We examined whether enhanced glutamate release contributes to the expression of persistent spontaneous nociceptive behaviours (SNBs) in rats induced by intrathecal (i.t.) administration of the selective group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG). Pretreatment with drugs that have been shown to inhibit glutamate release, including a group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group III mGluR agonist L-2-amino-4-phosphonobutyrate (L-AP4), or the use-dependent sodium channel blockers 3,5-diamino-6-(2,3-diclorophenyl)-1,2,4-triazine (lamotrigine) and 2-amino-6-trifluoromethoxybenzothiazole (riluzole), produced dose-dependent reductions in (RS)-DHPG-induced SNBs. We have also shown that incubation of rat lumbar spinal cord slices with (RS)-DHPG potentiates 4-aminopyridine-evoked (4-AP) release of glutamate. Furthermore, we found that destruction of unmyelinated primary afferent C-fibres by neonatal capsaicin treatment significantly reduced (RS)-DHPG-induced SNBs in adult rats. Together, these results suggest that (RS)-DHPG-induced nociception is dependent on spinal glutamate release, probably from primary afferent C-fibres.

Objective

To determine patterns of respiratory medications used in neonatal intensive care unit graduates.

Study design

The Prematurity Respiratory Outcomes Program enrolled 835 babies <29 weeks of gestation in the first week. Of 751 survivors, 738 (98%) completed at least 1, and 85% completed all 4, postdischarge medication usage in-person/telephone parental questionnaires requested at 3, 6, 9, and 12 months of corrected age. Respiratory drug usage over the first year of life after in neonatal intensive care unit discharge was analyzed.

Results

During any given quarter, 66%-75% of the babies received no respiratory medication and 45% of the infants received no respiratory drug over the first year. The most common postdischarge medication was the inhaled bronchodilator albuterol; its use increased significantly from 13% to 31%. Diuretic usage decreased significantly from 11% to 2% over the first year. Systemic steroids (prednisone, most commonly) were used in approximately 5% of subjects in any one quarter. Inhaled steroids significantly increased over the first year from 9% to 14% at 12 months. Drug exposure changed significantly based on gestational age with 72% of babies born at 23-24 weeks receiving at least 1 respiratory medication but only 40% of babies born at 28 weeks. Overall, at some time in the first year, 55% of infants received at least 1 drug including an inhaled bronchodilator (45%), an inhaled steroid (22%), a systemic steroid (15%), or diuretic (12%).

Conclusion

Many babies born at <29 weeks have no respiratory medication exposure postdischarge during the first year of life. Inhaled medications, including bronchodilators and steroids, increase over the first year.

OBJECTIVE:To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs). STUDY DESIGN:We enrolled ELGANs (<29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy. RESULTS:Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907. CONCLUSION:Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01435187.