictors of SGS and TM, identified by bronchoscopy. RESULTS: Moderate or severe airway abnormalities were identified in 32 patients (27.3%); 13 with SGS, 17 with TM, and 2 with both. All but one infant with TSG/VC less than 0.83 had signs and symptoms of airway dysfunction. Variables more commonly found in patients with SGS included greater number of intubations, use of inappropriately large endotracheal tubes, and longer duration of intubation. Higher averaged mean airway pressure during the first week after birth and lower gestational age were clinical features associated with TM. CONCLUSIONS: Flexible bronchoscopic evaluation of a high-risk population demonstrated a higher incidence of moderate or severe SGS or TM than previously suspected. Subglottic stenosis and TM appear to have different etiologies based on different factors associated with their development. The TSG/VC ratio correlated well with obstructive symptoms and may represent a means to quantitate clinically subglottic narrowing. Infants with chronic lung disease who have persistently elevated partial pressure of carbon dioxide, apnea, or phonation abnormalities are most likely to have airway abnormalities identifiable by bronchoscopy.

Growth patterns for infants weighing less than 801 grams at birth to 3 years of age.

Anthropometric measurements of infants weighing < 801 gm were monitored to evaluate growth patterns from birth to 36 months chronologic age, using both standard growth percentiles and Z score descriptors. Mean gestational age was 25.8 weeks, and birth weight was 708.4 gm. The infants had growth delay at hospital discharge with some catch-up growth occurring in the first year. Discrete changes in body growth using the Z score as a descriptor showed movement from a negative SD at 12 months toward the reference mean of zero at 36 months. However, mean length remained < 5th percentile, and mean weight was at approximately the 10th percentile for chronologic age. At 36 months 45% of infants had a head circumference smaller than the 5th percentile for chronologic age. Birth weight < 701 gm was a significant predictor of smaller occipital-frontal circumference at 3 years (p = 0.03). Interruption of intrauterine growth after extremely premature birth appears to have long-term effects on growth outcome much like prenatal growth retardation.

Acquired subglottic cysts in the low-birth-weight infant. Characteristics, treatment, and outcome.

OBJECTIVE: To provide a descriptive summary of characteristics, including demographics, symptoms, risk factors, and outcome of acquired subglottic cysts identified in the neonatal period. DESIGN: Patient series. SETTING: A tertiary neonatal care unit and referral neonatal follow-up clinic. PARTICIPANTS: One hundred seventy-four preterm infants undergoing flexible bronchoscopy, 21 (12%) referred for airway evaluation because of symptoms and 153 (88%) examined consecutively following 7 days or more of endotracheal intubation. INTERVENTION: None. MEASUREMENTS/RESULTS: Subglottic cysts were identified in 11 (7.2%) of 153 preterm infants examined prospectively at discharge from the neonatal intensive care unit after prolonged intubation and two (10%) of 21 infants referred for airway evaluation. Infants with subglottic cysts were extremely preterm (mean +/- SEM gestation, 26.7 +/- 0.5 weeks) and very low birth weight (894.6 +/- 64.6 g). The mean duration of intubation was 28.5 +/- 5.0 days. Most infants, particularly those with large cysts, were symptomatic with stridor, hoarseness, or obstructive apnea. In two cases, airway symptoms began after discharge from the neonatal intensive care unit. Ten (91%) of the 11 patients were discharged receiving home oxygen. Generally, multiple cysts were present in the subglottic space, most prominently located in the posterior aspect of the trachea. Three of five patients with large cysts received a tracheostomy. Two additional patients had surgical marsupialization of the cysts, and six others experienced resolution without treatment. One patient with large cysts died of viral pneumonia 10 months after surgical intervention. An additional patient with large cysts died before surgical intervention secondary to chronic lung disease and cor pulmonale. All surviving infants had resolution of signs of airway obstruction and 10 of the 11 did not require supplemental oxygen or have symptoms of chronic pulmonary disease at age 1 year. CONCLUSION: Intubation-acquired subglottic mucous cysts in the neonate may occur more commonly than was previously recognized. Symptoms of this lesion may mimic features of chronic lung disease. Early identification of the cysts with flexible bronchoscopy is important since airway compromise may progress and surgical intervention may be lifesaving.