Does duration of caffeine therapy in preterm infants born ≤1250 g at birth influence neurodevelopmental (ND) outcomes at 3 years of age?

OBJECTIVE: To evaluate the effect of duration of caffeine use on long-term neurodevelopmental (ND) outcomes at 3 years corrected age (CA) in preterm infants with birthweights (BW) ≤ 1250 g. DESIGN/METHODS: All surviving infants with BW ≤ 1250 g admitted to the Foothills Medical Center neonatal intensive care unit (NICU) from January 2002 to December 2009 who received the first dose of caffeine in the first week of life and were followed up at three years CA were included in the study. Demographics and follow-up outcomes were compared based on early cessation of caffeine ≤ 14 days (ECC), intermediate cessation of caffeine 15-30 days (ICC), and late cessation of caffeine >30 days (LCC). The primary outcome of ND impairment was present if a child had any one of the following: cerebral palsy, cognitive delay, visual impairment, or hearing impairment or deafness. Univariate and logistic regression analyses were performed. RESULTS: Of the 508 eligible infants, 448 (88%) were seen at 3 years CA at follow-up. ECC (n = 139), ICC (n = 122) and LCC (n = 187) groups had a median (range) BW of 979 (560-1250), 1010 (530-1250), and 980 (520-1250) g (p = 0.524) and median (range) gestational age (GA) of 27 (23-33), 28 (24-33), and 27 (24-32) weeks, respectively (p = 0.034). In logistic regression models adjusting for GA, maternal smoking, and each neonatal risk factor separately (IVH, NEC, sepsis, blood transfusions, BPD, postnatal dexamethasone, SNAP-II, and ventilator days), none of the models showed a statistically significant association between caffeine duration and ND impairment. CONCLUSION: The duration of caffeine use in premature infants in the NICU does not impact on long-term ND outcomes at 3 years CA.

A review of international clinical practice guidelines for the use of oxygen in the delivery room resuscitation of preterm infants.

AIM: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery. METHODS: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life. RESULTS: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets. CONCLUSION: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice.

Neurodevelopmental outcomes of preterm infants resuscitated with different oxygen concentration at birth.

OBJECTIVE: To compare the neurodevelopmental outcomes at 18 to 21 months corrected age (CA) of infants born at <29 weeks that received room air, an intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. STUDY DESIGN: In this retrospective cohort study, we compared neonatal and neurodevelopmental outcomes at 18 to 21 months CA among inborn infants born before 29 weeks' gestation that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. RESULTS: Of 1509 infants, 445 received room air, 483 received intermediate oxygen concentrations and 581 received 100% oxygen. Compared to infants that received room air, the primary outcome of death or neurodevelopmental impairment (NDI) was not different in intermediate oxygen (adjusted odds ratio (aOR) 1.01; 95% confidence interval (CI) 0.77, 1.34) or 100% oxygen (aOR 1.03; 95% CI 0.78, 1.35). Compared to room air, there was no difference in odds of death or severe NDI in intermediate oxygen (aOR 1.14; 95% CI 0.82, 1.58) or 100% oxygen group (aOR 1.22; 95% CI 0.90, 1.67). The odds of severe NDI among survivors were significantly higher in infants that received 100% oxygen as compared to room air (aOR 1.57, 95% CI 1.05, 2.35). CONCLUSIONS: We observed no significant difference in the primary composite outcomes of death or NDI and death or severe NDI at 18 to 21 months CA between infants that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. However, use of 100% oxygen was associated with increased odds of severe NDI among survivors as compared to room air.

Effect of Nasal Continuous Positive Airway Pressure (NCPAP) Cycling and Continuous NCPAP on Successful Weaning: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of nasal continuous positive airway pressure (NCPAP) cycling with continuous NCPAP in the successful weaning of preterm infants of 25(0)-28(6) wk gestation to nasal prongs. METHODS: A total of 30 infants with a gestational age (GA) of 25(0)-28(6) wk, ventilated for respiratory distress syndrome (RDS) and extubated to NCPAP were eligible for the study. They were randomized to NCPAP cycling [Group A: cycling between NCPAP of 4 cm and 1 liter per minute (LPM) of nasal prongs] or to continuous NCPAP at 4 cm of H2O (Group B). Primary outcome was successful weaning off NCPAP to nasal prongs at the end of 72 h of the intervention and remaining off NCPAP for the next 72 h. RESULTS: The demographic characteristics were similar in both the groups. Infants were randomized to Group A (n = 13) and Group B (n = 17). The primary outcome was not significantly different between the groups (successful weaning to nasal prongs: 31 vs. 41 %; p 0.71). CONCLUSIONS: In this pilot, feasibility study there were no differences in the rates of successful weaning of NCPAP to nasal prongs using either cycling NCPAP or continuous NCPAP in preterm infants. A need exists for a large randomized controlled trial (RCT) to determine the role of cycling NCPAP on neonatal outcomes.

Does chronic oxygen dependency in preterm infants with bronchopulmonary dysplasia at NICU discharge predict respiratory outcomes at 3 years of age?

OBJECTIVE: To determine whether chronic oxygen dependency at the time of discharge from the neonatal intensive care unit (NICU) in infants with bronchopulmonary dysplasia (BPD) predicts respiratory outcomes at 3 years. STUDY DESIGN: Preterm infants ⩽1250 g without BPD, BPD and BPD with chronic oxygen dependency were identified from the Southern Alberta Perinatal Follow-up clinic database (1995-2007). Respiratory outcomes at 4, 8, 18 and 36 months corrected age following NICU discharge were examined. Univariate analyses were done. RESULTS: Out of 1563 infants admitted to the NICU, 1212 survived. Complete follow-up data at 36 months were available for 1030 (85%) children. Children with BPD with or without chronic oxygen dependency had significantly (P<0.001) lower birth weights and gestational ages, and greater post-natal steroid use, compared with those with no BPD. At 4, 8 and 18 months follow-up, the use of respiratory medications and supplemental oxygen were both significantly higher in the BPD infants with chronic oxygen dependency group compared with the no-BPD group and BPD group. At 36 months, children in the BPD with chronic oxygen dependency group were more likely to use respiratory medications and supplemental oxygen vs the no-BPD or the BPD groups. At 4, 8 and 36 months of age, more children in the BPD with chronic oxygen dependency group had post-neonatal chronic lung disease (PNCLD) than children in the other groups, but at 36 months the difference was significant only for the BPD with chronic oxygen dependency vs no-BPD group (P<0.001). CONCLUSIONS: At 36 months, children diagnosed with BPD with chronic oxygen dependency at NICU discharge were more likely to need respiratory medications and supplemental oxygen in the previous 12 months, as compared with no-BPD or BPD groups. They were also more likely to require frequent physician visits and have PNCLD at 3 years, as compared with the no-BPD group.

Relationship between oxygen saturation and the mode of oxygen delivery used in newborn resuscitation.

OBJECTIVE: To compare the rate of increase in oxygen saturation in babies receiving supplemental oxygen during resuscitation with those transitioning in room air. STUDY DESIGN: Prospective observational study. Infants were resuscitated with supplemental oxygen and continuous recording of preductal oxygen saturation was started immediately after birth. Oxygen saturation measurements from healthy newborns transitioned in room air were used for comparison. RESULT: A total of 186 infants were included--70 received supplemental oxygen and 116 were transitioned in room air. Compared with healthy infants transitioned in room air, infants receiving 100% oxygen by positive-pressure ventilation (PPV) did not differ significantly in the rate of increase in oxygen saturation (1.5% per minute, P=0.26), whereas infants receiving 100% free-flow oxygen had a significantly slower rate of increase in oxygen saturation (1.2% per minute, P=0.04). CONCLUSION: Babies receiving 100% oxygen by free flow had a slower increase in oxygen saturation compared with healthy infants transitioned in room air, whereas those receiving 100% oxygen by PPV had a similar increase in oxygen saturation compared with healthy infants transitioned in room air.

Oestradiol-induced taste avoidance is the result of a conditioned palatability shift.

Taste avoidances were conditioned in male rats by pairing ingestion of a novel sucrose (0.3 M solution) taste with injections of 17 beta oestradiol (100 micrograms kg-1, s.c.). Following conditioning and prior to a two-bottle choice test (sucrose vs water), taste reactivity responses to three 30 s intraoral sucrose infusions were quantified. A robust conditioned shift in palatability, consisting of reduced ingestive and increased aversive taste reactivity responses, was obtained in the oestradiol group but not the vehicle control group. This conditioned palatability shift was also reflected in subsequent strong avoidance of the sucrose solution in the two-bottle choice test. The findings that oestradiol can condition taste aversions and shift food preferences support a role for oestrogens in the production of anorexia.

Alcohol-induced conditioned taste aversions in chemically labyrinthectomized rats.

Male rats were chemically labyrinthectomized (n = 22) by intratympanic injections of sodium arsanilate, and control rats (n = 15) received intratympanic injections of isotonic saline. All rats were tested for labyrinthine integrity and then adjusted to a 23 h.d-1 water deprivation schedule. Both labyrinthectomized and control rats were exposed to a conditioned taste aversion (CTA) procedure or a control procedure. The CTA technique involved pairing a novel saccharin taste with subsequent intraperitoneal injection of ethanol (1.5 g.kg-1; 15% solution). The control CTA procedure paired a novel saccharin taste with injections of isotonic saline. Following two conditioning trials and 3 d of water only, saccharin preference ratios were obtained in two-bottle choice tests (saccharin vs. water) over 4 consecutive days. Control rats conditioned with ethanol exhibited a strong CTA (p < 0.01) relative to control rats injected with saline. Labyrinthectomized rats drinking saccharin followed by ethanol injections showed a strong CTA (p < 0.01) if conditioning occurred 29-30 d post-labyrinthectomy. However, CTA's were not apparent in labyrinthectomized rats conditioned with ethanol 19 d post-labyrinthectomy. Thus, ethanol-induced CTA formation varied across the post-labyrinthectomy time period.

Reductions in body temperature and spontaneous activity in rats exposed to horizontal rotation: abolition following chemical labyrinthectomy.

The effect of horizontal rotation of male rats (70 rpm) on core temperature and spontaneous motor activity levels was examined. In Experiment 1, subjects were chemically labyrinthectomized (VNX) by intratympanic (IT) injections of sodium arsanilate and control rats (VNS) received IT injections of saline. Half of the rats in each group were subsequently rotated and the other half sham rotated. Measurement of body temperature prior to, immediately after, and 20 min following rotation revealed significant (all p < 0.01) reductions in temperature immediately after treatment, and 20 min later, in VNS rats. Sham-rotated VNS and all VNX rats failed to exhibit any significant changes in temperature following treatment. In Experiment 2, motor activity level was monitored in chemically labyrinthectomized (VNX) and control (VNS) rats prior to, and following, horizontal rotation. The VNS rats exhibited large (all p < 0.01) depressions in measures of horizontal and vertical spontaneous motor activity following rotation treatment, whereas VNX rats exhibited similar levels of activity in the pre- and postrotation period. These experiments show that, as in humans, exposing rats to horizontal rotation results in reduction of body temperature and motor activity, and that these physiological and behavioral changes require a functional vestibular system.