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Congenital central hypoventilation syndrome (CCHS) is a rare disorder that affects central control of breathing and paediatric treatment varies worldwide. One approach is diaphragm pacing (DP), by phrenic nerve stimulation or direct diaphragm muscle stimulation, with or without a tracheostomy. In Sweden, non-invasive ventilation (NIV) has been the first-line ventilator support for patients with CCHS. However, disadvantages such as midface hypoplasia and unintentional leakage have required assessment over time. DP implants are provided at the National Reference Center for Diaphragm Pacing at Uppsala University Hospital, Sweden, at 3-4 years of age, when the upper airways have become more stable. Some international centres wait until children are older. Our aim was to evaluate switching patients with CCHS from mechanical ventilation, namely tracheostomy or NIV, to DP.

Background: The hyaluronan (HA) receptors CD44 and RHAMM (CD168) are involved in cellular proliferation, differentiation, and motility. As previously investigated, HA and RHAMM expression in human neonatal lungs correlates to gestational age (GA) and air content.

Methods:  CD44 immunofluorescence was analyzed in postmortem lung samples from infants (n=93;22-41GA) by digital image analysis together with clinical data, including RHAMM expression, lung air and HA content by hierarchical clustering.

Results: Five groups were defined according to RHAMM/CD44 expression, GA, and postnatal age (PNA): extremely-to-very preterm (EVP;22-31GA; Groups 1-2), moderately preterm-to-term (MPT;31-41GA; Groups 3-4) and mixed preterm-to-term (27-40GA; Group 5). CD44 correlated linearly with RHAMM in MPT (r=0.600;p<0.004). In EVP, high CD44 and low RHAMM corresponded with high PNA and lung air content independently of HA and GA (Group 1 vs 2;p<0.05 respectively). In MPT, high and low CD44 corresponded with low and high RHAMM independently of GA, HA and lung air content (Group 3 vs 4;p<0.001). No correlation between CD44 and GA/PNA at death was observed.

Conclusions: A linear correlation between CD44 and RHAMM expression occurs during the late saccular phase of lung development at birth, whereas postnatal influences on CD44 and RHAMM expression in extremely-to-very preterm infants cannot be excluded. 

BACKGROUND: The aim of the present study was to investigate pulmonary stretch receptor activity (PSR) under different peak inspiratory pressures (PIPs) and inspiratory pressure waveforms during partial liquid (PLV) and gas ventilation (GV).

METHODS: PSR instantaneous impulse frequency (PSRf_imp) was recorded from single fibers in the vagal nerve during PLV and GV in young cats. PIPs were set at 1.2/1.8/2.2/2.7 kPa, and square and sinusoidal pressure waveforms were applied.

RESULTS: PSRf_imp at the start of inspiration increased with increasing PIPs, and was steeper and higher with square than with sinusoidal waveforms (p < 0.05). Total number of impulses, peak and mean PSRf_imp were lower during PLV than GV at the lowest and highest PIPs (p < 0.025). Time to peak PSRf_imp was shorter with square than with sinusoidal waveforms at all pressures and ventilations (p < 0.005). Irrespective of waveform, lower PIPs yielded lower ventilation during PLV.

CONCLUSION: As assessed by PSRf_imp, increased PIPs do not expose the lungs to more stretching during PLV than during GV, with only minor differences between square and sinusoidal waveforms.

Aim

We assessed whether early haemodynamically significant patent ductus arteriosus (hsPDA) predicted persistent patent ductus arteriosus (PDA) in extremely preterm infants.

Methods

This prospective observational study of 60 infants born at 22–27 weeks of gestational age (GA) without any major congenital anomalies or heart defects was conducted at Uppsala University Children's Hospital from November 2012 to May 2015. Respiratory and systemic circulatory parameters were continuously recorded, and echocardiographic examinations performed daily during the first three days of life. Pharmacological treatment was initiated if hsPDA was found on days two to seven. Persistent PDA was diagnosed if hsPDA remained after pharmacological treatment or pharmacological treatment was contraindicated.

Results

The infants (56% male) had a median GA of 25 + 2 weeks and 50% received pharmacological treatment. PDA was persistent in 30% and ultimately closed or insignificant in 70%. hsPDA on days two to seven was not associated with future persistent PDA (p = 1.000). Mechanical ventilation (p = 0.025), high mean airway pressure (p = 0.020) and low ductal maximal flow velocity (V_max) (p = 0.024) on day two were associated with future persistent PDA.

Conclusion

Early hsPDA did not predict persistent PDA, but the early need for assisted ventilation and low ductal V_max were associated with future persistent PDA in these extremely preterm infants.

Background

Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.

Methods

Infants born at 22–27 weeks’ gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.

Results

High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.

Conclusions

High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.