Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report.

BACKGROUND: We report a case of the neonatal interstitial lung disease pulmonary interstitial glycogenosis in a girl with Jacobsen syndrome. While Jacobsen syndrome is caused by a deletion on the long arm of chromosome 11 and is genetically confirmed, pulmonary interstitial glycogenosis is of unknown etiology and is diagnosed by lung biopsy. Pulmonary interstitial glycogenosis has not previously been described in association with Jacobsen syndrome. CASE PRESENTATION: A term newborn small for gestational age Caucasian girl presented with respiratory distress, pulmonary hypertension, congenital heart defects, immunodeficiency, and thrombocytopenia. She was diagnosed with Jacobsen syndrome, but also had pulmonary interstitial glycogenosis, which contributed to significant morbidity. There was striking clinical improvement after steroid treatment of the pulmonary interstitial glycogenosis. CONCLUSIONS: Interstitial lung disease should be considered as a differential diagnosis when respiratory distress and hypoxemia in the perinatal period worsens or persists despite standard treatment. Importantly, pulmonary interstitial glycogenosis may be treatable with corticosteroids. Whether there is a genetic link between pulmonary interstitial glycogenosis and Jacobsen syndrome is still unknown.

Therapeutic hypothermia and N-PASS; results from implementation in a level 3 NICU.

BACKGROUND: Neonates that have been subjected to perinatal asphyxia and fulfill criteria for therapeutic hypothermia are cooled to 33.5 °C for 72 h. There is no consensus regarding sedation and analgesic use during hypothermia, but there is evidence supporting the importance of pain relief and adequate sedation. There is a need for assessment of the neonates need for pain relief and sedation, and for adjustments of medication to ensure adequate treatment. There are many different scoring tools available. We found the N-PASS (Neonatal Pain, Agitation and Sedation Scale) scoring tool to be the most suitable for this patient group as it assesses both pain and sedation. METHODS: We translated the scoring tool according to guidelines published by Wilder et al., and scored neonates treated with therapeutic hypothermia. Sedation and analgesia were adjusted according to scoring results. At the end of the study a questionnaire was filled out by the nurses in charge of this group of patients. RESULTS: Both pain and sedation scores did not reach the desired levels until day 3. The nurses reported a high level of satisfaction (79.7% were extremely of very satisfied), and 96.7% of the nurses found the neonates to be better pain relieved after the initiation of the study. CONCLUSION: The implementation of the N-PASS scoring tool in our unit has been successful, and has led to better pain relief and sedation than before the implementation.

Severe persistent pulmonary hypertension of the newborn and dysmorphic features in neonate with a deletion involving TWIST1 and PHF14: a case report.

BACKGROUND: Persistent pulmonary hypertension is a well-known disease of the newborn that in most cases responds well to treatment with nitric oxide and treatment of any underlying causes. Genetic causes of persistent pulmonary hypertension of the newborn are rare. The TWIST1 gene is involved in morphogenetics, and deletions are known to cause Saethre-Chotzen syndrome. Deletions of PHF14 have never been reported in neonates, but animal studies have shown a link between severe defects in lung development and deletions of this gene. There have not, to the best of our knowledge, been any publications of a link between the genes TWIST1 and PHF14 and persistent pulmonary hypertension of the newborn, making this a novel finding. CASE PRESENTATION: We describe a white male neonate born at term to non-consanguineous white parents; he presented with dysmorphic features and a therapy-refractory persistent pulmonary hypertension. Array-based comparative genomic hybridization revealed the presence of a 14.7 Mb interstitial deletion on chromosome 7, encompassing the genes TWIST1 and PHF14. CONCLUSIONS: The TWIST1 gene can explain our patient's dysmorphic features. His severe persistent pulmonary hypertension has, however, not been described before in conjunction with the TWIST1 gene, but could be explained by involvement of PHF14, consistent with findings in animal experiments showing lethal respiratory failure with depletion of PHF14. These findings are novel and of importance for the clinical management and diagnostic workup of neonates with severe persistent pulmonary hypertension of the newborn and dysmorphic features.

Nicotine affects the expression of brain-derived neurotrophic factor mRNA and protein in the hippocampus of hypoxic newborn piglets.

Brain-derived neurotrophic factor (BDNF) is highly expressed in the developing brain. It has anti-apoptotic abilities, and protects the neonatal brain. In experimental settings in adult animals, pre-treatment with nicotine has shown increased BDNF levels, indicating a possible contribution to nicotine's anti-apoptotic effect. Apoptosis contributes to the development of brain damage in perinatal asphyxia. We examined the effects of nicotine on apoptosis-inducing factor (AIF), caspase-3 and BDNF in the hippocampus of a neonatal piglet model of global hypoxia. Forty-one anesthetized newborn piglets were randomized to one of four groups receiving different infusions after hypoxia (1) nicotine 130 microg/kg/h, 2) 260 microg/kg/h, 3) adrenaline, and 4) saline, all 2.6 mL/kg/h. Four hours after hypoxia they were euthanized. The left hemisphere/hippocampus was examined by histopathology and immunohistochemistry; the right hippocampus was analyzed using real time PCR. There was a significantly higher expression of BDNF mRNA and protein in the animals treated with nicotine 130 microg/kg/h vs. the saline treated group (mRNA P=0.038; protein P=0.009). There were no differences regarding AIF or caspase-3. We conclude that nicotine (130 microg/kg/h), infused over 1 h after global hypoxia in neonatal piglets, increases levels of both BDNF mRNA and protein in the hippocampus. This might imply neuroprotective effects of nicotine in asphyxiated neonates.

Nicotine in a small-to-moderate dose does not cause a significant increase in plasma catecholamine levels in newborn piglets.

BACKGROUND: Nicotine has a wide range of effects. Several studies are being undertaken investigating the positive effects on inflammation and apoptosis. Recently, nicotine has been investigated in a piglet model of perinatal asphyxia, where the question has been raised whether nicotine's effect on the sympathetic nervous system can explain some of the positive effects. OBJECTIVES: We hypothesized that nicotine in small-to-moderate doses would not cause a significant increase in plasma catecholamine levels, whereas a higher dose would give a significant effect, confirming the believed dose-dependent matter in which nicotine exerts its effect on the sympathetic nervous system. METHODS: Seventeen anesthetized newborn piglets were randomized to one of three doses of nicotine (130, 260 or 1,000 microg/kg/h) that was given intravenously for 1 h. Blood samples for catecholamine analyzes were drawn at baseline and at the end of the infusion. Catecholamines were determined using HPLC. RESULTS: No significant increase in catecholamines was detected in the animals treated with the small or moderate nicotine doses, whereas the higher dose gave a significant increase in adrenaline (p = 0.019). CONCLUSION: Nicotine in small-to-moderate doses does not cause significant increase in plasma catecholamines, thus indicating that the positive effects of nicotine in studies using these doses most likely cannot be explained by the systemic release of catecholamines.

Effects of nicotine infusion on striatal glutamate and cortical non-protein-bound iron in hypoxic newborn piglets.

BACKGROUND: Perinatal asphyxia triggers a large cascade of mechanisms leading to brain damage. Release of glutamate and increased oxidative stress play substantial roles. Non-protein-bound iron (NPBI), which contributes to the production of free radical species through the Fenton reaction, increases in hypoxic-ischemic brain damage. Results from in vitro and adult animal studies show that nicotine can decrease extracellular levels of NPBI and glutamate. Nicotine's effects have further been shown to be dose-dependent, with lower doses showing neuroprotective, and higher doses showing neurotoxic effects. OBJECTIVES: We wished to assess nicotine's effect on levels of NPBI and glutamate in an animal model of neonatal hypoxic-ischemic brain damage. METHODS: 47 anesthetized newborn piglets were randomized to one of four infusions after hypoxia (nicotine 130 microg/kg/h, 260 microg/kg/h, adrenaline 0.05 microg/kg/min, saline 2.6 ml/kg/h). Glutamate in striatum and NPBI in cortex were analyzed in microdialysate. RESULTS: Striatal glutamate presented a significant rise for all the animals from baseline to the end of hypoxia (p < 0.001). There was a significant difference for nicotine 130 microg/kg/h versus saline (p = 0.002) 2 h after hypoxia. Cortical NPBI presented a significant rise from baseline to the end of hypoxia for all the animals (p < 0.001), and a significant difference between nicotine 130 microg/kg/h versus saline 2 h after hypoxia (p = 0.013). CONCLUSION: Our findings support the hypothesis that nicotine can decrease extracellular levels of glutamate and NPBI in a neonatal model of hypoxic-ischemic brain damage. This suggests possible neuroprotective effects of a low dose of nicotine in neonates, as it has already been shown in adult models.