Anne Marie Reynolds

Preterm cord blood CD4+ T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4+ T cells in bronchopulmonary dysplasia

BACKGROUND Chorioamnionitis (CA) is associated with premature delivery and bronchopulmonary dysplasia (BPD). We hypothesize that preterm infants exposed to CA have reduced suppressive regulatory T cells (Treg) and increased non-regulatory T cell pro-inflammatory cytokines, increasing risk for BPD. OBJECTIVE To evaluate cord blood CD4(+) T cell regulatory phenotype and pro-inflammatory cytokine production in CA and BPD groups. STUDY DESIGN Cord blood mononuclear cells from infants (GA ⩽32 weeks), with or without placental histological evidence of CA (hChorio), were analyzed by flow cytometry. Clinical information was collected by retrospective chart review. Numbers of putative Treg (CD4(+)FoxP3(+)CD25(+)CD127Dim), CD4(+) non-Tregs, and CD4(+) T cell intracellular cytokine content following in vitro stimulation were compared with CA status and oxygen requirement at 36weeks postmenstrual age. RESULT Absolute Treg numbers were not different in CA and non-CA exposed samples. However, the infants who developed BPD had a significant decrease in Treg and non-regulatory T cell numbers. Greater IL-6 production was observed in hCA group. CONCLUSION A pro-inflammatory CD4(+) T cell status is noted in CA and BPD but the later disease is also associated with decrease in Tregs, suggesting that the development of BPD is marked by distinct inflammatory changes from those of CA exposed infants.

Pilot trial of late booster doses of surfactant for ventilated premature infants.

Objective:Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant.Study Design:A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period.Result:For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO2 × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment.Conclusion:Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

Developmentally determined reduction in CD31 during gestation is associated with CD8+ T cell effector differentiation in preterm infants.

Homeostatic T cell proliferation is more robust during human fetal development. In order to understand the relative effect of normal fetal homeostasis and perinatal exposures on CD8+ T cell behavior in PT infants, we characterized umbilical cord blood CD8+ T cells from infants born between 23-42weeks gestation. Subjects were recruited as part of the NHLBI-sponsored Prematurity and Respiratory Outcomes Program. Cord blood from PT infants had fewer naïve CD8+ T cells and lower regulatory CD31 expression on both naïve and effector, independent of prenatal exposures. CD8+ T cell in vitro effector function was greater at younger gestational ages, an effect that was exaggerated in infants with prior inflammatory exposures. These results suggest that CD8+ T cells earlier in gestation have loss of regulatory co-receptor CD31 and greater effector differentiation, which may place PT neonates at unique risk for CD8+ T cell-mediated inflammation and impaired T cell memory formation.

Oxygen resuscitation and oxidative-stress biomarkers in premature infants

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Research and Reports in Neonatology 2014:4 91–99 Research and Reports in Neonatology

White blood cell left shift in a neonate: a case of mistaken identity

We present a full-term male infant who presented with tachypnea and an increased band count on his complete blood count (CBC) with an immature to total neutrophil (I:T) ratio of 0.6 raising suspicion of early onset sepsis. A blood culture was drawn and he was started on appropriate antibiotics. The patients clinical condition rapidly improved; however, the white cell count ‘left shift’ persisted. When a detailed family history was obtained, it was discovered that the father, paternal uncle and the grandfather had been diagnosed with Pelger-Huet anomaly (PHA). As the urine, blood and CSF cultures were all negative in this now well-appearing infant, the left shift on the CBC was believed to be due to inheritance of the PHA. We present this case to emphasize that even in this age of sophisticated laboratory evaluation, a good clinical history, including family history, and clinical evaluation, are essential for accurate diagnosis.

Apnea, bradycardia and desaturation spells in premature infants: impact of a protocol for the duration of ‘spell-free’ observation on interprovider variability and readmission rates

Objective:To study the impact of implementing a protocol to standardize the duration of observation in preterm infants with apnea/bradycardia/desaturation spells before hospital discharge on length of stay (LOS) and readmission rates.Study design:A protocol to standardize the duration of in-hospital observation for preterm infants with apnea, bradycardia and desaturation spells who were otherwise ready for discharge was implemented in December 2013. We evaluated the impact of this protocol on the LOS and readmission rates of very low birth weight infants (VLBW). Data on readmission for apnea and an apparent life-threatening event (ALTE) within 30 days of discharge were collected. The pre-implementation epoch (2011 to 2013) was compared to the post-implementation period (2014 to 2016).Results:There were 426 and 368 VLBW discharges before and after initiation of the protocol during 2011 to 2013 and 2014 to 2016, respectively. The LOS did not change with protocol implementation (66±42 vs 64±42 days before and after implementation of the protocol, respectively). Interprovider variability on the duration of observation for apneic spells (F–8.8, P=0.04) and bradycardia spells (F–17.4, P<0.001) decreased after implementation of the protocol. The readmission rate for apnea/ALTE after the protocol decreased from 12.1 to 3.4% (P=0.01).Conclusion:Implementing an institutional protocol for VLBW infants to determine the duration of apnea/bradycardia/ desaturation spell-free observation period as recommended by the American Academy of Pediatrics clinical report did not prolong the LOS but effectively reduced interprovider variability and readmission rates.

T cell developmental arrest in former premature infants increases risk of respiratory morbidity later in infancy

The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31-TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associate abnormal T cell development with health outcomes in infants.

Defining the effects of prematurity on the lymphocyte transcriptome.

Methods Peripheral blood samples were collected from premature infants at the time of hospital discharge at multiple sites and shipped to a central laboratory. Freshly purified PBMCs were isolated by Ficoll gradient centrifugation, sorted into individual lymphocyte cell types, and processed for total RNA. RNA isolated from CD8 lymphocytes (n=79) was used for RNA-Seq analysis using the Illumina HiSeq2500. Sequences were aligned using the SHRiMP algorithm and expression values were summarized using HTSeq. Normalized gene expression data were analyzed for significant changes in expression using various statistical approaches. Ingenuity Pathway Analysis software was used for gene set interpretation.

Ultrasound guided percutaneous relief of tension pneumomediastinum in a 1-day-old newborn.

A 35-week gestational age baby with antenatal diagnosis of probable infantile polycystic kidney disease born via normal vaginal delivery required immediate intubation and ventilation in the delivery room. On admission, the baby’s blood pressure was normal (mean of 42 mm Hg) and pulse oximetry read 96% on 100% Fio2. An x ray showed moderate pneumomediastinum. Within 2 h the baby’s blood pressure …